Community-acquired neonatal and infant sepsis in developing countries: efficacy of WHO's currently recommended antibiotics-systematic review and meta-analysis

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.