The InfectiousDiseases ManualDavid WilksMA, MD, FRCP, DTM&HConsultant Physician

Regional Infectious Diseases Unit

Western General Hospital

Edinburgh

Mark FarringtonMA, MB, BChir, FRCPathConsultant Microbiologist

Clinical Microbiology Laboratory

Addenbrooke’s Hospital

Cambridge

David RubensteinMA, MD, FRCPDepartment of Medicine

Addenbrooke’s Hospital

Cambridge

SECOND EDITION

Blackwell Science

The Infectious Diseases Manual

The InfectiousDiseases ManualDavid WilksMA, MD, FRCP, DTM&HConsultant Physician

Regional Infectious Diseases Unit

Western General Hospital

Edinburgh

Mark FarringtonMA, MB, BChir, FRCPathConsultant Microbiologist

Clinical Microbiology Laboratory

Addenbrooke’s Hospital

Cambridge

David RubensteinMA, MD, FRCPDepartment of Medicine

Addenbrooke’s Hospital

Cambridge

SECOND EDITION

Blackwell Science

© 2003 by Blackwell Science Ltda Blackwell Publishing companyBlackwell Science, Inc., 350 Main Street, Malden, Massachusetts 02148-5018, USABlackwell Science Ltd, 9600 Garsington Road, Oxford OX4 2DQ, UKBlackwell Science Asia Pty Ltd, 550 Swanston Street, Carlton, South Victoria 3053, AustraliaBlackwell Wissenschafts Verlag, Kurfürstendamm 57, 10707 Berlin, Germany

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All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, inany form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted bythe UK Copyright, Designs and Patents Act 1988, without the prior permission of the publisher.

First published 1995Second edition 2003

Library of Congress Cataloging-in-Publication DataWilks, David.

The infectious diseases manual / David Wilks, Mark Farrington, David Rubenstein. — 2nd ed.p. ; cm.

Includes index.ISBN 0-632-06417-X1. Communicable diseases—Handbooks, manuals, etc. 2. Infection—Handbooks, manuals, etc.

3. Medical microbiology—Handbooks, manuals, etc.[DNLM: 1. Communicable Diseases—Handbooks. WC 39 W688i 2003] I. Farrington, Mark.

II. Rubenstein, David. III. Title.

RC111 .W68 2003616.9 — dc21

2002013472ISBN 0-632-06417-X

A catalogue record for this title is available from the British Library

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Section I: Introduction

1 Introduction, 3

Section II: Clinical InfectiousDiseases

2 Upper respiratory tract infections, 17

3 Lower respiratory tract infections, 23

4 Mycobacteria and mycobacterialinfections, 37

5 Cardiac infections, 49

6 Gastrointestinal infections, 57

7 Hepatitis, 70

8 Urinary tract infection (UTI), 77

9 Gynaecological and obstetric infections, 82

10 Sexually transmitted diseases (STDs), 86

11 CNS infections, 96

12 Eye infections, 104

13 Skin infections, 111

14 Bone and joint infections, 120

15 Paediatric infections, 126

16 Human immune deficiency virus (HIV)infection and acquired immune deficiencysyndrome (AIDS), 143

17 Infections in the immunocompromisedhost, 170

18 Fever, 179

19 Septic shock, 185

Section III: Tropical and TravelMedicine

20 Pre-travel advice, 191

21 Tropical medicine and the returningtraveller, 206

22 Protozoa, 229

23 Helminths, 233

Section IV: Microbiology

Bacteria, 247

24 Staphylococci, 249

25 Streptococci and their relatives, 254

26 Aerobic Gram-positive rods, 263

27 Coliforms (syn. enterobacteria,Enterobacteriaceae), 273

28 Vibrios, 285

29 Campylobacters, 288

30 Pseudomonads, 291

31 Fastidious Gram-negative organisms, 296

32 Anaerobes, 312

33 Spirochaetes, 322

34 Mycoplasmas, chlamydias and rickettsias, 329

35 Virology, 334

36 Fungi, 363

Section V: Antibiotic Therapy

37 Antibiotics: theory, usage and abuse, 381

38 Antibiotics: Classification and dosingguidelines, 391

Appendix 1: Bioterrorism agents, 415

Appendix 2: Immunization schedule, 417

Index, 419

Contents

v

Section I

Introduction

There have been many changes in the practiceof microbiology and clinical infectious diseasessince the first edition of this manual was pub-lished in 1995. Molecular techniques, whichhad only recently been discovered, are now inroutine use. New antivirals and a new under-standing of viral kinetics have revolutionizedHIV care, and clinical guidelines, which werefew and far between then, are now available inalmost every area. Antibiotic-resistant organ-isms become more prevalent month by month,and for the first time in decades drugs fromtotally novel classes of antibiotics have beenlicensed. We were very encouraged by the positive response given to the first edition of the Manual by working clinicians, and webelieve that there is even more need now for a convenient and portable source of detailedand practical information on all aspects of infectious diseases and microbiology.

For the second edition, the entire text of themanual has been carefully revised. Some sec-tions, such as the chapter about HIV infection,have been completely rewritten. Our aim hasbeen to produce a handbook that every SpR ininfectious diseases will want in their white-coatpocket for consultant ward rounds, and everySpR in microbiology will keep by the telephonein the reporting room. As before, common conditions are described in detail. The clinicalpresentation of rarely seen and usually tropicalconditions is described in sufficient detail toallow their recognition, whereas their treat-ment, which would always be a matter for spe-cialist referral, is described in outline only.

Some areas have been given a more detailedtreatment than their frequency might suggest,either because of their potential significance,or because we think they are interesting. Someareas of specialist interest have been describedin more detail, because patients with neutro-penia or HIV may present outside their usualunits, and specialist help may not always beimmediately available.

We have not attempted to reference themanual comprehensively, but we have tried todemonstrate its evidence base by including keyreferences such as national guidelines, recentauthoritative reviews, or unique papers thathave significantly changed practice. We havealso included many useful website addresseswhich satisfy the same criteria and which arelikely to remain accessible during the life of thisedition (in general we have omitted the prefixhttp:// to save space).

To make the best use of space, we have usedsymbols and abbreviations, defined on the fol-lowing pages. Throughout the text, the symbol(ÿ000) indicates that further information isavailable on that particular page.

Tables of antibiotics, doses and side effectsare located in section IV. Whilst every care hasbeen taken to ensure that these tables containno errors, we cannot accept responsibility forany that have occurred. We regard it as goodpractice for prescribers to check the dose of anydrug with which they are unfamiliar by refer-ence to the manufacturer’s data sheet or theBritish National Formulary.

: bnf.vhn.net/home/

Chapter 1

Introduction

3

4 Chapter 1

Abbreviations

Abbreviations which are used only within one or two sections of the manual are definedtherein. Abbreviations listed here are those that are used many times throughout themanual.

AFB acid-fast bacillusAIDS acquired immune deficiency

syndromeARDS adult respiratory distress syndromeASOT anti-streptolysin O titreBAL broncho-alveolar lavageBT bioterrorismCAPD chronic ambulatory peritoneal

dialysisCCDC Consultant in Communicable

Disease ControlCDSC Communicable Disease

Surveillance Centre (Colindale)CF cystic fibrosisCMI cell-mediated immunityCMV cytomegalovirusCNS central nervous systemCNSt coagulase-negative staphylococcusCOAD chronic obstructive airways diseaseCSF cerebrospinal fluidCT computed tomography (scan)CXR chest X-rayDIC disseminated intravascular

coagulationEBV Epstein–Barr virusECHO echocardiogramELISA enzyme-linked immunosorbent

assayENT ear, nose and throatERCP endoscopic retrograde

cholecystopancreatogramFBC full blood countG6PD glucose-6-phosphate

dehydrogenaseGAS group A b-haemolytic

streptococcusGI gastrointestinalGN glomerulonephritish hourHAV hepatitis A virusHBV hepatitis B virusHCV hepatitis C virus

HD % drug removed by haemodialysisHDV hepatitis D virusHEPA high-efficiency particulate arresterHHV-6 human herpes virus type 6Hib Haemophilus influenzae type bHIG normal human immunoglobulinHIV human immunodeficiency virusHLGR high-level gentamicin-resistantHSV herpes simplex virusIA invasive aspergillosisICU intensive-care unitid intradermalIE infective endocarditisIFAT indirect fluorescent antibody testim/IM intramuscularip intraperitonealIUD intrauterine deviceiv/IV intravenousIVDU intravenous drug use(r)LP lumbar punctureLRTI lower respiratory tract infectionMAI Mycobacterium avium-intracellulareMBC minimum bactericidal

concentrationMDa megadaltonMIC minimum inhibitory concentrationmin minuteMOSF multi-organ system failureMRI magnetic resonance imagingMRSA methicillin-resistant Staphylococcus

aureusMSU mid-stream urineMW molecular weightNSAID non-steroidal anti-inflammatory

drugPCP Pneumocystis carinii pneumoniaPD % drug removed by peritoneal

dialysisPHLS Public Health Laboratory ServicePID pelvic inflammatory diseasepo orally (per os)PUO pyrexia of unknown originPVE prosthetic valve endocarditisRSV respiratory syncytial virusRUQ right upper quadrantSBC serum bactericidal concentrationsc subcutaneousSLE systemic lupus erythematosusSRSV small round structured virusSTD sexually transmitted disease

TB tuberculosisTPHA Treponema pallidum

haemagglutination assayTSS(T) toxic shock syndrome (toxin)URTI upper respiratory tract infectionUSS ultrasound scanUTI urinary tract infection

VDRL Venereal Disease ResearchLaboratory (syphilis)

VHF viral haemorrhagic feverVZV varicella zoster virusWBC white blood cell (count)WHO World Health OrganizationZN Ziehl–Nielsen

Introduction 5

6 Chapter 1

Symbols

Symbol Meaning Further details

ÿ Refer to page number

( Discussion with microbiology/specialist referral recommended

% Antibiotic level assay required ÿ388

S Cases per annum reported in England and Wales

Q Test performed by a reference laboratory

* Notifiable disease ÿ7

Å Standard isolation ÿ8

Ç Body fluids isolation ÿ8

É Infection risk from blood isolation ÿ8

Ñ Strict isolation ÿ8

¸ Antibiotic penetrates this fluid (e.g. CSF¸)

˚ Antibiotic does not penetrate this fluid (e.g. CSF˚)

: Internet resource —usually a website address (the prefix http:// is omitted

to save space)

Key reference. Usually a national guideline, a recent authoritative review,

or a unique paper that has significantly changed practice

N Organisms which are a hazard to laboratory staff

2 See manufacturer’s data sheet

* Notifiable diseases

In England and Wales, the following diseases must be notified to the local authority, via the local consultant in communicable disease control (CCDC).

Acute encephalitis (ÿ101)Acute poliomyelitis (ÿ348)Anthrax (ÿ263)Cholera (ÿ285)Diphtheria (ÿ268)Dysentery (amoebic or bacillary) (ÿ209)Food poisoning (ÿ57)Leprosy (ÿ46)Leptospirosis (ÿ327)Malaria (ÿ211)Measles (ÿ126)Meningitis (ÿ96)Meningococcaemia (ÿ185)Mumps (ÿ128)Ophthalmia neonatorum (ÿ107)

Introduction 7

Paratyphoid fever (ÿ280)Plague (ÿ305)Rabies (ÿ357)Relapsing fever (ÿ326)Rubella (ÿ127)Scarlet fever (ÿ135)Smallpox (ÿ341)Tetanus (ÿ315)Tuberculosis (ÿ38)Typhoid fever (ÿ280)Typhus (ÿ329)Viral haemorrhagic fever (ÿ206)Viral hepatitis (ÿ70)Whooping cough (ÿ136)Yellow fever (ÿ352)

Chickenpox (ÿ130) is a notifiable disease in Scotland. Certain other diseases may be made locallynotifiable.

Throughout text, recommended levels ofisolation are indicated by the use of symbols(e.g.Ñ).

Protective isolation is used to preventimmunocompromised patients from acquiringinfection. It is of less certain value, particularlyas most infections in neutropenic patients are

endogenous (ÿ174). Most units concentrate on protecting against specific organisms, e.g.nursing in HEPA-filtered air (vs. aspergillosis),antibiotic prophylaxis and microbiologicallyclean food (to avoid colonization with newstrains of Gram-negative bacteria).

8 Chapter 1

Isolation

Isolation is a key technique for preventingspread of infectious diseases in hospitals. It canbe physically and emotionally disturbing, anddisruptive of clinical care, and therefore shouldonly be used where there is proven or likelybenefit. Strong evidence of efficacy is availablefor some infections including MRSA, tubercu-losis and multiply-resistant coliforms. Isolationpolicies are made at individual hospitals, andlocal protocols should always be consulted.If these are not available, consult your micro-biologists ( and infection control team. Wehave not included detailed instructions for

medical and nursing procedures for the surveil-lance, control and prevention of infection inhospital; we refer readers searching for thisinformation to the excellent handbooks andcomprehensive reference texts that cover noso-comial infection control. Systematic reviews ofthe evidence for infection control interventionsare being published, e.g.

: www.epic.tvu.ac.uk

: www.cdc.gov/ncidod/hip

Source isolation is designed to preventinfected patients from transmitting theirdisease to others. It may generally be consideredin four categories:

Level ofisolation Examples Route Main suggested precautions

SUP All patients Aprons, gloves and handwashing, but no (standard need for separate room. Aprons and gloves universal should be used whenever there is the precautions) possibility of contact with patients’ body

fluids, and hands should be cleaned after every patient contact, irrespective of the diagnosis. These simple measures form the backbone of infection control in hospital

Å Standard Neisseria meningitidis, Airborne or Separate room. Negative pressure Group A b-haemolytic direct contact ventilation if available. Aprons, gloves ±streptococci masks for all entering room

Ç Body Salmonella spp., Contact Separate room. Aprons and gloves for fluids Shigella spp., with urine, patient contact

multiply-resistant faeces andAcinetobacter spp. secretions

É Infection Hepatitis B, HIV Contact Separate room only required if patients are risk from with blood bleeding, likely to bleed, undergoing majorblood or blood- invasive procedure, incontinent or confused.

stained Plastic aprons, gloves (±visors) for body fluids* procedures where contact with body fluids is

possible

Ñ Strict Lassa fever Airborne or Strict isolation in specialist unit —usuallydirect contact regional infectious diseases centre. Do not

send any specimens without discussion with lab

* Including CSF, pleural fluid, vaginal secretions, peritoneal fluid, synovial fluid, semen, pericardial fluid, amniotic fluid and breast milk.

Introduction 9

Recommendations for isolationFor category codes ÿ8.

Disease Category See

Anthrax* SUP 263

Bordetella pertussis1* Å 136

Borrelia recurrentis2* Å 326

Bronchiolitis (RSV)24 Å 23

Campylobacter jejuni3 Ç 288

Candida spp.4 Ç 367

Chickenpox*6 Å 130

Chlamydia trachomatis5 Ç 329

(ophthalmia neonatorum*,

conjunctivitis, genital

infection)

Cholera7* Ç 285

Clostridium difficile8 Ç 63

Coxsackievirus9 Ç 349

Cryptosporidium parvum Ç 230

Dermatitis10 (severely Å 111

infected)

Diarrhoea of unknown cause12 Ç 57

Diphtheria11* Å 268

Dysentery*

Amoebic13 or bacillary14 Ç 209

Ebola virus * Ñ 206

Eczema10 (severely Å 111

infected)

Encephalitis ?cause * Å 101

Erysipelas10 Å 113

Erythema infectiosum Å 135

Escherichia coli diarrhoea, Ç 275

travellers’ diarrhoea,

haemolytic uraemic syndrome

(O157, VTEC, EIEC, EPEC,

EAggEC, ETEC, etc.)

Exanthem subitum Å 134

Food poisoning *

Undiagnosed cause12 Ç 57

Campylobacter jejuni3 Ç

Salmonella15 Ç

Francisella tularensis15 Å 307

Gastroenteritis, viral Ç 350

Giardiasis Ç 218

Gonococcal conjunctivitis1 Ç 86

Haemolytic streptococcus10 Å 254

Lancefield group A, B3, C or

G (Streptococcus pyogenes)

Disease Category See

Hepatitis ?cause * Ç

Hepatitis A Ç 70

Hepatitis B, fulminant liver É 70

failure of undetermined

cause

Hepatitis C É 73

Herpes simplex17 Å 334

Herpes zoster6 Å 130

HIV É 143

Impetigo10 Å 111

Lassa fever * Ñ 206

Leprosy* 46

Smear negative —

Smear positive Å

Leptospirosis1* Ç 327

Lice, fleas1 Ç 94

Listeriosis18 Ç 267

Marburg virus disease * Ñ 206

Measles19* Å 126

Melioidosis15 Å 293

Meningitis*

Neisseria meningitidis1 Å 96

(including

meningococcal

septicaemia/other

invasive meningococcal

infections)

Neonatal Ç 139

Viral9 Å 100

Meningoencephalitis, Å 348

acute (acute

poliomyelitis)*

MRSA20 Å 251

Multiply-resistant Gram- Ç

negative bacteria20

Mumps9* Å 128

Ophthalmia neonatorum1* Ç 107

Parvovirus B19 Å 135

Penicillin-resistant Streptococcus Å 261

pneumoniae11

Pertussis1* Å 136

Plague* Ñ 305

Poliomyelitis, acute * Å 348

Pseudomonas pseudomallei15 Å 293

(continued...)

10 Chapter 1

Psittacosis Å 329

PUO21 Å 179

Rabies* Ñ 357

Ratbite fever1 Ç 306

Relapsing fever2* Å 326

Respiratory syncytial virus24 Å 23

Rotavirus Ç 350

Rubella16* Å 127

Salmonellosis15 (excluding Ç 57

typhoid and paratyphoid)

Scabies1 Å 95

Scarlet fever10* Å 135

Smallpox22* Ñ 341

Streptococcus pyogenes —see

Haemolytic streptococcus

Syphilis (1° or 2° only)1 Ç 89

Tapeworms Ç 237

Tuberculosis23 (open pulmonary,

wound, urinary) * Å 38

Tularaemia15 Å 307

Typhoid, paratyphoid and Ç 280

carriers7*

Typhus2* Å 329

Vaccinia, generalized Ñ 341

Vancomycin-resistant Gram- Å 262

positive organisms20 (usually

Enterococcus faecalis or

faecium)

Varicella *6 Å 130

Vibrio parahaemolyticus15 Ç 287

Viral haemorrhagic fever * Ñ 206

Whooping cough1* Å 136

Yersinia enterocolitica Ç 284

and pseudotuberculosis15

1 For first 24 h of treatment. 2 Until patient and contacts deloused. 3 Neonates only. 4 If part of proven out-

break. 5 For first 48 h of treatment. 6 Until vesicles are crusted and dry. Staff in contact should be immune.

Notifiable in Scotland. 7 Until asymptomatic with three negative stool cultures. 8 Until asymptomatic for 3

days. 9 For 10 days after onset. 10 Until cultures known to be negative for b-haemolytic streptococci. 11 Until

culture negative. 12 Until transmissible pathogens excluded. 13 Until asymptomatic and treated for cyst car-

riage. 14 Until asymptomatic and one negative stool culture. 15 Until asymptomatic. 16 Until 7 days after

onset of rash. 17 Only for infants with disseminated infection. 18 Infants and mothers only. 19 Until 4 days

after onset of rash. 20 Until agreed by microbiologist. 21 If outside Europe and N. America within 4 weeks.22 Even if only suspected. 23 For first 14 days of therapy. 24 Cohorting on children’s ward whilst symptomatic.

Disease Category See Disease Category See

Introduction 11

Details of sample collection and transport varyfrom laboratory to laboratory, but a generalsummary of principles follows. Laboratoriesdiffer (based on local prevalence) on whetherthey routinely perform certain tests on particu-lar specimens (e.g. Clostridium difficile toxin onall faeces). The importance of listing full clini-cal details has been emphasized throughoutthis book. Always give details of recent hospitalin-patient stays and travel, and also occupationif the patient has diarrhoea or skin infectionand works in catering, school or hospital. Simi-larly, details of past, current and intendedantibiotic therapy are valuable for interpreta-tion of many culture results. Virus culture isusually only worth attempting early in thecourse of infection. Specimens for culture ofbacteria and fungi should always be takenbefore antibiotic therapy is commenced;sputum, mucosae and open wounds becomecolonized particularly rapidly with resistantbacteria.• Screening of contacts, or of cases for clearance, is only occasionally useful for anypathogen out of hospital, and should always bedone only according to locally written policiesor after discussion with a microbiologist, IDphysician or CCDC.• Specimens are always best transportedimmediately to the laboratory. If delay is neces-sary, in general all samples should be refriger-ated at 4°C, except inoculated blood culturebottles, which should be incubated at 37°C.

Swabs, tissue and pusSend pus, if available, in a sterile universal con-tainer, because additional rapid tests can be per-formed (e.g. HPLC for short-chain fatty acids

from anaerobes); a swab is an inferior substituteupon which delicate organisms die. Use firmpressure when taking swabs and always use theappropriate swab transport medium (bacterial,viral, chlamydial). Inclusion of charcoal intransport media or swab tips increases recoveryof many bacteria, especially Neisseria gonor-rhoeae. Use special pernasal swabs for Borde-tella pertussis. Gonococcal culture plates arebest inoculated at the bedside. Surface swabs ofdeeply infected lesions (e.g. sinus tracks fromosteomyelitis) usually grow surface contami-nants (e.g. coliforms and pseudomonads) andrarely grow the causative organism. Only isola-tion of Staphylococcus aureus from this type ofspecimen correlates with true deep infection.Culture of bone marrow, liver biopsies etc. isoccasionally useful, but should be discussed inadvance with a microbiologist. Samples fromdrainage bags (e.g. biliary, wound, nephros-tomy) are not representative of the microbialpopulation within the patient; cultures are fre-quently overgrown with commensal bacteria,especially Bacillus spp. Take samples of freshlydrained fluid from close to the patient.

Medical devicesThe tips of iv catheters suspected of beinginfected should be cut off with alcohol-wipedscissors and sent in a sterile universal containerfor semiquantitative culture. Growth of >15–20colonies of coagulase-negative staphylococci or diphtheroids suggests infection, and anygrowth of other bacteria or fungi is likely to besignificant. Small infected prostheses (e.g. heartvalves) can be sent entire, but it is best to scrapeadherent material from larger prostheses andsend that.

UrinePrepuce and labia should be held away from theurine stream, but periurethral cleaning does notadditionally reduce contamination of MSUsfrom adults as long as the initial stream is dis-carded. Most laboratories supply universal con-tainers with borate preservative, or dip-slidesfor urine collection in domiciliary practice. Theformer preserves both host and bacterial cellsfor 48 h. Dip-slides should be only dipped intourine, and the transport container should not

Microbiological specimens

Getting the best out of yourmicrobiology service depends on . . .

• Collecting the right specimens in the right

way, before starting antibiotics

• Always giving the lab full clinical details

• Discussing unusual specimen requirements,

and unusual or unexpected results

be filled with it. Catheter urine specimensshould be taken by aseptic puncture of the sampling area close to the patient. Culturingurinary catheter tips is a waste of time. Paedi-atric bag collection systems are often conta-minated, but this is reduced by cleaning theperineum with antiseptic; a negative culture isuseful, but positive results must be interpretedwith care. Suprapubic aspiration is the goldstandard for detecting bladder urine infection.Early morning urine (EMU) specimens for AFBmicroscopy and culture should be �150 mLvolumes, and taken on different days.

SputumEfforts, such as vigorous physiotherapy, toobtain expectorated sputum before antibioticshave been given improve the isolation rate ofpneumococci and other significant pathogens.Three samples on successive days are needed to exclude open pulmonary tuberculosis.Broncho-alveolar lavage is the most sensitivediagnostic procedure, but induced sputum issimpler, with adequate sensitivity for Pneumo-cystis carinii diagnosis. In ventilated patients,non-directed lavage allows recognition ofsignificant isolates by quantitative culture(>105/mL).

FaecesA walnut-sized sample is needed; this is mosteasily collected by passing stool onto foldedtoilet paper in the lavatory bowl, and scoopingthe sample into a universal container with aspatula attached to the inside of the lid. The bestchance of isolating causative agents of acutediarrhoea is on the first sample, and only if it is taken early in the course of illness. Manypathogens are only transiently excreted (e.g.Escherichia coli O157), so multiple samples areonly required for exclusion of some parasites(e.g. Giardia) and to detect carriage of typhoidbacilli in food handlers (ÿ63). ‘Hot’ stoolsamples for visualization of trophozoites ofEntamoeba histolytica are only useful if thepatient has dysentery, i.e. bloody diarrhoea.

Blood culturesBlood cultures should be taken from anypatient who is systemically ill in whom an in-

fective diagnosis is being considered. Beforevenepuncture, the skin should be carefully dis-infected with an alcoholic antiseptic, which isallowed to dry. Most laboratories now use auto-mated blood culture systems, which come withinstruction sheets and should be inoculatedwith the specified volumes of blood (both over-and under-inoculation impair performance).Check the expiry date on the bottles and do notuse if cloudy. Modern systems have greatlyimproved efficiency, and 2–3 cultures are suffi-cient for all indications, except when the patienthas received antibiotics recently. In this case,when IE is suspected, it is worth taking two cul-tures on day 1, and daily cultures for the next3–4 days. It is not necessary to change needlesbefore injecting the culture bottles. It is oftenrecommended to inoculate small volumes ofnormally sterile fluids (e.g. CAPD, ascitic, joint)to blood culture bottles. Unfortunately, bloodculture broths are optimized for bacterialrecovery only when blood is included, andother laboratory procedures become impossi-ble (e.g. microscopy, incubation at differenttemperatures and atmospheres, mycobacterialculture). Always also send some fluid in a sterileuniversal container or capped syringe if bloodculture broths are inoculated.

CSFBest taken in three consecutively labelledbottles, and transported immediately to the lab-oratory. Take simultaneous blood glucose. For areasonable chance of detecting AFB, 10 mL ormore CSF is required.

SerumListing the times of doses and samples isimportant for interpretation of antibioticassays. Specifying the date of onset of illness isvital for choosing and interpreting serologicaltests; acute and convalescent (10–14 days later)sera are often needed to prove recent infection.Most laboratories will store many such sera,issue a request for a convalescent sample, andonly perform the assays (in parallel) if a laterserum is received. IgM assay diagnosis on singleacute sera is possible for some infections (e.g. Mycoplasma, Rubella, hepatitis viruses,Toxoplasma), and very high single titres are

12 Chapter 1

Introduction 13

diagnostic for others (e.g. Legionella, respira-tory Chlamydia, Coxiella). Exposure historyand date of leaving the endemic area are essential for performance of tests for many geographically-restricted infections (e.g.brucellosis, schistosomiasis).

Molecular testsLocal protocols for sampling and transportshould always be followed. Care with these

stages is as important as for conventional diagnostic testing if potential cross-reactionsand inhibition of PCRs are to be avoided.Details of construction of the swab and ofthe composition of the transport medium may affect the sensitivity and specificity of the result. EDTA blood samples are preferred by many laboratories, but these bottles are frequently contaminated withpseudomonads.

Section II

Clinical InfectiousDiseases

Sinusitis

Most often affects the maxillary sinuses. May beacute or chronic and recurrent. Complicationsare due to the proximity of the orbits andintracranial structures.

Risk factors: Frequently secondary to: acuteviral URTI, complicating �0.5% of child-hood URTIs. Dental sepsis or procedures, nasalpolyps or deviated septum. Rarely, immuno-deficiency (AIDS, IgG, IgA deficiency), cysticfibrosis, immotile cilia syndrome.

Clinical features: Facial pain, fever and purulentnasal discharge. Headache, nasal obstruction,halitosis, toothache and anosmia may occur.Cough is frequent in children.

Organisms: Acute: Streptococcus pneumoniae,Haemophilus influenzae, viruses, Moraxellacatarrhalis, rarely Staphylococcus aureus.Chronic: Streptococcus pneumoniae, Haemo-philus influenzae, Streptococcus ‘milleri’, mixedoral anaerobes, Staphylococcus aureus.

Microbiological investigations: Nasal swabs arenot helpful. Sinus aspiration to obtain materialfor Gram staining and culture for persistent orrecurrent infections.

Other investigations: Severe or persistent infec-tion merits sinus X-rays. Fluid level or opacitysuggest acute infection. Complete opacity ormucosal thickening alone may be seen inchronic infection. CT, MRI are more sensitive.

Differential diagnosis: Consider immunodefi-ciency, rare non-infectious causes (Wegener’s,carcinoma, lymphoma) unusual infections(TB, leprosy, syphilis).

Antibiotic management: Amoxicillin or co-amoxiclav or cefuroxime, but dubious clinicalefficacy.

Supportive management: Nasal decongestants:oxymetazoline hydrochloride nasal spray,0.05%, 1–2 sprays each nostril 8hly, or pseudo-ephedrine hydrochloride, 60 mg 8hly, po.ENT referral for persistent or recurrent infection.

Complications: Rare but serious. Orbital celluli-tis (ÿ109), osteomyelitis of facial bones(ÿ123), intracranial abscess (ÿ103), meningi-tis (ÿ96), cavernous and superior sagittal sinusthrombosis, orbital fissure syndrome (sphenoidsinus).

Comments: Chronic recurrent sinusitis reflectsimpaired drainage from the sinuses and meritsENT referral. Infection is usually due to mixedaerobic and anaerobic oral flora and respondspoorly to antibiotic therapy alone. Immuno-compromised patients may develop fungalsinusitis (Aspergillus spp., Mucor spp. and relatives ÿ369). Urgent ENT referral isrequired.

Otitis media (OM)Risk factors: Frequently follows URTI.Common in children because of short, straightEustachian tubes and blockage secondary tolymphoid hyperplasia.

Clinical features: Fever and earache. Otorrhoeaif perforation has occurred. Presentation maybe non-specific in infants. Tenderness over themastoid process and redness and bulging ofthe tympanic membrane, which may have perforated.

Chapter 2

Upper respiratory tract infections

17

18 Chapter 2

Organisms: Streptococcus pneumoniae, non-capsulate Haemophilus influenzae, Moraxellacatarrhalis; �30% are viral, frequently due to respiratory syncytial virus. Staphylococcusaureus, Mycoplasma pneumoniae, and GAS areseen rarely. Chronic infection may proceed tocholesteatoma with involvement of Proteus spp.and pseudomonads.

Microbiological investigations: In uncompli-cated cases, none.

Antibiotic management: Role of antibioticscontroversial. Distinguish between acute OMwith fever, otalgia and erythema of tympanicmembrane, which may merit antibiotics, andchronic OM with effusion, which does not.Chronic suppurative OM with perforation hasa different microbial aetiology and requiresENT referral.

Goal of therapy in acute OM is to reduce the duration of pain and to prevent complica-tions (mastoiditis, meningitis, intracranialabscess) In the pre-antibiotic era, these affected up to 40%, but they are now very rare. Spontaneous recovery occurs in �80%of acute OM without antibiotics. Systematicreview suggests small benefit from antibio-tics, especially in prevention of complications.We recommend giving antibiotics for acuteOM; they can be withheld in patients over 2 years, who are not systemically unwell,have normal host defences and who are likely to return for follow-up assessment at 48 h.If not improved at 48 h, commence antibiotics.All authorities agree that children under 6months should receive antibiotics. Amoxicillinis the drug of choice (erythromycin if allergic).

Supportive management: Analgesia.Schloss MD, Can Respir J 1999; 6 (Suppl. A): 51A

Otitis externaA hypersensitivity reaction of the skin lining theexternal auditory canal. Symptoms includeitching, pain and a feeling of fullness. On otoscopy, oedema and redness of the walls ofthe meatus. Often responds to careful cleansingand topical steroids. If infection is present,it is usually mixed due to diphtheroids,

pseudomonads and coliforms. Neomycin andhydrocortisone drops may be used. If there isevidence of local skin infection, such as a boil, flucloxacillin is given. Perforation must be excluded before drops are prescribed.Aspergillus and other fungal infections are besttreated with clotrimazole drops.

Malignant otitis externa is a rare infectionusually with Pseudomonas aeruginosa whichaffects diabetics and the immunocompro-mised. It has a significant mortality, due toinfection of adjacent bone and soft tissue,and requires aggressive systemic treatment with anti-pseudomonal antibiotics and surgicaldebridement. Urgent ENT referral is essential.

Dental and oral infections

Dental caries is related to acid production fromfermentation of dietary carbohydrates by bac-teria, including Streptococcus mutans and lacto-bacilli. Its significance for the physician lies inits effects on nutrition and as a risk factor forgingival disease, dental abscesses and Vincent’sangina.

Vincent’s anginaRisk factors: Poor oral hygiene, poor nutrition,smoking and severe intercurrent illness.

Clinical features: Oral pain, gingival bleed-ing, halitosis, fever and anorexia. On exami-nation there is necrosis and pseudomem-brane formation on tonsils and gums. Theremay be local lymphadenopathy and excess salivation.

Organisms: Mixed infection due to Leptotrichiaspp., Bacteroides spp. and Fusobacterium spp.

Differential diagnosis: Candidiasis (ÿ367),herpes simplex stomatitis (ÿ129), diphtheria(ÿ268).

Microbiological investigations: Gram stain ofscrapings from the affected area. Throat swabfor Candida albicans and Corynebacteriumdiphtheriae if suspected.

Antibiotic management: Penicillin V/amoxi-cillin + metronidazole or co-amoxiclav.

Supportive management: Attention to oral anddental hygiene.

Complications: In the severely malnourished orimmunocompromised patient progression tonoma, a severe gangrenous stomatitis, mayoccur rarely.

ring. Most cases are viral; management is aimedat relieving symptoms. Differential diagnosisincludes acute bacterial epiglottitis and, rarely,diphtheria.

Clinical features: Fever, malaise, sore throat and myalgia. On examination, erythema andoedema of the tonsils and pharyngeal mucosa.It is usually impossible to determine the causeclinically, although some features are suggestiveof particular organisms. Cough and coryzasuggest influenza or rhinoviruses, whereas con-junctivitis suggests adenovirus. Vesicles andulceration affecting both the pharynx andmouth are seen in herpes simplex stomatitis; inCoxsackie A herpangina (ÿ135), small vesiclesand ulcers are usually confined to the posteriorpharynx. Purulent tonsillar exudate suggestsstreptococcal infection or EBV; the latter isoften accompanied by generalized lympha-denopathy and/or hepatosplenomegaly. Puru-lent tonsillar exudate is rare in influenza orrhinovirus infection.

Organisms: Rhinovirus, coronavirus, adeno-virus, influenza A and B, parainfluenza, herpessimplex virus, coxsackievirus A, EBV, and CMVinfection. Group A b-haemolytic streptococci(GAS), less often groups C or G. Rarely,Arcanobacterium haemolyticum, Neisseria gonorrhoeae. Very rarely, Corynebacterium diphtheriae.

Microbiological investigations: A rise in ASOTmay give retrospective confirmation of strepto-coccal infection. Throat swab is often sent. Latexagglutination tests for the rapid diagnosis ofGAS antigens in throat swabs are widely used inUSA, and are specific and quite sensitive whencompared to throat swab. However, neitherantigen tests nor throat swabs are sensitive orspecific for GAS infection when compared toASOT,due to asymptomatic GAS carriage.Florarecovered from the surface of the tonsil corre-lates poorly with that of tonsillar crypt butquantitative culture may predict true infection.Viral culture may be positive, particularly inHSV infection. Viral serology may be useful inretrospect.

: med.mssm.edu/ebm/cpr/strep_cpr.html

Upper respiratory tract infections 19

Practice point

Patients with agranulocytosis may present with

severe oral and pharyngeal ulceration due

to Candida spp., herpes simplex or Capnocy-

tophaga spp. infection, which may subsequently

act as a portal of entry for oral streptococcal

bacteraemia.

Dental abscessRisk factors: Poor dental hygiene, pregnancy.

Clinical features: Fever, toothache, facial painand swelling.

Organisms: Mixed oral aerobes and anaerobes.

Antibiotic management: Penicillin V/amoxicillin + metronidazole or co-amoxiclav.

Ludwig’s angina refers to a severe cellulitis of the

floor of the mouth, almost always arising from

the second or third mandibular molars. Infection

is polymicrobial and may become extensive.

Parapharyngeal abscessMay complicate quinsy (ÿ21), but usuallyarises from dental abscess. Infection by mixedoral flora in lateral pharyngeal space displacestonsil towards midline and causes lateral neck swelling below mandible. Severe trismusis characteristic; may progress rapidly to sys-temic sepsis and local suppurative complica-tions, including involvement of jugular veinand carotid artery (see also Lemierre’s diseaseÿ20).

Pharyngitis

Infection of the posterior oral cavity, ofteninvolving the lymphoid tissue of Waldeyer’s

20 Chapter 2

Differential diagnosis: Diphtheria is extremelyrare in the developed world, but has recentlybecome endemic in parts of the former SovietUnion and should be suspected in an unimmu-nized patient who is unwell, particularly if thereis a grey tonsillar exudate spreading from thetonsils to involve the uvula, palate or posteriorpharyngeal wall (ÿ268). If diphtheria is sus-pected, liaison with the microbiology depart-ment is essential (.

Antibiotic management: As most cases are viral,the value of antibiotics for sore throat has beenquestioned. Trial of penicillin vs. no treatmentvs. delayed treatment showed no benefit,although patients who were unwell, had recur-rent tonsillitis or suspected rheumatic feverwere excluded. Immunological sequelae ofGAS infection (ÿ256) are now very rare in theUK, so value of antibiotics in preventing them isunquantifiable. There is some evidence tosuggest that antibiotic therapy prevents localsuppurative complications such as quinsy. For afull discussion see:

: www.sign.ac.uk/guidelines/fulltext/34/

Zwart S, BMJ 2000; 320: 150

If patients are unwell, give penicillin V for 10days. For recurrent tonsillitis, cefuroxime andclindamycin have been shown to be superior topenicillin V. Consider ENT referral.

Lemierre’s disease‘Anaerobic tonsillitis’: Severe pharyngitis asso-ciated with fever, septicaemia, metastatic pul-monary infection and jugular vein thrombosisis rarely seen in young adults and is caused byFusobacterium necrophorum (ÿ321).

LaryngitisIn addition to the symptoms of pharyngitis,some patients with URTI may develop hoarse-ness and odynophagia.Laryngitis is usually viralin aetiology, although it may accompany infec-tion by streptococci or Mycoplasma pneumo-niae. Persistent hoarseness is usually due tonon-infectious causes, but may indicate chronicgranulomatous laryngitis. Causes includeCandida albicans and herpes simplex virus;diagnosed on biopsy.

Practice point

Patients with 1° EBV infection develop a wide-

spread maculopapular rash after treatment

with ampicillin or amoxicillin. These antibiotics

should be avoided in sore throat unless the

diagnosis of bacterial infection has been firmly

established.

Complications: Lower respiratory tract infec-tion, peritonsillar (ÿ21) and retropharyngealabscess (ÿ21).

Comments: Scarlet fever *, now rare in theUK, is caused by streptococcal erythrodermictoxin, which may be produced in streptococcalinfection at any site (ÿ254).

Croup (acute laryngotracheobronchitis)

Croup typically affects children from a few

months old to the age of 3 years, and occurs in

epidemics in autumn and early spring. During

the course of a viral URTI, inspiratory stridor and

a distinctive ‘seal’s bark’ cough develop. Cyanosis

and intercostal recession indicate more severe

airway obstruction. Antibiotics, steroids and

mist inhalation have not been shown to be of

value. Hypoxia is common. Careful observation is

needed, with a view to timely intubation or tra-

cheotomy should airway obstruction progress.

The important differential diagnosis is acute

epiglottitis (ÿ21).

Bacterial tracheitisRetrosternal discomfort commonly accompa-nies viral URTI. Rarely, bacterial tracheitis mayfollow with fever, dyspnoea and stridor withpurulent sputum. Gram stain and culture ofsputum and blood culture are required if severe.Infection is most often due to Staphylococcusaureus, GAS and Haemophilus influenzae type b.Lateral soft-tissue X-ray of neck may show subglottic narrowing with a normal epiglottis(‘pencil sign’). Bacterial tracheitis may followintubation and trauma.

Antibiotic management: Flucloxacillin or co-amoxiclav or parenteral cephalosporin — tobe guided by the results of sputum culture.

QuinsyQuinsy (peritonsillar abscess) usually followsbacterial pharyngitis. It is usually polymicrobialin origin, with oral anaerobes and GAS predominating. Patients present with abruptincrease in pain and dysphagia. On examina-tion, there is asymmetrical tonsillar enlarge-ment with swelling in the neck and often apalpable fluctuant mass. Management consistsof ENT referral for consideration of surgicaldrainage and benzylpenicillin or co-amoxiclav,given parenterally.

Retropharyngeal abscessUnusual but important complication of bacter-ial pharyngitis and pharyngeal trauma (e.g.fish-bone). Retropharyngeal space lies posterior topharynx, anterior to cervical vertebrae and con-tains lymphatic tissue. Commoner in children.

Clinical features: Sore throat, dysphagia andneck pain. Bulging of the posterior pharyngealwall may only be visible with indirect laryn-goscopy. Lateral soft tissue X-ray of neck showswidening of pre-vertebral tissue, ±gas in tissues.Airway obstruction may occur.

Organisms: GAS and mixed oral flora.

Differential diagnosis: Cervical osteomyelitis,meningitis.

Antibiotic management: Benzylpenicillin plusclindamycin or parenteral cephalosporin plusmetronidazole.

Supportive management: Urgent ENT referralfor incision and drainage; �30% require tracheostomy.

Comments: Consider the diagnosis in thepatient with neck stiffness and fever who has anormal lumbar puncture.

Acute epiglottitisInflammation, oedema and obstruction of thesupraglottic structures including the epiglottisdue to Haemophilus influenzae type b (rarelyother capsular types) typically affecting chil-dren aged 3 to 7 yrs.

Clinical features: Abrupt onset, over hours, ofsevere sore throat and fever. Children areunwell, with stridor, drooling and dysphagia.They may adopt a typical posture, sitting up and leaning forward. The swollen, cherry redepiglottis may be visible, but attempts to use atongue depressor should be avoided, as this mayprecipitate fatal acute total obstruction.

Antibiotic management: Parenteralcephalosporin or amoxicillin plus chloram-phenicol should be given. Rifampicin pro-phylaxis should be given to the patient and allhousehold and nursery/day-care contactsincluding adults if there are other susceptiblechildren in the family (ÿ100).

Supportive management: Management of theairway is paramount. Elective intubation isassociated with reduced mortality, as emer-gency intubation may be very difficult. Throatexamination and iv cannulation should bedelayed until arrival of suitably experiencedanaesthetist.

Other investigations: Lateral soft-tissue neck X-ray may show the engorged epiglottis (the‘thumb sign’).

Differential diagnosis: It is essential to distin-guish between viral croup and epiglottitis.Salient features are the abrupt onset, toxicappearance, dysphagia and drooling associatedwith epiglottitis. Diphtheria and inhaledforeign body may also need to be considered.

Complications: Systemic spread, bacteraemia,meningitis, arthritis and cellulitis.

Comments: This condition has been reportedrarely in adults. All forms of invasiveHaemophilus influenzae type b are less commonwith the introduction of the Hib vaccine.

ThyroiditisSudden onset of pain, tenderness and swellingin the thyroid may be due to infection byStaphylococcus aureus, Streptococcus pneumo-niae or mixed oral anaerobes. ENT referral forconsideration of needle aspiration (send for

Upper respiratory tract infections 21

22 Chapter 2

culture). Acute suppurative thyroiditis is rare.Often associated with a persistent thyroglossalduct, or a third or fourth branchial archanomaly with a congenital fistula from the pyriform fossa to the thyroid. Confirmation

by barium swallow. Inflammation is more oftensubacute, sometimes related to recent viralinfection (e.g. mumps, measles, influenza andEBV).