Emerging resistance to empiric antimicrobial regimens for pediatric bloodstream infections in Malawi (1998-2017)

Abstract

Background The adequacy of the WHO Integrated Management of Childhood Illness (IMCI) antimicrobial guidelines for the treatment of suspected severe bacterial infections is dependent on a low prevalence of antimicrobial resistance (AMR). We describe trends in etiologies and susceptibility patterns of bloodstream infections (BSI) in hospitalized children in Malawi. Methods We determined the change in population-based incidence of BSI in children admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi (1998-2017). AMR profiles were assessed by the disc diffusion method and trends over time were evaluated. Results A total 89,643 pediatric blood cultures were performed, and 10,621 pathogens were included in the analysis. Estimated minimum incidence rates of BSI for those ≤5 years of age fell from a peak of 11.4 per 1,000 persons in 2002 to 3.4 per 1,000 persons in 2017. Over two decades, resistance of Gram-negative pathogens to all empiric first-line antimicrobials (ampicillin/penicillin, gentamicin, ceftriaxone) among children ≤5 years increased from 3.4% to 30.2% (p<0.001). Among those ≤60 days, AMR to all first-line antimicrobials increased from 7.0% to 67.7% (p<0.001). Among children ≤5 years, Klebsiella spp. resistance to all first-line antimicrobial regimens increased from 5.9% to 93.7% (p<0.001). Conclusions The incidence of BSI among hospitalized children has decreased substantially over the last 20 years, although gains have been offset by increases in Gram-negative pathogens resistant to all empiric first-line antimicrobials. There is an urgent need to address the broader challenge of adapting IMCI guidelines to the local setting in the face of rapidly expanding AMR in childhood BSI