Contents
Cover
Series
Title Page
Copyright
About the Author
Preface
Chapter 1: How to search for evidence
1.1 Obstacles to searching for evidence
1.2 Sources of evidence
1.3 Statistical terms and explanations
1.4 Useful websites
References
Chapter 2: Epidemiology
2.1 Incidence and mortality
2.2 Pathogenesis
2.3 Outcome of neonatal infection
2.4 Prevention of neonatal infections
References
Chapter 3: Clinical manifestations
3.1 Fever or hypothermia
3.2 Meconium
3.3 Jaundice
3.4 Rash
3.5 Respiratory signs or symptoms
References
Chapter 4: Laboratory tests
4.1 Microbiology
4.2 Rapid tests for sepsis
4.3 Haematologic tests
4.4 Biochemical and immunologic tests
4.5 Molecular assays
4.6 Proteomics and gene expression profiling
References
Chapter 5: Rational antibiotic use
5.1 Choice of antibiotics for suspected early-onset sepsis
5.2 Prophylactic antibiotics
5.3 Which babies to treat?
5.4 Common clinical scenarios
5.5 Duration of antibiotics
References
Chapter 6: Adjunctive treatment
6.1 Resuscitation
6.2 Intravenous immunoglobulin
6.3 Granulocyte transfusions
6.4 Colony-stimulating factors
6.5 Exchange transfusion
6.6 Activated protein C
6.7 Pentoxifylline
6.8 Lactoferrin
6.9 Melatonin
6.10 Central line removal: if and when to pull the line
6.11 Prophylactic antimicrobials
References
Chapter 7: Bacterial meningitis
7.1 Epidemiology
7.2 Pathogenesis
7.3 Organisms
7.4 Clinical manifestations
7.5 Diagnosis
7.6 Antibiotic therapy
7.7 Repeat lumbar punctures
7.8 Neuroimaging
7.9 Dexamethasone
7.10 Shunt infections
References
Chapter 8: Respiratory tract infections
8.1 Pneumonia
8.2 Otitis media
References
Chapter 9: Osteomyelitis and septic arthritis
9.1 Epidemiology
9.2 Pathogenesis
9.3 Clinical
9.4 Organisms
9.5 Diagnosis
9.6 Treatment
9.7 Prognosis
References
Chapter 10: Urinary tract infections
10.1 Epidemiology
10.2 Pathogenesis
10.3 Clinical
10.4 Laboratory
10.5 Radiology
10.6 Treatment
10.7 Prevention
References
Chapter 11: Necrotizing enterocolitis and gastrointestinal infections
11.1 Necrotizing enterocolitis
11.2 Neonatal diarrhoeal infections
11.3 Peritonitis
References
Chapter 12: Eye infections
12.1 Conjunctivitis
12.2 Endophthalmitis
12.3 Nasolacrimal duct obstruction and dacryocystitis
12.4 Orbital abscess
References
Chapter 13: Skin and soft tissue infections
13.1 Host and environmental factors
13.2 Organism factors
13.3 Epidemiology
13.4 Clinical manifestations
References
Chapter 14: Bacterial infections
14.1 Gram-positive cocci
14.2 Gram-negative bacilli
14.3 Gram-positive bacilli
14.4 Gram-negative cocci
14.5 Anaerobes
References
Chapter 15: Mycoplasmas
15.1 Microbiology
15.2 Epidemiology
15.3 Chorioamnionitis
15.4 Ureaplasmas and respiratory distress syndrome
15.5 Ureaplasmas, Mycoplasmas and neonatal pneumonia
15.6 Ureaplasmas and chronic lung disease of prematurity
15.7 Mycoplasma hominis, Ureaplasma and central nervous system infection
15.8 Treatment of Mycoplasma or Ureaplasma
15.9 Prevention
References
Chapter 16: Fungal infections
16.1 Epidemiology
16.2 Microbiology
16.3 Clinical features of Candida infections
16.4 Diagnosis
16.5 Treatment
16.6 Outcome
16.7 Prevention
16.8 Malassezia
16.9 Pichia
16.10 Zygomycosis
References
Chapter 17: Viral infections
17.1 Cytomegalovirus
17.2 Herpes simplex virus
17.3 Varicella zoster virus
17.4 Rubella
17.5 Enteroviruses
17.6 HIV
17.7 Parvovirus B19
17.8 Respiratory viral infections
Useful Websites
References
Chapter 18: Other congenital infections
18.1 Tuberculosis
18.2 Toxoplasmosis
18.3 Syphilis
18.4 Tetanus
18.5 Malaria
18.6 Hemophagocytic lymphohistiocytosis
Useful Websites
References
Chapter 19: Breast milk
19.1 Mechanisms of defence against infection
19.2 Prevention of infection
19.3 Prevention of necrotizing enterocolitis
19.4 Transmission of infection through human breast milk
19.5 Breast milk expression
19.6 Human breast milk banks
19.7 Accidental breast milk exposure
19.8 Antimicrobials in breast milk
Useful websites
References
Chapter 20: Surveillance
20.1 Surveillance cultures
20.2 Sepsis surveillance
20.3 Antibiotic surveillance
References
Chapter 21: Infection control
21.1 Infection control programmes
21.2 Standard precautions
21.3 Transmission-based precautions
21.4 Environmental and workforce issues
21.5 Outbreak management
21.6 Outbreaks due to non-fermentative Gram-negative bacilli
21.7 Outbreaks due to Enterobacteriaceae
21.8 Outbreaks due to Staphylococcus aureus
21.9 Outbreaks due to vancomycin-resistant enterococci
21.10 Bordetella pertussis
21.11 Mycobacterium tuberculosis
21.12 Herpes simplex virus infection
21.13 Varicella zoster virus infection
References
Chapter 22: Developing countries
22.1 Antenatal care
22.2 Birth
22.3 Community-based interventions
22.4 Pathogens
22.5 Antibiotics
22.6 Cost-effectiveness
22.7 Feasibility
References
Chapter 23: Prevention of neonatal infections
23.1 Feeding-related interventions
23.2 Infection control measures
23.3 Physical interventions
23.4 Immunomodulatory interventions
23.5 Immunization
23.6 Prophylactic antibiotics
23.7 Maternal antibiotics for pre-term rupture of membranes
References
Chapter 24: Neonatal antimicrobials
24.1 Penicillins
24.2 Cephalosporins
24.3 Aztreonam
24.4 Carbapenems
24.5 Glycopeptides
24.6 Linezolid
24.7 Daptomycin
24.8 Macrolides and lincosamides
24.9 Aminoglycosides
24.10 Quinolones
24.11 Metronidazole
24.12 Rifampin (rifampicin)
24.13 Antifungals
24.14 Trimethoprim– sulfamethoxazole (cotrimoxazole)
24.15 Chloramphenicol
References
Index
Website: Evidence-Based Medicine Series
The Evidence-Based Medicine Series has a website at:
www.evidencebasedseries.com
Where you can find:
How to access the companion sites with additional resources and updates:
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Library of Congress Cataloging-in-Publication Data
Isaacs, David, 1950– author.
Evidence-based neonatal infections / David Isaacs.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-0-470-65460-6 (pbk.)
I. Title.
[DNLM: 1. Communicable Diseases–Handbooks. 2. Infant, Newborn, Diseases–therapy–Handbooks. 3. Evidence-Based Medicine–Handbooks. WS 39]
RJ254
618.92′01–dc23
2013026696
A catalogue record for this book is available from the British Library.
Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books.
Cover design by Meaden Creative
About the Author
David Isaacs was born in London and has an identical twin brother, Stephen, who is a child psychiatrist. They went to different schools and once swapped schools for a day. His mother was also a child psychiatrist and his father, Alick Isaacs, discovered interferon in 1957. David trained as a general paediatrician in London and Sydney and in paediatric infectious diseases in Oxford. He moved to Sydney in 1989 to head the new Department of Immunology and Infectious Diseases at the Royal Alexandra Hospital for Children, but was the only member of the Department. He is a Clinical Professor in Paediatric Infectious Diseases at the Children's Hospital at Westmead and at the University of Sydney. His research is mainly in neonatal infections, respiratory viral infections, immunization and bioethics. He loves writing and has published extensively, over 300 original peer-reviewed papers and 10 books on paediatric infectious diseases, neonatal infections, immunizations and ethics. This is the third book he has written on neonatal infections, but the first to use a systematic evidence-based approach.
Preface
This book is aimed primarily at clinicians working with neonates, although I hope policymakers will also be interested. It is based on evidence from the literature but also on over 30 years attending neonatal unit ward rounds to learn, advise and teach about neonatal infections.
My special thanks to Dr Phil Britton and Dr David Andresen of the Children's Hospital at Westmead for their extraordinary but characteristic generosity in reading all the chapters and their invariably helpful and incisive advice. I would also like to thank Professor Craig Mellis of the University of Sydney and Professor Ruth Gilbert of the Institute of Child Health in London for help with the chapter on evidence and Associate Professor Ben Marais of the Children's Hospital at Westmead for his help with the section on tuberculosis. I would also like to thank John Yeats and Paul de Sensi from the Children's Hospital at Westmead for help with medical imaging.
I would like to thank my wife Carmel and my children for putting up with me spending long hours researching and writing this book.
Finally, I would like to acknowledge all my colleagues in neonatology who have shared their knowledge and discussed the management of neonatal infections. I dedicate this book to you, the neonatologists at the coal face making the difficult clinical decisions. I hope this book helps a bit.
David Isaacs
University of Sydney
CHAPTER 1
How to search for evidence
1.1 Obstacles to searching for evidence
Clinicians who do not search the literature for evidence quote lack of time1-5 and lack of knowledge as the main constraints.6,7
In this brief chapter, we will suggest a rapid and easy approach to searching for evidence. For more detail, one journal publication8 and three books9-11 can be consulted.
1.2 Sources of evidence
1.2.1 The Cochrane library
The Cochrane Collaboration was established in 1993 and named for the British epidemiologist Archie Cochrane. It is an international non-profit making organization which publishes online evidence about health care in the Cochrane Library including almost 5000 systematic Cochrane Reviews. Cochrane Reviews of treatment interventions are usually restricted to randomized controlled trials (RCTs) because this is the best study design to avoid bias. The Cochrane Library is free in developing countries, in the United Kingdom (where the NHS pays for it) and in Australia (paid for by the Federal Government). In the United States, access requires a subscription, but many libraries and hospitals subscribe so that it is readily available to many clinicians. The Cochrane Library website is http://www.thecochranelibrary.com/.
For the evidence for an intervention, search the Cochrane Library (Figure 1.1) first by typing your topic into the box marked SEARCH THE COCHRANE LIBRARY and clicking on Go. Try different search terms because they will give different information.
1.2.2 Medline and PubMed
PubMed is provided free by the US National Library of Medicine and the National Institutes of Health and gives access to the comprehensive database Medline to anyone with internet access. The website is http://www.pubmed.gov/.
The best approach to find evidence is to use the Clinical Queries option in PubMed. Click on Clinical Queries, under PubMed Tools, currently in the centre of the PubMed home page (Figure 1.2), which brings up a new screen (Figure 1.3). Enter your search terms into the Search box and click on SEARCH. PubMed automatically finds RCTs in the first column (set the Category to “therapy” and Scope to “narrow” to find RCTs) and systematic reviews including Cochrane reviews in the middle column (Figure 1.3). Ignore the third column (only used by geneticists). Experiment with search terms until you find the best ways of expanding or narrowing the search to find what you want.
1.3 Statistical terms and explanations
Cluster randomized trial: a trial in which a group of individuals is randomized. For example, whole villages could be randomized to have a study intervention or no intervention, rather than individuals. The village becomes the unit of randomization. Outcomes are compared between those who do and do not receive the intervention.
Confidence Intervals (CI): a way of quantifying measurement uncertainty. This is usually expressed as the 95% CI, which means that the true value will be within the range 95% of the time. If the Relative Risk of dying with treatment compared with placebo is 0.50 (95% CI 0.20–0.75), the treatment reduces the risk of dying by 50%, and 95% of the time it will reduce the risk by somewhere between 20% and 75%.
Negative predictive value (NPV): the proportion of subjects with a negative test result who are correctly diagnosed. The negative predictive value of a test for sepsis is a reflection of the test sensitivity and the incidence of sepsis in the population. The higher the negative predictive value of a test, the safer it is to use a negative test result as a basis to withhold treatment. If a test for sepsis has an NPV of 100%, then no child with sepsis will have a false negative result and all septic children will be identified by the test.
Number Needed to Treat (NNT): the number of patients you need to treat in order to achieve one extra favourable outcome. For example, if 19 of 20 patients treated with antibiotics for an infection get better compared with 14 of 20 treated with placebo, five extra patients get better for every 20 treated so the NNT is 20/5 or 4.
Odds Ratio (OR): the ratio of the odds of having the outcome in the treated group compared to the odds of having it in the control group. For example:
Positive predictive value (PPV): the proportion of subjects with a positive test result who are correctly diagnosed. The positive predictive value of a test for sepsis is a reflection of the test specificity and the incidence of sepsis in the population. If all infants with a positive test result receive antibiotics, for example, the higher the positive predictive value of a test for sepsis, the fewer children without sepsis will receive antibiotics.
Relative Risk or Risk Ratio (RR): the ratio of the risk in the treated group to the risk in the control group. For example:
[When the event rate is 10% or lower, the OR and RR are similar. For more common events, the difference between OR and RR becomes wider, with the RR always closer to one. In general, it is preferable to use RR.11]
Sensitivity: the sensitivity of a test is the proportion of true positives correctly identified by the test (e.g. the percentage of infected infants who are correctly identified as having infection).
Specificity: the specificity of a test is the proportion of negatives correctly identified by the test (e.g. the percentage of healthy infants who are correctly identified by a sepsis test as not having infection).
1.4 Useful websites
[N.B. This chapter is adapted from Chapter 1 of reference 10 and we acknowledge some repetition.]
References
1. Dawes M, Sampson U. Knowledge management in clinical practice: a systematic review of information seeking behavior in physicians. Int J Med Inf 2003; 71:91–95.
2. Riordan FAI, Boyle EM, Phillips B. Best paediatric evidence; is it accessible and used on-call?. Arch Dis Child 2004; 89:469–471.
3. D'Alessandro DM, Kreiter CD, Peterson MW. An evaluation of information-seeking behaviors of general pediatricians. Pediatrics 2004; 113:64–69.
4. Ely JW, Osheroff JA, Ebell MH, Chambliss ML, Vinson DC. Obstacles to answering doctors' questions about patient care with evidence: qualitative study. BMJ 2002; 324:1–7.
5. Coumou HC, Meijman FJ. How do primary care physicians seek answers to clinical questions? A literature review. J Med Libr Assoc 2006; 94:55–60.
6. Caldwell PHY, Bennett T, Mellis C. Easy guide to searching for evidence for the busy clinician. J Paed Child Health 2012; 48:1095–1100.
7. Cotten CM, Taylor S, Stoll B, et al. Prolonged duration of initial empirical antibiotic treatment is associated with increased rates of necrotizing enterocolitis and death for extremely low birth weight infants. Pediatrics 2009; 123:58–66.
8. Isaacs D. How to do a quick literature search. J Paed Child Health 2013; 49: In press.
9. Moyer VA (ed). Evidence-based pediatrics and child health, 2nd edn. London: BMJ Books, 2004.
10. Isaacs D. Evidence-based pediatric infectious diseases. Oxford, Blackwell Publishing, 2007.
11. Strauss SE, Glasziou P, Richardson WS, Haynes RB. Evidence-based medicine. How to practice and teach EBM, 4th edn. Edinburgh: Elsevier Churchill Livingstone, 2011. ISBN 978-0-7020-3127-4.