Community-acquired neonatal and infant sepsis in developing countries: efficacy of WHO's currently recommended antibiotics—systematic review and meta-analysis
- 1Centre for International Child Health, Department of Paediatrics, University of Melbourne, MCRI, Royal Children's Hospital, Melbourne, Victoria, Australia
- 2Departments of General Medicine, Infectious Disease and Intensive Care, Royal Children's Hospital, Melbourne, Victoria, Australia
- Correspondence to Professor Trevor Duke, Centre for International Child Health, Department of Paediatrics, University of Melbourne, MCRI, Royal Children's Hospital, Parkville, VIC 3052, Australia;
- Received 15 March 2012
- Revised 27 September 2012
- Accepted 29 September 2012
- Published Online First 9 November 2012
Objective To review the aetiology and antibiotic resistance patterns of community-acquired sepsis in developing countries in infants where no clear focus of infection is clinically identified. To estimate the likely efficacy of WHO's recommended treatment for infant sepsis.
Design A systematic review of the literature describing the aetiology of community-acquired neonatal and infant sepsis in developing countries. Using meta-analytical methods, susceptibility was determined to the antibiotic combinations recommended by WHO: (1) benzylpenicillin/ampicillin and gentamicin, (2) chloramphenicol and benzylpenicillin, and (3) third-generation cephalosporins.
Results 19 studies were identified from 13 countries, with over 4000 blood culture isolates. Among neonates, Staphylococcus aureus, Klebsiella spp. and Escherichia coli accounted for 55% (39–70%) of culture positive sepsis on weighted prevalence. In infants outside the neonatal period, the most prevalent pathogens were S aureus, E coli, Klebsiella spp., Streptococcus pneumoniae and Salmonella spp., which accounted for 59% (26–92%) of culture positive sepsis. For neonates, penicillin/gentamicin had comparable in vitro coverage to third-generation cephalosporins (57% vs 56%). In older infants (1–12 months), in vitro susceptibility to penicillin/gentamicin, chloramphenicol/penicillin and third-generation cephalosporins was 63%, 47% and 64%, respectively.
Conclusions The high rate of community-acquired resistant sepsis—especially that caused by Klebsiella spp. and S aureus—is a serious global public health concern. In vitro susceptibility data suggest that third-generation cephalosporins are not more effective in treating sepsis than the currently recommended antibiotics, benzylpenicillin and gentamicin; however, with either regimen a significant proportion of bacteraemia is not covered. Revised recommendations for effective second-line antibiotics in neonatal and infant sepsis in developing countries are urgently needed.