Antimicrobial Chemotherapy

429 Pages·2015·2.37 MB·English

by  Peter Davey

Antimicrobial
Chemotherapy
Antimicrobial
Chemotherapy
SEVENTH EDITION
Professor Peter Davey
Lead for Clinical Quality Improvement
Medical Education Institute
University of Dundee
Professor Mark Wilcox
Consultant / Head of Microbiology
Leeds Teaching Hospitals NHS Trust
Professor of Medical Microbiology & Sir Edward Brotherton Chair of
Bacteriology
University of Leeds
Lead on C. difficile infection
Public Health England
Professor William Irving
Professor and Honorary Consultant in Virology
University of Nottingham and Nottingham University Hospitals NHS Trust
Professor Guy Thwaites
Director of the Oxford University Clinical Research Unit
and the Wellcome Trust Major Overseas Research Programme, Viet Nam
Senior Research Fellow
Nuffield Department of Medicine
University of Oxford
Honorary Consultant in Infectious Diseases and Clinical Microbiology
Guy’s and St Thomas’ NHS Foundation, London
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First Edition published by Ballière Tindall in 1983
Second Edition published in 1989
Third Edition published in 1995
Fourth Edition published in 2000
Reprinted in 2001, 2003 (twice), 2004, 2005
Fifth Edition published in 2007
Sixth Edition published in 2012
Seventh Edition published in 2015
Impression: 1
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Preface
Almost everyone in the developed world will receive several antibiotic courses during their
lifetime. It is therefore not surprising that most clinicians and dentists will prescribe these drugs
on a regular basis throughout their professional career. Indeed, several antibiotics figure among
the most frequent of all prescribed drugs.
Antibiotics are not only life-saving with regard to severe infections, such as pneumonia, menin-
gitis, and endocarditis, but are also responsible for controlling much of the morbidity associated
with non-life-threatening infectious disease; illness is abbreviated, return to normal activities is
hastened, risk of infection transmission may be reduced and there is often economic benefit to
the individual, as well as society, by reducing the number of working days lost. In addition, infec-
tious complications of many commonly conducted surgical procedures are now preventable by
the use of peri-operative antibiotic prophylaxis. Likewise procedures such as bone marrow and
organ transplantation are also possible because of the effective control of complicating infections.
These benefits are well known to healthcare professionals and to the public who no longer fear
infection in the way earlier generations did. The very success of antimicrobial chemotherapy has
led to a perception that such agents are generally safe and that industry will continue to generate
new agents to ensure the effective control of most infectious problems.
Antibiotics have largely been derived from natural sources, mainly from environmental
bacteria and fungi. Their use in clinical medicine has been one of the major successes of the past
century. The term ‘antibiotic’ was coined by Selman A Waksman, who recognized that these
‘naturally derived substances were antagonistic to the growth of other micro-organisms in high
dilution.’ Over the years, other agents have been developed by chemical synthesis. More recently
much effort has been applied to identifying genomic research based products. The term ‘antimi-
crobial agents’ captures all such compounds which in turn have been subdivided into antibacte-
rial, antifungal, antiparasitic (anthelminthic and antiprotozoal) and antiviral agents according
to the target pathogen. However, this purist approach is often ignored in practice and the term
antibiotic is somewhat loosely applied to all these agents. The reader will find all such terms in
use in this book.
Antibiotics are unique among therapeutic agents in that they target invading micro-organisms
rather than any pathological process arising from host cells or tissues. Furthermore, unlike other
classes of drug, micro-organisms have the inherent or acquired ability to evade or inactivate anti-
microbial activity of these drugs. Such resistance presents a major threat to sustaining effective
treatment and prevention of infectious disease. In addition, there is increasing recognition of the
importance of the normal bacterial flora of the human body and of the consequences of collateral
damage from the use of antibacterials, such as the risk of Clostridium difficile infection.
Indeed, controlling antibiotic resistance is one of the greatest challenges facing healthcare
professionals and the public and is likely to remain so. While new drugs, vaccines and better diag-
nostic methods are still a requirement, the fundamental issue is to ensure that existing agents are
used effectively. This can only be achieved by ensuring those doctors, dentists, and, increasingly,
other healthcare professionals who use these agents in the care of their patients, pursue good
prescribing practice.
vi PREFACE
Good prescribing practice is the product of sound education, with particular emphasis on the
acquisition of appropriate knowledge, skills, and professional behaviour. Good science informs
good practice and since the knowledge base for prescribing practice is continuously expanding,
the need for life-long learning is self-evident.
Patient safety remains paramount in medicine. This is of particular importance since antibiotics
are often used in the management of mild to moderate community infections and the prophylaxis
of infections. The safety of antibiotics is monitored closely during drug development, at licensing
and in clinical use. Since no drug is free from side effects, it is essential that the balance of risks
and benefits of prescribing is understood by the prescribing practitioner. With more than 100
antimicrobial compounds currently available in the UK, this remains a particular challenge.
Setting forth the principles of rational antimicrobial chemotherapy is the whole purpose of this
book. In revisiting the contents, we welcome Dr Guy Thwaites among the editors. All chapters
have been revised, several rewritten and a new chapter introduced on Antimicrobial Stewardship,
Surveillance of Antimicrobial Consumption and Its Consequences to reflect the changes that have
taken place in guiding prescribing practices.
However, the basic plan of the book remains unchanged and much of the material provided by
former authors has been retained attesting to its durability. As such, it reflects the vision of Pro-
fessor David Greenwood, who was the inspiration for this book and Professor Roger Finch, who
guided the first six editions so successfully.
We sincerely hope that this 7th edition of Antimicrobial Chemotherapy will continue to furnish
students and all healthcare professionals throughout the world with the necessary framework for
understanding what antimicrobial agents will and will not do, and provide a firm basis for their
informed use in the treatment and control of infection.
March 2015
P.D.
M.W.
W.I.
G.T.
Contents
List of Abbreviations ix
Part 1 General properties of antimicrobial agents
1 Mechanisms of action and resistance to modern antibacterials, with a history
of their development 3
2 Inhibitors of bacterial cell wall synthesis 10
3 Inhibitors of bacterial protein synthesis 24
4 Synthetic antibacterial agents and miscellaneous antibiotics 36
5 Antiviral agents 44
6 Antiretroviral agents 58
7 Drugs used in the treatment of viral hepatitis 66
8 Antifungal agents 75
9 Antiprotozoal and anthelminthic agents 81
Part 2 Resistance to antimicrobial agents
10 The problem of resistance 91
11 The genetics and mechanisms of acquired resistance 101
Part 3 General principles of usage of antimicrobial agents
12 Laboratory investigations and the treatment of infection 121
13 General principles of the treatment of infection 133
14 Pharmacokinetic and pharmacodynamic principles 140
15 Prescribing in special groups: effects of age, pregnancy, body weight, and hepatic
and renal impairment 148
16 OPAT: outpatient parenteral antimicrobial therapy 159
17 Adverse drug reactions, and patient safety 168
18 Chemoprophylaxis and immunization 178
19 Guidelines, formularies, and antimicrobial policies 191
20 Antimicrobial stewardship, surveillance of antimicrobial consumption, and its
consequences 206
Part 4 Therapeutic use of antimicrobial agents
21 Respiratory tract infections 227
22 Topical use of antimicrobial agents 240
viii CONTENTS
23 Urinary tract infections 248
24 Sexually transmitted infections 257
25 Gastrointestinal infections 267
26 Serious bacterial bloodstream infections 279
27 Bone and joint infections 297
28 Infections of the central nervous system 303
29 Skin and soft-tissue infections 317
30 Tuberculosis and other mycobacterial diseases 326
31 Infections in immunocompromised patients, including HIV/AIDS 338
32 Viral infections 347
33 Management of HIV infection 357
34 Treatment of chronic viral hepatitis 364
35 Parasitic disease 373
36 The development and marketing of antimicrobial drugs 384
Appendix: Recommendations for Further Reading 397
Index 403
List of abbreviations
5FC flucytosine EMA European Medicines Agency
AASLD American Association for the Study of EoT end of treatment
Liver Disease EoTR end of treatment response
ACT artemisinin combination treatment ESAC European Surveillance of Antibiotic
ADR adverse drug reaction Consumption
AIDS acquired immune deficiency syndrome ESBL extended spectrum β-lactamases
ALT, alanine aminotransferase EVR early virological response
ASA American Society of Anesthesiologists FDA Food and Drug Administration
ATC anatomical therapeutic chemical G6PD glucose-6-phosphate
AZT azidothymidine (Zidovudine) dehydrogenase
BAN British Approved Name GABA gamma-amino butyric acid
BARDA Biomedical Advanced Research and GAIN Generating Antibiotic Incentives
Development Authority Now
BNF British National Formulary GRE glycopeptide-resistant enterococci
BNFC children’s version of the British HAART highly active antiretroviral
National Formulary therapy
cART combination antiretroviral therapy HBsAg hepatitis B surface antigen
CDC Centers for Disease Control HBV hepatitis B virus
CDI Clostridium difficile infection HCV hepatitis C virus
cEVR complete early virological response HHV-6 human herpesvirus 6
CMV cytomegalovirus HIV human immunodeficiency virus
COPD chronic obstructive pulmonary disease HLA human leukocyte antigen
CRB carbapenem-resistant bacteria HPV human papillomavirus
CRP C-reactive protein HSE herpes simplex virus encephalitis
CSF cerebrospinal fluid IDU idoxuridine
CSM Committee on Safety of Medicines IE infective endocarditis
DAA directly acting antivirals IFN interferon
DDD defined daily dose IGRA interferon-γ release assay
DEET diethyltoluamide IL interleukin
DHPG dihydroxypropoxymethylguanine IL-28B interleukin-28B
DNA pol DNA polymerase IMI Innovative Medicines Initiative
DRM drug resistance mutation INN International Non-Proprietary
Name (specified)IRES internal
EASL European Association for the Study of
ribosomal entry site
the Liver
IRIS immune reconstitution
EBV Epstein–Barr virus
inflammatory syndrome
ECDC European Centre for Disease
IV intravenous
Prevention and Control
IVOST intravenous to oral switch therapy
EDTA ethylenediaminetetraacetic acid
LRTI lower respiratory tract infections
eGFR estimated glomerular filtration rate
LVM lamivudine
EIA enzyme immunoassay
x LIST OF ABBREVIATIONS
MALDI-TOF matrix-assisted laser desorption/ pEVR partial early virological response
ionization time of flight PJI prosthetic joint infection
MDR-TB multidrug-resistant tuberculosis PI protease inhibitor
MERS-CoV Middle East respiratory syndrome PICC p eripherally inserted central
coronavirus catheters
MIC minimum inhibitory concentration PPD purified protein derivative
MHRA Medicines and Healthcare Products PVL Panton–Vallentine leukocidin (toxin)
Regulatory Agency
QIDP qualified infectious disease product
MIR magnetic resonance imaging
rINN r ecommended International Non-
miR-122 microRNA-122 Proprietary Name
MMR measles, mumps, and rubella RR relapser-responder
(vaccination)
rRNA ribosomal RNA
mRNA messenger RNA
RSV respiratory syncytial virus
MRSA methicillin-resistant Staphylococcus
RT reverse transcriptase
aureus
RTI reverse transcriptase inhibitors
MSM men who have sex with men
RV ribavirin
MSQ mental state questionnaire
RVR rapid virological response
NA neuraminidase
SAB Staphylococcus aureus bacteraemia
NANBH non-A non-B hepatitis
SARS-CoV severe acute respiratory syndrome
NCR non-coding region
ScRAP S cottish Reduction in Antimicrobial
NICE National Institute for Health and
Prescribing
Clinical Excellence
SIRS s ystemic inflammatory response
NNIS National Nosocomial Infections
syndrome
Surveillance
SNP single nucleotide polymorphism
NNRTI non-nucleoside analogue reverse
transcriptase inhibitor SVR sustained virological response
NR non-response SVR12 s ustained virological response
determined at 12 weeks after the end
NRTI nucleos(t)ide analogue reverse
of treatment
transcriptase inhibitor
SVR24 s ustained virological response
NSAID non-steroidal anti-inflammatory
determined at 24 weeks after the end
drug
of treatment
OPAT outpatient parenteral antimicrobial
TB tuberculosis
therapy
TESSy The European Surveillance System
ORF open reading frame
TK thymidine kinase
ORION O utbreak Reports and Intervention
studies Of Nosocomial (infection) USAN U nited States Adopted NameVRE
vancomycin-resistant enterococcal
PAS para-aminosalicylic acid
VZV varicella-zoster virus
PBP penicillin-binding protein
WHO World Health Organization
PCR polymerase chain reaction
XDR extensively drug resistant
PEG pegylated interferon
XDR-TB extensively drug-resistant tuberculosis
PEP post-exposure prophylaxis