title: The Treatment of Possible Severe Infection in Infants: An Open Randomized Safety Trial of Parenteral Benzylpenicillin and Gentamicin Versus Ceftriaxone in Infants <60 days of Age in Malawi.
abstract: BACKGROUND
  The World Health Organization recommends benzylpenicillin and gentamicin as antimicrobial treatment for infants with sepsis in low-income settings, and ceftriaxone or cefotaxime as an alternative. In a meta-analysis from 13 low-income settings, Staphylococcus aureus, Klebsiella spp. and Escherichia coli accounted for 55% of infants with sepsis. In a review of bacterial meningitis, resistance to third generation cephalosporins was >50% of all isolates, and 44% of Gram-negative isolates were gentamicin resistant. However, ceftriaxone may cause neonatal jaundice, and gentamicin may cause deafness. Therefore, we compared parenteral benzylpenicillin plus gentamicin with ceftriaxone as first-line treatment, assessing outcome and adverse events.
  
  
  METHODS
  This was an open randomized trial carried out in the Queen Elizabeth Central Hospital, Blantyre, Malawi, from 2010 to 2013. Infants <60 days of age with possible severe sepsis received either benzylpenicillin and gentamicin or ceftriaxone. Adverse events and outcomes were recorded until 6 months post discharge.
  
  
  RESULTS
  Three-hundred forty-eight infants were included in analyses. Outcome in the benzylpenicillin and gentamicin and ceftriaxone groups was similar; deaths were 13.7% and 16.5% and sequelae were 14.5% and 11.2%, respectively. More infants in the penicillin/gentamicin group required phototherapy: 15% versus 5%, P = 0.03. Thirteen (6%) survivors had bilateral hearing loss. There was no difference between the treatment groups. By 6 months post discharge, 11 more infants had died, and 17 more children were found to have sequelae.
  
  
  CONCLUSIONS
  Ceftriaxone and gentamicin are safe for infants in our setting. Infants should receive long-term follow-up as many poor outcomes occurred after hospital discharge.
authors.affiliation: From the *Department of Pediatrics, College of Medicine, †Department of Pediatrics, Queen Elizabeth Central Hospital, and ‡John Hopkins Research Unit College of Medicine, Blantyre, Malawi; §Department of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom; ¶Malawi Liverpool Wellcome Trust Clinical Research Programme, College of Medicine, Blantyre, Malawi; and ‖Division of Infection & Immunity, University College London, London, United Kingdom.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Molyneux
authors.forename: Queen
authors.initials: Q
authors.lastname: Dube
authors.forename: Francis M
authors.initials: FM
authors.lastname: Banda
authors.forename: Msandeni
authors.initials: M
authors.lastname: Chiume
authors.forename: Isaac
authors.initials: I
authors.lastname: Singini
authors.forename: Macpherson
authors.initials: M
authors.lastname: Mallewa
authors.forename: Edward C
authors.initials: EC
authors.lastname: Schwalbe
authors.forename: Robert S
authors.initials: RS
authors.lastname: Heyderman
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use; D001663:Bilirubin / Q000097:blood; D002443:Ceftriaxone / Q000009:adverse effects / Q000627:therapeutic use; D005839:Gentamicins / Q000009:adverse effects / Q000627:therapeutic use; D034381:Hearing Loss; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008295:Malawi; D016920:Meningitis, Bacterial / Q000188:drug therapy* / Q000453:epidemiology; D000071074:Neonatal Sepsis / Q000188:drug therapy* / Q000453:epidemiology; D010400:Penicillin G / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D002443:Ceftriaxone; D010400:Penicillin G; D001663:Bilirubin