Emerging Resistance to Empiric Antimicrobial Regimens for Pediatric Bloodstream Infections in Malawi (1998-2017)

Abstract

Background: The adequacy of the World Health Organization's 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 the 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 89643 pediatric blood cultures were performed, and 10621 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 1000 persons in 2002 to 3.4 per 1000 persons in 2017. Over 2 decades, the 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 < .001). Among those ≤60 days, AMR to all first-line antimicrobials increased from 7.0% to 67.7% (P < .001). Among children ≤5 years, Klebsiella spp. resistance to all first-line antimicrobial regimens increased from 5.9% to 93.7% (P < .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' resistance 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.

Keywords: Gram negative; antimicrobial resistance; neonatal; pediatric; sepsis.

Figure 1.

Negative binomial regression model–estimated annual incidence rate per 1000 person-years for children ≤5 years, for: (A) all pathogenic organisms among those ≤5 years and ≤60 days; (B) S. pneumoniae and S. aureus; (C) GAS and GBS; (D) S. Typhi and NTS; (E) E. coli and Klebsiella spp.; and (F) Haemophilus spp. and other Gram-negatives. Scales have been adjusted for each organism. Abbreviations: CI, confidence interval; GAS, Group A Strep; GBS, Group B Strep; NTS, non-typhoidal Salmonella.

Figure 2.

Proportion of culture-confirmed bloodstream pathogens resistant to empiric first-line antimicrobials by period, for children ≤5 years and ≤60 days. First-line antimicrobials in Malawi are ampicillin/penicillin with gentamicin, or ceftriaxone.

Figure 3.

Proportion of non-Salmonella, Gram-negative isolates with: (A) Gentamicin- or ceftriaxone-resistance, for children ≤5 years; or (B) E. coli and Klebsiella spp. resistance to empiric first-line antimicrobials, for children ≤5 years. First-line antimicrobials in Malawi are ampicillin/penicillin with gentamicin, or ceftriaxone.