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 Microbiology

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Nuts & Bolts
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Key Concepts of
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Microbiology & Infection

3rd Edition
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Dr David Garner
BM MSc MRCPCH FRCPath
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 Table of Contents

Abbreviations 9

Basic Concepts 15
What is Infection? Infection vs. Colonisation vs. Contamination ............... 16
Source of Infection: Endogenous vs. Exogenous .................................... 18
Bacteraemia vs. Septicaemia ............................................................... 18
Types of Infectious Microorganisms ...................................................... 19
The Anatomy of a Bacterium ............................................................... 20
What is Normal Flora and why is it Important? ...................................... 21
Circumstances Affecting Normal Flora ................................................... 22
How Antibiotic Prescribing Influences Normal Flora and the Ward

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Environment ..................................................................................... 23
Bacterial Flora in a Normal Person in the Community.............................. 24

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Bacterial Flora in a Normal Person in a Hospital or Long-term Care
Facility.............................................................................................. 25
Significance of Bacteria in the Bloodstream (Bacteraemia) ...................... 26
Diagnosing Infection: History .............................................................. 28
Diagnosing Infection: Examination and Non-Microbiological
Investigations.................................................................................... 29
Immunodeficiency States .................................................................... 31

Microbiology
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How to Take Microbiology Specimens ................................................... 34
Why Bother Completing Request Forms? ............................................... 36
33

What is Relevant Information for a Request Form? ................................. 36

Considerations When Contacting a Microbiologist for Advice .................... 37
A to Z of Microbiology Tests by Microorganism or Condition..................... 38
A to Z of Microbiology Tests by Specimen Type...................................... 50
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Microbiology Results (by Specimen Type).............................................. 54
How to Interpret Microbiology Results - Bacteriology .............................. 56
Examples of Bacteriology Requests, Results and Interpretations .............. 58
Why Can’t I Do Every Test? ................................................................. 60
Examples of Pre and Post-test Probability Results and
Interpretations .................................................................................. 62
How to Use Pre-test Probability, Likelihood Ratios and Post-test
Probabilities in the Clinical Setting........................................................ 64
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Basic Bacterial Identification by Microscopy ........................................... 65

Basic Bacterial Identification................................................................ 68
Table of Bacterial Causes of Infection ................................................... 70
How to Interpret Microbiology Results – Serology and Virology ................ 74
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Examples of Serology / Virology Requests, Results and

Interpretations .................................................................................. 75
Notifiable Infectious Diseases in the UK ................................................ 76
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Infection Control 77
What is Infection Control? ................................................................... 78
Root Cause Analysis (RCA) .................................................................. 78
Example of the RCA Process - A patient gets CDAD ................................ 79
Universal Precautions and Hand Hygiene............................................... 80
Personal Protective Equipment (PPE) .................................................... 81
Summary of Isolation Priority and Infection Control Precautions .............. 82
Influenza .......................................................................................... 84
Tuberculosis (TB) ............................................................................... 85
Multidrug Resistant Tuberculosis (MDR TB) ........................................... 86
Respiratory Spread Viral and Bacterial Infections ................................... 87
Clostridium difficile Associated Disease (CDAD) ..................................... 88
How Clostridium difficile can Spread in a Ward Environment .................... 90
 Diarrhoea and Vomiting (D&V) ............................................................ 91
Multiple Antibiotic Resistant Gram-negative Bacteria .............................. 92
New Antibiotics for Treating Resistant Gram-negative Bacteria ................ 95
Meticillin Resistant Staphylococcus aureus (MRSA) ................................. 96
Panton-Valentine Leukocidin (PVL) Positive Staphylococcus aureus .......... 98
Glycopeptide Resistant Enterococcus (GRE) ..........................................100
Viral Haemorrhagic Fever (VHF)..........................................................102
Needlestick Injuries...........................................................................107
Needlestick Injury HIV PEP Flowchart ..................................................110
Outbreaks ........................................................................................111

Clinical Scenarios 113

What do Junior Doctors need to be able to do? .....................................114

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Respiratory Infections 115

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Community Acquired Pneumonia (CAP)................................................116
Aspiration Pneumonia ........................................................................121
Hospital Acquired Pneumonia (HAP) ....................................................122
Ventilator Associated Pneumonia (VAP) ...............................................124
Infective Exacerbation of COPD ..........................................................125
Acute Bronchitis................................................................................126
Upper Respiratory Tract Infection (URTI) .............................................127
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Influenza .........................................................................................128
Tuberculosis (TB) ..............................................................................130
Multidrug Resistant TB (MDR TB) and Extensively Drug Resistant
TB (XDR TB).....................................................................................133

Head and Neck Infections 135

Otitis Media ......................................................................................136
Otitis Externa ...................................................................................137
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Orbital Cellulitis ................................................................................140
Sinusitis...........................................................................................141
Tonsillitis .........................................................................................142

Urogenital Infections 145

Urinary Tract Infection (UTI) ..............................................................146
Examples of Urology Requests, Results and Interpretations ....................150
Prostatitis ........................................................................................151
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Sexually Transmitted Diseases (STDs) .................................................152

Skin, Soft Tissue, Bone and Joint Infections 159

Cellulitis...........................................................................................160
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Bites ...............................................................................................162
Infected Burns, Skin Grafts and Post-Operative Wounds ........................164
Intravascular Device Associated Infection ............................................166
Osteomyelitis ...................................................................................168
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Septic Arthritis .................................................................................170

Gastrointestinal Infections 175

Gastroenteritis and Diarrhoea and Vomiting (D&V) ................................176
Clostridium difficile Associated Disease (CDAD) ....................................178
Necrotising Pancreatitis .....................................................................181
Cholecystitis and Cholangitis ..............................................................182
Peritonitis ........................................................................................184
Viral Hepatitis ...................................................................................186
Peptic Ulcer Disease ..........................................................................192
 Other Infections 193
Infective Endocarditis ........................................................................194
Pyrexia of Unknown Origin (PUO) ........................................................199
Rash Illness .....................................................................................202
Lyme Disease ...................................................................................204
Human Immunodeficiency Virus (HIV and AIDS) ...................................208
Fever in a Returned Traveller .............................................................212

Antibiotics 217
Antimicrobial Stewardship ..................................................................218
How Antibiotics Work - Mechanisms of Action .......................................219
How to Choose an Antibiotic ...............................................................220
Prophylaxis vs. Treatment ..................................................................222

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How to Prescribe an Antibiotic ............................................................222
The Daily Review of Antibiotic Therapy ................................................223

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Reasons for Failing Antibiotic Therapy..................................................224
Intravenous to Oral Switching of Antibiotics .........................................225
Therapeutic Drug Monitoring (TDM).....................................................226
Interpretation of TDM ........................................................................227
Antibiotic Dosing in Adult Renal Impairment .........................................231
Adjustment of Antibiotic Doses in Adult Renal Impairment .....................231
Antibiotic Dosing in Obesity ................................................................235
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What is Antibiotic Resistance? ............................................................237
How Resistance Occurs - Mechanisms of Resistance ..............................239
How is Antibiotic Resistance Spread? ...................................................240
How is Antibiotic Resistance Detected in the Laboratory? .......................241
Table of Antibiotic Spectrum of Activity ................................................244
Table of Antibiotic Tissue Penetration ..................................................248
Penicillins, Cephalosporins, Carbapenems and Aztreonam ......................250
Allergy to Beta-Lactam Antibiotics .......................................................254
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Trimethoprim and Co-Trimoxazole (Septrin).......................................256
Erythromycin, Clarithromycin, Azithromycin and Clindamycin .................258
Gentamicin, Amikacin and Tobramycin ................................................260
Ciprofloxacin and Levofloxacin ............................................................262
Vancomycin and Teicoplanin...............................................................264
Daptomycin......................................................................................266
Metronidazole ...................................................................................267
Doxycycline, Tigecycline and Tetracycline ............................................268
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Linezolid ..........................................................................................270
Rifampicin ........................................................................................271
Fusidic Acid ......................................................................................272
Colistin ............................................................................................273
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Chloramphenicol ...............................................................................274
Nitrofurantoin ...................................................................................276
Fidaxomicin ......................................................................................277
Fosfomycin.......................................................................................278
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Antimycobacterials ............................................................................280
Antifungals.......................................................................................285
Antivirals .........................................................................................288

Antibiotic Guidelines 291

Antibiotic Guidelines ..........................................................................292
Post-Splenectomy Antibiotic Guidelines................................................293
Adult Empirical Antibiotic Guidelines ....................................................294
Adult Empirical Antibiotic Guidelines Emergencies .................................306
Paediatric Empirical Antibiotic Guidelines .............................................308
Paediatric Empirical Antibiotic Guidelines Emergencies ...........................312
Paediatric Antibiotic Doses .................................................................314
Neonatal Empirical Antibiotic Guidelines ...............................................317
 Neonatal Empirical Antibiotic Guidelines Emergencies ............................317
Neonatal Antibiotic Doses...................................................................318

Emergencies 321
How to Recognise the Sick Patient ......................................................322
National Early Warning Score (NEWS) .................................................322
Paediatric Early Warning Score (PEWS)................................................323
Sepsis .............................................................................................324
Adult Sepsis “Golden-Hour” Management Flowchart ..............................327
Neutropaenic Sepsis and Febrile Neutropaenia ......................................328
Neutropaenic Sepsis Antibiotic Flowchart .............................................330
Toxic Shock Syndrome (TSS) .............................................................331
Meningitis ........................................................................................332

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Meningococcal Sepsis ........................................................................336
Initial Management of Bacterial Meningitis and Meningococcal

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Sepsis in Adults ................................................................................338
Initial Management of Bacterial Meningitis in Children ...........................339
Initial Management of Meningococcal Sepsis in Children.........................340
Encephalitis......................................................................................341
Epiglottitis........................................................................................344
Spinal Epidural Abscess .....................................................................345
Necrotising Fasciitis ...........................................................................346

Glossary
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Malaria ............................................................................................348

353

Appendix 1 Systematic Assessment of a Chest X-ray 356

Appendix 2 Bristol Stool Chart 356
Appendix 3 Name Changes for Common Bacteria, New and Old 357
Appendix 4 Zoonoses 358
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Index 359

Numbers & Notes 373

Sources of Information, Guidelines and Further Reading ........................374
Commonly Used 1st Line Antibiotics .....................................................376
Adult Sepsis “Golden-Hour” Management Flowchart ..............................377
Useful Telephone Numbers .................................................................378
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 Copyright © [2019] by [Dr David Philip Garner]
Published via IngramSpark by: J Garner. All rights reserved.
First published: 2013. Second edition: 2014. Third edition: 2019.
ISBN-13: 978-1-9160071-0-9
Hard work, artwork and front cover: J Garner
Editor Chief in Charge: J Garner

A clinically focused, no-nonsense pocket book to the key elements

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of microbiology and infection. A must-have guide to stop common

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and often unnecessary mistakes that occur in everyday medicine
and antibiotic prescribing.

Dedication
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To Jenny and the cat club who are still helping and hindering in equal measure
and using inappropriate terms in an untimely manner such as “that should be
straight-forward” and “it will be simple”!
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Disclaimer
The author and the publisher have made every effort to ensure that the
information is as accurate and up-to-date as possible (2019). Therefore,
except for any liability which cannot be excluded by law, neither the
publisher nor the author accept liability for damage of any nature
(including damage to property, personal injury or death) arising directly or
indirectly from the information in this book.
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If you like this book, recommend it to someone else. If you don’t,

then tell us why at...
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www.microbiologynutsandbolts.co.uk
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 Introduction

Microbiology Nuts & Bolts helps doctors and healthcare staff to confidently
identify the microorganisms causing an infection and understand how to treat
them. The book is set out by condition rather than microorganism allowing for
quick reference in a clinical setting. Readers regularly comment just how
amazing it is that so much information has been packed into such a small
book. It is not an all-encompassing reference text and is deliberately not
referenced extensively in order to keep its presentation simple. It is concise
enough to be of use on a daily basis, be it on a ward or in a clinic, yet detailed
enough to promote a thorough understanding of microorganisms, their
management and the treatment of patients. It has received fantastic feedback
in reviews by the Royal College of Physicians, the Royal College of Pathologists,

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the Royal Pharmaceutical Society, the Hospital Infection Society, the British
Society for Antimicrobial Chemotherapy, the Institute of Biomedical Science
and the Society for Applied Microbiology.

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The book is divided into six parts: Basic Concepts, Microbiology, Infection
Control, Clinical Scenarios, Antibiotics and Emergencies. It is best to read Basic
Concepts and Microbiology first, as this gives the building blocks to
understanding infection. After that, the Clinical Scenarios and Antibiotics
sections aid diagnosis and management of specific infections.
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Emergencies have been separated into their own section to ensure they can be
found quickly. Flowcharts help guide initial emergency treatment, which often
needs to be implemented immediately in order to save lives, although they are
not a replacement for experienced senior support. Infection Control does not
go into depth regarding policies and politics but gives practical advice about
preventing the spread of infections and what to do when you have too many
patients for the side rooms available.
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The previous editions were well received by doctors and healthcare staff and as
always their valuable feedback has been instrumental in shaping this, the
latest edition. Existing sections have been fully updated and new sections have
been added for acute bronchitis, necrotising pancreatitis and Lyme disease as
well as new antibiotics and updates for the management of sexually
transmitted infections and infection control precautions for viral haemorrhagic
fevers. The Emergencies section has undergone extensive revision to take into
account changes in UK national guidelines for the management of sepsis,
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meningitis, encephalitis and malaria. The size has also changed to

accommodate larger text but we hope it still remains small enough to be your
go to pocket book.

We have been asked many times why is there no App for Microbiology Nuts &
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Bolts? The short answer is that Apps are great at giving answers but less able
to “teach”, leading to healthcare staff blindly following algorithms and
proformas instead of understanding the fundamental principles of medicine...so
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no, there is no App!

The ultimate aim of the book is to empower doctors and healthcare staff to
manage patients with infections better; if it achieves this then it is a success.

P.S. Don’t forget to write a review on Amazon and like us on FaceBook where
you’ll find the latest edition of the Bug Blog.
 About the Author
The author has been described as a gifted teacher and educator,
who has an exceptional level of microbiology and infectious
diseases knowledge, with an even greater ability to translate that
knowledge so that others can also understand this often
complicated subject. His award-winning teaching is the highlight of
many medical students’ clinical attachments and as a result of his
dedication to the subject, many junior colleagues have been

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motivated and inspired to enter a career in Microbiology.

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He qualified from Southampton University Medical School in 1997
and has worked in diverse areas of medicine, general surgery,
emergency medicine and paediatrics. Now, as a Consultant Clinical
Microbiologist in a United Kingdom NHS hospital, he spends his
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days diagnosing, treating and managing infections as well as
teaching others how to do this safely and effectively.

Microbiology textbooks often considered by students to be dull and

contain long lists of boring bacterial names; they appear to have
little relevance to clinical medicine. The author recognised there
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was a need for a clinically-orientated no-nonsense microbiology

book, so he decided to get on and write one. The feedback has been
amazing, with both the first and second editions of Nuts & Bolts
regularly making the list of top 3 microbiology textbooks on
Amazon.co.uk. The website and accompanying Bug Blog are read
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worldwide by thousands of interested people every week and it is

clear that many of you out there really value “Nuts & Bolts”.

The author is ever grateful for your continuing support.

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www.microbiologynutsandbolts.co.uk
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 What is Infection? Infection vs. Colonisation vs. Contamination

Infection is the presence of microorganisms causing damage to body tissues,

usually in the presence of acute inflammation (pain, swelling, redness, heat
and loss of function). For example Staphylococcus aureus on intact skin does
not cause a problem; it is the normal flora for skin. However, if you cut your
skin, Staphylococcus aureus can cause infection in the cut with associated
inflammation and tissue damage.

Microorganisms can also cause damage in the absence of inflammation but it is

unusual, e.g. in neutropaenic patients with angio-invasive fungal infections
causing tissue infarction.

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Colonisation describes when bacteria grow on body sites exposed to the
environment, without causing infection. This is a normal process. These

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bacteria may form part of the normal flora of the individual; however
colonisation is not necessarily normal flora. Occasionally, bacteria which are
not normally regarded as part of the normal flora can also colonise body areas
e.g. Pseudomonas spp. in a wound is not normal flora of the skin or a wound
but it is not actually causing tissue damage or infection; it is just growing in
the warm wet conditions of the wound. Pseudomonas spp. are the normal flora
of warm wet places. Likewise, some prosthetic devices can also become
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colonised with bacteria without causing infection e.g. urinary catheters.

Colonisation does not normally harm the patient and does not usually need
treating with antibiotics e.g. Neisseria meningitidis can be found in up to 30%
of the healthy population in their oropharynx. However, infection can result in
harm and often needs treatment with antibiotics e.g. if Neisseria meningitidis
enters the bloodstream from the oropharynx to cause septicaemia, then it
needs urgent treatment.
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Examples of colonisation
Body Site or
Bacterial Colonisation
Prosthetic Device
• Skin flora e.g. Staphylococcus spp.
Pressure sores • Enteric flora e.g. Enterococcus spp.,
Escherichia coli, Pseudomonas spp.
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• Skin flora e.g. Staphylococcus spp.

Breaks in the skin e.g.
• Enteric flora e.g. Enterococcus spp.,
wounds
Escherichia coli, Pseudomonas spp.
• Mixed enteric flora in patients given
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antibiotics or who have been in healthcare

Upper respiratory tract settings for more than 4 days e.g.
Enterococcus spp., Escherichia coli,
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Pseudomonas spp.
• Enteric flora e.g. Enterococcus spp.,
Urinary catheter
Escherichia coli, Pseudomonas spp.
• Mixed enteric flora in patients given
Endotracheal tube
antibiotics or who have been in healthcare
OR
settings for more than 4 days e.g.
Tracheostomy tube in a
Enterococcus spp., Escherichia coli,
ventilated patient
Pseudomonas spp.

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 Warning
In the absence of good clinical information on request forms (see section
– Microbiology, Why Bother Completing Request Forms?) microbiology
laboratories are unable to distinguish between colonisation and infection
and so will just report the presence of bacteria. It is then up to the
clinician to decide if these bacteria are causing infection.

Better filled in request forms lead to better clinical advice from

microbiology services.

Contamination is the presence of a microorganism that has been introduced

into a microbiology sample from an external source e.g. poor technique when

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taking the sample, a swab touching a surface before being used, sneezing over
a patient whilst they provide a sputum sample. Contamination can also occur
when a sample is not collected correctly and the patients “normal flora”

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(microorganisms growing in their normal environment) gets into the sample
e.g. urine taken incorrectly can contact perineal skin and pick up the “normal
microorganisms” which then grow in the laboratory (the presence of epithelial
cells in the urine sample indicates definite contact with skin and therefore a
risk of contamination).
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 Source of Infection: Endogenous vs. Exogenous

It is important to understand how infections arise in patients in order to

manage them appropriately.

Endogenous infections are caused when the patient’s own bacterial flora gets
into a site it should not be in. This is responsible for about 85% of all
infections. Knowledge of the patient’s normal flora aids the management of
these types of infections. For example, pneumonia tends to be caused by
bacteria from the URT; knowing what the normal flora of the URT is allows
prediction of the antibiotics necessary to treat pneumonia.

Exogenous infections are much less frequent than endogenous and occur

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when the patient acquires a microorganism that directly invades and causes
disease. Knowledge of methods of transmission aids the management of

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outbreaks of these types of infections. For example, knowing that Norovirus is
transmitted by the faecal-oral route allows the precautions of hand hygiene,
individual toilets, isolation of infected patients and environmental cleaning to
be implemented to prevent transmission and control outbreaks.

Bacteraemia vs. Septicaemia

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Many healthcare professionals use the terms bacteraemia and septicaemia to
mean the same thing, however they are different. Bacteraemia is the
presence of bacteria in blood. Septicaemia is the presence of bacteria in blood
PLUS clinical features of sepsis e.g. temperature >38.3°C or <36°C, heart
rate >90bpm, respiratory rate >20 bpm, WBC <4x109/L or >12x109/L, blood
glucose >7.7mmol/L or altered mental state (see section – Emergencies,
Sepsis). WARNING: patients can be septic without being septicaemic if they
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have the clinical features of sepsis but do not have bacteria in their blood.

A patient can be bacteraemic without being septicaemic BUT cannot be

septicaemic without being bacteraemic.

Bacteraemia may be:

• Significant causing the patients infection or indicating where the infection is
occurring e.g. E. coli in pyelonephritis, Staphylococcus aureus in cellulitis or
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Alpha-haemolytic Streptococcus spp. in infective endocarditis

• Non-significant a contaminant in the specimen (e.g. coagulase-negative
Staphylococcus spp. from skin) or temporarily in the blood from another
site, known as “translocation” e.g. bacteria can be pushed into blood by
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simply brushing your teeth (Alpha-haemolytic Streptococcus spp.), grazing

your leg (coryneform bacteria) or squeezing a big spot (Staphylococcus
aureus). None of these are a “problem” as the body “deals” with them and
“clears” the blood
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BUT the examples use the same bacteria! How do you know if they are
significant or not? Answer: do they have the clinical features of the infection?
E.g. Staphylococcus aureus in cellulitis presents with a hot, red, swollen leg
whereas non-significant bacteraemia has no symptoms or signs, the test was
just done at an opportune moment to “catch” the presence of, or be
contaminated by, the bacteria.

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 Types of Infectious Microorganisms

Bacteria
Bacteria are free-living single cell microorganisms with no cell nucleus. Their
genes are found on chromosomes, free within the cell cytoplasm. They
reproduce by cell division to create identical daughter cells (clonal expansion).
Bacteria are widely spread throughout the environment with only a small
number causing human disease. There are approximately 15,000 times more
bacteria on 1 human, than humans on the earth. You can see them with a light
microscope in a laboratory. Examples: Staphylococcus aureus, Escherichia coli,
Listeria monocytogenes.

Viruses

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Viruses are small microorganisms consisting of genetic elements surrounded
by a protein coat. They cannot self-replicate. Viruses invade other cells and

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use their host’s reproductive mechanism to replicate. They are too small to be
seen with a light microscope and can only be seen with an electron
microscope. Examples: Varicella Zoster Virus (VZV), Influenza Virus,
Rhinovirus.

Parasites
Parasites are organisms that grow on, feed off and are sheltered by another
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living organism but which contribute nothing to the survival of that organism.
They are often multi-cellular and relatively large compared to bacteria and
viruses. All are visible with a light microscope but some are large enough to
see with the naked eye. A female Ascaris roundworm can be up to 30cm long.
They usually reproduce by sexual reproduction. Examples: Plasmodium
falciparum (malaria), Giardia lamblia, Ascaris lumbricoides.

Fungi
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Fungi are multi-cellular organisms with eukaryotic DNA and a chitinous cell
wall. They feed on organic matter and produce spores which can survive for
long periods of time in the environment. These spores aid the spread of the
fungi. Fungi are usually bigger than bacteria and are visible with a light
microscope and occasionally with the naked eye. They usually reproduce by
sexual reproduction. Examples: Candida albicans, Aspergillus spp., Mucor spp.
(Zygomycetes).
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Prions
Prions are infectious proteins folded in an abnormal way. When they enter
another cell they cause all the similar proteins to refold in the abnormal
fashion resulting in disease. They are very rare and not considered further in
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this book. Examples: Creutzfeldt Jakob Disease (CJD), Kuru, Bovine

Spongiform Encephalopathy (BSE).
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 The Anatomy of a Bacterium

Bacteria are the most common microorganisms treated with specific

antibiotics. Antibiotics have different mechanisms of action related to which
part of the bacterium they act upon; therefore it is helpful to know the basic
anatomy of a bacterium.

Flagella
The mechanism
by which bacteria
“swim”
Chromosome

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The main genetic material
of bacteria

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Cell Membrane
The flexible coat found
outside the cell wall in
Gram-negative bacteria

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The rigid structure
that maintains the
integrity of bacteria
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Cytoplasm
The jelly
interior of
bacteria
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Plasmid
A mobile genetic element
which can pass on DNA Ribosome
that can produce proteins The site of protein
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associated with synthesis

resistance, but is not in
itself a mechanism of
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resistance

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 What is Normal Flora and why is it Important?

Normal flora is the community of microorganisms that live on another living

organism (human or animal) or inanimate object without causing disease. The
human body is not sterile; we become colonised with bacteria from the
moment we are born. We are covered with, and contain within our intestines,
approximately one hundred trillion (1014) bacteria that form the normal flora of
our bodies. This normal flora helps prevent us being colonised with dangerous
bacteria, which might lead to infection.

Microbiome is the term for a community of normal microorganisms.

Dysbiosis is the term for the disruption of the microbiome, removing normal
microorganisms or the growth of abnormal microorganisms.

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Many circumstances can change normal flora. For example, the normal flora of
the human body begins to change after admission to a hospital or long-term

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care facility. The process usually begins around day 4 of admission; this is why
after 4 days of admission the antibiotics for hospital acquired infections
change. It is not because the severity of the illness is different.

Knowledge of the normal flora of the human body allows:

• Prediction of the pathogens causing infection as bacteria tend to grow in
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specific body sites e.g. Streptococcus pneumoniae from the upper
respiratory tract causing pneumonia or Staphylococcus aureus from the skin
causing intravenous cannula infections
• Investigation for underlying abnormalities in specific areas of the body when
bacteria are isolated from normally sterile sites e.g. Escherichia coli isolation
from blood cultures indicates probable intra-abdominal pathology as E. coli is
part of the normal gastrointestinal flora, or growth of an Alpha-haemolytic
Streptococcus sp. in blood cultures may indicate infective endocarditis as a
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result of poor dentition as Alpha-haemolytic Streptococcus spp. are part of
the normal mouth flora

Nothing is 100% accurate but knowing where bacteria normally live can help
work out when they are in the wrong place. This allows predictions of the likely
causes of disease and hence the choice of suitable antibiotics for empirical
therapy. Knowing which factors affect normal flora allows predictions to be
made as to what the flora will become under the influence of those factors,
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e.g. exposure to antibiotics removes sensitive bacteria, so if a patient with a

cut hand, and a sensitive Staphylococcus aureus (MSSA) in their normal flora,
is given Flucloxacillin for the cut, a void will be left behind which could be filled
by a Flucloxacillin resistant bacterium such as Meticillin resistant
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Staphylococcus aureus (MRSA).

Myth
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Bacteria have no place in our environment. FALSE - Bacteria are part of

the normal environment. Almost everything has its own normal flora.
Hospitals, the community, soil, animals, air conditioning units and
swimming pools all have their own “normal flora”. However, certain things
like surgical instruments and synovial fluid should be sterile. If something
contains its normal flora it is normal; if it grows something else’s normal
flora e.g. synovial fluid grows skin flora, it is abnormal. Knowing where
normal flora comes from allows you to identify the likely cause of infection
or know where to investigate.

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 How to Take Microbiology Specimens

Aseptic Technique
Aseptic technique is a procedure that is designed to minimise contamination.
Microbiology samples should be taken aseptically to prevent contamination
with bacteria e.g. if you take blood cultures without aseptic technique it is
likely that the result will be a skin contaminant rather than the cause of the
infection.

Examples of techniques to minimise the risk of contamination:

• Blood cultures and CSF - clean the skin with 2% Chlorhexidine and wear
gloves
• Midstream urine specimen (MSU) - part the labia or retract the foreskin, void

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the first part of the urine stream (10-20mls at least) and then collect the
next portion (approx. 10-20mls)

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• Wound swabs - remove slough (which is dead and detached tissue and is not
a sign of infection), debride the wound to reveal the fresh tissue beneath,
swab the fresh tissue
• Sputum - ask patients to cough sputum immediately into the specimen
container rather than holding it in the mouth whilst looking for a container

Sample Before Treatment

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If safe to do so, take microbiology samples before starting antibiotics
otherwise those antibiotics may inhibit the growth of bacteria, causing negative
cultures.

Blood Cultures First

Always take blood cultures before any other blood samples because other
blood sample collection bottles are not necessarily sterile and can therefore
contaminate the blood culture collection kit. This will lead to contaminated
ew
blood cultures, known as pseudobacteraemia.

Aerobic Bottle First

Take the aerobic bottle before the anaerobic bottle in case there is not enough
blood for both bottles e.g. if the needle comes out of the patient’s arm. You are
more likely to diagnose infection from the aerobic blood culture bottle because
more pathogenic bacteria grow in this type of bottle than the anaerobic bottle.
vi

Cerebrospinal Fluid
Do not forget to take a sample for peripheral blood glucose, at the same time
as CSF protein and CSF glucose. The glucose levels need to be compared and
therefore done at the same time. As glucose levels vary, if peripheral blood
e

glucose is forgotten you will not be able to take the sample later as the
comparison will not be valid. The comparison allows a distinction to be made
between bacterial meningitis and other causes of meningitis (see section –
Emergencies, Meningitis).
Pr

Avoid a Quick Swab

If possible send pus or tissue rather than swabs because pus and tissue can be
Gram stained allowing recognition of bacteria or fungi that are present but
which have failed to grow on culture.

34
 Hints and Tips
What’s the difference between cultures and Gram stains? Microscopy
includes any investigation using a microscope, including the Gram stain.
Culture is whatever grows after incubation e.g. on the agar plate. They
are not necessarily the same; antibiotics can inhibit growth in culture,
microorganisms may not grow fast enough or may have specific growth
requirements that prevent them being cultured even though they can be
seen on microscopy. Therefore microscopy may give a more complete
view whereas culture may not. Culture, however, will give the
microorganisms names and provide antibiotic sensitivities. Microscopy,
Culture and Sensitivities are often abbreviated to MC&S.

s
For example: At the time of appendicectomy the patient is on
Cefuroxime and Metronidazole. The intra-abdominal pus sample is sent to

ge
the laboratory, the result later shows:

Result
Specimen Pus
Appearance -
Gram-positive cocci in chains
Microscopy

Culture
Pa
Gram-negative bacilli
Yeasts
Enterococcus faecium
- Amoxicillin resistant
- Vancomycin sensitive

The microscopy shows a mixture of bowel flora, but the Enterococcus

faecium is the only bacterium that grows on culture because it is
ew
inherently resistant to Cefuroxime and Metronidazole. The yeast may not
have had sufficient time to grow on culture. It would be a mistake to only
treat the Enterococcus faecium as the microscopy clearly shows the
presence of other bowel flora.
vie
Pr

35
 A to Z of Microbiology Tests by Microorganism or Condition

Information is based upon a District General Hospital laboratory service.

Microorganism
Test Sample Container
or Condition

NPA
See Tests by
Sputum
Adenovirus PCR Specimen Type
BAL
Table
Stool

Galacto- Red or yellow

s
Serum
mannan vacutainer
Aspergillus spp.

ge
(1,3)-Beta-d- Red or yellow
Serum
glucan vacutainer

IgM Red or yellow

Bartonella spp. Serum
IgG vacutainer

Red or yellow
IgG
Pa Serum
vacutainer
Bordetella
pertussis
Culture Pernasal swab Pernasal swab
(Whooping
cough)
PCR NPA Sterile universal
ew
PCR CSF Sterile universal
Borrelia
burgdorferi
(Lyme disease)
Red or yellow
ELISA Serum
vacutainer

IgM Red or yellow

Brucella spp. Serum
vi

IgG vacutainer

(1,3)-Beta-d- Red or yellow

Candida spp. Serum
glucan vacutainer
e

Clostridium Blue stool

Toxin Stool
difficile toxin container
Pr

Red/Orange
Chlamydia spp. PCR Swab
Chlamydia swab

Coxiella burnetii IgM Red or yellow

Serum
(Q fever) IgG vacutainer

38
 Laboratories may vary slightly, if in doubt check with your local service.

Turnaround Time from Lab

Minimum Volume Required
Receipt

See Tests by Specimen Type

10 days
Table

s
1 tube 7 days

ge
1 tube 7 days

1 tube 14 days

1 tube Pa 10 days

1 swab Up to 7 days

7 days
2-5mls
Note: all +ves are phoned out

2-5 days
ew
0.5-1ml
Note: all +ves are phoned out

3 days
1 tube (+ve samples sent to Ref Lab for
confirmation)

1 tube 10 days
vi

1 tube 7 days
e

5ml 1 day
Pr

Eyes - 2 swabs (1 per eye)

3 days
Genital - 1 swab

1 tube 21 days

39
 Examples of Bacteriology Requests, Results and Interpretations

Clinical Details on the request form:

Right upper quadrant pain, fever and jaundice
Result
Specimen Blood culture
Appearance -
Microscopy Gram-negative bacilli
Escherichia coli
Culture - Amoxicillin sensitive
- Gentamicin sensitive

s
How is this Interpreted?
The Gram-negative bacillus identifies as E. coli. E. coli is normal flora for
the gut; finding it in a blood culture indicates a significant infection below

ge
the diaphragm, probably involving either the urinary tract or a
gastrointestinal tract related structure. In the clinical details (above) the
patient has Charcot’s triad (fever, RUQ pain and jaundice) indicating a
probable diagnosis of cholangitis (infection of the biliary tract).
Appropriate antibiotics have been provided for treatment.

Result
Specimen Sputum
Pa
Clinical Details on the request form:
Cough and shortness of breath

Appearance Salivary
Microscopy Gram-negative bacilli
ew
Culture Escherichia coli
How is this Interpreted?
The salivary appearance of the sample indicates that it has been held in
the mouth and is likely to be contaminated with upper respiratory tract
bacteria. The Gram-negative bacillus E. coli is not a common cause of
LRTI, but is a common URT bacterium in hospitalised patients. This result
therefore indicates URT contamination, not infection, and the E. coli does
not need treating. No antibiotics have been released to discourage
vi

unnecessary prescribing.

Clinical Details on the request form:

Acutely hot, painful, swollen knee
e

Result
Specimen Synovial fluid
Appearance Turbid
Pr

Microscopy Gram-positive cocci in clumps

Staphylococcus aureus
Culture - Flucloxacillin sensitive
- Fusidic Acid sensitive
How is this Interpreted?
The presence of Gram-positive cocci in clumps on microscopy is significant
as synovial fluid should be sterile. The identification of Staphylococcus
aureus confirms the diagnosis of septic arthritis. The patient should
normally be treated with IV Flucloxacillin and PO Fusidic Acid.

58
 Clinical Details on the request form:
Acute confusion in an elderly patient
Result
Specimen Urine
Appearance -
WBCs <10x106/L
Microscopy
Epithelial cells ++
Culture Pseudomonas aeruginosa
How is this Interpreted?
The culture result cannot be interpreted without first assessing whether a
UTI is likely from the microscopy. The absence of white blood cells
(<10x106/L) shows there is no evidence of inflammation in the urinary

s
tract. However, there is evidence that the urine has been in contact with
the skin of the perineum (presence of epithelial cells). Pseudomonas

ge
aeruginosa represents contamination from the perineum and not infection.
In addition, Pseudomonas spp. are not common causes of UTI except in
the presence of a urinary catheter. Seek another reason for the confusion.

Clinical Details on the request form:

Left iliac fossa pain, diverticular abscess found at laparotomy
Result
Specimen
Appearance

Microscopy
Pus
-
Pa
Gram-negative bacilli
Gram-positive cocci in chains
Klebsiella pneumoniae
- Amoxicillin resistant
Culture - Co-amoxiclav sensitive
ew
Enterococcus faecalis
- Amoxicillin sensitive
How is this Interpreted?
The bacteria seen on microscopy are consistent with what has grown on
culture, mixed bowel flora, and in keeping with the diagnosis of a
diverticular abscess. There will be anaerobes present in a diverticular
abscess because they make up most of the bowel flora, however they
have not grown as they do not survive in air (anaerobes) and therefore
vi

are difficult to transport alive to the laboratory. This patient will need
treatment with an antibiotic active against anaerobes, as well as the
bacteria cultured.
e

Clinical Details on the request form:

Returned traveller, diarrhoea 2 weeks
Result
Pr

Specimen Stool
Appearance Liquid
Microscopy Giardia lamblia oocysts seen
Salmonella, Shigella, Campylobacter and E.
Culture
coli O157 not isolated
How is this Interpreted?
No bacterial cause for the diarrhoea has been found. However, the history
of travel has prompted the laboratory to look for parasites which has
diagnosed giardiasis. There are no antibiotics given under culture as the
microorganism has been seen not grown (you cannot grow a parasite).
The treatment of giardiasis is PO Metronidazole. If the travel history had
not been mentioned, the diagnosis would not have been made.

59
 Table of Bacterial Causes of Infection

 = Common Cause − = Not a Common cause

Gram-positive Bacteria

Anaero-

Beta-haemolytic Streptococcus
Staphylococcus aureus (MRSA)
Staphylococcus aureus (MSSA)

Streptococcus pneumoniae

Listeria monocytogenes

Clostridium perfringens
Clinical

Enterococcus faecium
Enterococcus faecalis
Coagulase Negative
Scenarios

Clostridium difficile
Staphylococcus

s
(A, B, C, G)

ge
Respiratory Infections
Community Acquired 1 − − − − −  − − −
Pneumonia (CAP)
Hospital Acquired
Pneumonia (HAP)
Ventilator Associated
Pneumonia (VAP)






Pa −

−
−

−
−

−
−

−



−

−
−

−
−

Aspiration Pneumonia  − − − − −  − − −
Exacerbation of COPD  − − − − −  − − −
Acute Bronchitis − − − − − − − − − −
ew

Head and Neck Infections

Otitis Media − − − − − −  − − −
Otitis Externa  − −  − − − − − −
Orbital Cellulitis  − −  − −  − − −
Sinusitis  − −  − −  − − −
vi

Urogenital Infections
Urinary Tract
− − − − − − − − − −
Infection (UTI)
Prostatitis − − − − − − − − − −
e

STDs − − − − − − − − − −
Skin, Soft Tissue, Bone and Joint Infections
Pr

Cellulitis   −  − − − − − −
Cellulitis in Diabetes &   −  − − − −  −
Vascular Insufficiency
Bites  − −  − − − −  −
Burns, Skin Grafts,   −  − − − −  −
Post-Operative
Intravenous Device   − − − − − − − −
Associated Infection
Osteomyelitis   −  − − − − − −
Septic Arthritis   −  − − − − − −

70
 ? = Uncommon Cause OR only under specific circumstances (see notes)
Gram-negative Bacteria

bes Non-Culturable

ESBL-positive Escherichia coli

Pseudomonas aeruginosa

Mycoplasma pneumoniae
Haemophilus influenzae

Legionella pneumophila
Neisseria gonorrhoeae
Neisseria meningitidis

Moraxella catarrhalis
Enterobacteriaceae
Bacteroides fragilis

Chlamydia spp.
Escherichia coli

s
ge
− − −  − − − − −   

−
−

−
−

−



?2


Pa ?2








−

−
−

−
−

−
−

 − −     − − − − −
− − −  − − − −  − − −
− − − − − − − − − − − −
ew

− − −  − − − − − − − −
− − − − − − − − − − − −
− − − − − − − − − − − −
 − −  − − − − − − − −
vi

− − − −    ?3 − − − −

− − − −    ?3 − − − −
e

− −  − − − − − − − − 
Pr

− − − − − − − − − − − −

 − − −  −   − − − −

 − −  − − − − − − − −

 − − −  −   − − − −

− − − − − − ?4 ?4 − − − −

− − − − ?5 − ?5 − − − − −
− − − − ?5 − ?5 − − − − −

71
 Clostridium difficile Associated Disease (CDAD)

The bacterium Clostridium difficile was reclassified in 2016 to Clostridioides

difficile but as this has not yet become mainstream this book will continue to
use the old name. It is the most common cause of antibiotic associated
diarrhoea. It spreads very readily in the hospital environment unless infection
control measures are put in place. Clinical features of Clostridium difficile
Associated Disease (CDAD) range from asymptomatic carriage through to
diarrhoea, toxic megacolon and death.

Mode of Transmission
• Faecal-oral spread
• Clostridium difficile can survive for long periods of time in the environment

s
as spores which, if not removed, can then infect new patients

ge
Incubation Period
• Unknown
• Symptoms can occur at any time after prescribing antibiotics, however
usually 5-10 days

Period of Communicability
• Patients should remain in isolation until 48 hours after symptoms resolve

Best Practice Control Measures

Pa
Where possible avoid the use of antibiotics which
are regarded as particularly predisposing to
CDAD – the “4Cs”
• Cephalosporins
Careful antibiotic
• Ciprofloxacin and other quinolones
prescribing
ew
• Clindamycin
• Co-amoxiclav
Reduced Ciprofloxacin usage was the main driver
for decreasing CDAD in the UK
Hand hygiene With soap and water, alcohol gel is NOT effective
See section – Infection Control, Personal
PPE Protective Equipment
Remove ALL PPE before leaving room
vi

Isolation Side room preferably with own toilet facility

Environmental Deep cleaning of the clinical area daily and after
decontamination patient is discharged
e

Accurate recording of symptoms

Stool sample for Clostridium difficile toxin testing
Do not prescribe anti-motility agents
Pr

If patients require investigations in other

Patient care
departments, inform those departments of
patient’s condition in advance
Patient should be last on a list and deep cleaning
commence after patient’s departure

88
 Myth
Antibiotics cause CDAD. FALSE - Antibiotics do not cause CDAD they only
predispose to CDAD. If a patient does not come into contact with
Clostridium difficile bacteria the patient will not get CDAD even if they
have many predisposing factors (e.g. over 65 years old, cancer, bowel
surgery, previous antibiotics, nasojejunal tubes, Proton Pump Inhibitors,
hospitalisation or living in a long-term care facility). Eradicating
Clostridium difficile from the environment by good cleaning practices is of
fundamental importance in the control of CDAD.

The attitude that certain antibiotics should be avoided at all cost so as to

avoid CDAD is potentially dangerous. The correct antibiotic for the

s
infection should be given whilst being aware of the risk of predisposing to
CDAD. For example, an elderly patient with urosepsis who is allergic to
Penicillin, the doctors don’t want to use Ciprofloxacin as it predisposes to

ge
CDAD and don’t like using Gentamicin because it can cause renal failure.
As a result they choose a seemingly random antibiotic such as
Teicoplanin...Why? This is like putting diesel in a petrol car...it is simply
wrong. The antibiotic needs to be active against the causative
microorganism and able to penetrate the infected site.

Pa
Teicoplanin is probably the worst possible choice because it has no activity
against the common causes of urosepsis and therefore the patient may
die as a result of avoiding the use of Ciprofloxacin for fear of causing
CDAD infection. Interestingly, doctors don’t worry about prescribing
Ceftriaxone for meningitis even though this antibiotic also predisposes to
CDAD.

Don’t select the wrong antibiotic for the infection the patient
ew
currently has because you are worried they may acquire another
infection in the future.

Warning
In order to try and reduce the incidence of CDAD, hospitals are restricting
the use of high risk predisposing antibiotics. As a result there is an
increasing reliance on a small pool of antibiotics to treat a broad range of
infections. The heavy use of these antibiotics is leading to increasing
vi

bacterial resistance. For example, an empirical guideline that uses a lot of

Beta-lactam-Beta-lactamase inhibitor combinations (Co-amoxiclav and
Piptazobactam) leads to increased numbers of infections with AmpC and
ESBL-positive bacteria.
e

The increased rates of resistant bacteria mean an over reliance on

carbapenem antibiotics (e.g. Meropenem); this has led to a rapid rise in
Pr

carbapenemase producing Enterobacteriaceae. Not only are there no new

antibiotics becoming available to treat these resistant bacteria,
carbapenems also predispose to CDAD. Ultimately CDAD rates will
increase while our ability to treat resistant infections decreases.

The current strategy of restricting antibiotics is storing up a problem for

the future. Restrictive antibiotic guidelines put a strong selective pressure
on bacteria that are far better at evolving than humans. Controlling CDAD
in the environment may be a better long-term solution even though this
proves harder to implement.

89
 How Clostridium difficile can Spread in a Ward Environment

Doctor A examines Doctor A correctly gives

Patient W and diagnoses CDAD. Ciprofloxacin to Patient Z. Patient
He wrongly uses alcohol gel to Z acquires Clostridium difficile
clean his hands (alcohol gel does spores from the environment,
not kill spores ). Doctor A which exploit the niche left by
should have used soap and water Ciprofloxacin leading to Patient Z
and isolated patient W developing CDAD

Patient Z is in renal
Patient W has CDAD failure, has a catheter
associated UTI with

s
but is not isolated in a
side room Pseudomonas and a
severe Penicillin allergy

ge
Doctor B’s Patient
Pa Doctor B’s Patient

Doctor A transmits a few Doctor A does not transmit

Clostridium difficile spores to Clostridium difficile spores to
ew
Patient X via his hands but Patient Y. Even though Patient
there is no niche for the spores Y is on predisposing antibiotics
to exploit. Patient X is at risk of they do not develop CDAD
becoming a carrier of because they have not acquired
Clostridium difficile the bacteria

Patient Y with
Patient X with
vi

community acquired
asthma is examined,
pneumonia is on Co-
there is no need for
amoxiclav and
antibiotics
Clarithromycin
e

Doctor A washes his hands

at the sink with soap and
Pr

water removing the

Clostridium difficile spores

The development of CDAD is often multi-factorial and there are many

predisposing factors but ultimately the patient has to acquire the
bacterium Clostridium difficile before they can develop CDAD or become a
carrier of Clostridium difficile.

The root cause for CDAD in Patient Z is failure to isolate

Patient W in a side room NOT the antibiotic Ciprofloxacin

90
 Diarrhoea and Vomiting (D&V)

Diarrhoea and vomiting is not a common cause of mortality amongst most

people, however the old and frail or immunodeficient can die. The
microorganisms that cause diarrhoea and vomiting are so infectious they easily
spread around healthcare settings unless precautions are taken. The majority
of cases are caused by viruses such as Norovirus and Rotavirus.

Mode of Transmission
• Faecal-oral spread. In a patient with Norovirus each gram of stool contains
approximately 10-100 million infectious doses of virus

Incubation Period

s
• Norovirus - 24-48 hours • Rotavirus - 24-72 hours

ge
Period of Communicability
• Up to 48 hours after symptoms resolve
• Virus is often still detectable at low levels in stool after symptoms resolve, so
ongoing effective hand hygiene is essential

Best Practice Control Measures

Hand hygiene

PPE
Pa
With soap and water, alcohol gel is NOT effective
See section – Infection Control, Personal Protective
Equipment
Remove ALL PPE before leaving room
Isolation Side room preferably with own toilet facility
Only after advice from the Infection Control Team
Ward closure (ICT) and only if insufficient number of side rooms to
ew
isolate cases
If ward closed, access to ward for essential staff only
Staffing Symptomatic staff must not return to work until 48
hours after last episode of diarrhoea or vomiting
Environmental Deep cleaning of the clinical area daily and after
decontamination patient is discharged
vi

Accurate recording of symptoms

Stool sample for testing under advice from ICT
Do not prescribe anti-motility agents
If patients require investigations in other
Patient care
departments, inform those departments of patient’s
e

condition in advance
Patient should be last on a list and deep cleaning
commence after patient’s departure
Pr

Hints and Tips

Even with the very best cleaning regimens, a patient with diarrhoea will put
their normal gastrointestinal flora into the environment whatever the cause
of their diarrhoea. This can include Enterobacteriaceae, Enterococcus spp.
and Pseudomonas spp. even though these are not causes of diarrhoea. If
patients with diarrhoea due to the same cause (e.g. Norovirus or CDAD)
were kept together in the same clinical area (cohorted) transfer of normal
gastrointestinal flora will occur between patients. If one patient has
antibiotic resistant bacteria in their normal flora e.g. GRE, then all cohorted
patients will eventually acquire the antibiotic resistant bacteria. Therefore
cohorting patients should be avoided, source isolation is best practice.
91
 Ventilator Associated Pneumonia (VAP)

Ventilator associated pneumonia (VAP) is pneumonia developing >48 hours

after implementing endotracheal intubation or mechanical ventilation, which
was not present before intubation.

Clinical Features
• Patient mechanically ventilated for ≥ 48 hours PLUS
• New or worsening pulmonary infiltrates on chest X-ray PLUS
• Raised WBC PLUS
• Growth of a pathogenic bacterium at significant levels from a lower
respiratory tract sample (aspiration or BAL)

s
Causes
• Staphylococcus aureus (MSSA and MRSA)

ge
• Streptococcus pneumoniae
• Haemophilus influenzae
Common
• Pseudomonas spp.
• Enterobacteriaceae e.g. Escherichia coli, Klebsiella
spp., Enterobacter spp., Serratia marcescens

Investigations Pa
• Endotracheal secretions – culture and sensitivity indicates what a patient is
colonised with, not necessarily what is causing the infection
• Bronchoalveolar lavage (BAL) - either directed or non-directed, bypassing
upper respiratory tract flora, sampling directly from the lung
• Blood cultures – if systemic signs of infection

Treatment
1st line IV Piptazobactam
ew

nd st IV Teicoplanin OR IV Vancomycin
2 line (if 1 line
PLUS
contraindicated)
IV Ciprofloxacin
If MRSA positive ADD IV Teicoplanin OR IV Vancomycin

Total Duration
vi

5-7 days

Dosing
See section - Antibiotics, Empirical Antibiotic Guidelines.
e

Warning
Critical Care Units may have problems with specific bacteria, e.g.
Acinetobacter spp., so be aware of your own unit’s guidelines.
Pr

Prognosis and Complications

25-75% mortality depending on underlying co-morbidities and infection with
antibiotic resistant bacteria.

Prophylaxis and Prevention

• Regular suctioning of pooled secretions in upper respiratory tract
• Sterile water for mouth washes
• Effective hand hygiene

124
 Infective Exacerbation of COPD

Infective exacerbation of COPD is the term used for worsening respiratory

function in patients known to have chronic obstructive pulmonary disease
(COPD).

Clinical Features
• Increasing shortness of breath
• Increasingly purulent sputum
• Increasing amount of sputum
• Chest X-ray DOES NOT show changes indicative of pneumonia; if it does
then treat for pneumonia not infective exacerbation of COPD

s
Causes
• Respiratory Syncytial Virus (RSV)

ge
• Rhinovirus
Viral • Influenza Virus
• Parainfluenza Virus
• Adenovirus
• Streptococcus pneumoniae
• Staphylococcus aureus
Bacterial

Investigations
•
•
Pa
Haemophilus influenzae
Moraxella catarrhalis

• Sputum culture may help identify the causative microorganism, but may
only isolate upper respiratory tract normal flora

Treatment
ew

1st line PO Amoxicillin

2nd line (if 1st line
PO Clarithromycin OR PO Doxycycline
contraindicated)

Total Duration
5-7 days
vi

Dosing
See section - Antibiotics, Empirical Antibiotic Guidelines.

Prognosis and Complications

e

Most patients get better with treatment.

Prophylaxis and Prevention

Prophylactic antibiotics should be avoided; although they may reduce the
Pr

frequency of exacerbations ultimately they tend to lead to increasingly

resistant bacteria within the patient’s normal flora. This results in increasingly
difficult-to-treat infections with a higher mortality.

125
 Antimicrobial Stewardship

It is widely acknowledged that 50% of antibiotic prescriptions are

inappropriate; meaning that the antibiotic is incorrect for the condition, the
dose is wrong or infection is not the actual diagnosis, therefore antibiotics are
not the correct management. Global antibiotic resistance is becoming
increasingly prevalent and worryingly the world faces a post-antibiotic era
where there are no longer antibiotics to treat common infections.

Antimicrobial stewardship is the response to the increasing misuse of

antibiotics. It promotes the use of the right antibiotic, at the right dose, route
and duration, for the right infection at the right time in order to improve
patient care whilst reducing antibiotic resistance. At the forefront of this fight

s
are Antimicrobial Pharmacists; specialist clinical pharmacists who help optimise
antibiotic use within hospitals and the community.

ge
Common Mistakes in prescribing antibiotics
• Using antibiotics that do not cover the causes of the infection
• Unnecessary use of broad-spectrum (or narrow-spectrum) antibiotics
• Prescribing antibiotics where there is no evidence of infection
• Unnecessarily long courses of antibiotics
• Incorrect dosing Pa
• Overuse of intravenous antibiotics
• Delaying antibiotics in the critically ill
• Failing to modify antibiotic treatments when microbiology results are
available

The Role of the Antimicrobial Pharmacist involves:

• Expert advice regarding antibiotic usage in specific individual patients in
ew
conjunction with Microbiologists or Infectious Diseases Physicians
• Participation in Route Cause Analysis (RCA) for cases of Healthcare
Associated Infections e.g. Clostridium difficile Associated Disease and MRSA
bacteraemias
• Educating healthcare staff about prudent antibiotic usage
• Developing evidence-based guidelines for:
­ Empirical antibiotic treatment and surgical prophylaxis
­ Restricted antibiotics which specifically require the approval of a
vi

Microbiologist or Infectious Diseases Physician before their use

­ Intravenous to oral switching to reduce the unnecessary use of IV
antibiotics
­ Stop and review to reduce unnecessarily long courses of antibiotics
• Providing clinical tools such as antibiotic drug charts to facilitate compliance
e

with guidelines
• Surveillance and audit of antibiotic usage to ensure compliance with
guidelines
Pr

• Antibiotic formulary decision-making and horizon-scanning for information

about new antibiotics
• Representation at Infection Prevention and Control Committees and
Antibiotic Steering Groups (sub-committees of Hospital Drug and
Therapeutic Committees)

218
 How Antibiotics Work - Mechanisms of Action

Essentially there are only 5 basic mechanisms of action or sites where the
antibiotic works, either in the bacterium’s cytoplasm, on its chromosome, at its
cell membrane, on its ribosome or its cell wall. The flagella and plasmid have
no role in antibiotic mechanisms of action.

1. Cytoplasm 2. Chromosome
• Nitroimidazoles (e.g. • Diaminopyramidines (e.g.
Metronidazole) produce Trimethoprim) interfere with folic acid
oxygen free radicals which synthesis
damage proteins and DNA • Quinolones (e.g. Ciprofloxacin,
• Lipopeptides (e.g. Levofloxacin) inhibit DNA coiling

s
Daptomycin) depolarise cell • Rifampicin and Fidaxomicin inhibit RNA
membranes inside the cell polymerase

ge
• Nitrofurantoin’s actual mechanism is
unknown but it causes direct damage
to DNA

3. Cell Membrane
Pa • Polymyxin (e.g.
Colistin) binds to
phospholipids
disrupting the cell
membrane
ew

4. Ribosome
vi

• Macrolides and Lincosamides

(e.g. Erythromycin, Clarithromycin,
Azithromycin, Clindamycin) prevent
protein elongation and inhibit ribosome
formation
e

5. Cell Wall
• Aminoglycosides (e.g. Gentamicin,
• Beta-Lactams (e.g.
Amikacin, Tobramycin) interfere with
Penicillins,
translation and protein formation
Cephalosporins,
Pr

• Tetracyclines and Glycylcyclines (e.g.

Carbapenems) inhibit cell
Doxycycline, Tigecycline) prevent
wall formation
protein synthesis
• Glycopeptides
• Oxazolidinones (e.g. Linezolid) prevent
(Vancomycin,
ribosome formation
Teicoplanin) prevent
• Fusidic Acid blocks elongation factor G,
peptidoglycan cross-
preventing protein formation
linkage
• Chloramphenicol inhibits protein
• Fosfomycin blocks
synthesis
peptidoglycan synthesis
• Nitrofurantoin’s actual mechanism is
unknown but it interferes with
translation
219
 How to Choose an Antibiotic

Before deciding whether to prescribe an antibiotic there are a number of things

to consider and questions to ask. Firstly:
• Make sure you know normal flora and the causes of common infections
• Know your speciality’s serious and common infections, the microorganisms
that cause these and the usual treatments for them
• Use the British National Formulary (BNF) for interactions, cautions and
contraindications as well as dosing information
• Discuss patients with your own senior team members and Consultant
• Know your own hospital’s empirical antibiotic guidelines for your specialty

Empirical antibiotic guidelines are established by answering many of the

s
questions below. It is essential to understand the relevance of these questions
and the effect of the answers. Relying on empirical antibiotic guidelines without

ge
knowing why or how these guidelines are produced can be dangerous and is
poor practice.

Questions to ask:
There are many non-infectious reasons for
“signs of infections”

Does the patient have an

infection?
Pa
• Fever caused by drugs, malignancy,
connective tissue disorders
• Increased CRP caused by inflammation,
malignancy, connective tissue disorders
• Chest crackles caused by heart failure,
pulmonary fibrosis
• Pyuria caused by appendicitis, connective
tissue disorders, malignancy
ew
If the patient has an
Urine, respiratory tract, skin, bone, joint,
infection what is the
heart, CNS etc.…
likely source?
What are the likely
causative Viruses, bacteria, fungi, parasites
microorganisms?
Does the patient need an • Viral infections are usually self-limiting
vi

antibiotic or is the • Urethral syndrome and gastroenteritis do

infection self-limiting? not usually require antibiotics
There is often time to make a diagnosis before
starting treatment HOWEVER certain
e

infections require immediate management

without waiting for investigations:
• Sepsis
Does the patient need
Pr

• Neutropaenic sepsis
urgent treatment or is
• Meningitis
there time to make a
• Meningococcal sepsis
diagnosis?
• Encephalitis
• Epiglottitis
• Spinal epidural abscess
• Necrotising fasciitis
• Toxic shock syndrome
Is the antibiotic active See section
against the ­ Antibiotics, Table of Antibiotic Spectrum
microorganisms? of Activity

220
 See section
Does the antibiotic get
­ Antibiotics, Table of Antibiotic Tissue
into the site of infection?
Penetration
Does the patient need a
Immunodeficient patients require bactericidal
bactericidal antibiotic or
antibiotics because they are unable to fight
is bacteriostatic
infections themselves
adequate?
• DO NOT use oral antibiotics to treat
systemic infections if patients are unable to
What route of absorb from the gastrointestinal tract
administration should be • Antibiotics with good oral bioavailability
used? rarely need to be given intravenously (see

s
section – Antibiotics, for individual antibiotic
agents)

ge
• Patients in renal failure may need doses of
antibiotics reducing
• Patients over 60-70kg may need increased
How much antibiotic
doses of antibiotics as normal doses are
should be prescribed?
calculated for previously normal body size
(see section – Antibiotics, Antibiotic Dosing
Pa
in Obesity)
• DO NOT use any Beta-lactam antibiotics if
the patient has a history of severe penicillin
allergy
• Many antibiotics interact with Methotrexate
Are there any e.g. Trimethoprim, Ciprofloxacin,
contraindications or Doxycycline
cautions for prescribing • Many antibiotics are contraindicated in
ew
this antibiotic? myasthenia gravis e.g. macrolides,
quinolones, aminoglycosides, Colistin
• Always check the BNF for interactions,
cautions and contraindications as well as
dosing information
See section
What are the side effects
­ Antibiotics, for individual antibiotic agents
of this antibiotic?
vi

• Always check the BNF for side effects

• Septic patients should be reviewed within 1
hour of starting treatment
When should the patient • Daily review of ALL patients on antibiotics
e

be reviewed? • Don’t forget “stop and review” dates as

these help prevent over-treatment and
CDAD
Pr

See sections
When can I switch from
­ Clinical Scenarios, for individual
IV to oral, and how long
conditions
should I treat the patient
­ Antibiotics, IV to Oral Switching of
for?
Antibiotics
Once the cause is known, antibiotics should be
Do the results of the
narrowed down to cover the specific
microbiology
microorganisms identified e.g. CAP caused by
investigations identify a
Streptococcus pneumoniae can be treated
specific causative
with Penicillin rather than Co-amoxiclav and
microorganism?
Clarithromycin

221
 Table of Antibiotic Spectrum of Activity
 = Usually sensitive − = usually resistant OR inappropriate therapy
Gram-positive Bacteria
Anaero-

Staphylococcus aureus (MRSA)

Staphylococcus aureus (MSSA)

Beta-haemolytic Streptococcus

Streptococcus pneumoniae

Listeria monocytogenes

Clostridium perfringens
Enterococcus faecium
Enterococcus faecalis
Antibiotic

Coagulase Negative

Clostridium difficile
Staphylococcus

s
(A, B, C, G)

ge
Penicillins
Benzylpenicillin − − −   −    −
Amoxicillin /
− − −   −    −
Ampicillin
Co-amoxiclav
Flucloxacillin
Temocillin


−
−
−
−
Pa −
?
−


−

−
−
−
−
−


−
−
−
−

−
−
−
−
−
Pivmecillinam
− − − − − − − − − −
Hydrochloride
Piptazobactam  − −   −  −  −
ew
Cephalosporins
Cefradine  − ?  − −  − − −
Cefalexin  − ?  − −  − − −
Cefuroxime  − ?  − −  − − −
Ceftriaxone /  − −  − −  − − −
Cefotaxime
Ceftazidime − − − − − − − − − −
vi

Ceftazidime +
− − − − − − − − − −
Avibactam
Ceftolozane +
− − − − − − − − − −
Tazobactam
e

Ceftaroline     − −  −  −
Carbapenems
Pr

Ertapenem  − −   −  −  −
Meropenem  − −   −    −
Diaminopyramidines
Trimethoprim ? ? − − − − − − − −
Macrolides and Lincosamides
Erythromycin  ? −  − −  − − −
Clarithromycin  ? −  − −  − − −
Azithromycin  − −  − −  − − −
Clindamycin  ? −  − −  −  −

244
 ? = Variable sensitivity P = Prophylaxis only
Gram-negative Bacteria
bes Non-Culturable

ESBL-positive Escherichia coli

Pseudomonas aeruginosa

Mycoplasma pneumoniae
Haemophilus influenzae

Legionella pneumophila
Neisseria gonorrhoeae
Neisseria meningitidis

Moraxella catarrhalis
Enterobacteriaceae
Bacteroides fragilis

Chlamydia spp.
Escherichia coli

s
ge
−  ? − − − − − − − − −

−  ? ? ? − − − − − − −


−
−
−
−
−
?
−
−

−


−

Pa −
−

?1
−

−
−
−

−

−
−
−
−
−
−
−
−
−

− − − −    − − − − −

 − −   − 1   − − −
ew

− − − −  − − − − − − −
− − − −  − − − − − − −
− − −   − ? −  − − −

−     − 2 −  − − −

− − −   − 2   − − −
vi

− − −  6 6 6 6  − − −

− − −    −   − − −
e

− − −   − 2 −  − − −
Pr

 − −     −  − − −
  −       − − −

− − − ?  −  − − − − −

− − − − − − − −    
− − − − − − − −    
− − − − − − − −    
 − − − − − − −  − − −

245
 Adult Empirical Antibiotic Guidelines

Respiratory Infections 1st Line Antibiotic

PO Amoxicillin 500mg-1g TDS

Community Acquired
PLUS
Pneumonia (CAP)
PO Clarithromycin 500mg BD
(CURB-65 score 0-2)
(If Nil By Mouth use IV)

s
IV Co-amoxiclav 1.2g TDS
PLUS
Community Acquired
IV Clarithromycin 500mg BD
Pneumonia (CAP)

ge
(CURB-65 score 3-5)
If MRSA ADD IV Teicoplanin 400mg BD for 3
doses THEN OD (or 6mg/kg if >70kg)

Community Acquired
Aspiration Pneumonia
Pa
IV Co-amoxiclav 1.2g TDS

If MRSA ADD IV Teicoplanin 400mg BD for 3

doses THEN OD (or 6mg/kg if >70kg)
ew
Hospital Acquired IV Co-amoxiclav 1.2g TDS
Pneumonia (HAP)
(Onset 2-4 days after If MRSA ADD IV Teicoplanin 400mg BD for 3
admission) doses THEN OD (or 6mg/kg if >70kg)

Hospital Acquired IV Piptazobactam 4.5g TDS

Pneumonia (HAP)
vi

(Onset ≥4 days after If MRSA ADD IV Teicoplanin 400mg BD for 3

admission) doses THEN OD (or 6mg/kg if >70kg)
e

IV Piptazobactam 4.5g TDS

Hospital Acquired
Pr

Aspiration Pneumonia If MRSA ADD IV Teicoplanin 400mg BD for 3

doses THEN OD (or 6mg/kg if >70kg)

IV Piptazobactam 4.5g TDS

Ventilator Associated
Pneumonia (VAP) If MRSA ADD IV Teicoplanin 400mg BD for 3
doses THEN OD (or 6mg/kg if >70kg)

294
 2nd line Antibiotic Oral Treatment
Duration
(if 1st line contraindicated) (when appropriate)

PO Doxycycline 200mg stat

THEN 100mg OD
OR As for 1st and 2nd line 5-7 days
PO Levofloxacin 500mg BD
(If Nil By Mouth use IV)
PO Co-amoxiclav
625mg TDS

s
IV Teicoplanin 400mg BD for 3
PLUS
doses THEN OD (or 6mg/kg if
PO Clarithromycin
>70kg)
500mg BD 7 days

ge
PLUS
PO Levofloxacin 500mg BD
OR
(If Nil By Mouth use IV)
PO Levofloxacin
500mg BD
IV Teicoplanin 400mg BD for 3
doses THEN OD (or 6mg/kg if
>70kg)
PLUS
IV Ciprofloxacin 400mg BD-
TDS
Pa
PO Co-amoxiclav
625mg TDS
5-7 days

AND IV Metronidazole 500mg

TDS

IV Teicoplanin 400mg BD for 3

ew

doses THEN OD (or 6mg/kg if

PO Co-amoxiclav
>70kg) 5-7 days
625mg TDS
PLUS
PO Levofloxacin 500mg BD
IV Teicoplanin 400mg BD for 3
doses THEN OD (or 6mg/kg if PO Co-amoxiclav
>70kg) 625mg TDS
vi

5-7 days
PLUS depending on culture
IV Ciprofloxacin 400mg BD- results
TDS
IV Teicoplanin 400mg BD for 3
e

doses THEN OD (or 6mg/kg if

>70kg) PO Co-amoxiclav
PLUS 625mg TDS
5-7 days
Pr

IV Ciprofloxacin 400mg BD- depending on culture

TDS results
AND IV Metronidazole 500mg
TDS
IV Teicoplanin 400mg BD for 3
doses THEN OD (or 6mg/kg if
>70kg)
No oral treatment 5-7 days
PLUS
IV Ciprofloxacin 400mg BD-
TDS

295
 Sepsis

Sepsis is defined as life-threatening organ dysfunction caused by a

dysregulated host response to infection. Septic shock is sepsis with circulatory,
cellular or metabolic dysfunction, and has a high mortality.

Sepsis and septic shock are clinical diagnoses not laboratory diagnoses:
• Sepsis - infection with evidence of a systemic response to that infection e.g.
hypoxia, oliguria, confusion
• Septic shock - sepsis associated with organ dysfunction, hypoperfusion or
hypotension

Sepsis and septic shock are medical emergencies and early recognition

s
and treatment improve survival.

ge
Risk Factors for Sepsis
• Age <1 year or >75 years
• Frailty or comorbidities e.g. diabetes, renal failure, liver failure
• Trauma, surgery or other invasive procedure within 6 weeks
• Immunosuppression
• Intravascular device
• Breaches to skin integrity e.g. cuts, burns, blisters

Clinical Features
Pa
• Current or recent pregnancy (within 6 weeks)

Potential source of infection OR NEWS ≥4?

• Pneumonia • Meningitis • Skin/soft tissue infection

• Empyema • Infective • Bone/joint infection
• UTI endocarditis • Wound infection
ew
• Acute abdomen • CVC infection • Other

New signs or symptoms of infection? TWO or more of the

following:

• Temperature >38.3°C • Temperature <36°C

• Heart Rate >90bpm • Respiratory Rate >20 bpm
• WBC <4x109/L • WBC >12x109/L
vi

• Altered mental state • Blood glucose >7.7mmol/L

Evidence of organ dysfunction remote to the site of infection? ONE

of the following or SOFA ≥2 (see opposite):

• Lactate >2mmol/L • Bilateral pulmonary infiltrates

e

• Systolic blood pressure PLUS O2 required to keep O2

<90mmHg OR Mean arterial saturations >92%
pressure <65mmHg • Bilateral pulmonary infiltrates
Pr

• Systolic blood pressure PLUS PaO2/FiO2 ratio <300*

>40mmHg below baseline • Bilirubin >34 mmol/L
• Creatinine >175mmol/L OR • Coagulopathy INR >1.5 OR APTT
urine output 0.5ml/kg/hour for >60 seconds
more than 2 hours • Platelet count <100x109/L

If YES to questions 1 +2 + 3 = criteria for SEPSIS

Note: *PaO2 measured in mmHg (1kPa = 7.5mmHg), FiO2 as % converted into a
decimal e.g. 32% = 0.32

Adapted from: Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis
and Septic Shock www.survivingsepsis.org

324
 Treatment
Antibiotics should be given within 1 hour of the diagnosis of sepsis
(see section – Emergencies, Adult Sepsis “Golden-Hour” Management
Flowchart)

Adults
IV Piptazobactam
1st line PLUS
IV Gentamicin
IV Teicoplanin OR IV Vancomycin
PLUS
2nd line (if 1st line
IV Gentamicin

s
contraindicated)
PLUS
IV Metronidazole

ge
If previous ESBL
IV Meropenem
or
PLUS
AmpC positive
IV Gentamicin
bacteria
If MRSA positive ADD IV Teicoplanin OR IV Vancomycin
Pa
In addition to antibiotics a source of sepsis should be identified and managed
as soon as possible e.g. removal of infected CVC, drainage of abscess, repair of
perforated abdominal viscus.

For Children (see section – Emergencies, Initial Management of

Meningococcal Sepsis in Children)
ew
Children
IV Cefotaxime
1st line PLUS
IV Gentamicin
IV Chloramphenicol
2nd line (if 1st line
PLUS
contraindicated)
IV Gentamicin
vi

Total Duration
7-10 days
Unless a causative microorganism or focus of infection requires longer
treatment e.g. Staphylococcus aureus bacteraemia, listeriosis or meningitis
e

(see section – Antibiotics, Adult Empirical Antibiotic Guidelines)

Dosing
Pr

See section - Antibiotics, Empirical Antibiotic Guidelines Emergencies.

Warning - Prognosis and Complications

Mortality in sepsis increases if adequate antibiotic treatment is delayed:
• Septic shock - mortality increases by 7% per hour for the first 6 hours
that treatment is not adequate
• Sepsis without shock – mortality increases 1-1.5% per hour for the first
6 hours that treatment is not adequate

326
 Adult Sepsis “Golden-Hour” Management Flowchart

Call for senior support immediately

+/- Critical Care

Give high flow 02

First Hour of Surviving Sepsis - “The Golden Hour”

Aim for SaO2 >94%

(88-92% if risk of CO2 retention)

s
Fluid resuscitate
If hypotensive or lactate >2mmol/L

ge
Target
Systolic blood pressure >90mmHg
MABP ≥65mmHg
Lactate <2mmol/L

Administer
Pa
500ml stat OR 30ml/kg IV crystalloid to run
over 3 hours

Monitor
Lactate
Urine output
ew

Blood Cultures
Take 2 sets of blood cultures
(at least 1 set peripherally)

DO NOT unnecessarily delay antibiotics

vi

Antibiotics
Give antibiotics within 1hour of diagnosing
sepsis

Warning
e

Delaying antibiotics in the first 6 hours

increases mortality
Pr

Evaluate for focus of infection

Implement source control if possible e.g.
drainage of abscess

Further Treatment
Treat as per the management plan from
seniors or critical care or
www.survivingsepsis.org

327
 Sequential Organ Failure Assessment Score (SOFA)
Score
Parameter 0 1 2 3 4
<200 with <100 with
PaO2/FiO2
≥400 <400 <300 respiratory respiratory
mmHg
support support
Platelets
≥150 <150 <100 <50 <20
X 109/L
Bilirubin
<20 20-32 33-101 102-204 >204
µmol/L
Dopamine

s
Dopamine <5
Dopamine 5.1-15
OR
MABP MABP <5 OR
Cardiovascular Epinephrine
≥70 <70 OR Epinephrine

ge
status* OR
mmHg mmHg Dobutamine OR
Norepinephrine
any dose Norepinephrine
>0.1
≤0.1
Glasgow
15 13-14 10-12 6-9 <6
Coma Scale
Creatinine
µmol/L
or
Urine output
ml/day
110 110-170Pa 171-299 300-440

<500
>440

<200

Note: *Inotrope doses are in µg/kg/min

Warning
ew
If vasopressors (e.g. Norepinephrine) are required to keep MABP
≥65mmHg AND Lactate >2mmol/L despite fluid resuscitation then the
patient has SEPTIC SHOCK

Hints and Tips

Use the abbreviated qSOFA (quick Sepsis-Related Organ Failure
Assessment) to quickly assess sepsis severity, if ≥2 there is an increased
risk of death or prolonged ICU stay. Take action!
vi

• Respiratory rate ≥22/min

• Altered mental status
• Systolic blood pressure ≤100mmHg
e

Causes
• Staphylococcus aureus
• Group A Beta-haemolytic Streptococcus
Pr

• Enterobacteriaceae e.g. Escherichia coli, Klebsiella

Common
spp., Enterobacter spp.,
• Pseudomonas spp.
• Neisseria meningitidis

Investigations
• Blood cultures
• Urine for microscopy, culture and sensitivity if able
• Do not unduly delay treatment as mortality increases

325
Pr
ev
ie
w
Pa
ge
s