Authors: Amin Addetia, Alexander L Greninger, Amanda Adler, Shuhua Yuan, Negar Makhsous, Xuan Qin, Danielle M Zerr
Summary: Chlorhexidine gluconate (CHG) is a topical antiseptic widely used in healthcare settings. In Staphylococcus spp., the pump QacA effluxes CHG, while the closely related QacB cannot due to a single amino acid substitution. We characterized 1,050 cutaneous Staphylococcus isolates obtained from 173 pediatric oncology patients enrolled in a multicenter CHG bathing trial. CHG susceptibility testing revealed 63 (6%) of these isolates had elevated CHG MICs (≥4 μg/mL). Screening of all 1,050 isolates for qacA/B by restriction fragment length polymorphism (RFLP) yielded 56 isolates with a novel qacA/B RFLP pattern, qacAB273. The CHG MIC was significantly higher for qacAB273-positive isolates (MIC50: 4 μg/mL, [lsqb]range: 0.5–4 μg/mL[rsqb]) compared to other qac groups: qacA-positive (n=559, 1 μg/mL, [lsqb]0.5–4 μg/mL[rsqb]), qacB-positive (n=17, 1 μg/mL, [lsqb]0.25–2 μg/mL[rsqb]), and qacA/B-negative (n=418, 1 μg/mL, [lsqb]0.125–2 μg/mL[rsqb], p=0.001). The qacAB273-positive isolates also displayed a high proportion of methicillin resistance (96.4%) compared to other qac groups (24.9–61.7%, p=0.001). Whole genome sequencing revealed that qacAB273-positive isolates encoded a variant of QacA with 2 amino acid substitutions. This new allele, named qacA4, was carried on the novel plasmid pAQZ1. The qacA4-carrying isolates belonged to the highly resistant S. epidermidis ST2 clone. By searching available sequence datasets, we identified 39 additional qacA4-carrying S. epidermidis strains from 5 countries. Curing an isolate of qacA4 resulted in a four-fold decrease in the CHG MIC, confirming the role of qacA4 in the elevated CHG MIC. Our results highlight the importance of further studying qacA4 and its functional role in clinical staphylococci.
Source: Antimicrobial Agents and Chemotherapy, 2019