High Prevalence of Reduced Chlorhexidine Susceptibility in Organisms Causing Central Line–Associated Bloodstream Infections

Suwantarat, Nuntra; Carroll, Karen C.; Tekle, Tsigereda; Ross, Tracy; Maragakis, Lisa L.; Cosgrove, Sara E.; Milstone, Aaron M.

doi:10.1086/677628

Cited by 60 publications

(64 citation statements)

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“…Levels within the reported range of chlorhexidine MIC for enterococci (25)(26)(27)(28)(29) were detected on patient skin (24). In another study, chlorhexidine susceptibilities were monitored for CLABSI enterococcal isolates obtained from hospital wards using chlorhexidine bathing (30). It was observed that the chlorhexidine MIC increased significantly in those isolates compared to CLABSI isolates from nonbathing wards (30).…”

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confidence: 97%

“…In another study, chlorhexidine susceptibilities were monitored for CLABSI enterococcal isolates obtained from hospital wards using chlorhexidine bathing (30). It was observed that the chlorhexidine MIC increased significantly in those isolates compared to CLABSI isolates from nonbathing wards (30). The results of both studies indicate that enterococci are exposed to subinhibitory chlorhexidine concentrations in clinical settings as a result of chlorhexidine bathing.…”

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confidence: 99%

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Chlorhexidine Induces VanA-Type Vancomycin Resistance Genes in Enterococci

Bhardwaj

Ziegler

Palmer

2016

Antimicrob Agents Chemother

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Chlorhexidine is a bisbiguanide antiseptic used for infection control. Vancomycin-resistant E. faecium (VREfm) is among the leading causes of hospital-acquired infections. VREfm may be exposed to chlorhexidine at supra-and subinhibitory concentrations as a result of chlorhexidine bathing and chlorhexidine-impregnated central venous catheter use. We used RNA sequencing to investigate how VREfm responds to chlorhexidine gluconate exposure. Among the 35 genes upregulated >10-fold after 15 min of exposure to the MIC of chlorhexidine gluconate were those encoding VanA-type vancomycin resistance (vanHAX) and those associated with reduced daptomycin susceptibility (liaXYZ). We confirmed that vanA upregulation was not strain or species specific by querying other VanA-type VRE. VanB-type genes were not induced. The vanH promoter was found to be responsive to subinhibitory chlorhexidine gluconate in VREfm, as was production of the VanX protein. Using vanH reporter experiments with Bacillus subtilis and deletion analysis in VREfm, we found that this phenomenon is VanR dependent. Deletion of vanR did not result in increased chlorhexidine susceptibility, demonstrating that vanHAX induction is not protective against chlorhexidine. As expected, VanA-type VRE is more susceptible to ceftriaxone in the presence of sub-MIC chlorhexidine. Unexpectedly, VREfm is also more susceptible to vancomycin in the presence of subinhibitory chlorhexidine, suggesting that chlorhexidine-induced gene expression changes lead to additional alterations in cell wall synthesis. We conclude that chlorhexidine induces expression of VanA-type vancomycin resistance genes and genes associated with daptomycin nonsusceptibility. Overall, our results indicate that the impacts of subinhibitory chlorhexidine exposure on hospital-associated pathogens should be further investigated in laboratory studies.

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confidence: 97%

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confidence: 99%

Chlorhexidine Induces VanA-Type Vancomycin Resistance Genes in Enterococci

Bhardwaj

Ziegler

Palmer

2016

Antimicrob Agents Chemother

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“…A number of genes exist within S. aureus, most notably qacA or qacB (qacA/B) and smr, which encode multidrug efflux pumps whose presence is associated with higher minimum bactericidal concentrations (MBCs) of chlorhexidine and other antiseptics. Suwantarat et al (16) showed that these organisms existed at a higher prevalence in hospital units performing daily chlorhexidine bathing than in those units that did not. Studies at our own institution showed an increase in the proportion of S. aureus isolates with antiseptic tolerance following an increase in chlorhexidine use among oncology and cardiac surgery patients (17,18).…”

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confidence: 99%

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

McNeil

Kok

Vallejo

et al. 2016

Antimicrob Agents Chemother

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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.

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“…Finally although mupirocin and chlorhexidine resistance did not increase in our study or the REDUCE-MRSA trial [4], there is new concern that exposure to chlorhexidine might be associated with colistin resistance [8]. To the Editor-We read with great interest the study by Klompas et al suggesting that a very short course of antimicrobial therapy (1-3 days) might not be associated with a higher risk of ventilator or hospital death in patients with suspected ventilator-associated pneumonia (VAP), compared with a longer course [1]. We discuss some potential limitations of the study.…”

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confidence: 88%

“…To the Editor -Despite heightened concern for increased resistance to mupirocin and chlorhexidine [1][2][3][4], reports that assess the relationship between consumption of the agents and genotypic resistance are scarce. We sought to determine if there were any significant trends in mupirocin and chlorhexidine consumption in the nationwide healthcare system of the US Department of Defense (DOD) and in a subset of DOD hospitals in the National Capital Region (DOD-NCR) that also conduct active surveillance for mupA and qacA/B.…”

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confidence: 99%