Genetic relatedness and risk factor analysis of ampicillin-resistant and high-level gentamicin-resistant enterococci causing bloodstream infections in Tanzanian children

Abstract

Background: While enterococci resistant to multiple antimicrobials are spreading in hospitals worldwide, causing urinary tract, wound and bloodstream infections, there is little published data on these infections from Africa. Methods: We assessed the prevalence, susceptibility patterns, clinical outcome and genetic relatedness of enterococcal isolates causing bloodstream infections in children in a tertiary hospital in Tanzania, as part of a prospective cohort study of bloodstream infections among 1828 febrile children admitted consecutively from August 2001 to August 2002. Results: Enterococcal bacteraemia was identified in 2.1% (39/1828) of admissions, and in 15.3% (39/255) of cases of culture-confirmed bloodstream infections. The case-fatality rate in children with Enterococcus faecalis septicaemia (28.6%, 4/14) was not significantly different from those with Enterococcus faecium septicaemia (6.7%, 1/15, p = 0.12). E. faecium isolates commonly had combined ampicillin-resistance and high-level gentamicin resistance (HLGR), (9/17), while E. faecalis frequently displayed HLGR (6/15), but were ampicillin susceptible. None of the tested enterococcal isolates displayed vancomycin resistance by Etest or PCR for vanA and vanB genes. Multi-locus sequence-typing (MLST) showed that the majority of E. faecium (7/12) belonged to the hospital associated Bayesian Analysis of Population Structure (BAPS) group 3-3. Pulsed-field gel electrophoresis (PFGE) indicated close genetic relationship particularly among E. faecium isolates, but also among E. faecalis isolates. There was also correlation between BAPS group and PFGE results. Risk factors for enterococcal bloodstream infection in univariate analysis were hospital-acquired infection and clinical diagnosis of sepsis with unknown focus. In multivariate analysis, neonates in general were relatively protected from enterococcal infection, while both prematurity and clinical sepsis were risk factors. Malnutrition was a risk factor for enterococcal bloodstream infection among HIV negative children. Conclusion: This is the first study to describe bloodstream infections caused by ampicillin-resistant HLGR E. faecium and HLGR E. faecalis in Tanzania. The isolates of E. faecium and E. faecalis, respectively, showed high degrees of relatedness by genotyping using PFGE. The commonly used treatment regimens at the hospital are insufficient for infections caused by these microbes. The study results call for increased access to microbiological diagnostics to guide rational antibiotic use in Tanzania.