CURRENT Me dica l Dia gnos is & Tre a tme nt S tudy Guide S e cond Edition Edited by Gene R Quinn, MD, MS Division of Cardiovascular Disease Department of Medicine Beth Israel Deaconess Medical Center Boston Nathaniel W Gleason, MD Maxine A Papadakis, MD Stephen J McPhee, MD Department of Medicine University of California San Francisco New York Chicago San Francisco Athens London Madrid Milan New Delhi Singapore Sydney Toronto Mexico City Copyright © 2016 by McGraw-Hill Education All rights reserved Except as permitted under the United States Copyright Act of 1976, no part of this publication may be reproduced or distributed in any form or by any means, or stored in a database or retrieval system, without the prior written permission of the publisher, with the exception that the program listings may be entered, stored, and executed in a computer system, but they may not be reproduced for publication ISBN: 978-0-07-184804-6 MHID: 0-07-184804-5 The material in this eBook also appears in 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possibility of such damages This limitation of liability shall apply to any claim or cause whatsoever whether such claim or cause arises in contract, tort or otherwise Contents Preface v Skin Disorders Atopic Dermatitis Contact Dermatitis Psoriasis Pulmonary/Ear, Nose, and Throat Disorders Asthma Chronic Obstructive Pulmonary Disease Cough Dyspnea Lung Cancer Pharyngitis 10 Pneumonia 11 Pulmonary Embolism 12 Sinusitis (Bacterial) 12 17 13 Acute Myocardial In arction 14 Aortic Regurgitation 15 Aortic Stenosis 16 Chest Pain 17 Dyslipidemia 18 Heart Failure 19 Hypertension 20 Mitral Regurgitation 21 Mitral Stenosis 22 Shock 86 94 99 105 111 117 126 140 145 149 Hematologic Disorders 155 27 Acute Cholecystitis 28 Cirrhosis 29 Colorectal Cancer 38 Breast Cancer 39 Benign Prostatic Hyperplasia 40 Dysmenorrhea 41 Prostate Cancer 29 37 43 48 56 60 70 79 85 Gastrointestinal/Liver/ Pancreas Disorders Gynecologic/Urologic Disorders 18 Heart/Hypertension/Lipid Disorders 23 Hypercoagulable States 24 Iron De ciency Anemia 25 Deep Venous T rombosis and T romboembolism 26 Vitamin B12 De ciency Anemia 30 Crohn Disease 31 Diarrhea 32 Lower Gastrointestinal Bleeding 33 Upper Gastrointestinal Bleeding 34 Viral Hepatitis 35 Acute Pancreatitis 36 Chronic Pancreatitis 37 Ulcerative Colitis Musculoskeletal Disorders 42 Low Back Pain 43 Gout 44 Knee Pain 45 Rheumatoid Arthritis 46 Systemic Lupus Erythematosus Kidney/Electrolyte Disorders 47 Glomerulonephritis 48 Hypokalemia 49 Hyponatremia 50 Acute Kidney Injury 51 Chronic Kidney Disease 52 Kidney Stone Disease 53 Metabolic Acidosis 54 Nephrotic Syndrome Nervous System/Psychiatric Disorders 156 164 55 Altered Mental Status 56 Dementia 57 Depression 58 Epilepsy 59 Bacterial Meningitis 60 Myasthenia Gravis 61 Parkinson Disease 62 Stroke 63 Smoking Cessation 64 Substance Abuse 168 175 179 180 185 193 iii 199 205 216 221 226 241 248 255 263 264 274 280 284 291 292 298 304 313 321 329 330 338 342 349 354 361 367 373 379 380 387 394 401 408 415 420 426 435 441 iv CONTENTS Endocrine/Metabolic Disorders 65 Adrenocortical Insu ciency 66 Cushing Syndrome 67 ype Diabetes Mellitus 68 ype Diabetes Mellitus 69 Hyperaldosteronism (Aldosteronism) 70 Hypercalcemia 71 Primary Hyperparathyroidism 72 Hyperthyroidism 73 Hypothyroidism 447 448 456 463 470 482 487 492 499 506 74 Obesity 75 Osteoporosis Infectious Disorders 512 518 525 76 Fever 77 HIV-AIDS 78 Healthcare-Associated In ections 79 In ective Endocarditis 80 Sepsis 526 532 547 553 561 Index 567 Preface • Medical and nursing students, physician’s assistants, nurse practitioners, house o cers, and practicing physicians will nd the clear organization and current literature re erences use ul in devising proper management or patients with these conditions Purpose Current Medical Diagnosis and Treatment (CMDT) is the leading internal medicine textbook known or its comprehensive coverage o current inpatient and outpatient care with diagnostic tools relevant to day-to-day practice Facilitating its use ulness, this CMDT Study Guide, second edition, directs readers through a case analysis o 80 o the most common topics in internal medicine T e CMDT Study Guide provides a comprehensive and clearly organized synopsis o each medical topic that helps the reader review and study or a variety o examinations, such as the medicine clerkship shel exam, USMLE Step examinations, ABIM internal medicine boards, and recerti cation examinations As such it will be very use ul to medical, nursing (Adult and Family Nurse Practitioner Certi cation Exam), pharmacy, and other health pro essional students, Physician Assistant National Certi ying Exam (PANCE), to house o cers, and to practicing physicians T e CMDT Study Guide is engaging and patient-centered since each o the 80 topics begins with presentation o a typical patient to help the reader think in a step-wise ashion through the various clinical problem-solving aspects o the case For each topic, the CMDT Study Guide provides PubMed’s re erences to the most current and pertinent MEDLINE articles or that topic Each re erence provides PMID numbers to acilitate retrieval o the relevant articles Organization T e CMDT Study Guide provides comprehensive yet succinct in ormation Each CMDT Study Guide topic begins with a patient presentation, ollowed by Learning Objectives and Questions to help the learner work through the topic in the context o the patient presented Answers to the questions are organized as Salient Features, How to T ink T rough the Problem, Key Features (which contain Essentials o Diagnosis, General Considerations, and Demographics), Symptoms and Signs, Dif erential Diagnosis, Laboratory, Imaging, and Procedural Findings, reatments, Outcomes, and When to Re er and When to Admit Re erences are then provided that contain current literature citations complete with PubMed (PMID) numbers T e CMDT Study Guide is a complete source o patient care in ormation or these 80 most common clinical problems! T e 80 topics in the CMDT Study Guide were selected as the core topics or the learner because o their importance to the eld o internal medicine T e CMDT Study Guide ollows the organization o Quick Medical Diagnosis and Treatment (QMDT) (or Quick Dx & Rx at www.accessmedicinemhmedical com) and the QMDT App, and is divided into 11 sections: • Skin Disorders • Pulmonary/Ear, Nose, & T roat Disorders • Heart/Hypertension/Lipid Disorders • Hematologic Disorders • Gastrointestinal/Liver/Pancreas Disorders • Gynecologic/Urologic Disorders • Musculoskeletal Disorders • Kidney/Electrolyte Disorders • Nervous System/Psychiatric Disorders • Endocrine/Metabolic Disorders • In ectious Disorders Outstanding Features • Eighty common internal medicine topics use ul to learners and practitioners or patient care and to prepare or examinations • Material drawn rom the expert source, Current Medical Diagnosis and Treatment 2016, including tables about laboratory tests and treatments • In-depth, consistent, and readable ormat organized in a way that allows or quick study and easy access to in ormation • Emphasis on a standard approach to clinical problemsolving with Learning Objectives, Salient Features, Symptoms and Signs, reatment, Outcomes, When to Re er and When to Admit, and Re erences v vi PREFACE Intended Audience Acknowledgments Medical students on their internal medicine clerkship will nd this Study Guide a use ul aid as they care or patients with these common medical problems T e Study Guide will assist medical students, PA students, and NP students taking their internal medicine rotation and house o cers to review the core topics as they prepare or standardized examinations Practicing physicians, physician assistants and nurse practitioners will similarly nd the CMDT Study Guide use ul in order to stay current in clinical problemsolving, while providing a concise summary o relevant diagnostic laboratory, microbiologic, and imaging studies and treatments, and recent relevant publications We thank our Current Medical Diagnosis and Treatment authors or their contributions to it and we are grate ul to the many students, residents, and practitioners who have made use ul suggestions to this book We hope that you will share with us your comments about the CMDT Study Guide Gene R Quinn, MD, MS Nathaniel W Gleason, MD Maxine A Papadakis, MD Stephen J McPhee, MD Skin Disorders Musculoskeletal Disorders Pulmonary/Ear, Nose and Throat Disorders Kidney/Electrolyte Disorders Heart/ Hypertension/ Lipid Disorders Nervous System/ Psychiatric Disorders Hematologic Disorders Endocrine/ Metabolic Disorders Gastrointestinal/ Liver/Pancreas Disorders Infectious Disorders Gynecologic/ Urologic Disorders Skin Disorders Pulmonary/Ear, Nose, and Throat Disorders Heart/Hypertension/Lipid Disorders Hematologic Disorders Gastrointestinal/Liver/Pancreas Disorders Gynecologic/Urologic Disorders Musculoskeletal Disorders Kidney/Electrolyte Disorders Nervous System/Psychiatric Disorders Endocrine/Metabolic Disorders Infectious Disorders Atopic Dermatitis A 30-year-old woman presents to her primary care clinician with an itchy rash on her hands, wrists, and arms She states she has had similar rashes before, which had gone away with over-the-counter hydrocortisone cream, the rst episode occurring when she was very young Her past medical history includes asthma She takes loratadine occasionally for allergic rhinitis Physical examination reveals plaques on the hands, wrists, and antecubital folds, which are mildly exudative and without scale Laboratory testing shows eosinophilia on a complete blood count with di erential and an elevated serum immunoglobulin E (IgE) level LEARNING OBJECTIVES Learn the clinical mani estations and objective f ndings o atopic dermatitis, and the f ndings that distinguish it rom other skin conditions Understand the associated diseases that predispose to atopic dermatitis Know the di erential diagnosis o atopic dermatitis Learn the treatments or each clinical pattern o atopic dermatitis Know which patients are likely to have recurrent atopic dermatitis and how to prevent ares QUESTIONS What are the salient eatures o this patient’s problem? How you think through her problem? What are the key eatures, including essentials o diagnosis and general considerations, o atopic dermatitis? What are the symptoms and signs o atopic dermatitis? What is the di erential diagnosis o atopic dermatitis? What are the laboratory f ndings in atopic dermatitis? What are the treatments or atopic dermatitis? What are the outcomes, including complications, prognosis, and prevention, o atopic dermatitis? When should patients with atopic dermatitis be re erred to a specialist? 553 Infective Endocarditis 79 A 55-year-old man who recently emigrated from China presents to the emergency department with fever He states that he has had recurring fevers over the past weeks, associated with chills, night sweats, and malaise Today he developed new painful lesions on the pads of his ngers, prompting him to come to the emergency department His medical history is remarkable for “being very sick as a child after a sore throat.”He has recently had several teeth extracted for severe dental caries He is taking no medications On physical examination, he is febrile with temperature 38.5°C, blood pressure 120/80 mm Hg, heart rate 108 bpm, respiratory rate 16/min, and oxygen saturation of 97% on room air Skin examination is remarkable for painful nodules on the pads of several ngers and toes He has multiple splinter hemorrhages in the nail beds and painless hemorrhagic macules on the palms of the hands Ophthalmoscopic examination is remarkable for retinal hemorrhages Chest examination is clear to auscultation and percussion Cardiac examination is notable for a grade 3/6 holosystolic murmur heard loudest at the left lower sternal border, with radiation to the axilla LEARNING OBJECTIVES Learn the clinical mani estations and objective f ndings o in ective endocarditis (IE), di erentiating autoimmune and embolic phenomena Understand the actors that predispose to developing IE Learn the di erences between acute and subacute presentations o IE Know the di erential diagnosis o IE Learn the medical treatments or IE based on causative organism and antibiotic susceptibilities Know the indications or surgical intervention in IE QUESTIONS What are the salient eatures o this patient’s problem? How you think through his problem? What are the key eatures, including essentials o diagnosis, general considerations, and demographics, o IE? 554 INFECTIOUS DISORDERS What are the symptoms and signs o IE? What is the di erential diagnosis o IE? What are laboratory, imaging, and procedural f ndings in IE? What are the treatments or IE? What are the outcomes, including ollow-up, complications, prognosis, and prevention, o IE? When should patients with IE be re erred to a specialist or admitted to the hospital? ANSWERS Salient Features Constitutional symptoms ( ever, chills, night sweats, malaise); likely history o prior rheumatic heart disease; poor dentition; ever and tachycardia; pain ul Osler nodes; splinter hemorrhages, painless Janeway lesions; Roth spots on ophthalmoscopy; cardiac murmur How to Think Through Mortality rom IE is high (with rates dependent on the a ected valve and the organism) O en, only nonspecif c symptoms and signs are apparent at presentation, but delay in diagnosis can be catastrophic On presentation, this patient had the cardinal constitutional symptoms o ever, chills, night sweats, and malaise T ere ore, IE needs to be considered and a directed history and physical examination per ormed What historical risk actors raise the likelihood o IE? (History o rheumatic ever, prosthetic valves, and injection drug use.) T e physical f ndings o IE are crucial in establishing the diagnosis with this otherwise nonspecif c presentation What are the signs associated with IE? (Fever, murmur, embolic lesions, and peripheral stigmata.) IE can lead to embolic lesions in nonvisible locations as well, and detection o these can assist with the diagnosis What should you look or in your initial evaluation? (Altered mental status, in ammatory arthritis, hematuria, embolic in arctions on chest or abdominal imaging.) What are the key tests or diagnosis and treatment? (Blood cultures and echocardiography.) How many major Duke criteria or IE does this patient have? (1.) How many minor? (3.) What are the most common organisms in IE? (Viridans strains o streptococci, Staphylococcus aureus, enterococci, coagulase-negative staphylococci.) Which organisms tend to present with a more subacute course? (Viridans streptococci, enterococci, and other gram-positive and gram-negative bacilli, yeasts, and ungi.) Key Features Essentials of Diagnosis • Risk actors: preexisting organic heart lesion, prosthetic valve, injection drug use • Fever • New or changing heart murmur • Evidence o systemic emboli • Positive blood cultures • Evidence o vegetations on echocardiography General Considerations • Important actors that determine the clinical presentation — Nature o the in ecting organism — Valve that is in ected — Route o in ection • Acute presentation — Caused by more virulent organisms, particularly Staphylococcus aureus — Rapidly progressive and destructive in ection — Acute ebrile illnesses CHAPTER 79 • INFECTIVE ENDOCARDITIS — Early embolization — Acute valvular regurgitation — Myocardial abscess • Subacute presentation — Caused by viridans strains o streptococci, enterococci, and other gram-positive and gram-negative bacilli, yeasts, and ungi — Systemic and peripheral mani estations may predominate • Patients may have underlying cardiac disease, but its prevalence as a risk actor is decreasing • T e initiating event is in ection o the valve by bacteria during a transient or persistent bacteremia Native Valve Endocarditis • Most commonly due to — S aureus (~40%) — Viridans streptococci (~30%) — Enterococci (5%–10%) • Gram-negative organisms and ungi account or a small percentage • Injection drug users — S aureus in at least 60% o cases and 80% to 90% o tricuspid valve in ections — Enterococci and streptococci comprise the balance in about equal proportions Prosthetic Valve Endocarditis • Early in ections (within months o valve implantation) are commonly caused by — Staphylococci—both coagulase-positive and coagulase-negative — Gram-negative organisms and ungi • Late prosthetic valve endocarditis — Resembles native valve endocarditis — Most cases caused by streptococci, though coagulase-negative staphylococci cause a signif cant proportion o cases Demographics • Endocarditis occurs in individuals with — Injection drug use — Underlying valvular disease (eg, congenital or rheumatic heart disease) — Prosthetic valve replacement Symptoms and Signs • Most present with a ebrile illness that has lasted several days to weeks • Heart murmurs — In most cases, preexisting heart murmurs are stable — A new or changing murmur is signif cant diagnostically, but is the exception rather than the rule • Characteristic peripheral lesions occur in up to 20% to 25% o patients — Petechiae (on the palate or conjunctiva or beneath the f ngernails) — Subungual (“splinter”) hemorrhages — Osler nodes (pain ul, violaceous raised lesions o the f ngers, toes, or eet) — Janeway lesions (painless erythematous lesions o the palms or soles) • Roth spots (exudative, hemorrhagic lesions o the retinas) Di erential Diagnosis • Valvular abnormality without endocarditis — Rheumatic heart disease — Mitral valve prolapse — Bicuspid or calcif c aortic valve 555 556 INFECTIOUS DISORDERS • Flow murmur (anemia, pregnancy, hyperthyroidism, and sepsis) • Atrial myxoma • Nonin ective endocarditis, eg, systemic lupus erythematosus (Libman–Saks endocarditis), marantic endocarditis (nonbacterial thrombotic endocarditis) • Acute rheumatic ever • Vasculitis • Hematuria rom other causes, such as — Glomerulonephritis — Renal cell carcinoma Laboratory, Imaging, and Procedural Findings Laboratory ests • Blood culture — Most important diagnostic tool — o maximize the yield, obtain three sets o blood cultures rom di erent sites at least hour apart be ore starting antibiotics • In acute endocarditis, leukocytosis is common • In subacute cases, anemia o chronic disease and a normal white blood cell count are the rule • Hematuria and proteinuria as well as renal dys unction may result rom emboli or immunologically mediated glomerulonephritis • Duke criteria or the diagnosis o in ective endocarditis — Major criteria wo positive blood cultures or a typical microorganism o IE Positive echocardiogram (vegetation, myocardial abscess, or new partial dehiscence o a prosthetic valve) New regurgitant murmur — Minor criteria Presence o a predisposing condition Fever > 38°C Embolic disease Immunologic phenomena (Osler nodes, Janeway lesions, Roth spots, glomerulonephritis, and rheumatoid actor) Positive blood cultures with an organism not meeting the major criteria or serologic evidence o active in ection with an organism that causes endocarditis — A def nite diagnosis o endocarditis is made with 80% accuracy i two major criteria, or one major criterion and three minor criteria, or f ve minor criteria are ulf lled — Possible endocarditis is def ned as the presence o one major and one minor criterion, or three minor criteria — I these criteria thresholds are not met and either an alternative explanation or illness is identif ed or the patient’s ebrile illness has resolved within days, endocarditis is highly unlikely Imaging Studies • Chest radiograph may show f ndings indicating an underlying cardiac abnormality and, in right-sided endocarditis, pulmonary inf ltrates • Echocardiography — ransthoracic echocardiography has only a 55% to 65% sensitivity; there ore, it cannot rule out endocarditis but may conf rm a clinical suspicion — ransesophageal echocardiography has a 90% sensitivity in detecting vegetations and is particularly use ul or identi ying myocardial valve ring abscesses, and pulmonary valve and prosthetic valve endocarditis Diagnostic Procedures • T e ECG is nondiagnostic Changing conduction abnormalities suggest myocardial abscess ormation CHAPTER 79 • INFECTIVE ENDOCARDITIS Treatments Medications • For penicillin-susceptible viridans streptococcal endocarditis (ie, MIC ≤ 0.1 µg/mL) — Penicillin G, to million units intravenously (IV) every hours or weeks — Duration o therapy can be shortened to weeks i gentamicin, mg/kg intravenously every hours, is used with penicillin (do not use 2-week regimen i symptoms are present or at least months or there are complications such as myocardial abscess or extracardiac in ection) — Ce riaxone, g once daily IV or intramuscularly or weeks, is also e ective therapy and is a convenient regimen or home therapy — For the penicillin-allergic patient, vancomycin, 15 mg/kg IV every 12 hours or weeks, is given • For penicillin-resistant viridans streptococci (ie, MIC > 0.1 µg/mL but ≤ 0.5 µg/mL) — reat or weeks — Penicillin G, million units intravenously every hours, is combined with gentamicin, mg/kg intravenously every hours or the f rst weeks — In the patient with IgE-mediated allergy to penicillin, vancomycin alone, 15 mg/kg IV every 12 hours or weeks, should be administered • Streptococcus pneumoniae sensitive to penicillin (MIC < 0.1 µg/mL) can be treated with penicillin alone, to million units IV every hours or to weeks — Vancomycin should be e ective or endocarditis caused by strains resistant to penicillin • Group A streptococcal in ection can be treated with penicillin, ce riaxone, or vancomycin or to weeks • Groups B, C, and G streptococci — end to be more resistant to penicillin than group A streptococci — Some experts recommend adding gentamicin, mg/kg IV every hours, to penicillin or the f rst weeks o a 4- to 6-week course • For enterococcal endocarditis — Penicillin alone is inadequate; either streptomycin or gentamicin must be included — Gentamicin is the aminoglycoside o choice, because streptomycin resistance is more common — Ampicillin, g IV every hours, or penicillin G, to million units IV every hours (or, in the penicillin-allergic patient, vancomycin, 15 mg/kg intravenously every 12 hours), plus gentamicin, mg/kg IV every hours, are recommended or to weeks — Ampicillin, g IV every hours, plus ce riaxone, g intravenously every 12 hours, or 4–6 weeks may be as e ective and less toxic than the combination o ampicillin and an aminoglycoside • For methicillin-susceptible S aureus (MSSA) — Na cillin or oxacillin, 1.5 to g IV every hours or weeks, is the pre erred therapy — Uncomplicated tricuspid valve endocarditis probably can be treated or weeks with na cillin or oxacillin alone — For penicillin-allergic patients, ce azolin, g IV every hours, or vancomycin, 30 mg/ kg IV divided in or doses, may be used • For methicillin-resistant S aureus (MRSA), vancomycin remains the pre erred agent • For prosthetic valve in ection, a combination o vancomycin, 30 mg/kg/d IV divided in or doses or weeks, ri ampin, 300 mg every hours or weeks, and gentamicin, mg/kg IV every hours or the f rst weeks, is recommended • For endocarditis caused by HACEK organisms — Ce riaxone (or some other third-generation cephalosporin), g IV once daily or weeks is the treatment o choice — Prosthetic valve endocarditis should be treated or weeks — In the penicillin-allergic patient, experience is limited, but trimethoprim– sul amethoxazole, quinolones, and aztreonam should be considered 557 558 INFECTIOUS DISORDERS Surgery • Valve replacement surgery is indicated or — Regurgitation resulting in acute heart ailure that does not resolve promptly a er institution o medical therapy (even i active in ection is present), especially i the aortic valve is involved — In ections that not respond to appropriate antimicrobial therapy a er to 10 days (ie, persistent evers, positive blood cultures despite therapy) • Valve replacement is nearly always necessary or ungal endocarditis • Valve replacement is more o en necessary with — Gram-negative bacilli — In ection involving the sinus o Valsalva — In ection producing septal abscesses — Recurrent in ection with the same organism, especially with prosthetic valves — Continuing embolization when the in ection is otherwise responding T erapeutic Procedures • Colonoscopy should be per ormed to exclude colon cancer in patients with endocarditis caused by S bovis Outcomes Follow-Up • De ervescence occurs in to days on average i in ection is caused by — Viridans streptococci — Enterococci — Coagulase-negative staphylococci • Patients may remain ebrile or a week or more i in ection is caused by — S aureus — Pseudomonas aeruginosa Complications • Destruction o in ected heart valves • Myocardial abscesses leading to conduction disturbances • Systemic embolization • Metastatic in ections • Mycotic aneurysms • Right-sided endocarditis, which usually involves the tricuspid valve, o en leads to septic pulmonary emboli, causing pulmonary in arction and lung abscesses Prognosis • Higher morbidity and mortality is associated with nonstreptococcal organisms, and with aortic or prosthetic valvular in ection Prevention • Prophylactic antibiotics are given to patients with predisposing congenital, prosthetic or valvular anomalies ( able 79-1) who are to have any o a number o procedures ( able 79-2) • Current recommendations or endocarditis prophylaxis are given in able 79-3 When to Refer and When to Admit When to Refer • In ectious diseases consultation recommended • Patients with signs o heart ailure should be re erred or surgical evaluation When to Admit • Patients with evidence o heart ailure • Patients with a nonstreptococcal etiology • For initiation o antimicrobial therapy in suspected, def nite, or possible cases CHAPTER 79 • INFECTIVE ENDOCARDITIS Table 79-1 Cardiac conditions with high risk of adverse outcomes from endocarditis for which prophylaxis with dental procedures is recommended.a,b Prosthetic cardiac valve Previous infective endocarditis Congenital heart disease (CHD)c Unrepaired cyanoticCHD, including palliative shunts and conduits Completelyrepaired congenital heart defect with prostheticmaterial or device, whether placed bysurgeryor bycatheter intervention, during the first mo after the procedured Repaired CHDwith residual defects at the site or adjacent to the site of a prostheticpatch or prostheticdevice Cardiactransplantation recipients in whomcardiacvalvulopathydevelops a Reproduced, with permission, from the American Heart Association Circulation 2007;116(15):1736–1754 b See Table 79-3 for prophylactic regimens c Except for the conditions listed above, antibiotic prophylaxis is no longer recommended for other forms of CHD d Prophylaxis is recommended because endothelialization of prosthetic material occurs within mo after procedure Table 79-2 Recommendations for administration of bacterial endocarditis prophylaxis for patients according to type of procedure.a a Prophylaxis Recommended Prophylaxis Not Recommended Dental procedures All dental procedures that involve manipulation of gingival tissue or the periapical region of the teeth or perforation of the oral mucosa Respiratory tract procedures Onlyrespiratorytract procedures that involve incision of the respiratorymucosa Procedures on infected skin, skin structure, or musculoskeletal tissue Dental procedures Routine anestheticinjections through noninfected tissue, taking dental radiographs, placement of removable prosthodonticor orthodonticappliances, adjustment of orthodontic appliances, placement of orthodonticbrackets, shedding of deciduous teeth, and bleeding fromtrauma to the lips or oral mucosa Gastrointestinal tract procedures Genitourinary tract procedures Reproduced, with permission, from the American Heart Association Circulation 2007;116(15):1736–1754 Table 79-3 American Heart Association recommendations for endocarditis prophylaxis for dental procedures for patients with cardiac conditions.a–c Oral Amoxicillin g h before procedure Penicillin allergy Clindamycin 600 mg h before procedure or Cephalexin g h before procedure (contraindicated if there is historyof a β-lactam immediate hypersensitivityreaction) or Azithromycin or clarithromycin 500 mg h before procedure Parenteral Ampicillin g intramuscularlyor intravenously30 before procedure Penicillin allergy Clindamycin 600 mg intravenously1 h before procedure or Cefazolin a g intramuscularlyor intravenously30 before procedure (contraindicated if there is historyof a β-lactamimmediate hypersensitivity reaction) Data from the American Heart Association Circulation 2007;116(15):1736–1754 b For patients undergoing respiratory tract procedures involving incision of respiratory tract mucosa to treat an established infection or a procedure on infected skin, skin structure, or musculoskeletal tissue known or suspected to be caused by S aureus, the regimen should contain an anti-staphylococcal penicillin or cephalosporin Vancomycin can be used to treat patients unable to tolerate a β-lactam or if the infection is known or suspected to be caused by a methicillin-resistant strain of S aureus c See Table 79-1 for list of cardiac conditions 559 560 INFECTIOUS DISORDERS SUGGESTED REFERENCES Chirouze C et al In ective endocarditis epidemiology and consequences o prophylaxis guidelines modi ications: the dialectical evolution Curr Infect Dis Rep 2014 Nov;16(11):440 [PMID: 25233804] Chu VH et al; International Collaboration on Endocarditis (ICE) Investigators* Association between surgical indications, operative risk, and clinical outcome in in ective endocarditis: a prospective study rom the international collaboration on endocarditis Circulation 2015 Jan 13;131(2):131–140 [PMID: 25480814] Dayer MJ et al Incidence o in ective endocarditis in England, 2000–13: a secular trend, interrupted time-series analysis Lancet 2015 Mar 28;385(9974):1219–1228 [PMID: 25467569] Desimone DC et al; Mayo Cardiovascular In ections Study Group Incidence o in ective endocarditis caused by viridans group streptococci be ore and a ter publication o the 2007 American Heart Association’s endocarditis prevention guidelines Circulation 2012 Jul 3;126(1):60–64 [PMID: 22689929] Duval X et al; AEPEI Study Group emporal trends in in ective endocarditis in the context o prophylaxis guideline modi ications: three successive population-based surveys J Am Coll Cardiol 2012 May 29;59(22):1968–1976 [PMID: 22624837] Krzyściak W et al he pathogenicity o the Streptococcus genus Eur J Clin Microbiol Infect Dis 2013 Nov;32(11):1361–1376 [PMID: 24141975] Ohlsson A et al Intrapartum antibiotics or known maternal Group B streptococcal colonization Cochrane Database Syst Rev 2013 Jan 31;1:CD007467 [PMID: 23440815] huny F et al In ective endocarditis: prevention, diagnosis, and management Can J Cardiol 2014 Sep;30(9):1046-1057 [PMID: 25151287] 561 Sepsis 80 A 65-year-old woman is admitted to the hospital with communityacquired pneumonia She is treated with intravenous antibiotics and is given oxygen by nasal cannula A Foley catheter is placed in her bladder On the third hospital day she is switched to oral antibiotics in anticipation of discharge On the evening of hospital day 3, she develops fever and tachycardia Blood and urine cultures are obtained The following morning, she is lethargic and di cult to arouse Her temperature is 35°C, blood pressure 85/40 mm Hg, heart rate 110 bpm, and respiratory rate 25/min Lung examination is unchanged from admission, with rales in the left base Cardiac examination is notable for a rapid but regular rhythm, without murmurs, gallops, or rubs Abdominal examination is normal Extremities are warm Neurologic examination is nonfocal The patient is transferred to the ICU for management of presumed sepsis and given intravenous uids and broad spectrum antibiotics Blood and urine cultures are positive for gram-negative rods LEARNING OBJECTIVES Learn the clinical mani estations and objective f ndings that are diagnostic o systemic in ammatory response syndrome (SIRS), sepsis, and septic shock Understand the actors that predispose to higher mortality in sepsis and the common in ectious sources or gram-negative organisms Know the di erential diagnosis o sepsis Learn the empiric treatment or sepsis Know the possible complications o sepsis QUESTIONS What are the salient eatures o this patient’s problem? How you think through her problem? What are the key eatures, including essentials o diagnosis and general considerations, o sepsis? What are the symptoms and signs o sepsis? What is the di erential diagnosis o sepsis? 562 INFECTIOUS DISORDERS What are laboratory, imaging, and procedural f ndings in sepsis? What are the treatments or sepsis? What are the outcomes, including complications and prognosis, o sepsis? When should patients with sepsis be admitted to the hospital? ANSWERS Salient Features Foley catheter placement; hypothermia, tachycardia, tachypnea; hypotension; warm extremities suggesting decreased systemic vascular resistance (SVR); presumptive treatment with antibiotics and IV uids; bacteremia; blood and urine cultures are diagnostic How to Think Through First, consider other causes o shock (hypovolemic, cardiogenic, obstructive, and other distributive) to avoid prematurely settling on septic shock as the cause o her deterioration What examination f nding makes blood loss or cardiogenic shock less likely? (T ese are states o high SVR, but her skin is warm.) A high suspicion or sepsis is important, since early intervention improves outcomes Consider how to di erentiate SIRS, sepsis, and septic shock What are the key management components? (Restore per usion; ensure adequate oxygenation; institute early a goal-directed therapy protocol; identi y and treat the in ection [use broadspectrum antibiotics initially, ollowed by more targeted coverage based on blood cultures].) Initially, intravascular uids should be aggressively repleted, but ongoing assessment o volume status becomes a central challenge in sepsis When a patient remains hypotensive despite uid resuscitation, vasopressors must be employed What end-organ e ects o poor per usion can one evaluate and monitor? (Mental status; urine output; lactic acidemia; electrocardiographic evidence o cardiac ischemia or arrhythmia; peripheral per usion [pulses and capillary ref ll].) What are the important complications o sepsis? (Disseminated intravascular coagulation [DIC]; renal hypoper usion; hepatic hypoper usion; acute respiratory distress syndrome [ARDS].) Key Features Essentials of Diagnosis • Fever, tachycardia, and/or increased respiratory rate; elevated white blood cell (WBC) count • Proven or probable source o in ection • Bacteremia with positive blood cultures • Elevated lactate or end-organ dys unction in severe disease • Hypotension in septic shock General Considerations • Sepsis is def ned as meeting SIRS criteria with a known source o in ection • SIRS is def ned by meeting two or more o the our ollowing criteria: temperature < 36°C or > 38°C; heart rate > 90 bpm; respiratory rate > 20/min or Paco2 < 32 mm Hg; WBC count < 4000/µL or > 12, 000/µL or di erential with > 10% immature polymorphonuclear leukocytes (“bands”) • Gram-negative bacteremia usually originates rom the genitourinary system, hepatobiliary tract, gastrointestinal tract, and lungs, though may also be rom wounds and decubitus ulcers • Mortality rate is signif cantly higher in those with underlying serious diseases Symptoms and Signs • Fevers and chills, o en with abrupt onset • Hyperventilation with respiratory alkalosis CHAPTER 80 • SEPSIS • Altered mental status • Hypotension and shock are late f ndings and poor prognostic signs • Symptoms and signs o in ectious source, eg, abdominal or urinary symptoms, pneumonia Di erential Diagnosis • Gram-positive sepsis • Fungal in ection • Acid- ast bacillus in ection • SIRS due to another cause — rauma — Burns — Pancreatitis — Myocardial or bowel ischemia — Adrenal insu ciency — Pulmonary embolism — Aortic aneurysm rupture — Anaphylaxis — Cardiac tamponade — oxic ingestion • Shock rom another cause — Cardiogenic — Neurogenic — Hypovolemic — Anaphylactic Laboratory, Imaging, and Diagnostic Findings Laboratory ests • Complete blood count (CBC) may show neutropenia or neutrophilia and immature polymorphonuclear leukocytes (“bands”) • T rombocytopenia • Coagulation panel may show coagulation dys unction with or without disseminated intravascular coagulation (DIC) • Lactic acid elevation • T ree blood cultures should be obtained be ore starting antimicrobials, i possible Imaging Studies • Chest radiograph to look or pulmonary in ection Diagnostic Procedures • Urinalysis with culture, which may show positive leukocyte esterase, elevated WBCs, and positive nitrite • Culture o uid rom abscess, i applicable Treatments Medications • Antibiotic therapy should be given as soon as the diagnosis is suspected, as delayed antibiotic therapy leads to increased mortality rates • Initial antibiotic therapy should cover both gram-positive and gram-negative bacteria • able 80-1 lists examples o initial antimicrobial therapy or acutely ill, hospitalized adults pending identif cation o causative organism • A er initial empiric therapy, narrow antibiotics based on culture and sensitivity data • Aggressive initial intravenous uid repletion; vasopressors to maintain blood pressure i not responsive to IV uid repletion • Institute goal-directed therapy early using a set protocol or the treatment o septic shock by adjusting the use o uids, vasopressors, inotropes, and blood trans usions to meet 563 564 INFECTIOUS DISORDERS Table 80-1 Examples of initial antimicrobial therapy for acutely ill, hospitalized adults pending identification of causative organism Suspected Clinical Diagnosis a Likely Etiologic Diagnosis Drugs of Choice Meningitis, bacterial, community-acquired Pneumococcus,a meningococcus Cefotaxime,b 2–3 g intravenouslyevery6 h; or ceftriaxone, g intravenouslyevery12 h plus vancomycin, 15 mg/kg intravenouslyevery8 h Meningitis, bacterial, age > 50, community-acquired Pneumococcus, meningococcus, Listeria monocytogenes,cgram-negative bacilli Ampicillin, g intravenouslyevery4 h, plus cefotaxime, 2–3 g intravenouslyevery6 h; or ceftriaxone, g intravenouslyevery12 h plus vancomycin, 15 mg/kg intravenouslyevery8 h Meningitis, postoperative (or posttraumatic) Saureus, gram-negative bacilli (pneumococcus, in posttraumatic) Vancomycin, 15 mg/kg intravenouslyevery8 h, plus cefepime, g intravenouslyevery8 h Brain abscess Mixed anaerobes, pneumococci, streptococci Penicillin G, million units intravenouslyevery4 h, plus metronidazole, 500 mg orallyevery8 h; or cefotaxime, 2–3 g intravenouslyevery6 h or ceftriaxone, g intravenouslyevery12 h plus metronidazole, 500 mg orallyevery8 h Pneumonia, acute, community-acquired, nonICUhospital admission Pneumococci, Mpneumoniae, Legionella, Cpneumoniae Cefotaxime, g intravenouslyevery8 h (or ceftriaxone, g intravenouslyevery24 h or ampicillin g intravenouslyevery6 h) plus azithromycin 500 mg intravenouslyevery24 h; or a fluoroquinoloned alone Pneumonia, postoperative or nosocomial Saureus, mixed anaerobes, gram-negative bacilli Cefepime, g intravenouslyevery8 h; or ceftazidime, g intravenouslyevery8 h; or piperacillin-tazobactam, 4.5 g intravenouslyevery6 h; or imipenem, 500 mg intravenouslyevery6 h; or meropenem, g intravenouslyevery8 h plus tobramycin, mg/kg intravenouslyevery24 h; or ciprofloxacin, 400 mg intravenouslyevery12 h; or levofloxacin, 500 mg intravenouslyevery24 h plus vancomycin, 15 mg/kg intravenouslyevery12 h Endocarditis, acute (including injection drug user) Saureus, Efaecalis, gram-negative aerobic bacteria, viridans streptococci Vancomycin, 15 mg/kg intravenouslyevery12 h, plus gentamicin, mg/kg every8 h Septicthrombophlebitis (eg, IVtubing, IVshunts) Saureus, gram-negative aerobic bacteria Vancomycin, 15 mg/kg intravenouslyevery12 h plus ceftriaxone, g intravenouslyevery24 h Osteomyelitis Saureus Nafcillin, g intravenouslyevery4 h; or cefazolin, g intravenouslyevery8 h Septicarthritis Saureus, Ngonorrhoeae Ceftriaxone, 1–2 g intravenouslyevery24 h Pyelonephritis with flank pain and fever (recurrent urinarytract infection) Ecoli, Klebsiella, Enterobacter, Pseudomonas Ceftriaxone, g intravenouslyevery24 h; or ciprofloxacin, 400 mg intravenouslyevery12 h (500 mg orally); or levofloxacin, 500 mg once daily (intravenously/orally) Fever in neutropenicpatient receiving cancer chemotherapy Saureus, Pseudomonas, Klebsiella, Ecoli Ceftazidime, g intravenouslyevery8 h; or cefepime, g intravenouslyevery8 h Intra-abdominal sepsis (eg, postoperative, peritonitis, cholecystitis) Gram-negative bacteria, Bacteroides, anaerobicbacteria, streptococci, clostridia Piperacillin-tazobactam, 4.5 g intravenouslyevery h, or ertapenem, g every24 h Some strains may be resistant to penicillin b Most studies on meningitis have been with cefotaxime or ceftriaxone (see Bacterial Meningitis) c TMP-SMZ can be used to treat Listeria monocytogenes in patients allergic to penicillin in a dosage of 15–20 mg/kg/d of TMP in three or four divided doses d Levofloxacin 750 mg/d, moxifloxacin 400 mg/d CHAPTER 80 • SEPSIS hemodynamic targets (MAP > 65 mm Hg, CVP 8–12 mm Hg, ScvO2 > 70%,) and provides a signif cant mortality benef t; however, some data exist that the blood trans usion goals may more harm than good • Corticosteroids — Based on available data, cosyntropin stimulation testing is not recommended in patients with septic shock — Stress-dose hydrocortisone may benef t patients with severe septic shock (systolic blood pressure < 90 mm Hg or > hour despite adequate uid resuscitation and vasopressor administration) — However, such corticosteroid administration is unlikely to benef t those with lesssevere septic shock Surgery • May be required to control source o bacteremia, depending on etiology T erapeutic Procedures • Drainage or removal o source o bacteremia, eg, central venous catheter removal, abscess or empyema drainage • Management o any associated DIC Outcomes Complications • DIC • Acute lung injury/ARDS • End-organ dys unction, eg, acute kidney injury Prognosis • Mortality is < 5% in patients with no underlying disease; 15% to 20% in patients with cancer (solid tumors), cirrhosis, or aplastic anemia; 40% to 60% in patients with neutropenia or immunocompromised and underlying atal conditions When to Admit • All patients who meet sepsis criteria should be admitted to the hospital or management and intravenous antibiotics SUGGESTED REFERENCES Caironi P et al; ALBIOS Study Investigators Albumin replacement in patients with severe sepsis or septic shock N Engl J Med 2014 Apr 10;370(15):1412–1421 [PMID: 24635772] Dellinger RP et al; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup Surviving Sepsis Campaign: international guidelines or management o severe sepsis and septic shock: 2012 Crit Care Med 2013 Feb;41(2):580–637 [PMID: 23353941] Havel C et al Vasopressors or hypotensive shock Cochrane Database Syst Rev 2011;(5):CD003709 [PMID: 21563137] Patel GP et al E icacy and sa ety o dopamine versus norepinephrine in the management o septic shock Shock 2010 Apr;33(4):375–380 [PMID: 19851126] Patel GP et al Systemic steroids in severe sepsis and septic shock Am J Respir Crit Care Med 2012 Jan 15;185(2):133–139 [PMID: 21680949] Peake SL et al; ARISE Investigators; ANZICS Clinical rials Group Goal-directed resuscitation or patients with early septic shock N Engl J Med 2014 Oct 16;371(16):1496–1506 [PMID: 25272316] Rivers E et al Early goal-directed therapy in the treatment o severe sepsis and septic shock N Engl J Med 2001 Nov;345(19):1368–1377 [PMID: 11794169] Russell JA et al; VASS Investigators Vasopressin versus norepinephrine in usion in patients with septic shock N Engl J Med 2008 Feb 28;358(9):877–887 [PMID: 18305265] Society o Critical Care Medicine Surviving sepsis campaign http://survivingsepsis.org Yealy DM et al; ProCESS Investigators A randomized trial o protocol-based care or early septic shock N Engl J Med 2014 May 1;370(18):1683–1693 [PMID: 24635773] 565 This page intentionally left blank Index Acute Myocardial In arction, 86–93 Adrenocortical Insuf ciency, 448–455 Altered Mental Status, 380–386 Aortic Regurgitation, 94–98 Aortic Stenosis, 99–104 Asthma, 18–28 Atopic Dermatitis, 2–6 Back Pain, Low, 292–297 Benign Prostatic Hyperplasia, 274–279 Breast Cancer, Female, 264–273 Chest Pain, 105–110 Cholecystitis, Acute, 180–184 Chronic Obstructive Pulmonary Disease, 29–36 Cirrhosis, 185–192 Colorectal Cancer, 193–198 Contact Dermatitis, 7–11 Cough, 37–42 Crohn Disease, 199–204 Cushing Syndrome, 456–462 Deep Venous T rombosis and T romboembolism, 168–174 Dementia, 387–393 Depression, 394–400 Diabetes Mellitus, ype 1, 463–469 Diabetes Mellitus, ype 2, 470–481 Diarrhea, 205–215 Dyslipidemia, 111–116 Dysmenorrhea, 280–283 Dyspnea 43–47 Epilepsy, 401–407 Lung Cancer, 48–55 Fever, 526–531 Meningitis, Bacterial, 408–414 Metabolic Acidosis, 367–372 Mitral Regurgitation, 140–144 Mitral Stenosis, 145–148 Myasthenia Gravis, 415–419 Gastrointestinal Bleeding, Lower, 216–220 Gastrointestinal Bleeding, Upper, 221–225 Glomerulonephritis, 330–337 Gout, 298–303 Healthcare-Associated In ections, 547–552 Heart Failure, 117–125 Hepatitis, Viral, ypes A, B and C, 226–240 HIV-AIDS, 532–546 Hyperaldosteronism (Aldosteronism), 482–486 Hypercalcemia, 487–491 Hypercoagulable States, 156–163 Hyperparathyroidism, Primary, 492–498 Hypertension, 126–139 Hyperthyroidism, 499–505 Hypokalemia, 338–341 Hyponatremia, 342–348 Hypothyroidism, 506–511 In ective Endocarditis, 553–560 Iron De ciency Anemia, 164–167 Kidney Injury, Acute, 349–353 Kidney Disease, Chronic, 354–360 Kidney Stone Disease, 361–366 Knee Pain, 304–312 567 Nephrotic Syndrome, 373–377 Obesity, 512–517 Osteoporosis, 518–523 Pancreatitis, Acute, 241–247 Pancreatitis, Chronic, 248–254 Parkinson Disease, 420–425 Pharyngitis, 56–59 Pneumonia, 60–69 Prostate Cancer, 284–289 Psoriasis, 12–16 Pulmonary Embolism, 70–78 Rheumatoid Arthritis, 313–320 Sepsis, 561–565 Shock, 149–154 Sinusitis (Bacterial), 79–83 Smoking Cessation, 435–440 Stroke, 426–434 Substance Abuse, 441–446 Systemic Lupus Erythematosus, 321–327 Ulcerative Colitis, 255–261 Vitamin B12 De ciency Anemia, 175–178 ... mg/d as single or two divided doses for 3–10 d Prednisone 1, 2.5, 5, 10, 20, 50 mg tablets; mg/mL, mg/mL Inhaled Long-Acting β2-Agonists Salmeterol Formoterol DPI 50 g/ blister DPI 12 g /single-use... not controlled on medium- to high-dose inhaled corticosteroids Budesonide/ Formoterol HFA 45 g/ 21 g 115 g/ 21 g 230 g/ 21 g HFAMDI 80 g/ 4.5 g 160 g/ 4.5 g inhalations twice daily; dose... devising proper management or patients with these conditions Purpose Current Medical Diagnosis and Treatment (CMDT) is the leading internal medicine textbook known or its comprehensive coverage o current