Catheter-associated urinary tract infection - 1 INTRODUCTION: Catheter-associated urinary tract infection (CAUTI) is the most common nosocomial infection in hospitals and nursing homes worldwide, comprising more than 40% of all institutionally-acquired infections.(Stamm, 1991; Warren 1991; Kunin 1997) Up to 25% of patients requiring a urinary catheter for seven days or longer develop nosocomial bacteriuria or candiduria, with a daily incidence of 5% (Garibaldi et al 1982; Kunin 1997) CAUTI rarely progress to bloodstream infection However, overall, CAUTI is the second most common cause of nosocomial bloodstream infection because of the high frequency of this infection (Maki 1981; Krieger et al 1983; Bryan and Reynolds 1984) Studies by Platt et al (1982) and Kunin et al (1992) suggest that nosocomial CAUTIs are associated with increased institutional mortality, unrelated to the occurrence of urosepsis Asymptomatic urinary tract infections often precipitate unnecessary antimicrobial therapy CAUTIs comprise perhaps the largest institutional reservoir of nosocomial antibiotic-resistant pathogens.(Stamm 1991; Jarvis and Martone 1992; Siebert et al 1993; Jarlier et al 1996) The recognition of the role of the catheter in the pathogenesis of urinary tract infections dates back to the 1950s (Kass 1956) Most of what we know about CAUTI derives from studies done in the early 1970s and 1980s soon after the introduction of infection control programs in the United States and elsewhere Catheter-associated urinary tract infection - This was before the widespread changes in healthcare associated with the managed care era - increases in technology and the pressure towards early discharge and outpatient management of increasingly sicker patients (Warren 1991; Kunin 1997) Very little is known about the exact pathogenesis, symptomatology, association with pyuria and mortality as well as economic impact in the modern era This study was undertaken to try to address some of these gaps Catheter-associated urinary tract infection - AIMS: 2.1 Pathogenesis: Excluding rare hematogenously-caused pyelonephritis, mainly with S.aureus (Lee et al 1978; Arpi and Renneberg 1984) the vast majority of microorganisms causing endemic CAUTI are thought to derive from patients’ own perineal flora or from the hands of healthcare personnel inserting the catheter or manipulating the collection system.(Stamm, 1991; Warren 1991) These organisms are thought to gain access to the bladder by one of two mechanisms: extraluminally - early, by direct inoculation at the time of catheter insertion or later, ascending from the perineum in the mucus film contiguous to the external catheter surface; or intraluminally, most probably by reflux of organisms gaining access to the catheter lumen from failure of closed drainage or contamination of collection bag urine The relative contribution of each of the three routes has not been adequately delineated Strategies for prevention, especially technologic innovations, should be guided by the best understanding of pathogenesis The first aspect of this large prospective study encompassing 1497 evaluable newly catheterized patients was undertaken to better define the pathogenesis of CAUTI Catheter-associated urinary tract infection - 2.2 Risk factors: A small number of prospective studies (Garibaldi et al 1974; Shapiro et al 1984; Platt et al 1986; Johnson et al 1990) examined the risk factors for CAUTI mainly in the 1970s and 1980s The current era’s strong focus on compliance with published infection control guidelines, the effect of compliance with the individual aspects of catheter care has not been adequately examined Therefore, the second part of this large prospective observational study of CAUTI was to study risk factors for CAUTI, particularly the impact of noncompliance with recommended precepts of urinary catheter care on the risk of CAUTI 2.3 Clinical Features and Symptoms associated with CAUTI Although there have been recommendations to treat catheter-associated urinary tract infections only when symptomatic (Warren 1991; National Institute on Disability and Rehabilitation Research 1992; O’Grady et al 1998), the symptoms associated with CAUTI have not been clearly defined The third part of this prospective study of 1497 newly-catheterized hospitalized patients was undertaken to determine the prevalence of signs and symptoms attributable to Catheter-associated urinary tract infection CAUTI and the relative contribution of CAUTI to nosocomial bloodstream infection 2.4 Association with Pyuria: Pyuria has been shown to have excellent predictive value for identifying urinary tract infections in non-catheterized patients (Mabeck 1969, Stamm et al 1981) Although published guidelines recommend using pyuria as the criterion for obtaining a urine culture as part of the work-up of fever in the hospitalized patient (O’Grady et al 1998), the utility of pyuria to identify bacteriuria or candiduria in short-term catheterized patients has not been clearly defined previously The fourth part of this prospective study was to determine the relationship between pyuria and urinary tract infection in 761 hospitalized patients with short-term indwelling urinary catheters 2.5 Mortality and Morbidity: The contribution of CAUTI to hospital mortality has not been clearly defined In a widely cited study published in 1982, Platt et al reported that nosocomial CAUTIs were associated with greatly increased in-hospital mortality in Catheter-associated urinary tract infection catheterized patients (Platt et al 1982) Subsequently, Kunin et al reported a strong association between use of urinary catheters and mortality in nursing home patients (Kunin et al 1992) We reexamined this association in a prospective analysis of one thousand catheterized hospitalized patients to determine whether CAUTI is truly an independent predictor of increased hospital mortality 2.6 Economic Impact: Retrospective studies quantifying the economic impact of CAUTI were done mainly in the 1970s and 1980s, (Scheckler 1979; Givens and Wenzel 1980; Haley et al 1981; Coello et al 1993) before the widespread emergence of resistant nosocomial uropathogens and also before the advent of managed care in US hospitals In the final part of the analysis, we prospectively studied 1497 newlycatheterized hospitalized patients, obtaining daily urine cultures, and quantified the extra direct costs of hospitalisation incurred in the management of CAUTI in 123 infected patients, and compared the findings with those of earlier studies in the 1970s and 1980s before the era of managed care Catheter-associated urinary tract infection - METHODS: 3.0 Methods in Common to all six sections: 3.0.1 Patients: All patients hospitalized at the University of Wisconsin Hospital and Clinics or the William S Middleton Veterans Administration Medical Center, in Madison, WI, USA, scheduled to receive an indwelling urethral (Foley) catheter, who could be successfully catheterized with a 16Fr or 18Fr catheter and were expected to be catheterized for more than 24 hours were candidates for this study Patients were excluded if they were under the age of 18 years, pregnant or had known allergy to silicone After providing informed consent, patients were randomized to be catheterized with a standard silicone-coated catheter or a novel silver-hydrogel catheter (both C.R Bard., Inc, Covington, GA, USA) The two catheters were physically indistinguishable and investigators and the research team as well as the patients’ healthcare providers were blinded to each patient’s catheter assignment The study was approved by the institutional Human Subjects Committee, and written informed consent was obtained from all patients Catheter-associated urinary tract infection - 3.0.2 Study Procedures: On entry into the study, demographic and clinical data bearing on risk for CAUTI identified in previous studies (Garibaldi et al 1974; Shapiro et al 1984; Platt et al 1986; Johnson et al 1990) were collected, including age, gender, structural urologic disease, underlying systemic diseases including diabetes mellitus and cancer, immunosuppressive therapy, hospital service, confinement in an ICU, recent surgery and the purpose for catheterization A faint line was made across the catheter-collection tube junction at the outset and inspected every day permitting continuous assessment of the integrity of closed drainage (Garibaldi et al 1974) Catheter care was scored daily by trained research nurses, scoring compliance in each of the following areas (1) integrity of the tamper-evident line; (2) no other breaks in the closed drainage system; (3) immobilization of the catheter, taped to the thigh; (4) position of the catheter tubing below the level of the patient but above the bag, (5) position of the collection bag, below the level of the patient but off the floor; (6) intact clamp on the collection bag and (7) protection of the drainage port Each category was scored (0, non-compliance; 1, no violation noted), and the summed daily score was averaged for the duration of catheterization, yielding an overall score for each patient’s catheter, ranging from to Each day, the patient was questioned regarding discomfort or symptoms associated with the catheter Catheter-associated urinary tract infection (pain, sense of urgency or dysuria) and the patient’s record was reviewed for fever and other data suggesting infection; antimicrobial therapy given was also recorded 3.0.3 Microbiologic procedures: On entry into the study and daily therafter, approximately milliliters of urine was aspirated from the sampling port of the catheter with a sterile syringe, first disinfecting the port with 10% povidone iodine; a concommittant sample was obtained from the drainage bag with another sterile syringe, puncturing the drainage tube, after disinfecting the surface, just above the level of the clamp Each specimen was immediately brought to the laboratory and cultured using a technique capable of detecting colony-forming unit (CFU) per milliliter, evenly spreading milliliter of undiluted urine and using serial dilutions on predried sheep-blood agar plates (Stark and Maki 1984) After aerobic incubation at 37°C for 24 to 48 hours, each colony type was enumerated and fully identified using standard techniques and criteria (Balows et al 1992) 3.0.4 Definition of CAUTI: The new appearance of bacteriuria or funguria >103 CFU/mL in urine aspirated from the collection port was considered to represent nosocomial CAUTI It has previously been shown that isolation of >103 CFU/mL is highly predictive of CAUTI; if intercurrent antimicrobial therapy is not given to the patient, the level of bacteriuria or candiduria uniformly rises to 10 Catheter-associated urinary tract infection >105 within 24-48 hours (Stark and Maki 1984) 3.0.5 Definition of nosocomial bloodstream infection: The isolation of a recognized pathogen from a blood culture, with no evidence that the infection was present or incubating at the time of hospital admission With coagulasenegative staphylococci and other skin commensals, at least two positive cultures were required unless an intravascular device had also been shown by culture to be infected by the same species (Garner et al 1988) 3.0.6 Definitions of other infections: The criteria of the National Nosocomial Infection Study (NNIS) of the US Center for Disease Control and Prevention were used (Garner et al 1988) 58 Table 1.3 Mechanisms of CAUTI for groups of infecting microorganisms Infecting microorganisms Mechanism of infection Grampositive cocci Gramnegative bacilli Yeasts All species Extraluminal Early Late 43 10(18%) 33(60%) 38 11(16%) 27(39%) 34 9(18%) 25(51%) 115 30 85 Intraluminal 12(22%) 32(46%) 15(31%) 59 29 28 19 76 84 98 68 250 Indeterminate Total infections Percentages refer to total cases in which the mechanism of infection was determinable Comparing each microbial group against the others, overall, chi-square= 8.18 (2 DF), P=0.017 Comparing yeasts and gram-positive cocci with gram-negative bacilli, P=0.0006 59 Table 2.1: Multivariable stepwise regression model of risk factors predictive for CAUTI Catheterization >6 days Odds ratio 5.1 95% Confidence Interval 3.2-8.3 Female gender 3.7 2.4-5.7