Clinical and Molecular Features of Decreased Chlorhexidine Susceptibility among Nosocomial Staphylococcus aureus Isolates at Texas Children's Hospital

Abstract

One of the strategies utilized to decrease infections in the hospital setting relies on topical antimicrobials and antiseptics. While their use is beneficial, concerns arise over the potential to develop resistance or tolerance to these agents. We examined nosocomial Staphylococcus aureus isolates from 2007 to 2013 for the presence of genes associated with tolerance to chlorhexidine. Isolates and patients were identified from an S. aureus surveillance study at Texas Children's Hospital. Nosocomial S. aureus isolates (those causing infection at >72 h of hospitalization) were identified and underwent PCR for the qacA or qacB (qacA/B) and smr genes associated with elevated minimum bactericidal concentrations of chlorhexidine. Molecular typing with pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and agr typing and a review of the medical record were performed. Two hundred forty-seven nosocomial S. aureus infections were identified. Overall, 111 isolates carried one or both genes (44.9%); 33.1% were positive for smr, 22.7% were positive for qacA/B, and 10.9% of the isolates possessed both genes. The smr-positive isolates were more often resistant to methicillin, ciprofloxacin, and/or clindamycin. The isolates positive for qacA/B were more often associated with indwelling central venous catheters and a vancomycin MIC of >2 g/ml. Isolates carrying either smr or qacA/B were associated with a diagnosis of bacteremia. The smr-positive isolates more often belonged to sequence type 8 (ST8) than the isolates that were positive for qacA/B. Mupirocin resistance was detected in 2.8% of the isolates. Antiseptictolerant S. aureus strains are common in our children's hospital and are associated with decreased susceptibility to other systemic antimicrobials and with bloodstream infections. Further work is needed to understand the implications that these organisms have on the hospital environment and antiseptic use in the future.

Impact of Health Care Exposure on Genotypic Antiseptic Tolerance in Staphylococcus aureus Infections in a Pediatric Population

“…In S. aureus, the smr gene and the qacA/B gene complex have been associated with elevated MICs and minimum bactericidal concentrations (MBCs) of CHG. A number of investigators have discovered an increase in the incidence of organisms bearing these genes following widespread use of CHG in hospital units (12)(13)(14) and, more rarely, following exposure to CHG outside the hospital setting (15,16). Importantly, the presence of these genes has been associated with resistance to other systemic antimicrobial agents, including clindamycin and ciprofloxacin (smr), as well as higher MICs of vancomycin (qacA/B) (17,18).…”

“…The impact of the use of these agents on the development of genotypic or in vitro CHG resistance has been minimal in large clinical trials of CHG-based decolonization regimens (15,19). Previous studies of children have shown an association between antiseptic tolerance genes in S. aureus and the presence of central venous lines (CVLs), as well as a higher rate of invasive infection (18). Many previous pediatric studies, however, have been biased by including high-risk populations, such as neonates/infants and oncology and cardiac surgery patients (12,18,20,21).…”

Chlorhexidine and Mupirocin Susceptibility of Methicillin-Resistant Staphylococcus aureus Isolates in the REDUCE-MRSA Trial

“…Third, the intervention period was relatively short (18 months), and results may not be generalizable to longer periods of routine decolonization. Fourth, we looked for only two efflux pump genes; other efflux pumps that can use CHG as a substrate have been described in S. aureus (18,35).…”

“…Reduced susceptibility to CHG in MRSA occurs via efflux, and identification of plasmid-mediated genes, such as qacA and qacB, that encode multidrug efflux pumps has been considered genotypic evidence of CHG nonsusceptibility by some (16,17). However, the relationship between the carriage of multidrug efflux pump genes and decreased susceptibility to CHG is inconsistent; phenotypic susceptibility has been demonstrated in MRSA strains that carry qacA or qacB, and reduced susceptibility has been reported in strains that lack these or other multidrug efflux pump genes (15,(18)(19)(20). The inconsistency may be due in part to the ability of the pump encoded by qacA, but not that encoded by qacB, to utilize CHG as a substrate.…”

“…CHG has been used widely in health care for more than 50 years, and reduced susceptibility as measured by in vitro methods has been reported across the globe (18,(20)(21)(22)(23)(24)46), yet decolonization failure related to nonsusceptibility has been described only rarely (16,25,26). Of note, topical concentrations of CHG used for decolonization remain Ͼ200-fold higher than the highest CHG MICs and minimum bactericidal concentrations (MBCs) recorded for staphylococci (15,25).…”