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(BQ) Part 2 book Transplant infections presents the following contents: Viral infections, fungal infections, infection control, immune reconstitution strategies for prevention and treatment of infections, hot topics.
58202_ch22.qxd 2/1/10 SECTION 8:49 PM Page 311 V ■ Viral Infections CHAPTER Cytomegalovirus Infection after Stem Cell Transplantation 22 MORGAN HAKKI, MICHAEL J BOECKH, PER LJUNGMAN VIRUS STRUCTURE AND REPLICATION Human cytomegalovirus (HCMV) is a member of the beta ( ) subfamily of the herpesviridae, along with human herpesvirus (HHV)-6 and HHV-7 The CMV virion is composed of a double-stranded DNA genome encased in an icosahedral capsid Surrounding the capsid is a region known as the tegument (or matrix) and an outermost lipid membrane containing viral glycoproteins, which mediate viral binding to and entry into the host cell The genome contains approximately 230 thousand base pairs of DNA that encode approximately 200 proteins, and is organized into long and short unique segments that are flanked by inverted repeats (1,2) CMV genes are named based on their position within each segment of the genome For example, UL97 is the 97th open reading frame (ORF) in the unique long segment Some genes also have names based on historical usage or homologies to genes of other herpesviruses; UL55, for example, is also known as glycoprotein B CMV grows in a limited number of cell lines in the laboratory, such as diploid human fibroblasts, endothelial cells, and macrophages During human infection, however, CMV has been found in a wide range of cells, including endothelial cells, epithelial cells, blood cells including neutrophils, and smooth muscle cells (3) The presence of CMV in these cells may be due to active replication within the cell, phagocytosis of CMV proteins, or abortive (incomplete) replication, and likely contributes to dissemination and transmission The ability to persist in a latent state in which evidence of viral replication is undetectable but replication-competent virus is present is a hallmark of herpesviruses In the case of CMV, little is known about the site or mechanisms of latency Since CMV can be transmitted from seropositive blood donors, a blood component is likely to be one site of latency Several studies support the idea that cells of the granulocyte–monocyte lineage harbor latent CMV (4–6) Transplantation of solid organs clearly can transmit CMV, so it is possible that cells other than those mentioned above can harbor and transmit latent CMV However, whether the latently infected cell type in these organs is transitory blood cells, macrophages, or permanent cells is not yet clear INTERACTION OF CMV WITH THE HOST IMMUNE SYSTEM Adaptive Immunity The importance of a competent immune system in controlling CMV replication is manifested by the clear association of immunosuppression with CMV disease The role of humoral immunity in controlling CMV replication is not clear Antibodies to multiple different CMV proteins, primarily glycoproteins B (gB) and H (gH), develop during infection (7–9) Although antibodies to gB and gH can neutralize the virus in cell culture, they not appear to prevent primary infection in adults, but rather may function to limit disease severity (10,11) Paramount in controlling CMV replication is T-cell mediated cellular immunity CMV provokes a robust CD8ϩ cytotoxic T lymphocyte (CTL) response, and the proportion of circulating CD8ϩ T-cells in healthy individuals that are specific for CMV antigens ranges from 10% to 40%, depending on the age of the person (12–17) Numerous CMV proteins are targeted by the CD8ϩ T-cell response, the most immunodominant ones being the gene products of UL123 (IE-1), UL122 (IE-2), and UL83 (pp65) (14,17–23) Lack of CMV-specific CD8ϩ CTL responses predispose to CMV infection, whereas reconstitution of CMV-specific CD8ϩ CTL responses after hematopoietic cell transplantation (HCT) correlates with protection from CMV and improved outcome of CMV disease (24–28) After HCT, detectable CMV-specific CD4ϩ responses are associated with protection from CMV disease (24,29–31) The lack of CMV-specific CD4ϩ cells is associated with late CMV disease and death in patients who have undergone HCT (32) CMV-specific CD4ϩ cells likely function at least in part by helping to maintain robust CMV-specific CD8ϩ cell responses (28,33) Innate Immunity Innate immunity also functions to control CMV replication CMV triggers cellular inflammatory cytokine production upon binding to the target cell, mediated in part by the interaction of gB and gH with toll-like receptor (TLR) (34–36) Polymorphisms in TLR2 have been associated with CMV 311 58202_ch22.qxd 312 2/1/10 Section V 8:49 PM ■ Page 312 Viral Infections infection after liver transplantation (37) In mouse studies, TLR3 and TLR9 proved to be important components in limiting murine cytomegalovirus (MCMV) replication (38,39) Natural killer (NK) cells represent another arm of the innate immune response and have been shown to limit MCMV replication in mice (25,40–44) In humans, NK cell responses increase during CMV infection after renal transplantation, and a deficiency in NK cells is associated with severe CMV infection (among other herpesviruses) (45,46) The genotype of the donor activating killer immunoglobulin-like receptor (aKIR), which regulates NK cell function, has recently been demonstrated to influence the development of CMV infection after allogeneic HCT (47–49) The mechanisms behind these associations are not fully understood and these findings require validation in independent cohorts Finally, polymorphisms in chemokine receptor (CCR5) and interleukin (IL)-10 have been associated with CMV disease, whereas polymorphisms in monocyte chemoattractant protein (MCP-1) are associated with reactivation after allogeneic HCT (50) Much more work needs to be done to determine the role(s) of these components of innate immunity in regulating CMV replication in humans Immune Evasion An array of CMV genes has been found to function in immune evasion For example, CMV has genes that inhibit apoptosis (51), major histocompatibility complex (MHC)-I-restricted antigen presentation (52), and interferon-mediated pathways (53–56) CMV also encodes several homologues of cellular proteins, including MHC class-I molecules, CCRs, IL-10, TNF receptors, and CXC-1 homologues, that function to evade the host immune response (57–61) DIAGNOSTIC METHODS The serologic determination of IgG and IgM has an important role in determining a patient’s risk for CMV infection after transplantation (see “Risk Factors” section) or during immunosuppressive therapy, but is not useful in the diagnosis of CMV infection or disease Growth of CMV in tissue culture takes several weeks, limiting its clinical usefulness as a diagnostic tool Culture-proven viremia is highly predictive of CMV disease, but is of limited utility for screening since this finding frequently coincides with the onset of symptomatic disease (62–64) The shell-vial technique, in which monoclonal antibodies are used to detect CMV immediate-early proteins in cultured cells, can be performed within 18 to 24 h after inoculation This assay is not sensitive enough to use for routine blood monitoring (63), but is highly useful on bronchoalveolar lavage (BAL) fluid in the diagnosis of CMV pneumonia (65) The detection of the CMV pp65 tegument phosphoprotein in peripheral blood leukocytes offers a rapid, sensitive, and specific method of diagnosing CMV viremia In this assay, peripheral leukocytes are spread on a glass slide, stained with a fluorescent antibody directed against pp65, and the number of positive cells is reported per number of total leukocytes on the slide, thereby providing a rough quantitative assessment of the circulating viral load In the transplant setting, a positive CMV pp65 assay has been shown to predict the development of invasive disease (66,67) Since this assay relies on the detection of pp65 in circulating leukocytes, it may not be reliable in patients with profound leukopenia The predictive value of this assay has not been validated when performed on other body fluids such as BAL fluid Quantitative polymerase chain reaction (qPCR) relies on the amplification and quantitative measurement of CMV DNA PCR is the most sensitive method for detecting CMV (68), whereas at the same time maintaining high specificity In addition, it is very rapid, with results usually available within 24 h qPCR provides a direct quantitative measurement of CMV viral load, which is an accurate predictor of CMV disease after transplantation (32,69–72) qPCR testing has become the standard method for detecting CMV in blood (either whole blood or plasma) and spinal fluid at many, if not most, institutions Although PCR has been used on BAL fluid (73), viral-load cut-offs have not been defined And even though the sensitivity and negative predictive values are very high, the specificity and positive predictive values are not known The detection of CMV mRNA by nucleic acid sequencebased amplification (NASBA) on blood samples has proven to be as useful as DNA PCR or p65 antigenemia for guiding preemptive therapy after HCT (74,75) However, this method has not been as widely adopted as the pp65 antigenemia- or PCRbased assays The presence of characteristic CMV “owl’s eye” nuclear inclusions in histopathology specimens is useful in the diagnosis of invasive CMV disease This method has relatively low sensitivity, but can be enhanced by use of immunohistochemical techniques to identify CMV antigens even when classic inclusions may not be evident CLINICAL MANIFESTATIONS Care must be taken to distinguish CMV “infection” from CMV “disease.” CMV infection simply indicates the detection of CMV, typically by DNA PCR, pp65 antigenemia, or mRNA NASBA, from plasma or whole blood in a CMV-seronegative patient (primary infection) or a CMV-seropositive patient (reactivation of latent virus or superinfection with another strain of CMV) (76,77) International definitions of CMV disease, broadly defined as the presence of symptoms and signs compatible with CMV 58202_ch22.qxd 2/1/10 8:49 PM Page 313 Chapter 22 end-organ involvement along with the detection of CMV using a validated method in the appropriate clinical specimen, have been published (78) Fever is a common manifestation, but may be absent in patients receiving high-dose immunosuppression Almost any organ can be involved in CMV disease and therefore CMV infection has protean manifestations Pneumonia is the most important clinical manifestation of CMV disease due to its high associated mortality Patients who have undergone autologous or allogeneic HCT have mortality rates of 60% to 90% (79–81) This unacceptably high mortality rate has not changed much in the past 20 years, indicating that much more work needs to be done in order to optimize the management of these patients CMV pneumonia often manifests with fever, nonproductive cough, hypoxia, and interstitial infiltrates on radiography Rarely, nodules may be observed on radiography The onset of symptoms can occur over to weeks, often times with rapid progression to respiratory failure and the requirement for mechanical ventilation The diagnosis of CMV pneumonia is established by detection of CMV by shell-vial culture, or histology in BAL or lung biopsy specimens in the presence of compatible clinical signs and symptoms Pulmonary shedding of CMV is common, but CMV detection in BAL from asymptomatic patients who underwent routine BAL screening at day 35 after HCT was predictive of subsequent CMV pneumonia in approximately two thirds of cases (82) Therefore, the presence of CMV in a BAL specimen in the absence of clinical evidence of CMV disease must be interpreted with caution We not recommend PCR testing on BAL fluid since there is little data correlating CMV DNA detection by PCR in BAL fluid with CMV pneumonia However, due to the high negative predictive value afforded by its high sensitivity, a negative PCR result can be used to rule out the diagnosis of CMV pneumonia (73) CMV can affect any part of the gastrointestinal tract from the esophagus to the colon Esophagitis typically results in odynophagia, whereas abdominal pain and hematochezia occur with colitis Ulcers extending deep into the submucosal layers are seen on endoscopy, and visual differentiation of these lesions from other processes that may affect the gastrointestinal tract in these populations, such as graft-versus-host (GVHD) disease, is often difficult The diagnosis of gastrointestinal disease relies on detection of CMV in biopsy specimens by culture and/or histology Given the relative lack of sensitivity of each method, both methods should be used on biopsy specimens to diagnose CMV disease Notably, gastrointestinal disease can occur in the absence of CMV detection in the blood (83,84) Retinitis is relatively uncommon after HCT (85–88) Decreased visual acuity or blurred vision are typical presenting symptoms, and approximately 60% of patients will have involvement of both eyes (86) Most cases present later than day 100 after transplantation and are associated with prior ■ Cytomegalovirus Infection after Stem Cell Transplantation 313 CMV reactivation, delayed lymphocyte engraftment, and GVHD (86) Other manifestations, including hepatitis, encephalitis, and infection of the bone marrow resulting in myelosuppression, are all rare with current preventative strategies RISK FACTORS Allogeneic HCT Recipients In the setting of allogeneic HCT, the most important risk factor is the serological status of the donor and recipient CMV-seronegative patients who receive stem cells from a CMV-seronegative donor (DϪ/RϪ) have a very low risk of primary infection Primary infection can still occur if CMV is transmitted in transfused blood products or is acquired via sexual contact or through contact with another individual with primary CMV infection Approximately 30% of seronegative recipients who receive stem cells from a seropositive donor (Dϩ/RϪ) will develop primary CMV infection due to transmission of latent CMV via the allograft Although the risk of CMV disease is low due to pre-emptive treatment of CMV infection, mortality due to bacterial and fungal infections in these patients is higher than in similarly matched DϪ/RϪ transplants (18.3% vs 9.7%, respectively) (89) The reason for this is not entirely clear, one hypothesis being that CMV infection after HCT has additional immunomodulating effects (indirect effects) that increase a patient’s susceptibility to infection with other, unrelated organisms Without prophylaxis, approximately 80% of CMVseropositive patients will experience CMV infection after allogeneic HCT Again, current preventative strategies have resulted in a substantial decrease in the incidence of CMV disease, which had historically occurred in 20% to 35% of these patients (90) Although a CMV-seropositive recipient is at higher risk for transplant-related mortality (TRM) than a seronegative recipient (91,92), the impact of donor serostatus when the recipient in seropositive remains controversial Some studies have reported a beneficial effect of having seropositive donor with regards to a reduction in relapse- or nonrelapserelated mortality (NRM), whereas other studies have found no such benefit (93–104) A large CIBMTR study is presently underway to reconcile these controversial findings However, although the effects on NRM and overall survival are controversial, this serological combination has been reported as a risk factor for delayed CMV-specific immune reconstitution (105–108), CMV reactivation (106,109), late CMV recurrence (110), and CMV disease (72,106,111) Other risk factors for CMV infection after allogeneic HCT include the use of steroids at doses greater than mg/kg body weight/day, T-cell depletion, acute and chronic GVHD, and the use of mismatched or unrelated donors (69,72,111–115) 58202_ch22.qxd 314 2/1/10 8:49 PM Section V ■ Page 314 Viral Infections Whether the source of stem cells (peripheral blood vs bone marrow) has a significant impact on the development of CMV infection and disease is not clear, as several studies have yielded conflicting results (111,115–117) Interestingly, the use of sirolimus for GVHD prophylaxis appears to protect against CMV infection, possibly due to the inhibition of cellular signaling pathways that are co-opted by CMV during infection for synthesis of viral proteins (111,118) Late CMV Infection after Allogeneic HCT Whereas CMV was typically seen by 100 days after allogeneic HCT (119), in the current era of pre-emptive ganciclovir therapy, it has become a significant problem after day 100 following allogeneic HCT (32,110,120) In the absence of specific preventative measures, 15% to 30% of allogeneic HCT patients will experience late CMV infection and 6% to 18% will consequently develop the disease (32,69,110,121–123) Late CMV infection is strongly associated with NRM (110) Several factors predict the development of late CMV infection (Table 22.1) (24,30,32,110,112) Measures such as prolonged courses of therapy and continued weekly surveillance (Table 22.1) are warranted in these patients in order to reduce the risk of late CMV disease (32,123,124) Nonmyeloablative HCT The use of matched, related nonmyeloablative conditioning regimens generally results in a less CMV infection and disease early after HCT compared to standard myeloablative regimens (113,124) However, by year after HCT, the risk of CMV infection and disease is equal among nonmyeloablative and myeloablative groups (124,125) Conditioning regimens that include T-cell depletion show no reduction in CMV after nonmyeloablative transplantation compared to myeloablative regimens (126), and matched, unrelated nonmyeloablative TABLE 22.1 transplantation carries the same risk of CMV infection and disease as does myeloablative transplantation (124) Autologous HCT and Umbilical Cord Blood Transplantation After autologous transplantation, approximately 40% of seropositive patients will have detectable CMV infection (79,127) Although CMV disease is rare after autologous transplantation (116,128–130), the outcome of CMV pneumonia is similar to that after allogeneic HCT (79,131,132) Risk factors for CMV disease after autologous transplantation include CD34ϩ selection, high-dose corticosteroids, and the use of total-body irradiation or fludarabine as a part of the conditioning regimen (116) Therefore, although CMV is not typically considered a significant pathogen after autologous HCT, certain patients who are at high risk for CMV in this setting merit routine surveillance and pre-emptive therapy Umbilical cord blood transplantation (CBT) is a technique that is now utilized when a suitable donor for bone marrow or peripheral blood stem cell transplantation is not available (133) Since most infants are born without CMV infection, the transplanted allograft is almost always CMV-negative Among CMV-seropositive recipients who not receive antiviral prophylaxis, the rate of CMV infection after CBT is 40% to 80%, with one study reporting 100% (134–138) When patients receive prophylaxis with high-dose valacyclovir after CBT, it does not appear that CBT entails a significantly greater risk of CMV infection and disease than does peripheral blood stem cell or bone marrow transplantation (115) Impact of Novel Immunosuppressive Agents The increasing use of immunomodulating monoclonal antibodies in the setting of HCT and hematological malignancies poses a new risk for CMV infection (139) Alemtuzumab is an CMV Infection and Disease after Day 100 Following Allogeneic HCT: Risk Factors, Surveillance Strategies, and Treatment • Risk factors -CMV infection or disease before day 100, or use of prophylaxis (ganciclovir, valganciclovir, foscarnet, and cidofovir), PLUS any one of • Lack of CMV-specific T-cell immune reconstitution • Acute or chronic GVHD requiring systemic immunosuppression • Lymphopenia • Mismatched/unrelated transplant • Surveillance -Weekly PCR screening until • Immunosuppression tapered (Ͻ0.5 mg/kg/day prednisone, no further anti-T-cell therapy), and • Three consecutive negative assays • Pre-emptive therapy -IV ganciclovir or oral valganciclovir (if oral absorption is reliable) induction until viral load declines (at least week) or foscarnet in the setting of neutropenia -Maintenance therapy until viremia is cleared 58202_ch22.qxd 2/1/10 8:49 PM Page 315 Chapter 22 anti-CD52 monoclonal antibody that results in CD4ϩ and CD8ϩ lymphopenia that can last for up to months after administration CMV infection typically occurs during the period of maximal immunosuppression, which is to weeks after alemtuzumab therapy (140,141) Patients who received alemtuzumab as a part of the conditioning regimen or for GVHD prophylaxis during HCT experienced a higher rate of CMV infection compared to matched controls not receiving alemtuzumab (142,143) PREVENTION OF CYTOMEGALOVIRUS INFECTION AND DISEASE Pre- and Posttransplant Risk Reduction CMV serological status of the recipient and donor should be assessed as early as possible prior to HCT, as this is the most important predictor of subsequent CMV infection For the seronegative recipient, the main goal is to prevent primary CMV infection Therefore, recipients who are CMV seronegative before allogeneic HCT should ideally receive a graft from a CMV-negative donor Weighing the factor of donor CMVserostatus compared to other relevant donor factors, such as human leukocyte antigen (HLA)-match, is difficult No data exist indicating whether study HLA-matching is more important compared to CMV-serostatus in affecting a good outcome for the patient Given the choice, an antigen-matched donor for HLA-A, B, or DR would most likely be preferred to a CMV-negative donor For lesser degrees of mismatch (allelemismatches or mismatches on HLA-C, DQ, or DP), the CMV-serostatus of donor should be considered a factor even if the match was poorer Compared to other donor factors such as age or blood group, a CMV-seronegative donor would have preference The transfusion of blood products represents a significant source for CMV transmission in D−/R− patients (144) To reduce this risk, blood products from CMV seronegative donors or leukocyte-reduced, filtered blood products should be used in this setting (145–147) It is not clear which strategy is the most effective (148,149), and no controlled study has investigated whether there is an extra benefit from the use of both methods Immunoprophylaxis Intravenous immune globulin (IVIG) is not reliably effective as prophylaxis against primary CMV infection One study demonstrated a reduction in the rate of CMV infection but not disease with the use of CMV-specific immunoglobulin (150), whereas another study was unable to confirm protection from infection using anti-CMV hyperimmune globulin (151) Similarly negative results were observed using a CMV-specific ■ Cytomegalovirus Infection after Stem Cell Transplantation 315 monoclonal antibody (152) Likewise, the effect of immunoglobulin on reducing CMV infection in seropositive patients is modest, and no survival benefit among those receiving immunoglobulin has been reported in any study or metaanalysis (153–158) Therefore, the prophylactic use of immune globulin is not recommended Antiviral Prophylaxis and Pre-Emptive Therapy The prophylactic or pre-emptive use of antiviral agents after HCT has markedly reduced the incidence of early CMV disease and has improved survival among certain high-risk populations (63,112,159) Prophylaxis denotes the routine administration of antivirals to all at-risk patients regardless of the presence of active CMV infection Pre-emptive therapy, on the other hand, withholds antiviral therapy until CMV infection is detected, but prior to the development of CMV disease Both prophylaxis and pre-emptive therapy have their benefits and drawbacks Since prophylaxis involves the treatment of all at-risk patients, close monitoring is not required when ganciclovir or foscarnet are used, making this the easier strategy conceptually and useful in situations where rapid, sensitive CMV diagnostic methods are not available Additionally, prophylaxis may prevent the indirect effects associated with CMV infection However, since not all at-risk patients will experience CMV infection, prophylaxis strategies result in some patients receiving the drug unnecessarily, thereby exposing the patient to potential drug-related toxicities without discernable benefit This is not an issue with pre-emptive treatment, since by definition all patients who receive treatment will have active CMV infection The success of the pre-emptive treatment strategy is largely dependent on the early detection of viremia This, in turn, depends on access to rapid, sensitive CMV surveillance methods and on strict adherence to a surveillance-testing schedule By allowing a limited amount of viral replication, pre-emptive therapy may stimulate immune responses and thereby promote CMV-specific immune reconstitution (24) Since both strategies are equally effective in preventing CMV disease (159), most transplant centers have moved toward pre-emptive strategies as pp65 antigenemia and DNA PCRbased diagnostics techniques have become readily available (160–162) More recently, there has been great interest in utilizing methods to determine CMV-specific immune reconstitution after HCT as an additional means to stratify risk of CMV infection and disease (immune monitoring) and further tailor surveillance and pre-emptive therapy strategies The types of assays used, their strengths and limitations, and their predictive value in terms of CMV infection and disease after transplantation have been extensively reviewed elsewhere (12,163) The utility of measuring T-cell responses as a guide for withholding therapy was evaluated in a small pilot study involving 58202_ch22.qxd 2/1/10 316 Section V 8:49 PM ■ Page 316 Viral Infections HCT recipients more than 100 days after transplant (105) Although promising, the use of immune monitoring in this fashion requires validation in larger, randomized trials before it can be recommended Antiviral Agents Several antiviral drugs that demonstrate activity against CMV are available once the decision is made to employ either prophylaxis or pre-emptive treatment (Table 22.2) High-dose acyclovir reduces the risk for CMV infection and possibly disease (164,165) Valacyclovir is the valin-ester prodrug of acyclovir and is better absorbed, thereby attaining higher serum concentrations than acyclovir High-dose valacyclovir is more effective than acyclovir in reducing CMV infection and the need for pre-emptive therapy with ganciclovir after HCT, although the impact of this on survival after HCT is not clear (166) Routine monitoring for CMV infection is still required if valacyclovir or acyclovir prophylaxis is used TABLE 22.2 Ganciclovir is a nucleoside analogue of guanosine that acts as a competitive inhibitor of deoxyguanosine triphosphate incorporation into viral DNA A CMV gene, UL97, encodes a phosphotransferase that converts ganciclovir to ganciclovir monophosphate Cellular enzymes then convert ganciclovir monophosphate to the active triphosphate form Ganciclovir is currently the first-line agent for CMV prophylaxis and pre-emptive treatment barring contraindications Intravenous ganciclovir has been demonstrated to reduce the risk of CMV infection and disease compared to placebo, but did not improve overall survival (159,167–169) Neutropenia occurs in up to 30% of HCT recipients during ganciclovir therapy (170), thereby placing the patient at risk of invasive bacterial and fungal infections (159,167,170) Neutropenia often responds to dose reduction and support with granulocyte-colony stimulating factor, but occasionally discontinuation of ganciclovir is required, in which case foscarnet is typically the second-line agent of choice Measurement of ganciclovir concentrations can be helpful to guide therapy Antiviral Agents used for Prophylaxis, Pre-Emptive Therapy, and Treatment of CMV Disease after HCT Dose Based on Reason for Use Agents Toxicities Prophylaxis Pre-emptive Therapy Treatment of Disease Acyclovir Local injection reactions (IV), nephrotoxicity, headache, and nausea IV: 500 mg/m2 t.i.d., PO: 800 mg q.i.d (ജ40 kg) or 600 mg/m2 q.i.d (Ͻ40 kg) Not recommended Not recommended Valacyclovir Gastrointestinal upset, neutropenia, and TTP/HUSa g t.i.d to q.i.d (ജ40 kg) Not recommended Not recommended Ganciclovir Neutropenia, thrombocytopenia, and nephrotoxicityb Induction: mg/kg b.i.d., maintenance: mg/kg/day Induction: mg/kg b.i.d., maintenance: mg/kg/day Induction: mg/kg b.i.d., maintenance: mg/kg/day Valganciclovir Neutropenia, headache, nausea, and diarrhea Not established Induction: 900 mg b.i.d (ജ40 kg), maintenance: 900 mg/kg/day (ജ40 kg) Not established Cidofovir Nephrotoxicity Not established Induction: Induction: 3–5 mg/kg/week ϫ 2–3 doses 3–5 mg/kg/week for doses maintenance not established maintenance 3–5 mg/kg/every other week Foscarnet Nephrotoxicity, metabolic Induction: 60 mg/kg b.i.d., maintenance: Induction: 60 mg/kg b.i.d., maintenance: abnormalities c, and anemia aCausality bTypically 90–120 mg/kg/day 90 mg/kg/day remains to be determined observed with the concomitant use of nephrotoxic immunosuppressive agents cHypercalcemia, hypomagnesemia, hypokalemia, and hypo- or hyperphosphatemia Requires careful monitoring Induction: 60 mg/kg b.i.d or t.i.d maintenance: 90 mg/kg/day 58202_ch22.qxd 2/1/10 8:49 PM Page 317 Chapter 22 and reduce the risk for toxicity especially in the situation of pre-existing renal impairment Valganciclovir is the orally available prodrug of ganciclovir and achieves serum concentrations at least equivalent to intravenous ganciclovir (171–173) The results of several uncontrolled studies suggest that valganciclovir is comparable to intravenous ganciclovir in terms of efficacy and safety when used as pre-emptive therapy after allogeneic HCT (171, 174–176) As of the writing of this chapter, no data comparing valganciclovir to intravenous ganciclovir in the setting of a randomized, controlled trial have been published Preliminary data from a randomized trial have been presented indicating little or no difference in efficacy or toxicity compared to intravenous ganciclovir (177) Until more data are available, caution should be exercised when choosing valganciclovir as pre-emptive therapy Foscarnet is a pyrophosphate analogue that binds directly to and competitively inhibits the CMV DNA polymerase Foscarnet is generally considered to be as effective as ganciclovir for pre-emptive therapy after allogeneic transplantation (178) However, three uncontrolled studies have documented cases of breakthrough CMV disease during foscarnet therapy (179–181) These findings, combined with commonly encountered toxicities of foscarnet, have led to the use of foscarnet as a second-line agent when ganciclovir is contraindicated or not tolerated Cidofovir is a cytosine nucleotide analogue that does not require phosphorylation by viral enzymes for antiviral activity Cellular enzymes convert cidofovir to cidofovir triphosphate, which then inhibits the CMV DNA polymerase The long half-life of cidofovir allows a once-per-week dosing schedule However, the major toxicity with cidofovir—acute renal tubular necrosis—limits its utility after HCT, and it should therefore be considered third-line therapy after ganciclovir and foscarnet (182) Monitoring for CMV Infection and Initiation of Pre-Emptive Therapy qPCR assays for CMV DNA are increasingly used for surveillance because they offer two advantages First, they are more sensitive than pp65 antigenemia, thereby prompting treatment initiation in cases of CMV disease that have been missed with the pp65 antigenemia assay (159) Additionally, the quantitative nature of the assay may enable the development of institutionspecific viral load thresholds for beginning treatment, thereby avoiding unnecessary treatment of patients who are at low risk of progression to disease It has been reported that the initial viral load as well as the viral load kinetics are important as risk factors for CMV disease (183) Currently, there are no validated universal viral load thresholds, and such thresholds would be difficult to establish due to differences in assay performance and testing material (whole blood vs plasma) (184) ■ Cytomegalovirus Infection after Stem Cell Transplantation 317 With the exception of those receiving ganciclovir prophylaxis, all patients who have undergone allogeneic HCT, regardless of pretransplant donor and recipient serostatus, should be monitored on a weekly basis for CMV infection using pp65 antigenemia, DNA PCR, or mRNA NASBA Although CMV infection is rare in DϪ/RϪpatients, routine monitoring was effective in identifying CMV infection and preventing disease in a large cohort (185) Monitoring is generally performed until day 100 after engraftment or longer in patients at risk for late CMV disease (Table 22.1) The ideal duration and frequency of CMV monitoring in the later transplantation periods have not been determined (123,124) Routine monitoring of autograft recipients is not recommended, with the exception being high-risk patients as described above (161,162,186) A general approach to prophylaxis and pre-emptive therapy is presented in Table 22.3 If a pre-emptive strategy is used, the initial detection of CMV in peripheral blood after allogeneic HCT should prompt the initiation of antiviral therapy and a thorough evaluation of the patient in order to assess for signs and symptoms concerning for CMV disease (186) Various durations of pre-emptive antiviral treatment have been explored Initial studies administered ganciclovir until day 100 after engraftment, which ultimately entailed approximately to weeks of therapy in the average recipient Studies from the mid-1990s using short courses (2 to week) of ganciclovir based on negative PCR assays at the end of therapy were generally effective; however, resumption of pre-emptive therapy was necessary in approximately 30% of patients (63,178,188) Most centers now continue antiviral treatment until the designated viral marker is negative and the patient has received at least weeks of antiviral therapy If less sensitive markers than DNA PCR, such as the pp65 antigenemia assay, are used, then pre-emptive therapy should be continued until two negative assays are obtained (178) If a patient is still viremic by PCR or pp65 antigenemia assay after weeks of therapy, treatment should be extended at maintenance dosing until clearance is achieved It has been shown that a low rate of viral load decrease is a risk factor for later-occurring CMV disease (72) SPECIAL POPULATIONS Patients with CMV infection occurring prior to planned allogeneic HCT have a very high risk of death after transplantation (189) After transplantation, a patient with documented pretransplant CMV infection should either be monitored for CMV very closely (i.e., twice weekly), or be given prophylaxis with ganciclovir or foscarnet The optimal approach to CMV after CBT is not clear One study described successful pre-emptive treatment with ganciclovir (138), whereas another combined high-dose valacyclovir prophylaxis with continued monitoring and 318 pp65 Ag у cells/slide (or at any level if CD34ϩselected graph) At engraftment Ͻ100 days Ͻ100 days GCV mg/kg IV q.d GCV mg/kg IV q.d GCV mg/kg IV q.d GCV mg/kg IV q.d First Line Choice: Maintenance be combined with active surveillance for CMV infection use of total body irradiation (TBI) in conditioning, recent fludarabine or 2-chlorodeoxyadenosine, high-dose corticosteroids GCV mg/kg IV b.i.d ϫ 5–7 days GCV mg/kg IV b.i.d ϫ days and declining viral load GCV mg/kg IV b.i.d ϫ 7–14 days and declining viral load GCV mg/kg IV b.i.d ϫ 7–14 days and declining viral load First-Line Choice: Induction Foscarnet, acycyclovir,b and valacyclovirb Foscarnet, valganciclovir and cidofovir Valganciclovir, foscarnet Foscarnet, valganciclovir, and cidofovir Alternative Day 100 after HCT Until in dicator assay negative and weeks therapy Until in dicator assay negative and 2–3 weeks therapy Indicator test negative and 2–3 weeks Duration Transplant 2009;15(10):1143–1238; Bone Marrow Transplant 2009;44(8):part Association of Medical Microbiology and Infectious Diseases Canada (AMMI), the Centers for Disease Control and Prevention (CDC), and the Health Resources and Services Administration (HRSA) Biol Blood Marrow Marrow Transplantation (ASBMT), the Canadian Blood and Marrow Transplant Group (CBMTG), the Infectious Disease Society of America (IDSA), the Society for Healthcare Epidemiology of America (SHEA), the International Blood and Marrow Transplant Research (CIBMTR®), the National Marrow Donor Program (NMDP), the European Blood and Marrow Transplant Group (EBMT), the American Society of Blood and Modified from Tomblyn M, Chiller T, EinseleH, et al Guidelines for Preventing Infectious Complications among Hematopoietic Cell Transplant Recipients: A Global Perspective Recommendations of the Center for bMust aIncludes Allogeneic HCT recipients pp65 Ag у cells/slide or у consecutively positive PCR / viremia Ͼ100 days Allogeneic HCT or GVHD requiring steroid therapy or early CMV infection Autologous HCT and CMVseropositive and at high riska Prophylaxis At first detection of CMV infection Ͻ100 days Allogeneic HCT recipients Initiation Pre-emptive Timing Post-HCT 8:49 PM Patient Population Strategies for Pre-Emptive Therapy and Prophylaxis after HCT 2/1/10 Prevention Strategy TABLE 22.3 58202_ch22.qxd Page 318 58202_ch22.qxd 2/1/10 8:49 PM Page 319 Chapter 22 pre-emptive therapy (115) Due to initial experience in Seattle suggesting a high rate of infection and disease early posttransplant, the latter approach, coupled with ganciclovir prophylaxis for the week prior to transplant and continued CMV surveillance posttransplant, has been adopted Antiviral Resistance Drug resistance is relatively uncommon after HCT but can occur with all drugs used for the treatment and prophylaxis of CMV Risk factors for drug resistance include prolonged (months) antiviral therapy, intermittent low-level viral replication in the presence of drug due to profound immunosuppression or suboptimal drug levels, and lack of prior immunity to CMV (190) Drug resistance should be suspected in patients that are on an appropriate dosage of an antiviral drug and who have increasing quantitative viral loads for more than weeks After start of antiviral therapy in treatment-naïve patients, an increase in the viral load will occur in approximately one third of patients and is likely due to the underlying immunosuppression, not true drug resistance (67) If a patient has received ganciclovir before transplantation or if viral load increases occur in the late setting where most patients are not antiviral drug naïve anymore, drug resistance should be suspected An approach to the patient with suspected drug-resistant CMV is presented in Figure 22.1 Since ganciclovir is used as a first-line agent in most cases of CMV infection, resistance to ■ Cytomegalovirus Infection after Stem Cell Transplantation this antiviral is the most commonly encountered problem Resistance is most often due to mutations in the UL97 gene, and less often to mutations in the UL54-encoded DNA polymerase UL97 mutations that confer resistance have been described and genotypic assays are available for diagnostic analysis in reference laboratories (191) Phenotypic testing can be performed, but this type of assay is time-consuming and is therefore not as helpful as rapid genotypic testing in guiding patient management However, since different UL97 mutations confer varying degrees of ganciclovir resistance, some cases of genotypically defined ganciclovir-resistant CMV may still respond to ganciclovir therapy (192) and therefore care must be taken in interpreting genotype results If ganciclovir resistance is documented or suspected, foscarnet is generally the second-line agent of choice Unlike ganciclovir, foscarnet activity is not dependent on phosphorylation by the UL97 gene product; thus, CMV that has acquired ganciclovir resistance due to UL97 mutations will still be susceptible to foscarnet (193) Studies evaluating the utility of combination therapy of foscarnet and ganciclovir for ganciclovir-resistant CMV disease have been inconclusive and therefore this strategy is not routinely recommended (194) Resistance to foscarnet can occur and is due to mutations in UL54 Interestingly, cross-resistance between foscarnet and ganciclovir does not occur, as mutations in UL54 conferring resistance to foscarnet occur in regions distinct from those conferring ganciclovir resistance (195) Suspicion of ganciclovir (GCV) or valganciclovir (VGCV)resistance: Rising viral load after two weeks of ongoing GCV or VGCV therapy Prior GCV or VGCV exposure Symptomatic disease after or during extended GCV or VGCV therapy UL97 genotyping Presence of UL97 mutations conferring resistance? yes Change to foscarnet Less commonly used (input from expert recommended): Cidofovira Combination GCV+Foscamet HIgh-dose GCV Leflunomide Artesunate a Genotyping 319 No UL54 genotyping Pending UL54 genotyping results: If high-risk patient, symptomatic disease, or rapidly increasing viral load, switch to foscamet If stable viral load and clinically silent infection, continue GCV or VGCV at current dose or consider higher-dose GCV therapy of UL54 DNA polymerase is recommended to evaluate for mutations conferring cross-resistance to cidofovir FIGURE 22.1 Approach to the patient with suspected ganciclovir–valganciclovir-resistant CMV 58202_ch22.qxd 320 2/1/10 Section V 8:49 PM ■ Page 320 Viral Infections Since cidofovir is not phosphorylated by the CMV UL97 gene product, it is active against ganciclovir-resistant UL97 mutants However, certain UL54 mutations can confer causes crossresistance between ganciclovir and cidofovir (193,195) Therefore, additional genotype testing of UL54 is indicated to evaluate for potential cross-resistance conferring mutations There is limited experience with cidofovir for treatment of ganciclovir-resistant CMV, and its toxicity profile precludes its routine use as secondline treatment for ganciclovir-resistant CMV Drugs presently under evaluation, such as maribavir, may also provide therapeutic options in the future Maribavir inhibits the CMV UL97 kinase and is active and against wild-type and ganciclovir-resistant CMV strains (196) Other drugs with possible anti-CMV activity include the arthritis drug leflunomide and the antimalaria compound artesunate (197–199) None of these are approved by European or American regulatory authorities for the treatment of CMV Another potentially useful approach is to use the immunosuppressive drug sirolimus as adjunct therapy since it may impair CMV replication by regulating cellular signaling pathways, and has in fact been shown to reduce the risk of CMV reactivation after HCT and renal transplantation (111,118) Vaccination Given the costs and toxicities associated with antiviral therapy, a vaccine to prevent CMV infection would be of substantial benefit Indeed, the Institute of Medicine has given the development of a CMV vaccine the highest priority (200) Thus far, most vaccine candidates have yielded mixed results (201) Recently, a phase I trial of a bivalent vaccine containing plasmids encoding gB and pp65 showed promising results in CMV-seronegative vaccine recipients, but not CMV-seropositive recipients, which is a limitation common to many CMV vaccine candidates (202) Since it is the seropositive transplant patient who is at greatest risk for CMV infection, more work is required to provide protective immunity in these patients after HCT Management of CMV Disease As mentioned earlier, the diagnosis of CMV disease requires documenting the presence of CMV in the appropriate diagnostic specimen, coupled with symptoms and signs consistent with CMV For gastrointestinal disease, standard therapy generally entails induction treatment with an intravenous antiviral, most often ganciclovir, for to weeks followed by several weeks of maintenance Shorter courses of induction therapy (2 weeks) are not as effective (203) There is no role for concomitant IVIG in the treatment of gastrointestinal disease (204) Recurrence of gastrointestinal disease may occur in approximately 30% of patients in the setting of continued immunosuppression and such patients may benefit from secondary prophylaxis with maintenance antivirals until immunosuppression has been reduced Foscarnet can be used as an alternative if neutropenia is present Valganciclovir as maintenance treatment for gastrointestinal disease has not been well studied but may be reasonable if symptoms are improved, systemic viremia is suppressed, and there are no factors that would impair the absorption of an orally administered medication, such as severe gastrointestinal GVHD Several studies established the current standard of care for CMV pneumonia, which is treated with ganciclovir (or foscarnet as an alternative agent) in combination with IVIG (205–208) These studies showed improved survival rates compared to historical outcome results There does not appear to be a specific advantage of CMV-specific immune globulin (CMVIg) compared to pooled immunoglobulin (206) However, in specific clinical situations, such as volume overload, CMV-Ig may be preferred Several studies have raised doubt regarding the beneficial effect of concomitant IVIG (209,210) However, although the use of IVIG remains a controversial topic, it is still considered as standard of care at many centers until more data regarding its utility are available CMV retinitis is typically treated with systemic ganciclovir, foscarnet, or cidofovir, with or without intraocular ganciclovir injections or implants (86,211–213) Fomivirsen is an antisense RNA molecule that targets mRNA encoded by CMV and is approved as second-line therapy for CMV retinitis in patients with AIDS (214) Other manifestations of CMV disease, such as hepatitis and encephalitis, are uncommon and are typically managed with intravenous ganciclovir The duration of therapy for these manifestations has not been well established and should be tailored to the individual patient Adoptive Immunotherapy HCMV-specific T-cells can be generated via several different mechanisms in attempts to passively restore cellular immunity after transplantation (12) Several groups have reported a beneficial impact of adoptive immunotherapy on HCMV viral loads in patients who had undergone HCT (215) Despite these seemingly promising results, scientific questions remain unanswered (such as the optimal cell type and dose for infusion) and technical hurdles persist (availability of clinical grade reagents) that preclude adoptive immunotherapy from becoming a routine clinical procedure at the current time This topic is discussed in more detail in chapter 46 CONCLUSIONS AND FUTURE DIRECTIONS Although much progress has been made in the prevention of CMV disease after HCT over the past decade, several issues remain Increasing the specificity of pre-emptive therapy by combining detection of viremia with monitoring of CMVspecific T-cell immunity merits evaluation in a randomized 58202_Index.qxd 774 2/2/10 2:35 AM Page 774 Index Fungal infections (contd.) cryptococcosis, 209–210 diagnosis of, 491 donor-to-host transmission of, 122 growth factors and, 712 HAI, surveillance for, 673 in HCT, 59 histoplasmosis, 211 invasive opportunistic mycoses, 208 morbidity and attributable mortality of, 555 mucormycosis, 210–211 North American blastomycosis, 211 and pneumonia, 187 prevention of, 124–125, 670–671 prevention strategies for, 109 protothecosis, 211 risk factors for, 490, 555 skin infections, 207–211 stem cell transplantation and, 197 superficial mycoses, 207–208 T cells therapy, 736–737 timing of, 554–555 uncommon, 586–594, 586t Fusariosis, invasive diagnosis and therapy of, 545–546 microbiology and pathogenesis of, 544 risk factors and clinical syndromes of, 544–545, 545f Fusarium infection, 570, 587–588 Galactomannan (GM), 541–542 Ganciclovir for ADV infections, 452 for CMV infection, 127, 129–130, 316–317, 320, 338t, 341–342, 349–350, 349t for CNS infection, 229 fungal infections and, 169 for HHV-6 infection, 414–415 for HHV-7 infection, 415–416 for HSV infections, 396 for human herpesvirus (HHV-6), 226 in intestinal transplantation, 184 in liver transplantation, 172 oral form of, 172 in pancreas transplantation, 157, 158–159 for pneumonia, 193, 194 for posttransplantation lymphoproliferative disorder, 378 Ganciclovir-resistant cytomegalovirus (ganRCMV) infection lung transplantation and, 127 Ganciclovir-resistant HHV-6 disease, 415 ganRCMV infection See Ganciclovir-resistant cytomegalovirus (ganRCMV) infection Gastroenteritis, 684 Gastroesophageal reflux disease (GERD), 236 Gastrointestinal bleeding causes, 248–249 diagnosis, 249 Gastrointestinal (GI) tract, 162 Gastrointestinal infections after hematopoietic cell transplant, 239–241 after solid organ transplants, 236–239 heart and lung transplant, 238–239 intestine and intestine–liver transplant, 239 kidney and kidney–pancreas transplant, 236–237 liver transplant, 237–238 pancreas transplant, 238 diagnosis of abdominal pain, 246–248 anorexia, 243 diarrhea, 243–246 dysphagia, 241–243 gastrointestinal bleeding, 248–249 heartburn, 241–243 nausea, 243 odynophagia, 241–243 perianal pain, 248 vomiting, 243 by type of transplant, 236–241 Gastrointestinal involvement in posttransplantation lymphoproliferative disorder, 372–373 Gastrointestinal problems in long-term transplant survivors, 241 to transplant day 200, 240–241 before start of conditioning therapy, 239–240 G-CSF See Granulocyte colony-stimulating factor (G-CSF Gene therapy, 22 Genetic susceptibility to toxoplasmosis, 626 Genitourinary disease, 642 Gentamicin for coagulase-negative staphylococci, 263 for Enterobacteriaceae infection, 272 for enterococcal infection, 260–261 for listeria, 229 for Listeria monocytogenes, 296 for S aureus infection, 265 Giardia lamblia, 645 Giardiasis, 645 GI tract See Gastrointestinal (GI) tract Glomerulonephritis, 145 Glucose-6-phosphate dehydrogenase (G6PD), 73 Glycopeptide resistance, 257, 260 GM See Galactomannan (GM) GM-CSF See Granulocyte-macrophage colonystimulating factor (GM-CSF) GMP See Good manufacturing practice (GMP) Good manufacturing practice (GMP), 734 G6PD See Glucose-6-phosphate dehydrogenase (G6PD) Graft adaptation, 19 Graft failure, Graft pyelonephritis, 140 Graft-site candidiasis kidney transplantation and, 141–142 Graft-versus-host-disease (GVHD), 1, 6–8, 53, 56–57, 91, 691 ADV infections and, 449, 451 after HCT, 236, 240–241 antifungal prophylaxis in patients with, 519 and CNS infections, 214 cryptosporidiosis and, 639 and HHV-6 infection, 413 immune enhancement and, 707 lymphoid growth factors and, 715 modalities of, 8t mold infections and, 537 mucosal immunity, 509 murine models of, 709 pneumonia and, 192, 196 posttransplantation lymphoproliferative disorder and, 371 prevention of, 8t, 56 stem cell source, 7–8 toxoplasmosis and, 617 visceral VZV disease and, 400 Graft-versus-leukemia (GVL), 1, 55 effects of, 6–8 Graft-versus-tumor (GVT), 1, 55 Gram-negative bacilli, 166, 168 Gram-negative infections, 57 with Acinetobacter spp., 274 with Burkholderia cepacia, 273–274 with Enterobacteriaceae antimicrobial resistance, 269–270 epidemiology of, 269 incidence of, 269 management of, 270 manifestations of, 269 onset of, 269 outcome of, 269 prevention of, 270 with nonfermentative gram-negative bacilli antimicrobial resistance of, 271–272 epidemiology of, 270–271 incidence of, 270–271 management of, 272–273 manifestations of, 271 onset of, 271 outcome of, 271 with Stenotrophomonas maltophilia, 273 Gram-negative organisms Helicobacter, 301–302 Legionella, 300–301 Gram-positive infections, 57 with coagulase-negative staphylococci antimicrobial resistance, 263 drug resistance, 263 epidemiology, 262 factors associated, 262–263 incidence of, 262 management of, 263 manifestations of, 262 prevention of, 263 enterococci related antimicrobial resistance, 260 drug resistance, 260–261 epidemiology, 257–258 factors associated with, 259–260 glycopeptide resistance, 260 incidence of, 258 linezolid resistance, 260–261 management of, 261–262 manifestations, 259 onset of, 258–259 outcome of, 259–260 prevention of, 262 vancomycin-dependent, 260 vancomycin resistance, 260–261 with Staphylococcus aureus drug resistance of, 264 incidence of, 264 manifestations of, 264 outcome of, 264 prevention of, 265 transmission of, 264 treatment of, 265 with Streptococcus pneumoniae antibiotic prophylaxis for, 268 drug resistance of, 267 immunization for, 268 incidence of, 266–267 management of, 267–268 manifestations of, 267 outcome of, 267 prevention of, 268 with Streptococcus viridans drug resistance, 266 incidence of, 265 manifestation of, 265 outcome of, 265 prophylaxis for, 266 risk factors for developing, 265–266 treatment, 266 Gram-positive organisms anaerobic actinomycetes, 298 Clostridium difficile, 299–300 lactobacilli, 298–299 Listeria monocytogenes, 295–296 Nocardia, 296–298 Rhodococcus equi, 299 Granulocyte colony-stimulating factor (G-CSF), 1, 55 administration of, 709, 711 58202_Index.qxd 2/2/10 2:35 AM Page 775 Index clinical trials, 709, 710t dose schedule for, 711 effects of, 709 pegfilgrastim and, 713 potential applications of, 712–713 purpose of, 707 strategies for using, 708–709, 708t Granulocyte-macrophage colony-stimulating factor (GM-CSF) administration of, 709, 711 clinical trials, 709, 710t dose schedule for, 711 effects of, 709 pegfilgrastim and, 713 potential applications of, 712–713 purpose of, 707 strategies for using, 708–709, 708t Granulocyte recovery, 544 Granulocyte transfusions, 4, 546, 593, 713 Granulocytopenia, 5, 241, 245, 247, 249 Growth factors androgen blockade therapy, 716 hematopoietic, 707–714 lymphoid, 714–715 mucosal, 715–716 neutropenia and, 709 Guideline for Isolation Precautions, 2007, 655 GVHD See Graft-versus-host-disease (GVHD) GVL See Graft-versus-leukemia (GVL) GVT See Graft-versus-tumor (GVT) HAART See Highly active antiretroviral therapy (HAART) HAC See Hospital-Acquired Conditions (HAC) Haemophilus influenzae pneumonia and, 192, 192f, 197 type b (Hib), 757 Haemophilus influenzae type b (Hib) vaccine, 697 Hairy leukoplakia, 373 HAMA See Human antimurine antibody (HAMA) Hand hygiene for health care workers, 657 Hansenula anomala, 515, 596 Haploidentical transplants, 55 HAT See Hepatic artery thrombosis (HAT) HBIG See Hepatitis B immunoglobulin (HBIG) HBoV See Human bocavirus (HBoV) HBsAg See Hepatitis B surface antigen (HBsAg) HBV See Hepatitis B virus (HBV) infection HBV infection See Hepatitis B virus (HBV) infection HC See Hemorrhagic cystitis (HC) HCT See Hematopoietic stem cell transplantation (HSCT) HCV See Hepatitis C virus (HCV) infection HCV infection See Hepatitis C virus (HCV) infection Health care–associated infections (HAI) aspergillosis construction guidelines, 672–673 environmental concerns, 671–672 environmental control, 672 C difficile infection and, 678–679 CLABSI, 670 definition of, 669–670 fungal, 670–671 surveillance for, 673 health care workers and, prevention of, 670 legionellosis, 673–675 MDR-GNB, 677–678 MRSA, 677 prevention of, 667–669 VRE and, 675–677 waterborne, 673 Healthcare Infection Control Practices Advisory Committee (HICPAC), 653, 667 Health care workers artificial nails on, 657 hand hygiene for, 657 immunization of, 658, 670 VZV infection and, 682 Heartburn causes, 241–242 diagnosis, 242–243 Heart-lung transplantation See also Lung transplantation bacterial infections in, 117–119 fungal and parasitic infections in, 119–122 gastrointestinal infections in, 238–239 Nocardia infection in, 297 HeartMate vented electric LVAD, 105–106, 106f Heart transplantation ADV infections and, 461 antimicrobial prophylaxis for, 111 blood stream infection in, 108 Chagas disease in, 634 coagulase-negative staphylococci in, 262 Enterobacteriaceae infection, 269 enterococcal infections in, 259–260 gastrointestinal infections in, 238–239 infections after bacterial, 108 CMV, 109–110 fungal, 108–109 hypogammaglobulinemia, 110–111 LVAD See Left ventricular assist devices (LVAD) parasitic, 110 surgical, 108 viral, 110 Mycobacterium tuberculosis and, 108 pneumonia in, 108, 193–194 Rocky Mountain spotted fever after, 305 S aureus infection, 264 Streptococcus pneumoniae infection in, 267 Heart transplant recipients HCV infection and, 485 toxoplasmosis in, 626 Helicobacter, 301–302 Helicobacter pylori infection, 236 Hematomas, 152, 164, 242, 247 Hematopoietic stem cells (HSC), Hemopoietic growth factor (HGF) administration of, 709, 711 clinical trials, 709, 710t defined, 707 effects of, 709 neutropenic patients and, 711 pegfilgrastim and, 713 potential applications of, 712–713 purpose of, 707 role of, 708 strategies for using, 708–709, 708t infusion, sources of, Hematopoietic stem cell transplantation (HSCT), 53, 90 adenovirus infections in, 229, 240–241 antifungal agents used in, 508t aspergillus infection in, 214, 216–218 bacterial infections after, 57–59 bacterial infections in, 203–205 blastocystosis in, 645 brain abscesses infection in, 223–224 Burkholderia cepacia infections, 273–274 candida infection, 220 care after, central nervous system (CNS) infections in, 214–230 acanthamoeba infection, 229–230 adenovirus, 229 775 aspergillus, 216–218 brain abscesses, 223–224 candida, 220 clinical manifestations, 214–215 complications, 214 cryptococcus neoformans, 224–225 diagnostic criteria for, 215–216 etiology, 214 focal lesions, 215 human herpesvirus (HHV-6), 225–226 incidence, 214 JC virus, 226–227 listeria, 228–229 lymphocytic choriomeningitis virus, 229 measles inclusion bodies encephalitis (MIBE), 229 meningoencephalitis, 224 nocardia, 220–221 parasite, 229–230 parvovirus B19, 229 phaeohyphomycosis, 218–219 posttransplantation lymphoproliferative disorder (PTLD), 222–223 rabies, 229 risk factors, 214, 216–217 scedosporium apiospermum, 218 toxoplasma, 221–222 varicella zoster virus (VZV), 229 West Nile virus (WNV), 227–228 zygomycosis, 219–220 Chagas disease in, 634–635 Chlamydia, 303 CMV infection antiviral resistance, 319–320 diagnosis, 312 epidemiology, 328–331 gastrointestinal diease and, 330, 332 hepatitis and, 330, 332 manifestations, 312–313 pathogenesis of, 328–331 pre-emptive therapy, 315–317, 316t, 318t prevention of, 315–317, 335–348 prophylaxis, 315–316, 316t, 318t treatment of, 348–352, 349t CRV infections in, 428–429, 439 cryptosporidiosis in, 639–640 cryptococcus neoformans infection, 224–225 delayed complications of, 8–9, 9t detection of yeast infections in, 511t disease treated with, 1t EBV infection in, 362, 365–366, 373, 380 fungal infections, 207–211 fungal infections after, 59 gastrointestinal infections, 239–241 G-CSF and, 709 GM-CSF and, 709 graft-versus-host disease, 56–57 graft-versus-host-disease (GVHD) after, 236, 240–241 gram-negative infections in with Acinetobacter spp., 274 with Burkholderia cepacia, 273–274 with Enterobacteriaceae, 269–270 with nonfermentative gram-negative bacilli, 270–273 with Stenotrophomonas maltophilia, 273 gram-negative organisms Helicobacter, 301–302 Legionella, 300–301 gram-positive infections in with coagulase-negative staphylococci, 262–263 enterococci related, 257–262 with Staphylococcus aureus, 264–265 with Streptococcus pneumoniae, 266–268 with Streptococcus viridans, 265–266 gram-positive organisms anaerobic actinomycetes, 298 58202_Index.qxd 776 2/2/10 2:35 AM Page 776 Index Hematopoietic stem cell transplantation (HSCT) (contd.) Clostridium difficile, 299–300 lactobacilli, 298–299 Listeria monocytogenes, 295–296 Nocardia, 296–298 Rhodococcus equi, 299 HBV infection in, 498 acute events and risk factors, 499–500, 499t long-term sequelae of, 500 HCV infection in, 498 acute events and risk factors of, 501 de novo HCV infection, 501–502 long-term sequelae of, 502 hematologic recovery for, herpesvirus infections, 205–207 herpes zoster in, 399 HHV-6 infection in, 207, 225–226, 413, 414 HMPV infections in, 432 Hodgkin disease in, 376 HSV infection in clinical presentation of, 392–394 diagnosis of, 394–395 epidemiology of, 391 pathogenesis of, 392 prophylaxis for, 396–397, 397f therapy for, 395–396 individual characteristics and, 53–54 infection, risk of, 53–54 meningoencephalitis, 224 mold infections in Aspergillus species, 538–544 epidemiology of, 537 Fusarium species, 544–546 Scedosporium species, 546–547 zygomycosis, 547–549 immunologic recovery in, 5–6 indications for, 1–2 influenza infections in, 433 infection control issues after control of specific pathogens, 660–663 guideline recommendations for, 653, 655–660 surveillance cultures and, 663 KIV in, 473–474 malaria in, 638 mycobacterial infections after, 204, 282–291 mycoplasma, 303–304 Nocardia infection in, 220–221 parasitic infections after See Parasitic infections PIV infections in, 436 pneumonia in, See Pneumonia in See Pneumonia posttransplantation lymphoproliferative disease risk after, 370–371 preemptive strategies in, 381–382 procedure for, 3–4 rationale for, 1–2 RhV infections in, 437 rickettsiosis, 304–306 Bartonella, 304–305 Coxiella burnetti, 305 RSV infections in, 429–430 skin infections in, 203–212 bacterial infections, 203–205 fungal infections, 207–211 parasitic infections, 211–212 viral infections, 205–207 spirochetes Borrelia, 303 Leptospira, 303 Treponema pallidum, 302–303 T-cell–depleted, 449 toxoplasmosis after, 62 toxoplasmosis in case series of, 617, 618–619t EBMT-IDWP definitions for, 621t PB samples, 621t treatment and prophylaxis for, 622, 622t vaccination, of transplant recipiennts, 691–698 autologous bone marrow transplantation, 696–697 immune deficiency, 691–692 immunization of autologous HSCT recipients, 697–698 studies of immunizations after, 692–695 viral infections after, 59–62 BK virus, 62 bocavirus, 745 coronavirus, 745, 748 herpesviruses, 60–61 LCMV, 748 measles, 749 metapneumovirus, 748–749 mumps, 749 norovirus, 749 parvovirus B19, 749–750 rotavirus, 750 West Nile virus, 750–751 respiratory viruses, 61–62 VZV infection clinical presentation of, 398–400 diagnosis of, 400–401 epidemiology of, 397 pathogenesis of, 397–398 prevention of, 402–403 prophylaxis for, 401–402, 402f therapy for, 401 vaccination, 402–403 WUV in, 473–474 yeast infections in, 507, 507t, 508t acute disseminated candidiasis, 512 candidemia, 509–513 candidiasis, 509 chronic disseminated candidiasis, 512 Cryptococcus neoformans, 514 endemic dimorphic fungi, 515–516 Malassezia species, 515 mucosal immunity, 509 Pichia anomala, 515 Rhodotorula rubra fungemia, 515 Trichosporon species, 514–515 zygomycosis in, 592–593 Hematuria, 238, 470t Hemodialysis HCV infection and, 485 Hemophilus influenzae type b (HIB), 691, 694 Hemorrhagic cystitis (HC), 61, 470 HEPA See High-efficiency particulate air (HEPA) Hepatic artery thrombosis (HAT), 164, 237, 491 Hepatitis adenovirus and, 490 Hepatitis A virus (HAV) infection transplant tourism and, 759–760 vaccination for, 759–760 Hepatitis B immunoglobulin (HBIG), 483 Hepatitis B surface antigen (HBsAg), 110 Hepatitis B virus (HBV) infection, 691, 694 after hematopoietic stem cell transplantation acute events and risk factors, 499–500, 499t long-term sequelae of, 500 after liver transplantation, 173, 483 after renal transplantation, 483–484 antiviral therapy of, 502–503 biology and pathogenesis of, 498–499 de novo, 484, 500 in immune competent host, 499 immunization against, 759 interferon therapy for, 713 peritransplant, 484 pretransplantation screening, 67 prevalence of, 499 vaccination of, 694 Hepatitis C virus (HCV) infection, 85, 138 after hematopoietic stem cell transplantation acute events and risk factors of, 501 de novo HCV infection, 501–502 long-term sequelae of, 502 after liver transplantation, 173–174, 484 biology and pathogenesis of, 500 in immune competent host, 500–501 interferon therapy for, 714 kidney transplantation and, 139 and posttransplantation lymphoproliferative disorder risk, 370 pretransplantation screening, 67 prevalence of, 485 risk factors for, 485 transmission of, 485 Hepatocellular carcinoma, 412, 499, 714 Hepatosplenic candidiasis, 509, 512, 515, 517 Hepatotoxicity, 68, 492 Herpes simplex virus (HSV) infection, 60, 138, 166, 205–206, 236 after hematopoietic stem cell transplantation clinical presentation of, 392–394 diagnosis of, 394–395 epidemiology of, 391 pathogenesis of, 392 prophylaxis for, 396–397, 397f therapy for, 395–396 after liver transplantation, 486 after solid organ transplantation, 392–396 cellular immunotherapy for, 724 characterization of, 391 CMV infections and, 128 disseminated, 486, 487 esophagitis, 393 infection caused by See Herpes simplex virus (HSV) infection liver transplantation and, 172 mucocutaneous, 393 pretransplantation screening, 67 transmission of, 392 Herpesvirus infections, 60–61 characteristics of, 391 cytomegalovirus, 60 Epstein–Barr virus, 60–61 herpes simplex virus, 60 human herpesvirus (HHV-6), 61 immune evasion strategies, 729–730 T cells therapy for, 735–736 transmission of, 392 viral infections, 205–207 CMV infection, 206 HHV-6, 207, 225–226 HSV infection, 205–206 VZV infection, 206–207 VZV, 60 Herpes zoster dermatomal, 399 in heart transplant patient, 398, 398f in hematopoietic stem cell transplantation patients, 399 mortality rate for, 400 from reactivation of latent VZV, 397 risk factor for, 398 Herpetic gingivostomatitis, 393 Herpetic lesions, 393 Hexaplex assay, 427 HGF See Hematopoietic growth factor (HGF) HHV-6 See Human herpesvirus-6 (HHV-6) infection HHV-7 See Human herpesvirus-7 (HHV-7) Hib See Haemophilus influenzae type b (Hib) Hickman catheter, HICPAC See Healthcare Infection Control Practices Advisory Committee (HICPAC) 58202_Index.qxd 2/2/10 2:35 AM Page 777 Index High-efficiency particulate air (HEPA) hematopoietic stem cell transplant recipients and, 653, 655, 656 SOT and, 672 TB and, 680 Highly active antiretroviral therapy (HAART), 67, 165 High-pressure liquid chromatography (HPLC), 124 Histiocytes, 204, 205, 206, 426 Histoplasmosis, 211, 516 clinical manifestations of, 608–609 diagnosis of, 609 epidemiology of, 608 pathogenesis of, 608 treatment of, 609–610 HIV See Human immunodeficiency virus (HIV) HIV-AIDS polyomavirus-associated multifocal leukoencephalopathy in, 473 HIVTR multicenter trial, 67 HJ See Roux-en-Y hepaticojejunostomy (HJ) HLA See Human leukocyte antigen (HLA) HMPV See Human metapneumovirus (HMPV) H1N1 influenza, 662 Hodgkin disease, 305, 732 after solid organ transplantation and hematopoietic stem cell transplantation, 376 and shingles, 398 Hodgkin lymphoma-like PTLD, 376 Hospital-Acquired Conditions (HAC), 667 Hospital construction, aspergillosis and, 655–656, 672–673 Hospital Infection Control Practices Advisory Committee, 667 Host defenses, 706, 708t HPLC See High-pressure liquid chromatography (HPLC) HPV See Human papillomavirus (HPV) HRIG See Human rabies immunoglobulin (HRIG) HSC See Hematopoietic stem cells (HSC) HSCT See Hematopoietic stem cell transplantation (HSCT) HSV See Herpes simplex virus (HSV) HSV hepatitis, 394 HSV pneumonia, in transplant patients by HSV-1, 393–394 symptoms of, 394 in transplant recipients, 393 by viremia, 394 HTLV See Human T-cell lymphotropic virus (HTLV) Human antimurine antibody (HAMA), 32 Human bocavirus (HBoV), 437–438 Human ehrlichiosis, 305 Human granulocytic ehrlichiosis, 305 Human herpesvirus-8 (HHV-8) See Kaposi sarcoma herpesvirus (KSHV) Human herpesvirus-6 (HHV-6) infection, 57, 61, 207 biologic features of, 411 clinical manifestations, 225–226, 412–413, 412t, 489 CMV infections and, 126, 198–199, 413–414, 488–489 diagnosis of, 414 diagnostic criteria, 226 epidemiology of, 412 graft-versus-host disease and, 413 HCV infection and, 414 in hematopoietic stem cell transplantation recipients, 413 hepatitis C and, 413 imaging, 226 as immunomodulatory and immunosuppressive virus, 413 incidence of, 225 infection in SOT and HSCT, 225–226 laboratory examination, 226 management of, 414–415 pathogen, 225 prevention of, 414–415 risk factors, 225 in solid organ transplantation recipients, 413, 488–489 time after transplantation, 225 transmission of, 411–412 treatment of, 226, 415 Human herpesvirus-7 (HHV-7) infection after solid organ transplantation, 489 antiviral agents for managing, 415–416 CMV infection and, 488–489 renal transplantation and, 415 viremia due to, 415 Human immunodeficiency virus (HIV), 138 high risk populations for transmitting, 79t patients, liver transplantation in, 165 pretransplantation screening, 67 recipient, kidney transplantation in, 145 Human leukocyte antigen (HLA), 20, 53, 117, 143, 728 and toxoplasmosis susceptibility, 626 Human metapneumovirus (HMPV), 432 diagnosis of, 426 Human papillomavirus (HPV) infection after solid organ transplantation, 476–477 clinical presentation of, 476 genome of, 475–476 genotypes of, 474–475 incidence of, 476 and pathology in skin, 475f virions, 475 Human paplloma virus vaccine, 700 Human rabies immunoglobulin (HRIG), 761 Human T-cell lymphotropic virus (HTLV), 138 Humoral immunity, 705 Hyaline septate molds, 586–590 chemotherapy of invasive infections by, 591t Hyalohyphomycosis, 215t clinical manifestations of, 570, 571–572, 571t diagnosis of, 572 microbiology of, 570 treatment of, 572 Hydatid-alveolar cyst disease, 643–644 Hydatid disease in donor, 644 in liver transplantation, 643 in transplant recipient, 643 Hyperbilirubinemia, 165 Hypogammaglobulinemia heart transplantation and, 110–111 IAI See Intra-abdominal infection (IAI) ICRA See Infection control risk assessment (ICRA) ICU See Intensive care unit (ICU) IDSA See Infectious Diseases Society of America (IDSA) IFA See Indirect fluorescent antibody (IFA) IFIs See Invasive fungal infections (IFIs) IgG See Immunoglobulin G (IgG) IGRA See Interferon-␥ release assay (IGRA) IL-2 See Interleukin-2 (IL-2) IL-7 See Interleukin-7 (IL-7) IL-12 See Interleukin-12 (IL-12) IL-18 See Interleukin-18 (IL-18) Imipenem for Acinetobacter spp., 274 for B cepacia, 274 for Enterobacteriaceae infection, 269–271 for lactobacilli, 299 for Listeria monocytogenes, 296 for nocardia, 220 777 for Nocardia infection, 298 for Rhodococcus infection, 299 for S viridans infection, 266 Immune enhancement, 705–707 Immune evasion strategies herpesviruses, 729–730 Immune reconstitution strategies growth factors as, 707–716 IFN in, 713–714 Immune response to EBV infection, 365 to posttransplantation lymphoproliferative disorder, 366 to reactivation of HSV, 392 to toxoplasmosis, 626 Immunizations of autologous HSCT recipients, 697–698 against HBV infection, 759 of health care workers, 658, 670 of pretransplantation screening, 71–72 in solid organ transplant recipients, 698–701, 699t after transplantation, 700–701 before transplantation, 698–700 travel-associated infections and hepatitis A, 759–760 JE, 762 meningococcal disease, 761 polio, 760–761 rabies, 761 Salmonella enterica serovar Typhi, 760 yellow fever, 761 Immunocompromised hosts close contacts of, vaccination of, 762 diarrhea and, 762 malaria/dengue fever and, 762–763 parasitic infections and, 763 respiratory infections and, 762 Immunodeficiency factors that influence, 706t Immunofluorescence (IF) assays for HMPV identification, 426 for influenza virus infection, 426 for RSV identification, 425 Immunoglobulin G (IgG), 705 Immunomodulation with GM-CSF, 434 Immunoprophylaxis for RSV infection, 430–431 for VZV infection, 402–403 Immunoreconstitution ADV infections and, 453 Immunosuppressed host posttransplantation lymphoproliferative disorder in, 366–367, 367f respiratory viral infections in, 421, 422 RSV infections in, 424 Immunosuppression, 145 after liver transplantation, 165–166, 170 alveolar cyst disease and, 644 Chagas disease and, 633 CMV infections and, 127 immune enhancement and, 705 for intestinal transplantation, 179, 181, 184–185 for lung transplantation, 117 for pancreas transplantation, 153, 158 pneumonia and, 187–188 Immunosuppression, reduction of for ADV infections, 462–463 for KS management, 417 for posttransplantation lymphoproliferative disorder management, 377 for PyVAN management, 472 surgical resection and, 380 Immunosuppressive agents antilymphocyte antibodies, 32–35 cell cycle inhibitors, 35–36 58202_Index.qxd 778 2/2/10 2:35 AM Page 778 Index Immunosuppressive agents (contd.) corticosteroids, 26–28, 27t drug interactions, 42t signal transduction blockers, 28–32 Immunosuppressive therapy, long-term, 19 Immunotherapy clinical studies of cytomegalovirus-specific T cells, 730–732 preventing infections for, 724–725 IMPD See Inosine monophosphate dehydrogenase (IMPD) inactivated vaccines, 146, 692–694 IND See Investigational new drug application (IND) Indirect fluorescent antibody (IFA), 632–633 Induction therapy, 17–18, 158 Infected bilomas, 165, 269 Infection control guidelines for C difficile disease, 661 for catheter-related infections prevention, 659 contact with health care workers, 658 for CRVs, 661–663 for food and nutrition, 660 for hand hygiene, 657 for hospital construction, 655–656 for isolation precautions, 656–657 for legionellosis, 660 for MRSA, 660 for patient skin and oral care, 658–659 for room ventilation, 653, 655 for staphylococci, 660–661 by strength and quality of supporting evidence, 653 surveillance cultures and, 663 for transplantation center visitors, 658 for tuberculosis, 663 Infection control issues after HSCT control of specific pathogens, 660–663 guideline recommendations for, 653, 655–660 surveillance cultures and, 663 after SOT community-acquired infections, 679–684 HAI infections, 667–679 Infection control risk assessment (ICRA), 672 Infection control strategies, 438–439, 438t Infections after hematopoietic stem cell transplant See Hematopoietic stem cell transplant (HSCT) after intestinal transplantation See Intestinal transplantation after liver transplantation See Liver transplantation (LT) after lung transplantation See Lung transplantation after pancreas transplantation See Pancreas transplantation after solid organ transplantation See Solid organ transplantation catheter-related See Catheter-related infections classifications of, in pancreas transplantation, 150, 151t community-acquired See Community-acquired infections HAI See Health care-associated infections (HAI) ICRA, determination of, 672 prevention of, 724–725 surgical, 150 travel-associated, and immunizations hepatitis A, 759–760 JE, 762 meningococcal disease, 761 polio, 760–761 rabies, 761 Salmonella enterica serovar Typhi, 760 yellow fever, 761 Infectious Diseases Advisory Committee, INCUCAI, 635 Infectious Diseases Society of America (IDSA), 58, 171, 653, 654t, 757 Inferior vena cava (IVC), 163 Influenza A infections, 662 vaccination of, 692–694 Influenza antivirals, resistance to, 427 Influenza B infections vaccination of, 692–694 Influenza vaccine, 692–694 Influenza virus infection, 432 after hematopoietic cell transplantation, 433 after solid organ transplantation, 433–434 diagnosis of, 426–427 prevention of, 434, 438t prophylaxis for, 434 therapy for, 434 transmission of, 422 treatment of, 434–435 vaccination, 433, 658, 662, 683–684, 758 Injected inactivated poliovirus vaccine (IPV), 760 Inosine monophosphate dehydrogenase (IMPD), 31 Intensive care unit (ICU), 120, 162, 168, 193 Interferon-␣, 227 Interferon-␣ therapy purpose of, 713–714 therapeutic use of, 713–714 Interferon-␥ release assay (IGRA), 53, 138 Interferon (IFN) therapy for HCV infection, 485 for HSV infections, 395 for posttransplantation lymphoproliferative disorder, 378 Interleukin-2 (IL-2), 227, 714 Interleukin-7 (IL-7), 714–715 Interleukin-12 (IL-12), 715 Interleukin-18 (IL-18), 715 Intermediate maintenance period, 19 International Society for Heart and Lung Transplantation, 114, 118 International Society of Nephrology, 764 Intestinal amoebiasis, 644–645 Intestinal strongyloidiasis, 641–642 Intestinal transplantation (IT) adenovirus in, 185–186 ADV infections and, 462 antifungal prophylaxis against Candida in, 529 bacteremia infection after, 181–182 CMV infection after, 182–183 donors issues in, 179 fungemia infection after, 181–182 history of, 179 immunosuppression for, 179 infections in bacterial and fungal, 181–182 CMV, 182–183 EBV, 183–185 miscellaneous, 186 pathology, 180 PTLD, 183–185 timetable for, 181, 181t and ischemia, 180 rejection rate of, 180 risk factors for, 179–180 tacrolimus for, 182 tansplant recipient in, 180 TPN and, 179 Intestinal tuberculosis, 236 Intestine-liver transplant gastrointestinal infections in, 239 Intestine transplant gastrointestinal infections in, 239 Intra-abdominal Candida infections treatment of, 528 Intra-abdominal infection (IAI) in liver transplantation, 166 in pancreas transplantation, 153–155 treatment of, 154 Intracranial pressure, 223, 514, 531, 612 Intramural hematomas, 242, 247 Intravenous immune globulin (IVIG), 228, 759 for CMV infection, 182 Invasive aspergillosis, 490, 539f diagnosis of, 558–560 prevention of, 563–566, 564t treatment of, 560–563 Invasive candidiasis, 490 clinical manifestations of, 526 diagnosis of, 527 epidemiology of, 526 microbiology and pathogenesis of, 525–526 treatment of, 512–513, 528–529 Invasive fungal infections (IFI), 162 in liver transplantation, 169–170 prevention strategies, 171 morbidity of, 555 risk factors for, 169–170 Invasive lung infection, by Scedosporium prolificans, 567f Investigational new drug application (IND), 682 IPV See Injected inactivated poliovirus vaccine (IPV) Ischemia intestinal transplantation and, 180 lung transplantation and, 116 Ischemia– reperfusion injury, 18 Isolation precautions for HAI, 668, 669t for HSCT recipients, 656–657 Isoniazid (INH), 282 Israel Penn International Transplant Tumor Registry, 158 IT See Intestinal transplantation (IT) Itraconazole for Aspergillus infection, 218 for Aspergillus species colonization, prevention of, 124 for chemotherapy-induced neutropenia, 518 for phaeohyphomycosis, 219 toxicity, 240 IVC See Inferior vena cava (IVC) Ivermectin, 642 IVIG See Intravenous immunoglobulin (IVIG) Japanese encephalitis (JE), 762 JCV See JC virus (JCV) JC virus (JCV) clinical manifestations, 226–227 diagnosis, 227 imaging, 227 incidence of, 226 infection in SOT and HSCT, 226–227 laboratory examination, 227 pathogen, 226 polyomavirus-associated multifocal leukoencephalopathy (PyVML) and risk factors, 226 seroprevalence of, 465 time after transplantation, 226 treatment of, 227 JCV-specific immunity, 473 JE See Japanese encephalitis (JE) Kala azar, 94 Kaplan–Meier survival analysis, 106–107 Kaposi sarcoma herpesvirus (KSHV) biologic features of, 416 clinical manifestations of, 416–417 epidemiology of, 416–417, 416t management of, 417 58202_Index.qxd 2/2/10 2:35 AM Page 779 Index Kaposi sarcoma (KS), 416 in solid organ transplantation recipients, 489, 490 Karolinska Institute virus (KIV), 465, 467 in hematopoietic cell transplants, 473–474 Keratinocyte growth factor (KGF), 715, 716 Ketoconazole, 210 KGF See Keratinocyte growth factor (KGF) Kidney-pancreas transplant (KPT) See also Pancreas transplant gastrointestinal infections in, 236–37 Kidney transplantation (KT), 20 ADV infections and, 461 antifungal prophylaxis against Candida in, 529 antimicrobial agents and, 146 antiviral prophylaxis for CMV infection, 337t, 347t asymptomatic bacteriuria and, 141 C trachomatis infection after, 303 candiduria, 141 Chagas disease in, 633–634 CMV and, 142–143 CMV infection after, 312 cryptosporidiosis in, 638 donor infections, 139 screening of, 139 Enterobacteriaceae infection, 269 enterococcal infections in, 258–259 gastrointestinal infections in, 236–37 graft-site candidiasis and, 141–142 HBV infection and, 483 HCV and, 139 influenza infections in, 434 nephrotoxicity and, 146 nocardiosis in, 297 nonfermentative gram-negative bacilli infection, 271 pneumocystis prophylaxis, 146 pneumonia in, 194–195 posttransplantation lymphoproliferative disorder and, 368 pre-emptive therapy for CMV infection, 337t PVAN, 143–144 recipient pretransplant evaluation of, 138–139 Streptococcus pneumoniae infection in, 267 strongyloidiasis in, 641 technical problems after, 139–140 UTI and, 140–141 recurrent, 141 vaccinations, posttransplant, 146 viral infections post adenoviruses, 144 parvovirus B19, 144 WNV, 144–145 Killed vaccines, 695, 699t, 700 Kino isolated tacrolimus (TAC), 29 KIV See Karolinska Institute virus (KIV) Klebsiella, 154 Klebsiella pneumoniae, 117, 223 Klebsiella pneumoniae carbapenemase (KPC), 677 KPC See Klebsiella pneumoniae carbapenemase (KPC) KS See Kaposi sarcoma (KS) KSHV See Kaposi sarcoma herpesvirus (KSHV) Lactobacilli, 298–299 LAF See Laminar air flow (LAF) LAK cells See Lymphokineactivated killer (LAK) cells Laminar air flow (LAF), 653, 672 Lamivudine, 498, 503 for HBV infections, 484 Langerhans cell, Latent membrane proteins (LMP) LMP-1 expression in EBV, 364 Latent membrane proteins (LMP)-1, 363 Latent tuberculosis infection (LTBI), 90 LCMV See Lymphocytic choriomeningitis virus (LCMV) LD See Legionnaires disease (LD) LDLT See Living donor liver transplantation (LDLT) Leflunamide, 14 Leflunomide, 143, 469 for CMV infection, 320 Left ventricular assist devices (LVAD), 104 clinical promise of, 106–107 drive-line infection, 105f HeartMate vented electric, 105–106, 106f infections after heart transplantation, 106–107 Kaplan–Meier survival analysis and, 106–107 Leggenda Aurea, 13 Legionella infection, 300–301, 673 pneumonia and, 193, 195, 197 Legionella pneumophila, 118, 191, 673 Legionellosis control of, 660 prevention of, 673–675 in SOT, 673–675 Legionnaires disease (LD), 660 Leishmania aethiopica, 94 Leishmania donovani, 94 Leishmania infantum, 636 Leishmania major, 94 Leishmania mexicana, 636 Leishmaniasis, 94–95, 211 clinical manifestations of, 635 diagnosis of, 636 geographic distribution, 94 recommendations, 95 symptoms of, 635–636 transmission in transplant patients, 94–95 treatment of, 636 Leishmania tropica, 94 Leprosy, 92 geographic distribution, 92 in transplant recipients, 92 Leptospira, 303 leptospirosis, 303 Leucovorin for Toxoplasma, 222 Leukapheresis, Leukemia, 305 Leuprolide, 716 Leuprolide acetate, 716 Levofloxacin for Enterobacteriaceae infection, 270, 273 for S viridans infection, 266 LHRH See Luteinizing hormone-releasing hormone (LHRH) Linezolid for Nocardia infection, 298 resistance to enterococci infections, 260–261 resistant VREF, 260–261 for Rhodococcus infection, 299 for S aureus infection, 265 Lipopolysaccharides (LPS), Liposomal amphotericin B (LAMB), 516, 517 Listeria, 223 clinical manifestations, 229 diganosis, 229 incidence of, 228 infection in SOT and HSCT, 228–229 pathogen, 228 time after transplantation, 228 treatment and prevention, 229 Listeria monocytogenes, 70, 108, 295–296 and CNS infections, 214 Listeriosis, 295 Live-attenuated virus vaccines VZVoka, 402–403 779 Liver infections bacterial, 491 fungal, 490–491 viral, 483–490 Liver biopsy, 172, 394, 490, 493 Liver transplantation (LT), 20–21 See also Intestinal transplantation adenovirus in, 172–173 ADV infections and, 460–461 alveolar cyst disease in, 643–644 antibiotics for, 169 antifungal prophylaxis against Candida in, 529 bacterial infections after, 491 Chagas disease in, 634 classic, 163, 163f clinical approach to liver infection after, 493–494 CMV and, 171–172 coagulase-negative staphylococci in, 262–263 cryptosporidiosis in, 639 EBV infection and, 487–488 Enterobacteriaceae infection, 269 enterococcal infections in, 258–260 gastrointestinal infections in, 237–238 HBV infection and, 483 hepatic fungal infections after, 490, 491, 491f HHV-8 infection and, 489, 489f, 490 HSV and, 172, 492 hydatid disease in, 643 IAI in, 166 IFI in risk factors for, 169–170 strategies to prevent, 171 immunosuppression after, 165–166 infections after Aspergillus, 170 bacterial, 162, 166, 168–169 blood transfusion and, 162–163 candidal, 170 cryptococcosis, 170–171 frequency of severe, 163f HBV, 173 HCV, 173–174 host factors of, 165 postsurgical, 162–165 risk factors for, 167t Nocardia infection in, 297 parasitic liver infection after, 492 pathogens after, prophylactic regimen used for, 167t with piggyback technique, 163, 163f pneumonia in, 195–196 pre-emptive therapy for CMV infection, 345t risk factors, 490 for infection related to surgery after, 492 with Roux-en-Y hepaticojejunostomy (HJ), 164, 164f S viridans infection, 265 schistosomiasis and, 643 Streptococcus pneumoniae infection in, 267 targeted prophylaxis for CMV infection, 347t VRE and, 676 VZV infection and, 487 Live vaccines, HSCT recipients, 695–696 measles vaccine, 695 mumps vaccine, 696 rubella vaccine, 696 varicella-zoster virus vaccine, 696 Living donor liver transplantation (LDLT), 164 LMP See Latent membrane proteins (LMP) Long Term Surface Water Treatment Rule (LT2 rule), 673 Lower respiratory tract infection (LRTI), 421 RSV-associated, 430 Low-microbial diets, 660 LPS See Lipopolysaccharides (LPS) 58202_Index.qxd 780 2/2/10 2:35 AM Page 780 Index LRTI See Lower respiratory tract infection (LRTI) LTBI See Latent tuberculosis infection (LTBI) LT2 rule See Long Term Surface Water Treatment Rule (LT2 rule) Lung(s) biopsy, 191 native, 123–124 Lung transplantation ADV infections and, 461–462 altered pulmonary defense and, 187 B cepacia, 273–274 CMV disease in diagnosis of, 126 complications in, 123 cystic fibrosis and, 123 donor issues in, 122–123 donor-to-host transmission risk in, 122–123 Enterobacteriaceae infection, 269 immunosuppression for, 117 infections after bacterial, 117–119 fungal and parasitic, 119–122, 124–125 pathologic history of recipient, 116 risk factors for, 114–117, 115t mycobacterium tuberculosis and, 118 Nocardia infection in, 118–119, 297 nonfermentative gram-negative bacilli infection, 270–271 pneumonia in, 116–119, 194 preventing infections in, 124–125, 129–131 prophylaxis for, 124–125 S aureus infection, 264 valganciclovir in, 129–130 Luteinizing hormone-releasing hormone (LHRH), 716 LVAD See Left ventricular assist devices (LVAD) Lyme disease, 644 Lymphocytic choriomeningitis virus (LCMV), 139, 748 infection in SOT and HSCT, 229 Lymphoid growth factors, 714–715 Lymphokineactivated killer (LAK) cells, 714 Lymphopenia, 398 Lymphoproliferative disorders (PTLD), Lytic gene expression, 364 Lytic infection CD4+ and CD8+ CTL response against, 365 MAb See Monoclonal antibodies (MAb) Magnetic resonance imaging (MRI), 372, 413, 493, 539, 608, 620 Maintenance therapy, 350 Major histocompatibility complex (MHC), Malabsorption, 636 Malakoplakia, 205 Malaria, 95–96 diagnosis of, 637 geographic distribution, 95 in HSCT, 638 immunocompromised hosts and, 762–763 recommendations, 96 in SOT, 637–638 transmission in transplant recipients, 95–96 treatment of, 637 Malassezia infection, 533 Malassezia species, 515, 596 Mammalian target of rapamycin (mTOR) inhibitors posttransplantation lymphoproliferative disorder and, 369 Management of Multidrug-Resistant Organisms in Healthcare Settings, 2006, 57 Mannose binding lectin (MBL), 53 Mantoux method, 663 Mantoux test (PPD), 83 Maribavir for CMV infection, 320 Marrow harvest, Massachusetts Public Health Biologic Laboratories, 682 Matched sibling donor, 55 Matched unrelated donor (MUD), 55 MBL See Mannose binding lectin (MBL) MCC See Merkel cell carcinoma (MCC) MCMV See Mouse CMV (MCMV); Murine cytomegalovirus (MCMV) model M-CSF See Monocyte colony-stimulating factor (M-CSF) MCV See Merkel cell carcinoma virus (MCV) MDR-GNB See Multidrug-resistant gram-negative bacteria (MDR-GNB) MDRO See Multidrugresistant organism (MDRO) MDR-TB See Multidrug resistant (MDR)-TB MDS See Myelodysplastic syndrome (MDS) MDT See Multidrug therapy (MDT) Measles, 99–100, 749 current concerns, 100 geographic distribution, 99 recommendations, 100 transmission in transplant patients, 99 vaccination for, 758–759 vaccine, 695 in special circumstances, 99–100 Measles, mumps, and rubella (MMR) vaccine, 749, 758–759 Measles inclusion bodies encephalitis (MIBE) infection in SOT and HSCT, 229 Measles–mumps–rubella (MMR) vaccines, 700 Mechanical ventilation, 114 Mediastinitis, 108, 117, 118 MELD See Model for end-stage liver disease (MELD) Meningitis in CNS infections, 215t Meningoencephalitis, 224 in CNS infections, 215t infection in SOT and HSCT, 224 6-Mercaptopurine (6-MP), 14, 26 Merkel cell carcinoma (MCC), 474 Merkel cell carcinoma virus (MCV), 465, 467, 474 Meropenem for Acinetobacter spp., 274 for B cepacia, 274 for Enterobacteriaceae infection, 269–270, 273 for Listeria monocytogenes, 296 for S viridans infection, 266 Metapneumovirus, 748–749 Methicillin for coagulase-negative staphylococci, 263 for S aureus infection, 265 Methicillin-resistant S aureus (MRSA) infections, 264–265 control of, 660 liver transplantation and, 162, 168 SOT and, 677 Methotrexate, 240 Metronidazole for actinomycetes, 298 for C difficile infection, 300 for Helicobacter infection, 302 MHC See Major histocompatibility complex (MHC) MIC See Minimal inhibitory concentration (MIC) Microascus species, infections caused by, 590 Microbial diets, 660 Microsporidiosis diagnosis of, 640 features of, 640–641 prevention of, 641 treatment of, 641 Minimal inhibitory concentration (MIC), 660 Minocycline for enterococcal infection, 261 for nocardia, 220 for Nocardia infection, 298 for Stenotrophomonas maltophilia infection, 273 Mizorbine (MZB)., 14 MMF See Mycophenolate mofetil (MMF) MMF cover, 18 MMR See Measles–mumps–rubella (MMR) vaccines MMR vaccine See Measles, mumps, and rubella (MMR) vaccine Model for end-stage liver disease (MELD), 21 Mold infections after hematopoietic stem cell transplantation Aspergillus species, 538–544 epidemiology of, 537 Fusarium species, 544–546 Scedosporium species, 546–547 zygomycosis, 547–549 after solid organ transplantation aspergillosis, 555–566 dematiaceous fungi, 568, 568t, 570 dermatomycoses, 572–573 hyalohyphomycosis, 570–572, 571t mucormycosis, 566–568 Molluscum contagiosum, 207, 210 in SOT and BMT recipients, 207 Monoclonal antibodies (MAb), 3, 15 Monoclonal antilymphocyte agents, 32–34 basiliximab, 32–34 daclizumab, 32–34 experimenal agents, 34–35 alemtuzumab, 34 belatacept, 34 bortezomib, 34 eculizumab, 35 efalizumab, 34–35 muromonab (OKT3), 32 Monocyte chemoattractant protein (MCP), 21, 312 Monocyte colony-stimulating factor (M-CSF), 712 Mortality associated with Chagas disease, 634 related to strongyloidiasis, 641 Mouse CMV (MCMV), 730 Moxifloxacin for Nocardia infection, 298 6-MP See 6-mercaptopurine (6-MP) MPA See Mycophenolic acid (MPA) MRSA See Methicillin-resistant S aureus (MRSA) mTOR inhibitors, 36 Mucocutaneous HSV disease, 393 antiviral therapy of, 395–396 Mucorales infections caused by See Mucormycosis microbiology of, 567 Mucormycosis, 210–211 clinical presentations of, 567–568, 567f diagnosis of, 568 risk factors for, 567 in solid organ transplantation recipients, 566 treatment of, 568 Mucosa-associated lymphoid tissue (MALT) lymphomas, 302 Mucosal growth factors, 715–716 Mucosal immunity, 509 Mucositis, 265 Multidrug-resistant gram-negative bacteria (MDRGNB), 677–678 Multidrug resistant (MDR)-TB, 679 Multidrug resistant organism (MDRO), 660 Multidrug therapy (MDT), 92 Mumps, 749 vaccine, 696 Murine cytomegalovirus (MCMV) model, 727 Muromonab (OKT3), 32 Mycobacteium bovis, 762 58202_Index.qxd 2/2/10 2:35 AM Page 781 Index Mycobacterial infections bacteriology, 282 after bone marrow transplantation, 204, 285, 286t–287t epidemiology and pathogenesis, 282–283 in hematopoietic stem cell transplants epidemiology, 285 manifestations and diagnosis, 285–287 after HSCT or SOT, 204, 282–291 immune defects in transplant receipients, 283–284 prophylaxis, 284–285, 291 in solid organ transplants epidemiology, 288–290 immune defects in, 287–288 manifestations and diagnosis, 290 reports of, 288t–289t treatment of, 290–291 Mycobacteria tuberculosis, 86 Mycobacterium abscessus, 59, 118 Mycobacterium bovis, 92 Mycobacterium chelonae, 118 Mycobacterium fortuitum, 59 Mycobacterium leprae, 92 Mycobacterium tuberculosis, 78, 90, 165, 491 bacteriology, 282 epidemiology and pathogenesis, 282–283 heart transplantation and, 108 and lung transplantation, 118 pneumonia and, 188 stem cell transplantation and, 197 treatment of, 290 Mycobacterium xenopi, 673 Mycophenolate mofetil (MMF), 28, 31–32, 41, 56, 140, 240 Chagas disease and, 634 in liver transplantation, 165 pneumonia and, 187 posttransplantation lymphoproliferative disorder and, 369 Mycophenolic acid (MPA), 30 Mycoplasma, 303–304 Mycoses invasive opportunistic, 208 superficial, 207–208 Myelodysplastic syndrome (MDS), 53 Myelosuppression, Myocarditis Chagas disease with, 634 MZB See Mizorbine (MZB) N95, 662 Nafcillin for S aureus infection, 265 NAIs See Neuraminidase inhibitors (NAIs) Nasal aspiration, 423 NAT See Nucleic acid testing (NAT) National Comprehensive Cancer Network (NCCN), 711 National Healthcare Safety Network (NHSN), 669 National Institute for Occupational Safety and Health (NIOSH), 680 National Marrow Donor Program, National Nosocomial Infections Surveillance (NNIS), 669 National Organ Transplantation Act, 84 National Surveillance of Healthcare Workers (NHSW), 669 Native lung complications, incidence of, 123–124 Natural killer (NK) cells, 5, 6, 365, 725 interferon-␣ therapy and, 713 Natural killer (NK) T cells, 14 Nausea causes, 243 diagnosis, 243 NCCN See National Comprehensive Cancer Network (NCCN) Nebulized liposomal amphotericin B (n-LAB), 119, 120, 121, 125, 563, 565 treatment of, voriconazole and, 121 Neisseria meningitidis, 656 Nephrotoxicity kidney transplantation and, 146 Neuraminidase assay, 426 Neuraminidase inhibitors (NAIs) resistance to, 427 Neurocysticercosis, 224 Neutralizing antibodies in response to EBV infection, 365 Neutropenia growth factors and, 709 immune enhancement and, 705–706 Neutropenia, therapy during antifungal prophylaxis in chemotherapy-induced neutropenia, 518–519 in graft-versus-host disease, 519 empirical antifungal therapy, 516–517 New-onset type II diabetes mellitus after transplantation (NODAT), 16 NFAT See Nuclear factor of activated T cells (NFAT) NHL See Non-Hodgkin lymphoma (NHL) NHSN See National Healthcare Safety Network (NHSN) NHSW See National Surveillance of Healthcare Workers (NHSW) Nifurtimox, 110, 633 NIOSH See National Institute for Occupational Safety and Health (NIOSH) NK See Natural killer (NK) cells NK cells See Natural killer (NK) cells n-LAB See Nebulized liposomal amphotericin B (nLAB) NNIS See National Nosocomial Infections Surveillance (NNIS) Nocardia asteroides, 220 Nocardia farcinica, 119 Nocardia infections, 296–298 clinical manifestations, 220 diagnosis of, 297 imaging, 220 incidence, 220 infection in SOT and HSCT, 220–221 in lung transplantation, 118–119 pathogen, 220 risk factors, 220 time after transplantation, 220 treatment, 220–221 Nocardia nova, 119 Nocardiosis, 204–205, 297 in bone marrow transplantation, 297 manifestation of, 297 prognosis of, 297 in renal transplantation, 297 NODAT See New-onset type II diabetes mellitus after transplantation (NODAT) Non–AIDS-associated cryptococcal disease, 514 Nonfermentative gram-negative bacilli, infections with antimicrobial resistance of, 271–272 epidemiology of, 270–271 incidence of, 270–271 management of, 272–273 manifestations of, 271 onset of, 271 outcome of, 271 Nonherpes viral respiratory infection, 129 Non-Hodgkin lymphoma (NHL) development of, 369 781 incidence of, 368, 368f Nonmelanoma skin cancers, 477 Nonmyeloablative conditioning with ATG and posttransplantation lymphoproliferative disorder isk, 371 Nonmyeloablative regimens, 55 Nonneutralizing antibodies in response to EBV infection, 365 Norovirus infection, 749 and diarrhea, 245 North American blastomycosis, 211 Norwalk virus group, 684 Norwegian scabies, 211 Nosocomial infection pneumonia and, 194 NRTI See Nucleoside reverse transcriptase inhibitor (NRTI) Nuclear factor of activated T cells (NFAT), 16 Nucleic acid testing (NAT), 139 Nucleoside analogues, 417 Nucleoside reverse transcriptase inhibitor (NRTI), 145 Obesity, 154, 156 Occult bleeding, 249 Occupational Safety and Health Administration (OSHA), 667 Ocular toxoplasmosis, 626 Odynophagia causes, 241–242 diagnosis, 242–243 OKT3 See Muromonab (OKT3) Older age lung transplantation and, 114 Omeprazole for Helicobacter infection, 302 Onychomycosis, 208, 572, 573, 587 Oocysts, 624 Opportunistic pathogens, infection with, 421 OPTN See Organ Procurement and Transplantation Network (OPTN) OPV See Orally administered, live, attenuated virus vaccine (OPV) Oral care, 658–659 Orally administered, live, attenuated virus vaccine (OPV), 760 Oral mucosal candidiasis diagnosis of, 509 Organ Procurement and Transplantation Network (OPTN), 77 Oritavancin for enterococcal infection, 260, 262 Orolabial lesions, 393 Oropharynx, 658 Orthotopic liver transplantation (OLT), 237 Oseltamivir for influenza infection, 434, 435 Oseltamivir-resistant influenza, 662 OSHA See Occupational Safety and Health Administration (OSHA) Oxacillin for S aureus infection, 265 P aeruginosa antimicrobial resistance of, 271–272 management of, 272–273 Paecilomyces infection, 570 Paecilomyces lilacinus, 659 Paecilomyces species, infections caused by, 590 PAK transplantation See Pancreas after kidney (PAK) transplantation PALE See Posttransplant acute limbic encephalitis (PALE) Pancreas after kidney (PAK) transplantation, 151, 153 58202_Index.qxd 782 2/2/10 2:35 AM Page 782 Index Pancreas transplant alone (PTA), 151, 152f, 153 Pancreas transplantation, 21 antifungal prophylaxis against Candida in, 529 CMV infection in epidemiology, 156–157 prevention, 157 treatment of, 157–158 donors issues in, 151–152 duodenal leaks, 155 EBV and, 158–159 gastrointestinal infections in, 238 immunosuppression and, 153 infections classification in, 150, 151t intra-abdominal infections in, 153–155 other infections in, 159 and peritonitis, 154 procedure, 151–152, 152f PTLD and, 158–159 risk factors for, 152–153 UTI in, 155–156 wound infections after, 156 Pancreatitis, 152, 154, 157, 236, 238 Parainfluenza virus (PIV) infections, 207 after hematopoietic cell transplantation, 436 after solid organ transplantation, 436 in children, 435–436 diagnosis of, 427 in lung transplantation, 128 PIV-associated URI and LRTI, 436 prophylaxis and therapy of, 436 viral shedding following, 435 Parasite infection in SOT and HSCT, 229–230 Parasitemia, 634 Parasitic infections after heart transplantation, 110 after lung transplantation, 119–122 amoebiasis, 644–645 babesiosis, 644 blastocystosis, 645 Chagas disease See Chagas disease cryptosporidiosis, 638–640 echinococcosis, 643–644 giardiasis, 645 immunocompromised hosts and, 763 leishmaniasis, 635–637 malaria, 637–638 microsporidiosis, 640–641 schistosomiasis, 642–643 skin infections, 211–212 strongyloidiasis, 641–642 Paromomycin, 639 Parvovirus B19, 144, 749–750 infection in SOT and HSCT, 229 Passive immunoprophylaxis for RSV infection, 430–431 PBSC See Peripheral blood stem cells (PBSC) PCP See Pneumocystis carinii pneumonia (PCP); Pneumocystis jirovecii pneumonia (PCP) PCR See Polymerase chain reaction (PCR); Polymerase change reaction (PCR) PCV7 See Pneumococcal vaccine (PCV7) PE See Protective environment (PE) Pediatric patients See Children Pegfilgrastim, 713 Pegylated interferon (IFN) plus ribavirin, 485 Penicillin for actinomycetes, 298 for coagulase-negative staphylococci, 263 for enterococcal infection, 260–261 for lactobacilli, 298 for Listeria monocytogenes, 296 for S aureus infection, 265 for S viridans infection, 266 for Streptococcus pneumoniae infection, 267 for T pallidum, 302 Penicillium marneffei, 762 Penicillium stoloniferum, 31 Peptide nucleic acid-fluorescent in situ hybridization (PNA-FISH), 527 Peramivir, 662 Perianal HSV disease, 393 Perianal pain causes, 248 diagnosis, 248 Peripheral blood stem cells (PBSC), 2, 55, 708 Peritonitis pancreas transplantation and, 154 Peritransplant HBV infection, 484 Persistent neutropenic fever empirical antifungal therapy for, 516–517 Pertussis, 695 P-glycoprotein (P-gp), 41 P-gp See P-glycoprotein (P-gp) Phaeohyphomycosis, 215t clinical presentation, 219 incidence, 219 infection in SOT and HSCT, 218–219 pathogen, 219 treatment, 219 Phenotypic testing, 319 Phlegmonous gastritis, 246 PHS See Public Health Service (PHS) Pichia anomala, 515 Piggyback technique for liver transplantation, 163, 163f Piperacillin for B cepacia, 274 for Enterobacteriaceae infection, 272 Piperacillin-tazobactam for Enterobacteriaceae infection, 269–270 Pityriasis versicolor, 572 PIV See Parainfluenza virus (PIV) Plasma BKV loads, 469 Plasmodium falciparum, 95 Plasmodium malariae, 95 infection, 637–638 Plasmodium ovale, 95 Plasmodium vivax, 95 Pleural effusions, 299, 745, 748, 749 PML See Progressive multifocal leukoencephalopathy (PML) Pneumatosis intestinalis, 238 Pneumococcal infections in bone marrow transplantation, 197 vaccination of, 694 Pneumococcal vaccine (PCV7), 691, 694 Pneumocysitis pneumonia diagnosis of, 597 prophylaxis for, 599t risk of, 597 Pneumocystis, 140 infections with, 596–598 Pneumocystis carinii, 166 Pneumocystis carinii pneumonia (PCP), 55 Pneumocystis jirovecii, 138 Pneumocystis jirovecii pneumonia (PCP), 62, 146, 186, 628 heart transplantation and, 109 incidence of, 198 kidney transplantaion and, 195, 195f pneumonia, 195 pneumothorax in, 188, 189f Pneumocystis pneumonia, 597 Pneumocystis prophylaxis, 146 Pneumonia bacterial, 187, 193, 196 CMV and, 187–188 evaluation of, with X-ray, 188–189 evolution of, 187–188 fungal, 187 in heart transplantation, 108, 193–194 idiopathic interstitial, 192 immunosuppression and, 187–188 in kidney transplantation, 194–195 legionella pneumophila and, 118 in liver transplantation, 195–196 in lung transplantation, 116–119, 122, 194 management of clinical approach to, 188–189 diagnostic investigation, 189–191 measles, 199 noninfectious causes of, 191–193, 192t nosocomial, 194 re-evaluation of, 193 in stem cell transplant, 196–199 treatment of, 119, 193 ventilatory support in, 193 Pneumonitis, 126 adenovirus and, 128 HSV type and, 128 Pneumothorax, 188, 189f Polio See Poliomyelitis Poliomyelitis, 760–761 Poliovirus vaccine, 695 Polyclonal antilymphocyte agents, 32 Polyclonal B-cell proliferation, 368 Polymerase chain reaction (PCR), 144 for ADV detection, 450 for aspergillosis, 542 for cerebral toxoplasmosis, 620, 621t for Chagas disease, 632, 634 cryptosporidiosis and, 639 for PIV identification, 427 for RhV diagnosis, 427 for toxoplasmosis, 542 use of, in BAL, 191 for VZV DNA detection, 400 Polymerase change reaction (PCR), 81 Polymyxin B for Enterobacteriaceae infection, 271 Polyomavirus-associated hemorrhagic cystitis (PyVHC) in allogenic HCT, 471 clinical manifestations of, 470 diagnosis of, 470 pathogenesis of, 471 risk factors for, 470 treatment of, 471, 472 Polyomavirus-associated multifocal leukoencephalopathy (PyVML) after HCT, 472 clinical manifestations of, 472 diagnosis of, 472, 472t, 473 in HIV-AIDS, 473 incidence of, 472 pathogenesis of, 473 risk factors of, 473 treatment of, 473 Polyomavirus-associated nephropathy (PyVAN), 143–144 after solid organ transplantation and allogenic HCT, 469 diagnosis of, 467, 468t, 469t BKV replication screening, 469 JCV loads, 469, 470 incidence of, 467 PyV replication and pathology in, 468f risk factors of, 467 treatment of, 469 Polyomavirus nephropathy, 159 Polyomavirus (PyV) infections, 438 detected in humans, 466t discovery of, 465 genomes, 465 replication and pathology in hemorrhagic cystitis, 471f seroepidemiology of, 465 58202_Index.qxd 2/2/10 2:35 AM Page 783 Index in transplant patients MCC, 474 PyVAN, 467–470 PyVHC, 470–472 PyVML, 472–473 23-valent polysaccharide pneumococcal vaccine (PPV23), 692 Posaconazole for aspergillus infection, 218 for mucormycosis, 568 for zygomycosis, 220 Post–kala azar cutaneous disease, 636 Post-SCT liver disease in HCV infection, 501f Posttransplant acute limbic encephalitis (PALE), 61 Posttransplantation, risk of infections, 69–71 in early period, 70 epidemiologic exposure of, 69 intermediate period, 70 late period, 70–71 standardized immunosuppressive therapy, 69 Posttransplantation lymphoproliferative disorders (PTLD), 150, 362 after hematopoietic stem cell transplants, 370–371 after lung transplantation, 128 ancillary pathological studies for categorization of, 375t categories of, 374t clinical manifestations, 223 clinical presentation of, 371–373 diagnosis of, 184, 223, 373–377 EBER-positive cells in, 372 EBV associated, 128, 158–159 in intestinal transplantation, 183–185 EBV infection in, 366, 367t, 368, 487, 488 endoscopic image of, 183f future prospects in, 382–383 heart transplantation and, 110 incidence of, 222, 368 management of, 185 monomorphic, 374, 375 pathogenesis of, 366–367, 367f prevention of, 381–382, 381t prognosis of, 380 retransplantation after, 380 risk factors for developing, 222–223, 368–371 in SOT and HSCT, 222–223 T-cell-derived, 375 time after transplantation, 222 treatment of, 377–381, 377t and prevention, 223 Posttransplantation spindle cell lesion (PTSD), 184 Posttransplant lymphoproliferative disease (PTLD), 16, 34, 60–61, 71, 85 Posttransplant viral hepatitis, 502 PPD See Mantoux test (PPD); Purified protein derivative (PPD) PPV23 See 23-valent polysaccharide pneumococcal vaccine (PPV23) Praziquantel, 643 Predisposing factors liver transplantation, 164 Prednisone therapy for cryptococcus neoformans, 224 Preemptive therapy (PT) for ADV infections, 452–453 drawbacks of, 130 in intestinal transplantation, 184, 185f for invasive aspergillosis, 563, 564–565 for pneumonia, 198 for RSV upper respiratory tract illnesses, 431 for viral infections, 129–131 Pretransplantation screening, 67–69 immunizations of, 71–72 screen organ donors, 69–70 transplant candidates, 67–68 Pretransplant evaluation of kidney recipient, 138–139 Primary sclerosing cholangitis (PSC), 164 Progressive multifocal leukoencephalopathy (PML), 165, 226–227 Proliferation signal inhibitors (PSI), 16–17 ProMACE-CytaBOM (cytarabine, bleomycin, vincristine, methotrexate, and prednisone), 379 Prope tolerance, 22 Prophylactic adoptive immunotherapy for posttransplantation lymphoproliferative disorder, 381 Prophylactic strategies in solid organ transplantation, 72–74 Prophylaxis, 141, 143 for CMV infection, 315–316, 316t, 318t, 336, 336t–339t, 340–344 for HBV infection, 483 for influenza infection, 434 for invasive aspergillosis, 565–566, 565t for lung transplantation, 124–125 for PIV infections, 436 for Pneumocysitis pneumonia, 599t pneumocystis, 146 for RSV infection, 430–431 for Streptococcus viridans infections, 266 for surgical infections, 156 for toxoplasmosis, 622, 622t for VZV infections, 401–402, 402f Protective environment (PE), 668 Protothecosis, 211 Protozoan infections, 92–96 chagas disease, 92–94 leishmaniasis, 94–95 malaria, 95–96 PSC See Primary sclerosing cholangitis (PSC) Pseudallescheria boydii, infections caused by, 588–589 Pseudomonas, 154 Pseudomonas aeruginosa, 117, 673 PSI See Proliferation signal inhibitors (PSI) PT See Preemptive therapy (PT) PTA See Pancreas transplant alone (PTA) PTLD See Lymphoproliferative disorders (PTLD); Posttransplantation lymphoproliferative disorders (PTLDs); Posttransplant lymphoproliferative disease (PTLD) PTSD See Posttransplantation spindle cell lesion (PTSD) Public Health Service (PHS), 77 Pulmonary aspergillosis, 541f in heart transplant patient, 557f Pulmonary cryptococcosis, 530 Pulmonary embolism, 189f, 539 Pulmonary toxoplasmosis, 199 Purging, Purified protein derivative (PPD), 67, 762 Pyelonephritis, 140 Pyrazinamide for mycobacterial infections, 290 Pyrimethamine, 628 for Toxoplasma, 222 Pyrimidine, 14 Pytiriasis versicolor in a heart transplant patient, 573f Pyuria, 140 PyV See Polyomavirus (PyV) PyVAN See Polyomavirus-associated nephropathy (PyVAN) PyVHC See Polyomavirus-associated hemorrhagic cystitis (PyVHC) PyVML See Polyomavirus-associated multifocal leukoencephalopathy (PyVML) QC/PCR assay See Quantitative competitive polymerase chain reaction (QC/PCR) assay 783 Q fever, 305 QuantiFERON-TB Gold testing, 284 QuantiFERON tests, 92 Quantitative competitive polymerase chain reaction (QC/PCR) assay, 184 Quinolones, 270, 271, 273, 677 for S viridans infection, 266 Quinupristin-dalfopristin for enterococcal infection, 260–262 Rabies, 100–101, 761 geographic distribution, 100 infection in SOT and HSCT, 229 in transplant recipients, 100–101 Radioimmuno-precipitation assay (RIPA), 83, 633 Radiotherapy, 380 Ramoplanin for enterococcal infection, 262 Randomized evaluation of mechanical assistance for the treatment of congestive heart failure (REMATCH), 106, 107 Ranitidine for Helicobacter infection, 302 Rapamune, 283–284 Rapid plasma reagin (RPR), 67, 86 Reduced intensity, 55 Reduced-intensity conditioning (RIC), Regulatory T cells (Tregs), 365 REMATCH See Randomized evaluation of mechanical assistance for the treatment of congestive heart failure (REMATCH) Renal disease in HIV-positive individuals, 145 Renal transplantation (RT) See Kidney transplantation (KT) Replacement therapy, Respiratory distress syndrome, 191–192 Respiratory hygiene/cough etiquette, 656, 668 Respiratory infections after intestinal transplantation, 186 after SOT, 683–684 and immunocompromised hosts, 762 nonherpes viral, 129 treatment of in lung transplant recipients, 119 Respiratory syncytial virus (RSV) infection, 61, 724 after hematopoietic cell transplantation, 429–430 after lung transplantation, 430 after pediatric liver transplantation, 430 after solid organ transplantation, 430 after SOT, 683–684 CRV and, 661–663 diagnosis of, 424, 425–426 isolation precautions and, 656 pneumonia and, 199 prevention strategies, 431–432, 438t prophylaxis for, 430–431 ribavirin for, 662 therapy for, 430–431 Retinitis, 313 Reverse-transcription polymerase chain reaction (RTPCR), 748 for coronavirus diagnosis, 428 for influenza virus infection, 427 for PIV identification, 427 for RhV diagnosis, 427 for RSV identification, 425–426 rhinocerebral disease, 548 Rhinovirus (RhV) infection after hematopoietic stem cell transplantation, 437 diagnosis of, 427–428 prevention and treatment modalities, 438t Rhodococcus equi, 195, 299 Rhodotorula rubra fungemia, 515 Rhodotorula species, 532 58202_Index.qxd 784 2/2/10 2:35 AM Page 784 Index RhV See Rhinovirus (RhV) infection Ribavirin for ADV infections, 452 for influenza infection, 435 and metapneumovirus, 749 for PIV infections, 436 for RSV bronchiolitis and pneumonia, 431–432 for RSV infection, 662 RIC See Reduced-intensity conditioning (RIC) Rickettsiosis, 304–306 Bartonella, 304–305 Coxiella burnetti, 305 Rifampicin, 119 Rifampin for Enterobacteriaceae infection, 272 for enterococcal infection, 260 for Legionella infection, 301 for M hominis, 304 for mycobacterial infections, 290 for Rhodococcus infection, 299 for S aureus infection, 265 Rimantadine/amantadine for influenza infection, 434, 435 RIPA See Radioimmuno-precipitation assay (RIPA) Rituximab for EBV infection, 488 for posttransplantation lymphoproliferative disorder, 223, 379 Rocky Mountain spotted fever after heart transplantation, 305 Room ventilation, 653, 655 Roseola infantum, 207, 488 Rotavirus infection and diarrhea, 245 transmission of, 684 viral gastroenteritis and, 684 Roux-en-Y choledochojejunostomy (CJ), 164 Roux-en-Y hepaticojejunostomy (HJ) liver transplantation with, 164, 164f RPR See Rapid plasma reagin (RPR) RSV infection See Respiratory syncytial virus (RSV) infection RSV-shedding patients, 662 RSV upper respiratory tract illnesses prevention of, 431 RT-PCR See Reverse transcription polymerase chain reaction (RT-PCR) Rubella vaccine, 696 Sabin, 760 Saccharomyces boulardii, 661 Saccharomyces cerevisiae infection, 515, 533 Salk, 760 Salmonella enterica serovar Typhi, 760 Sandwich ELISA technique, 542 SARS See Severe acute respiratory syndrome (SARS) SARS coronavirus (SARS-CoV), 745 SARS-CoV See SARS coronavirus (SARS-CoV) SBD See Selective bowel decontamination (SBD) Scedosporium apiospermum, 588–589 infection in SOT and HSCT, 218 Scedosporium species infections, 570–572 diagnosis and therapy for, 547 microbiology and pathogenesis of, 546 risk factors and clinical syndromes of, 546–547 Scedosporium prolificans, infections caused by, 589 Schistosoma haematobium, 642 Schistosoma mansoni, 642 Schistosomiasis diagnosis of, 642–643 in liver transplantation, 643 treatment of, 643 SCID See Severe combined immunodeficiency (SCID) Scientific Registry of Transplant Recipients (SRTR), 31 SCIP See Surgical Care Improvement Program (SCIP) Scopulariopsis species, infections caused by, 572, 590 SCT See Stem cell transplantation (SCT) Selective bowel decontamination (SBD), 166, 169 Sepsis-related Organ Failure Assessment (SOFA), 193 Serologic testing for antibodies to Aspergillus antigens, 541 Serologic testing methods, 82t Serratia marcescens, 117 Settle plates, 671 Severe acute respiratory syndrome (SARS), 745 Severe combined immunodeficiency (SCID), 3, 733 SHEA See Society for Healthcare Epidemiology of America (SHEA) shell vial assay, 414, 462 Shingles See Herpes zoster Signal transduction blockers, 28–32 antimetabolites, 30–31 calcineurin inhibitors, 28–29 mycophenolate mofetil, 31–32 tacrolimus, 29–30 Simultaneous pancreas–kidney (SPK) transplantation, 151, 153 sources of surgical infections after, 152f SIR See Sirolimus (SIR) Sirolimus (SIR), 17, 35, 41, 166, 283–284 posttransplantation lymphoproliferative disorder and, 370 toxicity, 240 Skin biopsy, 208, 211–212 cancer, transplant recipients and, 763 care of, 658–659 Skin infections bacterial, 203–205 malakoplakia, 205 mycobacterial infections, 204 nocardiosis, 204–205 fungal infections, 207–211 aspergillosis, 209 candidiasis, 208–209 coccidioidomycosis, 211 cryptococcosis, 209–210 histoplasmosis, 211 invasive opportunistic mycoses, 208 mucormycosis, 210–211 North American blastomycosis, 211 protothecosis, 211 superficial mycoses, 207–208 after hematopoietic stem cell transplantation, 203–212 parasitic infections, 211–212 after solid organ transplantation, 203–212 viral infections, 205–207 CMV infection, 206 herpesvirus infections, 205–207 HHV-6, 207 HSV infection, 205–206 molluscum contagiosum, 207 papillomavirus infections, 207 VZV infection, 206–207 Skin lesions, 203, 208, 398, 545f Skin malignancy in kidney transplant patients, 477 Small intestinal biopsy, 546 Society for Healthcare Epidemiology of America (SHEA), 667 SOFA See Sepsis-related Organ Failure Assessment (SOFA) Solid organ transplantation (SOT), 90 adenovirus infections after, 229, 240–241 aspergillus infection after, 214, 216–218 bacterial infections after, 203–205 Burkholderia cepacia infections after, 273–274 candida infection after, 220 central nervous system (CNS) infections after, 214–230 acanthamoeba, 229–230 adenovirus, 229 aspergillus, 216–218 brain abscesses, 223–224 candida, 220 clinical manifestations, 214–215 complications, 214 cryptococcus neoformans, 224–225 diagnostic criteria for, 215–216 etiology, 214 focal lesions, 215 human herpesvirus (HHV-6), 225–226 incidence, 214 JC virus, 226–227 listeria, 228–229 lymphocytic choriomeningitis virus, 229 measles inclusion bodies encephalitis (MIBE), 229 meningoencephalitis, 224 nocardia, 220–221 parasite, 229–230 parvovirus B19, 229 phaeohyphomycosis, 218–219 posttransplantation lymphoproliferative disorder (PTLD), 222–223 rabies, 229 risk factors, 214, 216–217 scedosporium apiospermum, 218 toxoplasma, 221–222 varicella zoster virus (VZV), 229 West Nile virus (WNV), 227–228 zygomycosis, 219–220 Chagas disease in, 633–634 Chlamydia, 303 clinical immunosuppression, 14–17 antiproliferative agents, 14–15 calcineurin inhibitors, 16–17 history of, 14 proliferation signal inhibitors, 16–17 regimens according to posttransplant phase, 17t therapeutic antibodies, 15–16 CMV infection after, 328–352 acquiring CMV infection, 328–329 antiviral drug strategies, 335–336 antiviral prophylaxis, 336, 336t–339t, 340–344 antiviral resistance, 351–352 clinical syndromes, 331–335 diagnosis of, 333t epidemiology, 328–331 immunoglobulin preparations, 351 immunotherapy, 348 impact of, 332–335, 332t methods used for diagnosis of, 332, 333t pathogenesis, 328–331 pre-emptive therapy, 336t–337t, 344–348, 345t prevention of, 335–348 reactivation of CMV, 329 risk factors, 329–331 seronegative blood products and protective matching, 348 superinfection (CMV Dϩ/Rϩ), 329 treatment of, 348–352, 349t vaccination, 348 composite organ transplantation, 21 cryptococcus neoformans infection after, 224–225 cryptosporidiosis in, 638–639 fungal infection after, 207–211 future prospects, 21–23 donor-specific tolerance, induction of, 22–23 xenografting, 21–22 gastrointestinal infections after, 236–239, 239–241 graft-versus-host-disease (GVHD) after, 236, 240–241 gram-negative infections after with Acinetobacter spp., 274 58202_Index.qxd 2/2/10 2:35 AM Page 785 Index with Burkholderia cepacia, 273–274 with Enterobacteriaceae, 269–270 with nonfermentative gram-negative bacilli, 270–273 with Stenotrophomonas maltophilia, 273 gram-negative organisms Helicobacter, 301–302 Legionella, 300–301 gram-positive infections after with coagulase-negative staphylococci, 262–263 enterococci related, 257–262 with Staphylococcus aureus, 264–265 with Streptococcus pneumoniae, 266–268 with Streptococcus viridans, 265–266 gram-positive organisms anaerobic actinomycetes, 298 Clostridium difficile, 299–300 lactobacilli, 298–299 Listeria monocytogenes, 295–296 Nocardia, 296–298 Rhodococcus equi, 299 HHV-6 infection after, 207, 225–226 history of, 13–14 immunobiology of alloresponsiveness, 13–14 in mythology, 13 surgical advances, 13 immunosuppressive regimens, 17–20 acute rejection episodes, therapy for, 19–20 early maintenance therapy, 18–19 immunosuppressive therapy, long-term, 19 induction therapy, 17–18 intermediate maintenance period, 19 infection control issues after community-acquired infections, 679–684 HAI and See Health care-associated infections (HAI) kidney transplantation, 20 legionellosis in, 673–675 liver transplantation, 20–21 malaria in, 637–638 meningoencephalitis, 224 molluscum contagiosum, 207 mycobacterial infections after, 204, 282–291 mycoplasma, 303–304 Nocardia infection after, 220–221 pancreas transplantation, 21 parasitic infections after See Parasitic infections pneumonia after See Pneumonia posttransplantation, 69–71 pretransplantation screening, 67–69 prevention of infection, 71–74 avoidance of infectious exposures, 72 immunizations, 71–72 prophylaxis, 72–74 recipients, neutropenia and, 706 rickettsiosis, 304–306 Bartonella, 304–305 Coxiella burnetti, 305 skin infections after, 203–212 bacterial infections, 203–205 fungal infections, 207–211 parasitic infections, 211–212 viral infections, 205–207 spirochetes Borrelia, 303 Leptospira, 303 Treponema pallidum, 302–303 thoracic transplantation, 21 tissue transplantation, 21 viral infections after bocavirus, 745 coronavirus, 745, 748 LCMV, 748 measles, 749 metapneumovirus, 748–749 mumps, 749 norovirus, 749 parvovirus B19, 749–750 rotavirus, 750 Solid organ transplant recipients vaccination of, 698–701 Solid organ transplants (SOT), 724 after ADV infection diagnosis of, 462 epidemiology of, 459–460 hepatitis and, 490 transmission of, 460 treatment of, 462–463 CRV infections in, 429 dematiaceous fungi infections after, 569t EBV infection in, 362, 365–366, 375 endemic mycoses after, 608–613 HBV infection and, 483–484 hepatotoxicity in, 492 HHV-6 infection after, 413, 488–489 HHV-7 infection after, 489 HMPV infections in, 432 Hodgkin disease after, 376 HPV infection after, 476–477 HSV infection and, 392–396, 486–487 influenza infections in, 433–434 Kaposi sarcoma after, 489, 490 mold infections after aspergillosis, 555–566 dematiaceous fungi, 568, 568t, 570 dermatomycoses, 572–573 hyalohyphomycosis, 570–572, 571t mucormycosis, 566–568 mucormycosis after, 566 nonmelanoma skin cancers in, 477 PIV infections in, 436 posttransplantation lymphoproliferative disorder in, 369, 372, 375, 380 precancerous skin lesions in, 476–477 preemptive strategies in, 381–382 PyVAN after, 469 RSV infections in, 430 timing of fungal infections in, 554–555, 554t toxoplasmosis after clinical manifestations of, 626–627 diagnosis, 627–628, 627t epidemiology of, 625–626 etiologic agent for, 624–625 immune response and genetic susceptibility of host, 626 prevention of, 628–629, 629t, 630t VZV infection after, 398–402 warts in, 476–477 yeast infections after, 525 clinical manifestations of, 526 cryptococcosis, 529–532 diagnosis of, 527 epidemiology of, 526 Malassezia, 533 Rhodotorula and Sporobolomyces, 532 S cerevisiae, 533 treatment of, 527–529 Trichosporon, 532–533 zygomycosis after, 592–593 SOT See Solid organ transplantation (SOT) “Spanish flu,” 427 Spiramycin, 639 Spirochetes Borrelia, 303 Leptospira, 303 Treponema pallidum, 302–303 SPK transplantation See Simultaneous pancreaskidney (SPK) transplantation Spondylodiscitis, 595 Sporobolomyces infection, 532 Sputum, diagnosis of, 189–190 Squamous cell carcinoma, 477, 477f 785 SRL See Sirolimus (SRL) SRTR See Scientific Registry of Transplant Recipients (SRTR) SSI See Surgical site infection (SSI) Standardized immunosuppressive therapy, 69 Staphylococci, 660–661 Staphylococcus aureus infections, 117, 162, 223 drug resistance of, 264 incidence of, 264 manifestations of, 264 outcome of, 264 prevention of, 265 transmission of, 264 treatment of, 265 Staphylococcus epidermidis, 119 Stem cells alternative sources, 3–4 source, 7–8 source of, 55–56 Stem cell transplantation (SCT), 725 cytomegalovirus infection after, 311–321 pneumonia in, 196–199 vaccination in, 693t Stenotrophomonas maltophilia, 117, 273, 657, 675 Sterile diets, 660 Steroid-refractory, 57 Steroids for PyVHC treatment, 471, 472 Steroid therapy, 19 Stool examination for microsporidial infections, 640 Streptococcus, 57 Streptococcus epidermidis, 223 Streptococcus pneumoniae infections, 58, 189 antibiotic prophylaxis for, 268 drug resistance of, 267 immunization for, 268 incidence of, 266–267 management of, 267–268 manifestations of, 267 outcome of, 267 prevention of, 268 Streptococcus viridans infections, 196 drug resistance, 266 incidence of, 265 manifestation of, 265 outcome of, 265 prophylaxis for, 266 risk factors for developing, 265–266 treatment, 266 Streptomyces tsukubaensis, 16, 29 Streptomycin for enterococcal infection, 260–261 Strictures, 140 Strongyloides stercoralis infection travelers and, 763 Strongyloidiasis, 211, 236, 641–642 Suicide gene, Sulfadiazine for Toxoplasma, 222 Sulfadoxine for Toxoplasma, 222 Surgical Care Improvement Program (SCIP), 111 Surgical infections pancreas transplantation, 150 prophylaxis of, 156 sources of, after SPK transplantation, 152f Surgical site infection (SSI), 670 Surveillance cultures in hematopoietic cell transplantation, 663 Survival rates before and after EBV, 185f intestinal transplantation, 181, 181f LVAD, 107 Symptomatic disease, 461 Symptomatic primary infection, 626 58202_Index.qxd 786 2/2/10 2:35 AM Page 786 Index Syndrome of inappropriate antidiuretic hormone release (SIADH), 226 Syphilis, 302 Systemic antifungal agents, 543t Systemic sepsis, 492 TAC See Kino isolated tacrolimus (TAC); Tacrolimus (TAC) Tachyzoite, 624 Tacrolimus (TAC), 16, 29–30, 41, 166, 240, 283 after posttransplantation lymphoproliferative disorder, 369 for intestinal transplantation, 182 toxicity, 240 Target of rapamycin (TOR) inhibitors, 69 TB See Tuberculosis (TB) TBI See Total body irradiation (TBI) T-cell-derived PTLD, 375 T-cell receptor (TCR), 15 T-cell replete, 56 T-cell(s), 6, 59 ADV infection and, 448, 449 Aspergillus specific, 737 CD8ϩ ␣ϩ cytomegalovirus-specific T Cells, 728–729 CD8ϩ ␣ϩ cytotoxic T-lymphocyte effector functions, 727 CD4ϩ ␣ϩ T helper effector functions, 726–727 current technologies of enriching virus-specific, 734–735 cytomegalovirus-specific, 727–728 depletion of donor marrow, effector mechanisms of ␣ϩ, 726–729 immune reconstitution, 449–450 immunity, 724 targets, 447 T cells therapy for adenovirus infection, 736 for fungal infection, 736–737 for herpesviruses, 735–736 TCR See T-cell receptor (TCR) Tdap, 757 Teicoplanin for coagulase-negative staphylococci, 263 for enterococcal infection, 261 for S aureus infection, 265 for S viridans infection, 266 Terbinafine, 572, 573, 592 Tetanus toxoid, 695 transplant recipients and, 757 Tetracycline for C burnetti, 305 for chlamydial infection, 303 for coagulase-negative staphylococci, 263 for Helicobacter infection, 302 for Legionella infection, 301 for M hominis, 304 for Streptococcus pneumoniae infection, 267 TGF– See Transforming growth factor- (TGF–? TH2 See T helper type cell (TH2) Th17 cells, T helper type cell (TH2), 709 Thiabendazole, 642 Thoracic transplantation, 21 Ticarcillin for Enterobacteriaceae infection, 272 Tigecycline for Acinetobacter spp., 274 for Enterobacteriaceae infection, 273 for enterococcal infection, 260, 262 for Nocardia infection, 298 Tinea corporis, 208 Tinea pedis, 208 Tinea versicolor, 208 Tissue cyst, 624 Tissue transplantation, 21 TLR4 See Toll-like receptor protein (TLR4) T lymphocytes, 2, 15 TMP-SMX therapy See Trimethoprim-sulfamethoxazole (TMP-SMX) therapy TMP-SMZ See Trimethoprim-sulfamethoxazole (TMP-SMZ) TNF-␣ See Tumor necrosis factor (TNF)-␣ Tobramycin for Enterobacteriaceae infection, 272 Toll-like receptor protein (TLR4), 53 Tolypocladium inflatum, 16, 28 TOR See Target of rapamycin (TOR) inhibitors Total body irradiation (TBI), Total parenteral nutrition (TPN) in HSCT patients, 660 intestinal transplantation and, 179 Toxoplasma chorioretinitis, 620 Toxoplasma disease See Toxoplasmosis Toxoplasma encephalitis, 620 and CNS infections, 214, 221 Toxoplasma gondii, 67, 195–196, 492 and CNS infections, 214, 221 different forms of, 617, 625f heart transplantation and, 110 life cycle of, 625 reactivation of latent infection, 626–627 serologic screening, 624 seroprevalence for, 617 transmission of, 625 Toxoplasmosis, 62, 86 acute, 626 after hematopoietic stem cell transplantation case series of, 617, 618, 619t EBMT-IDWP definitions for, 621t PB samples, 621t treatment and prophylaxis for, 622, 622t after solid organ transplantation clinical manifestations of, 626–627 diagnosis, 627–628, 627t epidemiology of, 625–626 etiologic agent for, 624–625 immune response and genetic susceptibility of host, 626 prevention of, 628–629, 629t, 630t clinical manifestations, 221 and CNS infections, 214 diagnostic criteria, 221 imaging, 222 incidence of, 221 infection in SOT and HSCT, 221–222 laboratory diagnosis, 221–222 prevention, 222 risk factors, 221 time after transplantation, 221 treatment, 222 Tracheobronchitis in lung transplantation, 120 treatment of, 120–121 Transbronchial biopsy, 191 Transforming growth factor- (TGF–?, 19, 715 Transmission-Based Precautions, 656 TRANSNET See Transplant Associated Infection Surveillance Network (TRANSNET) Transplant Associated Infection Surveillance Network (TRANSNET), 73 Transplantation Society, The, 764 Transplant candidates, 67–68 infectious diseases screening for solid organ, 68t Transplant centers, visitors to, 658 Transplant conditioning modalities for, rationale for, Transplant infections, developing countries bacterial infections, 90–92 protozoan infections, 92–96 viral infections, 96–101 Transplant recipient(s) aspergillosis and, 655–656 Chagas disease in kidney, 633–634 control of C difficile in, 661 diarrhea in, 659, 762 hepatitis A vaccine and, 759–760 hydatid disease in, 643 in intestinal transplantation, 180, 182 for isolation precautions, 656–657 in liver transplantation, 165 in pancreas transplantation, 156 room ventilation for, 653, 655 skin and oral care of, 658–659 tetanus and, 757 vaccination in, 758t Transplant-related mortality (TRM), 448 Transplant tourism, 764–765 defined, 764 infectious risks of, 145–146 Treponema pallidum, 302–303 Triatoma infestans, 93 Trichoderma species, infections caused by, 589 Trichosporon beigelii infection, 198f Trichosporonosis, 532–533 Trichosporon species, infection caused by, 514–515, 532–533, 594–595 Trimethoprim for coagulase-negative staphylococci, 263 Trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis and CNS infections, 205, 214, 222 for Legionella infection, 301 for Listeria monocytogenes, 296 Trimethoprim-sulfamethoxazole (TMP-SMX) therapy, 140, 145, 188 for pneumonia, 194 Trimethoprim-sulfamethoxazole (TMP-SMZ), 72, 598 traveler’s diarrhea and, 762 TRM See Transplant-related mortality (TRM) Tropical and neglected diseases distribution of, 91 Trypanosoma cruzi, 83, 632 heart transplantation and, 110 TST See Tuberculin skin testing (TST) TT See Tuberculoid (TT) Tuberculin skin testing (TST), 53, 91, 139, 284, 680 Tuberculoid (TT), 92 Tuberculosis (TB), 53, 90–92, 138 diagnosis of, 680 geographic distribution, 91–92 isolation issues in, 679–680 pneumonia and, 188 postexposure follow-up, 680–681 pretransplantation screening, 67 prevention of, 663 recommendations, 92 screening of kidney donors for, 139 transmission in transplant recipients, 91–92 treatment of, 119 Tumor necrosis factor (TNF)-␣, 28 Typhlitis, 239, 247 UCB See Umbilical cord blood (UCB) Ultrasonography for cryptosporidiosis, 639 Umbilical cord blood (UCB), 55, 371 United Network for Organ Sharing Thoracic Registry, 107 58202_Index.qxd 2/2/10 2:35 AM Page 787 Index United Network for Organ Sharing (UNOS), 78, 145, 675 UNOS See United Network for Organ Sharing (UNOS) UNOS policy, 79, 79t Upper respiratory tract (URT) infection, 190 Urinary BKV shedding, 467 Urinary tract candidiasis treatment of, 528 Urinary tract infection (UTI), 138 clinical presentations of, in kidney transplant recipients management of, 142t kidney transplantation and, 140–141 recurrent, 141 in pancreas transplantation, 155–156 risk factors for, 140 URT infection See Upper respiratory tract (URT) infection UTI See Urinary tract infection (UTI) Vaccinations, 83–84 of close contacts of immunocompromised hosts, 762 for HAV, 760 of health care workers, 670 for influenza, 658, 662, 683–684, 758 influenza virus infection, 433 for JE, 762 for measles, 758–759 for meningococcal disease, 761 for polio, 760–761 posttransplantation, kidney, 146 for rabies, 761 routine, 757–759 for Salmonella enterica serovar Typhi, 760 in transplant recipients, 758t of transplant recipients hematopoietic stem cell transplantation (HSCT), 691–698 solid organ transplant recipients, 698–701 VZV and, 402–403, 658, 681–683 for yellow fever, 761 Valacyclovir for CMV infection, 316 for HSV infections, 395 Valacyclovir prophylaxis, 143 Valganciclovir for CMV infection, 316–317, 338t, 341–342, 349–350 in liver transplantation, 172 in lung transplantation, 129–130 in pancreas transplantation, 157 Vancomycin for C difficile infection, 300 for coagulase-negative staphylococci, 263 dependent enterococci infections, 260 for Legionella infection, 301 for Listeria monocytogenes, 296 resistant S aureus, 264 for Rhodococcus infection, 299 for S aureus infection, 265 for S viridans infection, 266 and staphylococci with reduced susceptibility, 660–661 Vancomycin-resistant enterococci (VRE) infections, 258–261, 653 control of, 661 liver transplantation and, 162, 168 prevention of, 675–677 Vancomycin-resistant enterococcus faecium (VREF), 258–261 Vancomycin-resistant S aureus (VRSA), 677 Vancomycin-sensitive enterococci (VSE), 676 Varicella-zoster immunoglobulin (VZIG), 402, 658, 682 Varicella zoster virus (VZV) infection, 60, 116, 138, 206–207, 236, 724 after bone marrow transplantation, 398, 399 after hematopoietic stem cell transplantation clinical presentation of, 398–400 diagnosis of, 400–401 epidemiology of, 397 pathogenesis of, 397–398 prevention of, 402–403 prophylaxis for, 401–402, 402f therapy for, 401 vaccination, 402–403 after liver transplantation, 487 after lung transplantation, 399 after renal transplantation, 403 after solid organ transplantation, 398–402 cutaneous dissemination of, 400 herpes zoster from reactivation of latent, 397 infection in SOT and HSCT, 229 isolation issues with, 681 patient screening for, 681–682 postexposure follow-up with, 682 pretransplantation screening, 67 primary, 487 reactivation of, 399, 400 staff considerations for, 682–683 transmission of, 397 vaccine, 658, 691, 696 VDRL See Venereal disease research laboratory (VDRL) Venereal disease research laboratory (VDRL), 67, 86 Veno-venous bypass, 163 Ventilatory support, 193 Vidarabine for HSV infections, 395 Viral gastroenteritis, 684 Viral inclusions, 487 Viral infections, 96–101 adenovirus, 490 after heart transplantation, 110 after liver transplant adenovirus, 172–173 CMV, 171–172 HSV, 172 recurrent hepatitis, 173–174 after lung transplantation features and treatment of, 126–129 prevention, 129–131 CMV, 485–486, 485f dengue, 96–98 EBV, 487, 488f after hematopoietic stem cell and solid organ transplantation, 205–207 bocavirus, 745 coronavirus, 745, 748 CMV infection, 206 herpesvirus infections, 205–207 HHV-6, 207 HSV infection, 205–206 LCMV, 748 measles, 749 metapneumovirus, 748–749 molluscum contagiosum, 207 mumps, 749 norovirus, 749 papillomavirus infections, 207 parvovirus B19, 749–750 rotavirus, 750 skin infections, 205–207 VZV infection, 206–207 West Nile virus, 750–751 hepatitis, 483–485 herpesvirus infections, 205–207 HHV-6, HHV-7 and HHV-8, 488, 489f, 490 787 HSV, 486–487 measles, 99–100 post kidney transplant adenoviruses, 144 parvovirus B19, 144 WNV, 144–145 PT for, 129–131 in transplant patients, 391 VZV, 487 yellow fever, 98–99 Viral load EBV and, 380 in lung transplantation, 126, 127 monitoring of, 130 Viremia detection of, BKVAN and, 144 Viruria, 467 Visceral leishmaniasis (VL), 94 Visceral VZV disease, 400 Vision loss, 219, 546 VL See Visceral leishmaniasis (VL) Vomiting causes, 243 diagnosis, 243 Voriconazole, 516, 517, 528 for aspergillus infection, 218 for chemotherapy-induced neutropenia, 518 for fungal infections, 120, 121 for invasive aspergillosis, 561–562 for phaeohyphomycosis, 219 toxicity, 240 treatment of n-LAB with, 121 VRE See Vancomycin-resistant enterococci (VRE) infections VRSA See Vancomycin-resistant S aureus (VRSA) VSE See Vancomycin-sensitive enterococci (VSE) VZIG See Varicella-zoster immunoglobulin (VZIG) VZV See Varicella zoster virus (VZV) infection Warts in solid organ transplants (solid organ transplantations), 476–477 Washington University virus (WUV), 465, 467 in hematopoietic cell transplants, 473–474 West Nile virus (WNV), 139, 144–145, 750–751 clinical manifestations, 227–228 diagnostic criteria, 228 incidence of, 227 infection in SOT and HSCT, 227–228 pathogen, 227 risk factors, 227 time after transplantation, 227 treatment and prevention, 228 WHO See World Health Organization (WHO) WNV See West Nile virus (WNV) World Health Organization (WHO), 90, 633 Wounds complications, risk factors for, 140 infections abdominal, 162 pancreas transplantation and, 156 WUV See Washington University virus (WUV) XDR-TB See Extensively drug-resistant (XDR)-TB Xenografting, 21–22 X-ray, pneumonia evaluation with, 188–189 Yeast infections after hematopoietic stem cell transplantation, 507, 507t, 508t acute disseminated candidiasis, 512 58202_Index.qxd 788 2/2/10 2:35 AM Page 788 Index Yeast infections (contd.) candidemia, 509–513 candidiasis, 509 chronic disseminated candidiasis, 512 Cryptococcus neoformans, 514 endemic dimorphic fungi, 515–516 Malassezia species, 515 mucosal immunity, 509 Pichia anomala, 515 Rhodotorula rubra fungemia, 515 Trichosporon species, 514–515 after solid organ transplantation, 525 clinical manifestations of, 526 cryptococcosis, 529–532 diagnosis of, 527 epidemiology of, 526 Malassezia, 533 Rhodotorula and Sporobolomyces, 532 S cerevisiae, 533 treatment of, 527–529 Trichosporon, 532–533 uncommon, 594–598 Yellow fever, 761 Yellow fever virus (YFV), 98–99 current concerns and, 98–99 geographic distribution, 98 transmission in transplant patients, 98 YFV See Yellow fever virus (YFV) Zanamivir, 662 for influenza infection, 434, 435 Zygomycetes, 673 taxonomy of, 567 Zygomycosis, 215t chemotherapy of invasive infections by, 594t clinical manifestation, 219–220 diagnosis and therapy for, 548–549 in immunocompromised solid organ transplantation or hematopoietic stem cell transplantation, 592–593 incidence of, 219 infection in SOT and HSCT, 219–220 microbiology and pathogenesis of, 547 pathogen, 219 risk factors and clinical syndromes of, 547–548 time of appearance, 219 treatment of, 220 ... Pre-Emptive Therapy and Prophylaxis after HCT 2/ 1/10 Prevention Strategy TABLE 22 .3 5 820 2_ch 22. qxd Page 318 5 820 2_ch 22. qxd 2/ 1/10 8:49 PM Page 319 Chapter 22 pre-emptive therapy (115) Due to initial... Infection after Stem Cell Transplantation 20 9 21 0 21 1 21 2 21 3 21 4 21 5 21 6 21 7 327 cytomegalovirus-associated interstitial pneumonia in bone marrow allograft recipients Transplantation 1988;46:905–907... blood transplantation: a comprehensive review Bone Marrow Transplant 20 06;38:83–93 5 820 2_ch 22. qxd 2/ 1/10 8:49 PM Page 325 Chapter 22 134 Albano MS, Taylor P, Pass RF, et al Umbilical cord blood transplantation