Washington manual of infectious diseases 2nd ed subspeciality consult

B abco ck, MD Assistant Professor of Medicine Division of I nfectious Diseases Department of I nternal Medicine Washington University School of Medicine Kath erin e E.. Babco ck, MD Assi

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THE WASHINGTON MANUAL™

Infectio us Diseases Su bspecial ty Co n su l t

SECO ND EDITIO N

Editors

Nigar Kirman i, MD

Professor of Medicine

Division of I nfectious Diseases

Department of I nternal Medicine

Washington University School of Medicine

St Louis, Missouri

Keith F W o el tje, MD, Ph D

St Louis, Missouri

Hil ary M B abco ck, MD

Assistant Professor of Medicine

Kath erin e E Hen derso n , MD

Assistant Professor of Clinical Medicine

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Department of Medicine

Barnes-Jewish Hospital

St Louis, Missouri

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Senior Acquisitions Editor: Sonya Seigafuse

Senior Product Manager: Kerry Barrett

Vendor Manager: Alicia Jackson

Senior Marketing Manager: Kimberly Schonberger

Senior Manufacturing Manager: Benjamin Rivera

Editorial Coordinator: Katie Sharp

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Printed in China

All rights reserved This book is protected by copyright No part of this book may be reproduced in any form by any means, including photocopying, or utilized by any information storage and retrieval system without written permission from the copyright owner, except for brief quotations embodied in critical articles and reviews Materials appearing in this book prepared by individuals as part of their official duties as U.S government employees are not covered by the above-mentioned copyright.

Library of Congress Cataloging-in-Publication Data

The Washington manual infectious diseases subspecialty consult —2nd ed / editors, Nigar Kirmani, Keith F Woeltje, Hilary M Babcock.

p ; cm — (Washington manual subspecialty consult series)

Infectious diseases subspecialty consult

Includes bibliographical references and index.

ISBN 978-1-4511-1364-8 — ISBN 1-4511-1364-1

I Kirmani, Nigar II Woeltje, Keith F III Babcock, Hilary IV Washington University (Saint Louis, Mo.) School of Medicine V Title: Infectious diseases subspecialty consult VI Series: Washington manual subspecialty consult series.

[DNLM: 1 Communicable Diseases—Handbooks 2 Diagnosis, Differential—Handbooks 3 Patient Care Planning—Handbooks WC 39]

616.9—dc23

2012025731

The Washington Manual™ is an intent-to-use mark belonging to Washington University in St Louis to which international legal protection applies The mark is used in this publication by LWW under license from Washington University.

Care has been taken to confirm the accuracy of the information presented and to describe generally accepted practices However, the authors, editors, and publisher are not responsible for errors or omissions or for any consequences from application of the information in this book and make no warranty, expressed or implied, with respect to the currency, completeness, or accuracy of the contents of the publication Application of the information in a particular situation remains the professional responsibility of the practitioner.

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recommended agent is a new or infrequently employed drug.

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10 9 8 7 6 5 4 3 2 1

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Contributing Authors

Hil ary M Babco ck, MD

St Louis, Missouri

Tho mas C Bail ey, MD

St Louis, Missouri

Erik R Dubberke, MD

St Louis, Missouri

Michael J Durkin , MD

I nstructor in Medicine

St Louis, Missouri

Jessica R Grubb, MD

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St Louis, Missouri

José E Hagan , MD

Clinical Fellow

St Louis, Missouri

Zhuo l in Han , MD

Clinical Fellow

St Louis, Missouri

Jeffrey P Hen derso n , MD

St Louis, Missouri

Hito shi Ho n da, MD

Clinical Fellow

St Louis, Missouri

Cyn thia John so n , MD

Clinical Fellow

St Louis, Missouri

Amel ia M Kasper, MD

Resident

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St Louis, Missouri

Nigar Kirman i, MD

St Louis, Missouri

Robyn S Kl ein , MD

Associate Professor of Medicine

St Louis, Missouri

F Matthew Kuhl man n , MD

I nstructor of Medicine

St Louis, Missouri

Michael A Lan e, MD

St Louis, Missouri

Steven J Lawren ce, MD

St Louis, Missouri

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Susan a Lazarte, MD

Clinical Fellow

St Louis, Missouri

Stephen Y Lian g, MD

Clinical Fellow

St Louis, Missouri

Luis A Marco s, MD

Clinical Fellow

St Louis, Missouri

Jon as Marschal l , MD

St Louis, Missouri

Jay R McDo n al d, MD

St Louis, Missouri

Dian a Nurutdin o va, MD

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St Louis, Missouri

Rachel Presti, MD

St Louis, Missouri

Hil ary Ren o , MD

St Louis, Missouri

David J Riddl e, MD

St Louis, Missouri

David J Ritchie, PharmD

Clinical Pharmacist, I nfectious Diseases

Barnes-Jewish Hospital

Professor of Pharmacy Practice

St Louis College of Pharmacy

St Louis, Missouri

Carl o s San to s, MD

St Louis, Missouri

Mo l l y F Sariko n da, MD

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Clinical Fellow

St Louis, Missouri

To shibumi Tan iguchi, MD

Clinical Fellow

St Louis, Missouri

Bren t W Wiel an d, MD

Clinical Fellow

St Louis, Missouri

Keith F Wo el tje, MD, PhD

St Louis, Missouri

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Washington Manual Subspecialty Series addresses this challenge by concisely and

practically providing current scientific information for clinicians to aid them in thediagnosis, investigation, and treatment of common medical conditions

I want to personally thank the authors, who include house officers, fellows, andattendings at Washington University School of Medicine and Barnes-JewishHospital Their commitment to patient care and education is unsurpassed, and theirefforts and skill in compiling this manual are evident in the quality of the finalproduct In particular, I would like to acknowledge our editors, Drs Nigar Kirmani,Keith Woeltje, and Hilary Babcock, and the series editors, Drs Tom De Fer andKatherine Henderson, who have worked tirelessly to produce another outstandingedition of this manual I would also like to thank Dr Melvin Blanchard, Chief of theDivision of Medical Education in the Department of Medicine at WashingtonUniversity School of Medicine, for his advice and guidance I believe thisSubspecialty Manual will meet its desired goal of providing practical knowledgethat can be directly applied at the bedside and in outpatient settings to improvepatient care

Victoria J Fraser, MD

Dr J William Campbell ProfessorInterim Chairman of MedicineCodirector of the Infectious Disease DivisionWashington University School of Medicine

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Infectious disease is an exciting field in constant evolution Even since therelease of the first edition of this manual, there have been new diseases, newdiagnostic methods, and new treatment challenges with the development of multiple-drug–resistant organisms There continues to be a need for specialists in this field.Infectious disease specialists treat patients of all ages, deal with all organ systems,and collaborate with nearly all other medical specialties and subspecialties Ininfectious disease, no case is exactly the same, so there is no “cookbook” approach

to these problems This makes each case intriguing, and even the most mundanecases have appeal It is our hope that this manual stimulates interest in infectiousdisease among its readers and inspires them to pursue a career in this specialty

This manual complements the Washington Manual of Medical Therapeutics by

providing more in-depth coverage of infectious diseases We have focused onproviding easy-to-follow guidance for the diagnosis and treatment of infectiousdiseases likely to be seen by medical house officers and hospitalists Diseases areorganized primarily by organ system to facilitate generating a useful differentialdiagnosis based on a patient’s presentation By providing practical guidance forcommon problems, the manual serves not as a comprehensive textbook, but rather as

a go-to reference that can be kept handy on the wards

It should be noted that the dosing information in the text assumes normal renalfunction unless otherwise indicated Dosing information for impaired renal function

is available in Chapter 20: Antimicrobial Agents

We would like to offer special thanks to Katie Sharp for her extensive assistance

in keeping the project organized and moving forward This book wouldn’t have beenpossible without her We would also like to thank Dr Tom De Fer in the Department

of Medicine for his editorial guidance And finally we’d like to recognize Dr.Victoria Fraser, the J William Campbell Professor in the Department of Medicine.She is an outstanding clinician, researcher, and administrator Initially as a facultymember, then as cochief of the Infectious Diseases Division, and now as Chair ofMedicine, her mentorship has been invaluable Thanks for everything, Vicky, even if

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it is exhausting trying to keep up with you.

N.K.K.F.W.H.M.B

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Contributing Authors

Chairman’s Note

Preface

1 Approach to the Infectious Disease Consultation

F Matthew Kuhlmann and Hilary M Babcock

2 The Acute Febrile Patient and Sepsis

Stephen Y Liang and Jay R McDonald

3 Fever of Unknown Origin

Stephen Y Liang and Nigar Kirmani

4 Bacteremia and Infections of the Cardiovascular Systems

Brent W Wieland and Rachel Presti

5 Respiratory Infections

Michael J Durkin, Thomas C Bailey, and Michael A Lane

6 Infections of the Gastrointestinal and Hepatobiliary Tract

Zhuolin Han and Erik R Dubberke

7 Urinary Tract Infections

Amelia M Kasper and Jeffrey P Henderson

8 Infections of the Bone and Joint

Molly F Sarikonda and Jonas Marschall

9 Skin and Soft Tissue Infections

Molly F Sarikonda and David J Riddle

10 Central Nervous System Infections

Susana Lazarte and Robyn S Klein

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11 Sexually Transmitted Infections

Amelia M Kasper and Hilary Reno

12 Human Immunodeficiency Virus Infection

Toshibumi Taniguchi and Diana Nurutdinova

13 Opportunistic Infections Associated with HIV

Toshibumi Taniguchi and Jessica R Grubb

14 Infection in Non-HIV Immunocompromised Hosts

Cynthia Johnson and Carlos Santos

15 Endemic Mycoses

Brent W Wieland and Keith F Woeltje

16 Zoonotic Infections and Ectoparasites

José E Hagan and Steven J Lawrence

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1 Approach to the Infectious Disease Consultation

F Matthew Kuhl man n an d Hil ary M Babco ckGENERAL PRINCIPLES

The greatest challenge in the infectious disease consultation is the breadth of thesubspecialty Disease manifestations involve all specialties and organ systems.Infectious disease consultation requires thorough evaluation, organized thoughtprocesses, and an ability to appropriately consider rare but significant diagnoses

Four general categories of infectious disease consults

Diagnostic dilemmas are by far the most challenging consultation; they are

classified as consults where a diagnosis remains elusive Types of consultsinclude evaluations for fever of unknown origin and other seemingly mysteriousillnesses Thorough evaluation and history describing details of the patient’spotential exposures is critical

Therapeutic management involves management of a specific infection as it

relates to the overall care of the patient, such as an infected knee implant

Antibiotic management ensures appropriate choice, dose, and duration of

antibiotics for a given infection

Occupational health and infection prevention ensure the health of employees,

patients, and visitors within health care facilities

The ten commandments for effective consultation

Established in 1983 by Goldman and others and modified by Salerno in 2007, thefollowing rules provide a framework for effective patient care and communicationwith requesting physicians.1,2 Knowing the specific expectations of the requestingphysician allows you to address the concerns leading to the consultation Alwaysremember that a physician requests a service from the consultant much like aconsumer buys products from a vendor

Determine your customer Are you providing management for a surgeon or

guidance for an internist? What specific question should be answered?

Establish urgency How quickly should the patient be seen? Several potential

infectious diseases, such as necrotizing fasciitis or cerebral malaria, requireemergent consultation to initiate proper therapy

Look for yourself Although one does not need to repeat every excruciating

detail in written consultation, each important detail should be reconfirmed

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Be as brief as appropriate Write concise assessments that adequately explain

your rationale

Be specific and humble Write clear plans Provide help in executing the plans

when requested Such help may include order writing or obtaining additionalinformation from hospitals or health departments

Provide contingency plans Determine likely problems and provide guidance

for their remediation Provide around-the-clock contact information in order toassist in addressing such problems when they arise

Determine the appropriate level of management How much should you

intervene regarding order writing and dictating patient care? This should benegotiated with the requesting physician during initial discussions

Teach with tact and pragmatism Provide educational materials or discussions

appropriate to the given situation

Talk is essential Always call the requesting physician with your

recommendations

Follow up daily Daily written notes should be provided until problems are no

longer active as determined by yourself and the requesting physician Provideappropriate long-term follow-up care

“Curbside” consultation

Frequently, requesting physicians ask for opinions based on limited conversation.Such consultations, called “curbside consultations,” are considered a courtesy andpromote collegiality When providing curbside consultation, one should alwaysspeak in general terms and avoid providing absolute recommendations.Frequently, important historical details are unintentionally omitted, limiting theability to provide accurate advice Generalized guidelines for providing curbsideconsultation are provided below

Appropriate for curbside consultation

Dose or duration of antibiotics for simple infections

Choice of antibiotics for simple infections

Inappropriate for curbside consultation

Complex patient problems

Uncertainty regarding question asked by the requesting physician

Infections due to highly resistant organisms, rare organisms, or bloodstreaminfections

Patient concerns

Many patients may feel that additional questioning by a consultant is redundant orinsulting Frequently, a thorough review of the written record followed byempathetic consultations will provide improved rapport with the patient Thefollowing suggestions may be beneficial in alleviating patient fear:

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Advise patients that you are visiting them on the request of their primaryphysician and that you will work closely with that physician to provide the bestcare possible.

Consider telling the patient that you have reviewed his/her history and haveadditional specific questions that you would like to ask before providing anopinion on his/her care

Ask the patient to confirm your brief understanding of his/her history and tosupplement information with important details After the initial conversation,specific or open-ended questions regarding the history of the patient’s illnesscan be asked

Do not provide information that directly contradicts the clinical care of theprimary provider Reasons for following a specific care plan may not be readilyapparent at the time of the patient encounter and should be clarified with therequesting physician prior to instituting changes

STRUCTURE O F CO NSULT NO TES

Consult notes are written in a fashion similar to the admission history and physical.Details relating to specific sections follow

History of present illness (HPI) The admission HPI provides the structure for

the consultation HPI Provide a thorough review of the patient’s current illness(onset, severity, duration, location, etc.) and hospital course Specific details ofpositive findings or pertinent negative findings from the review of systems, pastmedical/surgical history, family history, and social history should be included

Review of systems A thorough review of systems should be obtained Patients

may forget to include significant history in their initial encounters Such detailsmay provide additional information leading to a diagnosis

Past medical and surgical history

Specific details should be summarized in the HPI, with additional informationsupplemented in the body of the consultation note

Review detailed histories of immunosuppression due to illness or medications Details of surgeries and surgical findings related to infections should besummarized

Pertinent vaccination history can be summarized

Medications

Review histories of any antimicrobial therapy that has been administered in thepast several months Note doses, durations, and any available drug levels

Any immunosuppressive medications should be noted

Note drugs that frequently interact with antimicrobials, especially warfarin

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Allergies Note not only the drugs, especially antibiotics, but also the type of

reaction (rash vs anaphylaxis, etc.)

Social history This section could be alternatively named exposure history, as

many behaviors place patients at risk for specific infections General topics toreview include the following:

Living environment In what geographical region does the patient reside? Does

the patient live in a stable home or is he/she homeless? Does the patient live in

an urban or rural environment?

Work history Different jobs involve exposures to various infectious or toxic

agents

Animals Specific zoonoses can be diagnosed based on the exposures to certain

domestic or wild animals

Travel history The patient may have traveled to areas that harbor specific

infections, even within their native country Any travel history over a patient’slifetime may be considered important

Sexual history The number of partners places a patient at risk for sexually

transmitted infections, and the nature of such interactions may be important,leading to additional diagnoses, e.g., oropharyngeal gonococcal infections

Physical exam A detailed exam can provide additional clues to the cause of a

patient’s illness or complications from a patient’s medical interventions Rashesare highly indicative of specific infections or toxicities from antibiotics Thoroughdermatological, oral, ocular, and lymph node exams are especially important.Detailed descriptions of infected lesions remain essential

Data

One should review all serological, radiological, and pathological studies andconsider reviewing the data with the microbiologist, radiologist, or pathologist Trends in routine chemistries should be described, as they are much moreinformative than one isolated time point Note the differential on complete bloodcounts as neutropenia and lymphopenia are not evident from the total blood cellcount For patients receiving long-term antibiotics, recent liver function testingshould be noted

Note specific details of microbiological culture data, both positive and negativecultures

Site of collection (e.g., peripheral vs central line, right arm vs left arm,specific drains)

Time of collection

Full susceptibility profiles

All identified microorganisms

Especially note any prior serological data such as viral, fungal, or bacterial

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antibody titers.

Assessment Summarize the case and describe the rationale for your

recommendations as noted in the ten commandments for effective consultation;communicate your assessment directly to the requesting physician

Plan Outline your recommendations in an easy-to-read format, supplement with

details only if they are not provided in your assessment

REFERENCES

1 Goldman L, Lee T, Rudd P Ten commandments for effective consultations Arch Intern Med.

1983;143:1753-1755.

2 Salerno SM, Hurst FP, Halvorson S, Mercado DL Principles of effective consultation: an update for the

21st-century consultant Arch Intern Med 2007;167:271-275.

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2 The Acute Febrile Patient and Sepsis

Stephen Y Lian g an d Jay R McDo n al dAPPRO ACH TO THE ACU TE FEB RILE PATIENT

GENERAL PRINCIPLES

Defin itio n

Fever has classically been defined as a body temperature of ≥38.0°C (100.4°F).Recent evidence suggests that the upper limit of normal oral temperature may be37.2°C (98.9°F) in the early morning and 37.7°C (99.9°F) overall in healthyadults, though significant variability exists between individuals.1

Febrile response in the elderly patient is frequently blunted, leading some todefine fever in this population as a persistent oral temperature ≥37.2°C (98.9°F),rectal temperature ≥37.5°C (99.5°F), or a rise in temperature of ≥1.3°C (2.3°F)above baseline.2

Oral temperatures are generally 0.4°C (0.7°F) lower than rectal temperatures.Axillary and tympanic temperatures may be unreliable

Etio l o gy

Infectious causes of fever lasting less than 2 weeks are legion and may range fromself-limited viral to serious bacterial infections Differential diagnosis hingesheavily upon the history and physical examination Fevers of unknown originlasting more than 3 weeks are discussed in Chapter 3

Noninfectious causes of fever may include neoplastic, rheumatologic, endocrine,thromboembolic, and medication-related disorders

While hyperpyrexia (>41.5°C or 106.7°F) may be encountered with severeinfection, it is more common with central nervous system hemorrhage

Hyperthermia is a distinct entity apart from fever and may result from

environmental factors, endocrine disorders (hyperthyroidism), and certainmedications (e.g., anesthetics, neuroleptic agents, recreational drugs)

Patho physio l o gy

Thermoregulation is mediated by the hypothalamus

Exogenous pyrogens (e.g., microbes, toxins) induce host macrophages and otherphagocytic cells, triggering the release of endogenous cytokines (e.g., interleukin

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[IL]-1, IL-6, tumor necrosis factor [TNF]-α, interferons).

These endogenous pyrogens modulate an inflammatory acute phase response andpromote prostaglandin E2 (PGE2) synthesis It is thought that PGE2 acts upon thehypothalamus, precipitating a rise in body temperature

DIAGNO SIS

Cl in ical Presen tatio n

History

Clarify the patient’s definition of “fever,” whether it is subjective, tactile, or

measured, and if so, by what route Characterize the magnitude, duration, andconsistency of the fever

Establish a time line of all symptoms in relation to the start of the fever While

the cause may be obvious in many cases, a thorough review of systems mayuncover additional symptomatology characteristic of specific infections (e.g.,myalgias, rashes, lymphadenopathy) Look for temporal relationships betweenfever and medical interventions (e.g., surgeries, catheters, mechanical ventilation,antibiotics, prolonged hospitalizations)

Ascertain the immune status of the patient Neoplasm, chemotherapy,

immunosuppressive therapy (to prevent transplant rejection or treat rheumatologicdisorders), corticosteroid use, human immunodeficiency virus (HIV) infection, andprimary immunodeficiency disease (e.g., humoral immune or severe combinedimmunodeficiencies) all influence the spectrum of infections possible

Obtain a complete past medical history, surgical history (including all prosthetics,foreign materials, and implantable devices), and medication list (prescription,over-the-counter, alternative) Use of antipyretics should be noted Whenavailable, a vaccination record should be reviewed, particularly in asplenic andimmunocompromised patients

A social history should identify environmental, occupational, recreational, sexual,dietary, animal, and travel exposures as well as sick contacts

Family members can frequently provide additional insight into the patient’s illnessand exposure history

Physical Examination

A thorough and methodical approach to the physical examination helps ensure thatsubtle findings are not missed (see Table 2-1)

Febril e Syn dro mes

When used in conjunction with the history and physical, common febrile

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syndromes help guide the differential diagnosis by suggesting organ-specificdisease processes.

Fever and headache is concerning for meningitis, while fever with focalneurological deficits or seizure may suggest encephalitis, cerebral abscess,subdural empyema, or epidural abscess

Fever and chest pain mandates a search for pneumonia, but may also be seen withpericarditis, esophagitis, and mediastinitis

Depending on the location and history, fever and abdominal pain may raise thesuspicion of cholecystitis, appendicitis, intra-abdominal abscess, peritonitis,diverticulitis, colitis, or a host of other pathologies

Other febrile syndromes (e.g., rash [Table 2-2], lymphadenopathy [Table 2-3],jaundice, and splenomegaly) may be indicative of an underlying systemic infection(Table 2-4)

TAB LE 2 -1 PHY SICAL EXAMINATION FINDINGS AND CLINICAL SY NDRO MES TO CO NSIDER IN

THE PATIENT W ITH FEVER

Lo catio n Fin din gs an d asso ciatio n s

Eyes Retinitis and other lesions (e.g., Roth spots), uveitis, hypopyon, conjunctival

suffusion/hemorrhage, conjunctivitis, visual field deficits Ears Otitis media/externa, mastoiditis

Face, nose, throat Sinus tenderness, pharyngitis (erythema, exudate), mucosal lesions, thrush, periodontitis,

peritonsillar abscess, muffled voice (epiglottitis)

Neck Neck stiffness (meningitis, retropharyngeal abscess), tenderness along the sternocleidomastoid

muscle (internal jugular septic thrombophlebitis), thyromegaly Heart Murmurs (endocarditis), rubs, distant sounds

Lungs Crackles, rhonchi, wheezes, dullness to percussion

Abdomen Focal tenderness, peritoneal signs, hepatomegaly, splenomegaly, ascites

Genitourinary/rectum Male: urethritis, prostatitis, orchitis, epididymitis

Female: cervicitis, adnexal mass/tenderness, foreign body (e.g., tampon) Rectum: perirectal fluctuance (abscess), ulcers, Fournier gangrene Back Pressure sores, decubitus ulcers, costovertebral angle tenderness

Extremities Stigmata of endocarditis (Osler nodes, Janeway lesions, splinter hemorrhages), clubbing,

palmar/plantar rashes, track marks Neuro Altered mental status, focal neurologic deficits, ataxia

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Skin Cellulitis, cutaneous abscess, sinus tracts, crepitus, necrotizing soft tissue infection, rash

(petechiae, purpura, macules, papules, vesicles, ulcers, eschars) Musculoskeletal Effusion, septic arthritis, spinous process tenderness

Lymph Any lymphadenopathy, lymph node fluctuance or drainage

Devices Pacemaker/defibrillator, tunneled intravenous catheter, implantable port, orthopedic hardware

Diagn o stic Testin g

Laboratories

Initial testing

Laboratory evaluation of fever should be driven by the nature and severity of thepatient’s symptoms In the inpatient setting, the following tests are a reasonablestarting point to screen for abnormalities:

Complete blood count with differential (leukocytosis, neutrophilia, bandemia,neutropenia, anemia, thrombocytopenia)

Metabolic panel (hyponatremia, acidosis, impaired renal function)

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Liver tests (transaminitis, cholestasis)

Coagulation studies (disseminated intravascular coagulation)

Urinalysis (urinary tract infection, active urinary sediment)

HIV screening is strongly recommended, particularly in high-prevalence areas

Cultures should be obtained prior to antimicrobials whenever possible.

However, collection of cultures should not delay antimicrobial administration in

an unstable patient

Blood cultures (preferably a minimum of 2 to 3) should be obtained from afebrile patient within the first 24 hours of presentation when endocarditis,bacteremia, or catheter-associated bloodstream infection is suspected Eachculture should consist of 20 to 30 mL of blood drawn from a single site at asingle time point In the case of catheter-associated bloodstream infection, at

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least one culture should be obtained through the infected catheter Specializedblood culture media may be required to effectively isolate fungi,

mycobacteria, viruses, and rare organisms (e.g., Brucella spp.).

Urine cultures should be obtained if a urinary tract infection is suspected

Sputum and bronchoalveolar lavage cultures may be obtained to guideantibiotic therapy of pneumonia, particularly in intensive care unit (ICU) andseverely immunocompromised patients where fungal and mycobacterialinfections are also suspected

Stool cultures, parasite examination, and tests for Clostridium difficile

infection should be considered in a febrile patient with diarrhea

If osteomyelitis is suspected, an erythrocyte sedimentation rate and C-reactive

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protein may be helpful if highly elevated.

Subsequent testing

In cases where meningitis or encephalitis is suspected, lumbar puncture should

be performed before the initiation of antibiotics if possible Cerebrospinal fluidshould be sent for cell count, glucose, protein, culture, Gram stain, culture, andother specialized tests based on clinical suspicion

As a general rule, all fluid collections suspected of being infected (e.g., pleuralfluid, ascites, abscess) should be sampled and sent for cell count, culture, andother appropriate analytic studies

Superinfected chronic wounds (e.g., decubitus or diabetic foot ulcers) should bedebrided first and then cultured from the base of the wound Superficial cultures

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are contaminated with skin flora that may or may not be responsible for theinfection.

Intravascular catheters strongly suspected as sources of infection should beremoved after blood cultures are obtained through the lumen and the catheter tipshould be sent for culture

Throat and nasopharyngeal cultures may help identify viral and streptococcalupper respiratory infections Testing for influenza, particularly inimmunocompromised and elderly patients, should be considered if the season isappropriate or an epidemic is underway

Disease-specific serologies and other specialized laboratory tests (e.g.,polymerase chain reaction [PCR]) may be indicated in the appropriate clinicalcontext

I maging

Chest radiography should be obtained if pulmonary complaints exist

Computed tomography (CT), magnetic resonance imaging, ultrasound, and nuclearstudies may be indicated based on presenting symptoms and clinical suspicion.Consultation with a radiologist regarding the best modality for visualizingpathology (e.g., abscess, osteomyelitis, cerebral disease) can be helpful inavoiding excessive imaging

Echocardiography should be pursued if endocarditis is suspected based on thepresence of a new heart murmur and other clinical criteria

Diagnostic Procedures

Tissue biopsy for pathology, culture, and other specialized testing may be needed

to establish diagnoses of osteomyelitis, disorders associated withlymphadenopathy (e.g., cat scratch disease, toxoplasmosis), and disseminatedinfections (e.g., tuberculosis, atypical mycobacteria, histoplasmosis)

When possible, appropriate cultures should be obtained during any surgicalintervention to treat an infectious complication (e.g., endocarditis, pacemaker leadinfection, graft or hardware infection)

TREATMENT

An timicro bial Therapy

In the outpatient setting, most fevers in healthy adults are associated with transient,self-limited viral infections and are frequently overtreated with antimicrobials

An emphasis should be placed on establishing an infectious etiology for the fever

to guide appropriate antimicrobial coverage

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Situations warranting empiric antimicrobial therapy before a definitive diagnosiscan be made include the following:

Acute clinical deterioration (e.g., respiratory distress, altered mental status,hemodynamic instability, sepsis)

Immunocompromised state (e.g., HIV, neoplasm, transplant, immunosuppressivetherapy)

Elderly patients (in whom atypical and muted presentations of serious infectionare common)

Choice of empiric antimicrobial should be based upon the type of infectionsuspected (e.g., pneumonia, meningitis, cellulitis), common microorganismsimplicated, concern for multidrug resistance among those organisms, and localantimicrobial susceptibility patterns

An tipyretic Therapy

Antipyretics can be given for symptom relief but they do not alter outcomes Inpatients with cardiovascular or pulmonary disease, antipyretics may reduce some

of the metabolic demands of fever

Nonsteroidal antiinflammatory drugs including acetaminophen, ibuprofen, andaspirin inhibit the synthesis of inflammatory prostaglandins through thecyclooxygenase pathway and trigger other antipyretic pathways, reducinghypothalamus-mediated fever

Corticosteroids also have antipyretic properties but generally are not indicated forfever control alone

External cooling methods including cooling blankets, fans, and water spongingeffect heat loss through conduction, convection, and evaporation, respectively.Rebound hyperthermia may result if antipyretic medications are not used andshivering is not controlled

SPECIAL CO NSIDERATIO NS

Fever in the In ten sive Care Un it

New, unexplained fevers complicate a significant number of ICU admissions andprolonged hospitalizations.3,4 The causes can be wide ranging, underscoring thecomplexity of these patients (Table 2-5)

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In reviewing the medical history of the ICU patient, a strong emphasis should beplaced on understanding not only the patient’s initial clinical presentation andprimary diagnosis but also the sequence of medical interventions (e.g., newmedications, procedures, surgeries, health care–associated devices, respiratorysupport) that have taken place since admission.

Nursing observations regarding patient hemodynamics, oxygen requirements,tracheal secretions, catheter sites, skin breakdown, wounds, diarrhea, and otherclinically relevant conditions can lend valuable insight into the patient’s hospitalcourse

Health care–associated infections are responsible for a sizable portion of these

fevers

Intravascular catheter–associated bloodstream infection.5 Infection rates

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differ by type (uncuffed > tunneled > peripheral), location (femoral vein >internal jugular vein > subclavian vein), duration, frequency of manipulation,and method of placement (use of sterile precautions).

At least one blood culture should be obtained through the infected catheter andone culture from a peripheral site by venipuncture

The intravascular catheter in question should be promptly removed and thecatheter tip sent for culture if sepsis, embolic disease, or tunnel infection issuspected

Peripheral intravenous catheters should be changed every 72 hours regardless

of fever

Ventilator-associated pneumonia Infection occurring more than 48 hours after

endotracheal intubation and mechanical ventilation

Chest radiography or CT with evolving infiltrates coupled with clinical cues(increased purulent tracheal secretions and/or oxygen requirement) helpsecure the diagnosis

Bronchoscopy to obtain accurate lower respiratory tract cultures and Gramstains should be considered

Blood cultures and diagnostic thoracentesis of associated pleural effusionsmay also be helpful in identifying a causative organism

Urinary tract infection.6 Risk factors include having an indwelling urethralcatheter, suprapubic catheter, ureteral stent, or nephrostomy

Urinalysis and urine culture should be obtained from the sampling port of thecatheter and never the drainage bag

Infected catheters should be removed promptly if possible

C difficile infection.7 Spectrum of disease may range from diarrhea to ileus andtoxic megacolon Leukemoid reactions with extremely high white blood cellcounts are occasionally seen

Send a stool specimen for C difficile toxin by enzyme immunoassay or PCR

and for fecal leukocytes

Consider empiric therapy with metronidazole or oral vancomycin if illness issevere

Sinusitis Nasotracheal/nasogastric intubations, nasal packing, and maxillofacial

trauma may prevent drainage of the facial sinuses (especially maxillary) leading

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Wound infection Prolonged or chronic debilitation increases the risk of

pressure sores and decubitus ulcers, which are prone to infection

Examine the back, sacrum, and other dependent areas thoroughly for wounds Document the number, size, and depth of any wounds and any signs ofsuperinfection or necrosis

Transfusion-related infection However rare, bacterial infection may be

transmitted through blood product transfusion Cytomegalovirus (CMV)transmitted by donor leukocytes present in the blood product can precipitate amononucleosis-like syndrome in healthy adults or disseminated disease in theimmunocompromised (particularly if the recipient is CMV seronegative)

Identify the timing of all blood product transfusions in relation to onset offever If a bacterial infection is suspected, obtain a recipient blood culturefrom a site opposite that of the transfusion and culture the donor bloodproduct

Administer leukocyte-reduced blood components to immunocompromisedpatients to prevent CMV disease

Noninfectious causes of a new, unexplained fever in the ICU include the

following:

Drug fever Antimicrobials (e.g., sulfonamides, penicillins, cephalosporins,

vancomycin, nitrofurantoin), anticonvulsants (e.g., phenytoin, carbamazepine,barbiturates), H1- and H2-blocking antihistamines, antihypertensives (e.g.,hydralazine, methyldopa), and antiarrhythmics (e.g., quinidine, procainamide)are common offenders Relative bradycardia, rash, leukocytosis, andeosinophilia may or may not be present

Establish a time line of start and stop dates for all suspect medications(particularly antimicrobials)

The time between discontinuation of the offending agent and resolution offever can be variable and up to a week

Thromboembolic disease Deep vein thrombosis and pulmonary embolus

occasionally present with isolated fever

Endocrine disease Adrenal insufficiency and thyroid storm may present with

fever, tachycardia, and hypotension that can be easily mistaken for sepsis

Transfusion reactions

Febrile nonhemolytic transfusion reactions are common (1 in 100 units)

and occur when recipient antibodies react against antigens on donorleukocytes and platelets, triggering cytokine release anywhere from 30minutes to several hours after a transfusion

Acute hemolytic transfusion reactions result from ABO mismatch and occurwhen preformed recipient antibodies rapidly destroy donor erythrocytes

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leading to fever, flank pain, and hemoglobinuria This is considered a medicalemergency.

Recent guidelines suggest that a body temperature of ≥38.3°C (100.9°F) or <36°C(96.8°F) is a reasonable threshold for initiating an evaluation for infection in theICU patient Remember that critically ill patients with serious infection may benormothermic or hypothermic in the context of extensive burns, open abdominalwounds, continuous renal replacement therapy, extracorporeal membraneoxygenation, or a host of medical illnesses (e.g., congestive heart failure, end-stage liver or renal disease, myxedema coma) Evaluation for infection should beguided ultimately by clinical suspicion

If infection is suspected, empiric antimicrobial therapy should be initiatedimmediately after appropriate cultures have been obtained The risk of infectionwith multidrug-resistant pathogens should be taken into account along with localantimicrobial susceptibility patterns

Po sto perative Fever

Fever within the first 72 hours after surgery is common and generally

self-limited Cytokine release from surgical trauma is thought to play a part

Wound infections are uncommon during the first three postoperative days.

When an early infection is evident, myonecrosis secondary to Clostridium

species and group A streptococci must be considered and may requireantibiotics and emergent surgical debridement Toxic shock syndrome may

accompany serious infection with group A streptococci or Staphylococcus aureus.

Noninfectious causes of fever may include thromboembolism, hematoma,transfusion reactions, and adrenal insufficiency Malignant hyperthermia maymanifest as muscle rigidity, tachycardia, and hyperthermia up to 10 hours afterinduction of general anesthesia

Fever more than 72 hours after surgery is significant and more likely to be

associated with infection

Wound infections, intra-abdominal infections, abscesses, infected hematomas,and the sequelae of anastomotic leaks are typically seen around the fourth orfifth day after surgery

Health care–associated infections including pneumonia, urinary tract infection(in the setting of urinary catheterization), intravenous catheter–related infections

(cellulitis, thrombophlebitis, bloodstream infection), and C difficile infection

related to antibiotic exposure are also more common

Acalculous cholecystitis, pancreatitis, and thromboembolism are noninfectiousetiologies that must also be considered

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Postoperative fever may also result from surgical site inflammation, seroma, orhematoma without infection.

Classic teaching maintains that the differential diagnosis of postoperative fever

should focus on the “five Ws”: wind (pneumonia), water (urinary tract infection),

wound, walking (thromboembolism), and “wonder” drugs (medication reaction).

Opinions differ on whether atelectasis causes fever

History gathering should focus on understanding the preoperative presentation(including existing infection), surgical procedure (duration, complexity, bloodproducts, perioperative prophylactic antibiotics, complications including intra-operative contamination; Table 2-6), and postoperative course (cough, diarrhea,pain, and changes in character or volume of surgical drain output or wounddrainage) Hardware and foreign material inserted during the surgery should bedocumented The possibility of drug fever should be examined through achronology of all medications (e.g., antibiotics, anesthetics) received during andafter surgery

Chest radiography, urinalysis, and urine culture are suggested for the evaluation offever presenting more than 72 hours after surgery and for any febrile postoperativepatient who has had a urinary catheter in place for ≥72 hours Hemodynamicinstability with concern for bacteremia or pending sepsis should prompt bloodcultures

All surgical wounds should be examined daily for erythema, induration, andpurulent discharge Surgical and percutaneous drain reservoirs and their exit sitesshould likewise be inspected for evidence of infection

All infected surgical wounds should be cultured and in many cases opened tofacilitate drainage

Superficial wound cultures are seldom helpful in the absence of a clinically

apparent infection.

If an abscess or deep infection is suspected, be aggressive about obtaining furtherimaging and surgical evaluation to determine whether operative or radiology-guided drainage is necessary All fluid collections requiring drainage should besent for culture

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Be vigilant of intravenous catheter–associated infections, C difficile infection,

and noninfectious causes of fever already discussed with fever in the ICU patient Empiric antimicrobial therapy is generally unnecessary for fever presenting withinthe first 72 hours of surgery, unless infection is clinically evident or uncovered onlaboratory evaluation or imaging Continuation of perioperative prophylacticantibiotics for early postoperative fever does not prevent infection and likelyselects for resistant organisms

Fever in the Immun o co mpro mised Patien t

Immunocompromised patients are at heightened risk not only for acquired infections but also for an extensive range of opportunistic infections Atypical and nonspecific clinical presentations abound Muted inflammatoryresponses arising from neutropenia, corticosteroids, and other forms of

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community-immunosuppressive therapy may conceal serious infections.

The medical history should assess the severity of the patient’simmunocompromised state and risk factors for primary infection or reactivation oflatent disease (Table 2-7)

The etiology of fever in the immunocompromised patient varies depending uponthe underlying disease and its subsequent therapy Markers of immune status andapproximately derived windows of susceptibility to infection help inform thedifferential diagnosis

In addition to the opportunistic infections discussed below, it is important to keep

in mind that immunocompromised patients are also at risk for common acquired infections (e.g., bacterial pneumonia, influenza) as well as health care–associated infections (e.g., intravascular catheter–associated bloodstream

community-infection, C difficile infection), given their frequent contact with the hospital

environment and exposure to antimicrobials either as chemoprophylaxis or to treatactive infection

TAB LE 2 -7 KEY ASPECTS O F THE MEDICAL HISTO RY IN EVALU ATING THE

IMMU NO CO MPRO MISED PATIENT W ITH FEVER All immunocompromised patients • Any history of tuberculosis

• Chronic infections (e.g., hepatitis B and C)

• Disseminated infections (e.g., mycobacteria, endemic mycoses)

• Opportunistic infections (e.g., Pneumocystis jiroveci, Cryptococcus neoformans, Toxoplasma gondii, Mycobacterium avium complex)

• Chemoprophylaxis against opportunistic infections (dose, duration)

• Baseline serologies (e.g., CMV, T gondii)

• Known colonization with multidrug-resistant organisms

• Presence of long-term intravascular access (tunneled catheters vs.

implantable ports)

• Sick contacts

• Environmental exposures

HI V infection • CD4+ cell count and HI V viral load

• Antiretroviral therapy (date started, adherence)

• Recent unprotected sex

• Presence of immune reconstitution inflammatory syndrome

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Chemotherapy-related neutropenia • Type and location of neoplasm (solid organ vs hematologic)

• Chemotherapy (dose, duration, number of days since last cycle)

• Other therapies (e.g., surgery, radiation) and any associated complications

• Relapse vs remission of disease Solid organ transplantation • Date and type of organ transplant

• I mmediate and delayed surgical complications associated with transplant

• I mmunosuppressive regimens (dose, duration, serum levels)

• Presence of graft rejection

• Donor and recipient CMV serology Hematopoietic stem cell transplantation • Date and type of transplant (allogeneic vs autologous)

• I mmunosuppressive regimen (dose, duration)

• Presence of GVHD

• Donor CMV serology (if allogeneic transplant)

CMV, cytomegalovirus; HI V, human immunodeficiency virus; GVHD, graft versus host disease.

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Human immunodeficiency virus

The CD4+ lymphocyte cell count is a reasonably accurate gauge ofsusceptibility to opportunistic infections in the HIV patient (Table 2-8)

Patients recently started on antiretroviral therapy may present with immunereconstitution inflammatory syndrome, an inflammatory immune responseagainst pathogens that may have previously been clinically silent (e.g.,

mycobacteria, Pneumocystis jiroveci, endemic fungi, CMV).

Noninfectious causes of fever particular to HIV include neoplasm (non–Hodgkin lymphoma and occasionally visceral Kaposi sarcoma), drug fever(e.g., trimethoprim–sulfamethoxazole, dapsone), hypersensitivity reaction(abacavir, nevirapine, efavirenz), and Castleman disease (angiofollicularlymph node hyperplasia)

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