Choice and Duration of Antimicrobial Therapy for Neonatal Sepsis and Meningitis

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Abstract

Neonatal sepsis is associated with increased mortality and morbidity including neurodevelopmental impairment and prolonged hospital stay. Signs and symptoms of sepsis are nonspecific, and empiric antimicrobial therapy is promptly initiated after obtaining appropriate cultures. However, many preterm and low birth weight infants who do not have infection receive antimicrobial agents during hospital stay. Prolonged and unnecessary use of antimicrobial agents is associated with deleterious effects on the host and the environment. Traditionally, the choice of antimicrobial agents is based on the local policy, and the duration of therapy is decided by the treating physician based on clinical symptoms and blood culture results. In this paper, we discuss briefly the causative organism of neonatal sepsis in both the developed and developing countries. We review the evidence for appropriate choice of empiric antimicrobial agents and optimal duration of therapy in neonates with suspected sepsis, culture-proven sepsis, and meningitis. Moreover, there is significant similarity between the causative organisms for early- and late-onset sepsis in developing countries. The choice of antibiotic described in this paper may be more applicable in developed countries.

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Most cited references 62

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Neonatal candidiasis among extremely low birth weight infants: risk factors, mortality rates, and neurodevelopmental outcomes at 18 to 22 months.

Daniel K Benjamin, Barbara J Stoll, Avory A Fanaroff … (2006)

Neonatal candidiasis is associated with substantial morbidity and mortality rates. Neurodevelopmental follow-up data for a large multicenter cohort have not been reported. Data were collected prospectively for neonates born at or =14 days. Death or neurodevelopmental impairment (NDI) was observed for 73% of extremely low birth weight infants who developed candidiasis. Death and NDI rates were greater for infants who had delayed removal or replacement of central catheters (>1 day after initiation of antifungal therapy), compared with infants whose catheters were removed or replaced promptly. Blood cultures were negative for approximately one half of the infants with Candida meningitis. Persistent candidiasis was common. Delayed catheter removal was associated with increased death and NDI rates.

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Society for Healthcare Epidemiology of America and Infectious Diseases Society of America Joint Committee on the Prevention of Antimicrobial Resistance: guidelines for the prevention of antimicrobial resistance in hospitals.

Simon J McGowan, P. Levy, Steven Duncan … (1997)

Antimicrobial resistance results in increased morbidity, mortality, and costs of health care. Prevention of the emergence of resistance and the dissemination of resistant microorganisms will reduce these adverse effects and their attendant costs. Appropriate antimicrobial stewardship that includes optimal selection, dose, and duration of treatment, as well as control of antibiotic use, will prevent or slow the emergence of resistance among microorganisms. A comprehensively applied infection control program will interdict the dissemination of resistant strains.

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Serial serum C-reactive protein levels in the diagnosis of neonatal infection.

W E Benitz, M. Han, A. Madan … (1998)

To evaluate serial serum C-reactive protein (CRP) levels for diagnosis of neonatal infection. A regional intensive care nursery and two community intensive care nurseries. All neonates treated for suspected bacterial infection were prospectively evaluated using a standardized clinical pathway. Infants were categorized as having proven sepsis (bacteria isolated from blood, cerebrospinal fluid, or urine culture), probable sepsis (clinical and laboratory findings consistent with bacterial infection without a positive culture), or no sepsis (findings not consistent with sepsis), without consideration of CRP levels. Infants whose blood cultures yielded skin flora but who demonstrated no other signs of bacterial infection were not considered to have sepsis. CRP levels were determined at the initial evaluation and on each of the next two mornings. Sensitivity, specificity, predictive values, and likelihood ratios were calculated for the first (CRP #1), second (CRP #2), higher of the second and third (CRP #2 and #3), or highest of all three CRP levels (CRP x 3). Sepsis was suspected within the first 3 days after birth in 1002 infants (early-onset) and on 184 occasions in 134 older infants (late-onset). There were 20 early-onset and 53 late-onset episodes of proven sepsis, and 74 early-onset and 12 late-onset episodes of probable sepsis. CRP #1 had sensitivities of 39.4% and 64.6% for proven or probable sepsis and 35.0% and 61.5% for proven sepsis in early-onset and late-onset episodes, respectively. CRP levels on the morning after the initial evaluation (CRP #2) had higher sensitivities (92. 9% and 85.0% for proven or probable sepsis and 78.9% and 84.4% for proven sepsis in early-onset and late-onset episodes, respectively), and normal results were associated with lower likelihoods of infection (likelihood ratios for normal results of 0.10 and 0.19 for proven or probable sepsis and 0.27 and 0.21 for proven sepsis, in early-onset and late-onset episodes, respectively). Three serial serum CRP levels had sensitivities of 97.8% and 98.1% for proven or probable sepsis and 88.9% and 97.5% for proven sepsis in early-onset and late-onset episodes, respectively. The negative predictive values for CRP x 3 were 99.7% and 98.7% for both proven or probable sepsis and for proven sepsis in early-onset and late-onset episodes, respectively. A CRP level obtained at the time of the initial evaluation can be omitted without significant loss of sensitivity or negative predictive value: the sensitivities of CRP #2 and #3 were 97.6% and 94.4% for proven or probable sepsis and 88.9% and 96.4% for proven sepsis in early-onset and late-onset episodes, respectively; negative predictive values were 99.7% both for proven and for proven or probable early-onset sepsis, 97.6% for proven or probable late-onset infection, and 98.8% for proven late-onset infection. Serial normal CRP levels were associated with a markedly reduced likelihood of infection as compared with that in the entire population before testing, with likelihood ratios ranging from 0.03 to 0.16 for the various subgroups. Maximum CRP levels >3 mg/dL had positive predictive values >20% for proven or probable early-onset infections and for proven or probable and proven late-onset infections, but only those >6 mg/dL had such a high positive predictive value for proven early-onset sepsis. Serial CRP levels are useful in the diagnostic evaluation of neonates with suspected infection. Two CRP levels <1 mg/dL obtained 24 hours apart, 8 to 48 hours after presentation, indicate that bacterial infection is unlikely. The sensitivity of a normal CRP at the initial evaluation is not sufficient to justify withholding antibiotic therapy. The positive predictive value of elevated CRP levels is low, especially for culture-proven early-onset infections.

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Author and article information

Journal

Journal ID (nlm-ta): Int J Pediatr

Journal ID (publisher-id): IJPED

Title: International Journal of Pediatrics

Publisher: Hindawi Publishing Corporation

ISSN (Print): 1687-9740

ISSN (Electronic): 1687-9759

Publication date (Print): 2011

Publication date (Electronic): 20 November 2011

Volume: 2011

Electronic Location Identifier: 712150

Affiliations

¹Division of Neonatology, Department of Pediatrics, University of Calgary, Calgary, AB, Canada T2N 1N4

²Institute for Maternal and Child Health, University of Calgary, Calgary, AB, Canada T2N 4N1

Author notes

*Amuchou S. Soraisham: asoraish@ 123456ucalgary.ca

Academic Editor: N. B. Mathur

Article

DOI: 10.1155/2011/712150

PMC ID: 3228399

PubMed ID: 22164179

SO-VID: b26d828e-980b-4091-b648-9a3b24eb89a2

License:

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.