Efficacy of susceptibility-matched antibiotic treatment of nontyphoidal Salmonella bloodstream infections: a prospective observational study in hospitalized children under 5 in the Democratic of Congo

Objectives
In sub-Saharan African children aged under 5 years, nontyphoidal Salmonella (NTS) frequently cause fatal bloodstream infections. Antimicrobial resistance and absence of antibiotic treatment efficacy data challenge effective treatment. In this prospective observational study, we provide treatment efficacy data of susceptibility-matched antibiotic regimens from the treatment of NTS bloodstream infections in children in Kisantu district hospital (Democratic Republic of Congo).

Methods
Children (>28 days to <5 years) admitted with severe febrile illness were enrolled after blood culture sampling. Clinical and microbiological data of children with NTS bloodstream infection were collected in-hospital and at 1-month after discharge.

Results
NTS bloodstream infection was diagnosed in 12.7% (239/1867) of enrolled children. Extensive drug-resistance (concurrent ampicillin, cotrimoxazole, chloramphenicol, third-generation cephalosporin and fluoroquinolone nonsusceptibility) occurred in 60% (144/236), i.e. 69% (71/103) in O5-antigen positive Typhimurium, 85% (72/85) in O5-antigen negative Typhimurium but only 2% (1/48) in Enteritidis serovars. Only 64% (146/228) of children received susceptibility-matched antibiotics and overall in-hospital case fatality was 25.1% (60/239). Compared with susceptibility-mismatched antibiotic treatment, susceptibility-matched third-generation cephalosporin treatment on hospital day 0–1 had better 14-day in-hospital survival (hazard ratio at death [HRdeath]: 0.37 [0.16–0.88]). Similarly, susceptibility-matched third-generation cephalosporin, ciprofloxacin or azithromycin treatment on hospital day 2–6 had better 28-day in-hospital survival (HRdeath: 0.21 [0.06–0.68], 0.15 [0.02–1.10] and 0.26 [0.08–0.84], respectively). After ≥5 days of susceptibility-matched antibiotics, NTS persisted in control blood cultures in 15% (13/88).

Conclusions
NTS bloodstream infections were often extensively drug resistant, leading to susceptibility-mismatched antibiotic treatment. When NTS were susceptible, third-generation cephalosporin, ciprofloxacin and azithromycin treatment appeared to be effective.