Considerations in the pharmacologic treatment and prevention of neonatal sepsis.
The management of neonatal sepsis is challenging owing to complex developmental and environmental factors that contribute to inter-individual variability in the pharmacokinetics and pharmacodynamics of many antimicrobial agents. In this review, we describe (i) the changing epidemiology of early- and late-onset neonatal sepsis; (ii) the pharmacologic considerations that influence the safety and efficacy of antibacterials, antifungals, and immunomodulatory adjuvants; and (iii) the recommended dosing regimens for pharmacologic agents commonly used in the treatment and prevention of neonatal sepsis. Neonatal sepsis is marked by high morbidity and mortality, such that prompt initiation of antimicrobial therapy is essential following culture collection. Before culture results are available, combination therapy with ampicillin and an aminoglycoside is recommended. When meningitis is suspected, ampicillin and cefotaxime may be considered. Following identification of the causative organism and in vitro susceptibility testing, antimicrobial therapy may be narrowed to provide targeted coverage. Therapeutic drug monitoring should be considered for neonates receiving vancomycin or aminoglycoside therapies. For neonates with invasive fungal infections, the development of new antifungal agents has significantly improved therapeutic outcomes in recent years. Liposomal amphotericin B has been found to be safe and efficacious in patients with renal impairment or toxicity caused by conventional amphotericin B. Antifungal prophylaxis with fluconazole has also been reported to dramatically reduce rates of neonatal invasive fungal infections and to improve long-term neurodevelopmental outcomes among treated children. Additionally, several large multicenter studies are currently investigating the safety and efficacy of oral lactoferrin as an immunoprophylactic agent for the prevention of neonatal sepsis.
Division of Clinical Pharmacology, Department of Paediatrics, University of Utah School of Medicine, Salt Lake City, USA.
Chris
C
Stockmann
Michael G
MG
Spigarelli
Sarah C
SC
Campbell
Jonathan E
JE
Constance
Joshua D
JD
Courter
Emily A
EA
Thorell
Jared
J
Olson
Catherine M T
CM
Sherwin
D000666:Amphotericin B / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000627:therapeutic use; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D016903:Drug Monitoring; D016469:Fungemia / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009181:Mycoses / Q000188:drug therapy* / Q000382:microbiology
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; C068538:liposomal amphotericin B; D000666:Amphotericin B