# In Vitro Evaluation of Antimicrobial Synergy Against Multidrug-Resistant Gram-Negative Paediatric Bloodstream Pathogens in South Africa

## TL;DR

This study tested antibiotic combinations against drug-resistant bacteria in children in South Africa and found tigecycline and meropenem to be effective.

## Contribution

The study identifies tigecycline and meropenem as a promising combination for treating multidrug-resistant Gram-negative infections in children.

## Key findings

- Tigecycline and meropenem showed 92.1% synergy against carbapenem-resistant Enterobacterales.
- The same combination showed 76.7% synergy against XDR Acinetobacter species.
- Colistin and meropenem showed poor synergy and high rates of indifference or antagonism.

## Abstract

Background: In vitro synergy testing (ST) is a useful means to gauge the performance ofantibiotic combinations against multidrug-resistant (MDR) Gram-negative bacteria (GNB). This study aimed to determine synergy of antibiotics against paediatric bloodstream (BS) carbapenem-resistant Enterobacterales (CRE) and extremely drug-resistant (XDR) Acinetobacter species. Methods: This cross-sectional study was conducted at a public tertiary hospital in South Africa, from January 2023 to December 2023. Sixty-eight isolates from children with bloodstream infections (BSI), comprising 55.9% (38/68) CRE and 44.1% (30/68) XDR Acinetobacter species, were performed ST using the fixed-ratio Epsilometer-test method. Combinations of colistin and meropenem, colistin and fosfomycin, colistin and tigecycline, meropenem and fosfomycin, meropenem and tigecycline, and fosfomycin and tigecycline were tested. Results: In vitro synergy for CRE was best demonstrated with tigecycline and meropenem, at 92.1% (35/38), and fosfomycin and meropenem at 73.7% (28/38). Among the XDR Acinetobacter species, the highest rates of synergy of 76.7% (23/30) were observed with tigecycline and meropenem. The absence of synergy was noted with colistin and meropenem for the CRE, with many displaying indifference and antagonism at rates of 65.8% and 22%. Most XDR Acinetobacter species (56.7%; 17/30) expressed indifference to colistin and meropenem with synergy and antagonism displayed in 23.3% and 10% of isolates. Conclusions: This study highlights tigecycline and meropenem displaying impressive in vitro synergy when compared to the in-use colistin and meropenem for CRE and XDR Acinetobacter species. Tigecycline and meropenem may be a viable salvage therapeutic option for MDR Gram-negative paediatric infections. Future research is warranted to confirm in vivo synergy clinically.