scholarly journals Resistance Mechanisms, Epidemiology, and Approaches to Screening for Vancomycin-Resistant Enterococcus in the Health Care Setting

2016 ◽  
Vol 54 (10) ◽  
pp. 2436-2447 ◽  
Author(s):  
Matthew L. Faron ◽  
Nathan A. Ledeboer ◽  
Blake W. Buchan
Keyword(s):  
Health Care ◽  
Infection Control ◽  
Control Strategies ◽  
Resistance Mechanisms ◽  
Clinical Microbiology Laboratory ◽  
Laboratory Methods ◽  
Content Type ◽  
Important Health ◽  
Vancomycin Resistant ◽  
Hospital Acquired

Infections attributable to vancomycin-resistantEnterococcus(VRE) strains have become increasingly prevalent over the past decade. Prompt identification of colonized patients combined with effective multifaceted infection control practices can reduce the transmission of VRE and aid in the prevention of hospital-acquired infections (HAIs). Increasingly, the clinical microbiology laboratory is being asked to support infection control efforts through the early identification of potential patient or environmental reservoirs. This review discusses the factors that contribute to the rise of VRE as an important health care-associated pathogen, the utility of laboratory screening and various infection control strategies, and the available laboratory methods to identify VRE in clinical specimens.

scholarly journals Genomic Insights to Control the Emergence of Vancomycin-Resistant Enterococci

mBio ◽  
2013 ◽  
Vol 4 (4) ◽  
Author(s):  
Benjamin P. Howden ◽  
Kathryn E. Holt ◽  
Margaret M. C. Lam ◽  
Torsten Seemann ◽  
Susan Ballard ◽  
...  
Keyword(s):  
Health Care ◽  
Infection Control ◽  
Enterococcus Faecium ◽  
De Novo ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Content Type ◽  
New Findings ◽  
Cross Transmission ◽  
Vancomycin Resistant

ABSTRACTNosocomial outbreaks of vancomycin-resistantEnterococcus faecium(VREfm) are thought to occur by transmission of VREfm between patients, predicting that infection control interventions will limit cross-transmission. Despite implementation of such strategies, the incidence of VREfm infections continues to rise. We aimed to use genomics to better understand the epidemiology ofE. faeciumwithin a large hospital and investigate the reasons for failure of infection control strategies. Whole-genome sequencing was performed on 61E. faecium(36 VREfm) isolates, predominately from blood cultures collected at a single hospital between 1998 and 2009, and on fivevanB-positive anaerobic commensal bacteria isolated from human feces. Phylogenomic analysis and precise mapping of thevanBgene, which contains the Tn1549transposon, showed that at least 18 of the 36 VREfm isolates had acquired the transposon via independent insertion events, indicatingde novogeneration of VREfm rather than cross-transmission. Furthermore, Tn1549sequences found in 15 of the 36 VREfm isolates were the same as the Tn1549sequence from one of the gut anaerobes. National and international comparatorE. faeciumisolates were phylogenetically interspersed with isolates from our hospital, suggesting that our findings might be globally representative. These data demonstrate that VREfm generation within a patient is common, presumably occurring in the human bowel during antibiotic therapy, and help explain our inability to reduce VREfm infections. A recommendation from our findings is that infection control practices should include screening patients for specific hospital clones of vancomycin-susceptibleE. faeciumrather than just VREfm.IMPORTANCEEnterococcus faeciumis an increasingly important human pathogen causing predominantly antibiotic-resistant infections in hospitalized patients. Large amounts of health care funding are spent trying to control antibiotic-resistant bacteria in hospitals globally, yet in many institutions around the world, vancomycin-resistantE. faecium(VREfm) infections continue to rise. The new findings from this study help explain the failures of our current approaches to controllingvanBVREfm in health care institutions. Given the importance of this bacterium as a cause of hospital-acquired infections and the difficulties faced by infection control units in trying to prevent colonization in their institutions, the novel findings from this study provide evidence that a new approach to controlling VREfm in hospitals is required. In particular, more attention should be given to understanding the epidemiology of hospital-adapted vancomycin-susceptibleE. faecium, and patients at higher risk forde novogeneration of VREfm need to be identified and optimally managed.

scholarly journals Comparative Genomics of Vancomycin-Resistant Staphylococcus aureus Strains and Their Positions within the Clade Most Commonly Associated with Methicillin-Resistant S. aureus Hospital-Acquired Infection in the United States

mBio ◽  
2012 ◽  
Vol 3 (3) ◽  
Author(s):  
Veronica N. Kos ◽  
Christopher A. Desjardins ◽  
Allison Griggs ◽  
Gustavo Cerqueira ◽  
Andries Van Tonder ◽  
...  
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
The United States ◽  
Methicillin Resistant ◽  
Content Type ◽  
Mrsa Infection ◽  
Vancomycin Resistant ◽  
Foreign Dna ◽  
Mrsa Strains ◽  
Hospital Acquired

ABSTRACTMethicillin-resistantStaphylococcus aureus(MRSA) strains are leading causes of hospital-acquired infections in the United States, and clonal cluster 5 (CC5) is the predominant lineage responsible for these infections. Since 2002, there have been 12 cases of vancomycin-resistantS. aureus(VRSA) infection in the United States—all CC5 strains. To understand this genetic background and what distinguishes it from other lineages, we generated and analyzed high-quality draft genome sequences for all available VRSA strains. Sequence comparisons show unambiguously that each strain independently acquired Tn1546and that all VRSA strains last shared a common ancestor over 50 years ago, well before the occurrence of vancomycin resistance in this species. In contrast to existing hypotheses on what predisposes this lineage to acquire Tn1546, the barrier posed by restriction systems appears to be intact in most VRSA strains. However, VRSA (and other CC5) strains were found to possess a constellation of traits that appears to be optimized for proliferation in precisely the types of polymicrobic infection where transfer could occur. They lack a bacteriocin operon that would be predicted to limit the occurrence of non-CC5 strains in mixed infection and harbor a cluster of unique superantigens and lipoproteins to confound host immunity. A frameshift indprA, which in other microbes influences uptake of foreign DNA, may also make this lineage conducive to foreign DNA acquisition.IMPORTANCEInvasive methicillin-resistantStaphylococcus aureus(MRSA) infection now ranks among the leading causes of death in the United States. Vancomycin is a key last-line bactericidal drug for treating these infections. However, since 2002, vancomycin resistance has entered this species. Of the now 12 cases of vancomycin-resistantS. aureus(VRSA), each was believed to represent a new acquisition of the vancomycin-resistant transposon Tn1546from enterococcal donors. All acquisitions of Tn1546so far have occurred in MRSA strains of the clonal cluster 5 genetic background, the most common hospital lineage causing hospital-acquired MRSA infection. To understand the nature of these strains, we determined and examined the nucleotide sequences of the genomes of all available VRSA. Genome comparison identified candidate features that position strains of this lineage well for acquiring resistance to antibiotics in mixed infection.

scholarly journals Automatic Digital Analysis of Chromogenic Media for Vancomycin-Resistant-Enterococcus Screens Using Copan WASPLab

2016 ◽  
Vol 54 (10) ◽  
pp. 2464-2469 ◽  
Author(s):  
Matthew L. Faron ◽  
Blake W. Buchan ◽  
Christopher Coon ◽  
Theo Liebregts ◽  
Anita van Bree ◽  
...  
Keyword(s):  
Health Care ◽  
Digital Images ◽  
Package Insert ◽  
Improve Patient Care ◽  
Standard Of Care ◽  
Labor Cost ◽  
High Definition ◽  
Content Type ◽  
Chromogenic Agar ◽  
Vancomycin Resistant

Vancomycin-resistant enterococci (VRE) are an important cause of health care-acquired infections (HAIs). Studies have shown that active surveillance of high-risk patients for VRE colonization can aid in reducing HAIs; however, these screens generate a significant cost to the laboratory and health care system. Digital imaging capable of differentiating negative and “nonnegative” chromogenic agar can reduce the labor cost of these screens and potentially improve patient care. In this study, we evaluated the performance of the WASPLab Chromogenic Detection Module (CDM) (Copan, Brescia, Italy) software to analyze VRE chromogenic agar and compared the results to technologist plate reading. Specimens collected at 3 laboratories were cultured using the WASPLab CDM and plated to each site's standard-of-care chromogenic media, which included Colorex VRE (BioMed Diagnostics, White City, OR) or Oxoid VRE (Oxoid, Basingstoke, United Kingdom). Digital images were scored using the CDM software after 24 or 40 h of growth, and all manual reading was performed using digital images on a high-definition (HD) monitor. In total, 104,730 specimens were enrolled and automation agreed with manual analysis for 90.1% of all specimens tested, with sensitivity and specificity of 100% and 89.5%, respectively. Automation results were discordant for 10,348 specimens, and all discordant images were reviewed by a laboratory supervisor or director. After a second review, 499 specimens were identified as representing missed positive cultures falsely called negative by the technologist, 1,616 were identified as containing borderline color results (negative result but with no package insert color visible), and 8,234 specimens were identified as containing colorimetric pigmentation due to residual matrix from the specimen or yeast (Candida). Overall, the CDM was accurate at identifying negative VRE plates, which comprised 84% (87,973) of the specimens in this study.

scholarly journals Vancomycin-Resistant Enterococci: The Value of Infection Control and Antibiotic Control Policy

2006 ◽  
Vol 17 (suppl b) ◽  
pp. 9B-12B ◽  
Author(s):  
Karl Weiss
Keyword(s):  
Health Care ◽  
Infection Control ◽  
Health Care System ◽  
Control Measures ◽  
Canadian Health Care System ◽  
Infection Control Measures ◽  
Vancomycin Resistant Enterococci ◽  
Canadian Health ◽  
Canadian Health Care ◽  
Vancomycin Resistant

Vancomycin-resistant enterococci (VRE) represent a major challenge for the Canadian health care system. The clinical significance of VRE in the Canadian health care system has increased over the past two decades, with outbreaks reported in Ontario and Quebec, although most provinces have been affected. This organism has been a substantial human and financial burden for Canadian institutions. VRE have been shown to be associated with an increased mortality, a longer hospital stay and a much higher overall cost compared with vancomycinsusceptible strains. Enterococci are now the third most important nosocomial pathogen in American intensive care units. The two most common species,Enterococcus faecalisandEnterococcus faecium, have shown remarkable adaptability in responding to antibiotics. The arrival of VRE in Canada has forced hospitals to implement stringent and costly infection control measures. A multifaceted approach, including antibiotic restriction and stringent infection control measures, is important in managing VRE prevalence in Canadian institutions.

scholarly journals First Report of Nosocomial Outbreak of Vancomycin-Resistant Enterococcus Faecium Infection Among COVID-19 Patients Hospitalized in a Non-Intensive Care Unit Ward in Central Europe

2021 ◽  
Author(s):  
Yashar Jalali ◽  
Igor Šturdík ◽  
Monika Jalali ◽  
Ján Kyselovič ◽  
Adriána Liptáková ◽  
...  
Keyword(s):  
Infection Control ◽  
Central Europe ◽  
Control Strategies ◽  
Health Care Systems ◽  
Blood Stream ◽  
Control Measures ◽  
Outbreak Investigation ◽  
Strain Identification ◽  
Strict Adherence ◽  
Vancomycin Resistant

Abstract Background: The COVID-19 pandemic in 2020 exerted immense pressure on health care systems worldwide, causing substantial resources to be diverted to respond to the pandemic. These changes raise the concern about the potential for reduction in adherence to long-established measures in the prevention of healthcare-associated infections (HAI). Enterococcus species account for most of human enterococcal HAI and multidrug-resistant infections and have become a major threat to modern public health. We examine the rise in the number of vancomycin resistant E. faecium blood stream and urinary tract infections in a COVID-19 department during an epidemiologic outbreak investigation to detect and eliminate nosocomial clusters of the bacteria. Methods: Strain identification was performed by classical isolation and biochemical and cultivation methods. Antibiotic testing results were interpreted according to European committee on antimicrobial susceptibility testing (EUCAST) guidelines. Six isolated samples underwent whole genome sequencing (WGS) during the outbreak investigation. Isolate relatedness was determined using core genome multilocus sequence typing.Results: WGS revealed two genotypically distinct VRE clusters, one of which had genetically closely related patient and environmental isolates. The cluster was terminated by enhanced infection control strategies.Conclusions: This study provides the first description of an outbreak caused by vanA-ST17 E. faecium strains among COVID-19 patients in central Europe, and the first description of an outbreak caused by vanB-ST117 and vanA-ST17 E. faecium strains in Slovakia. This study can help raise awareness about the need for strict adherence to infection control measures and the implementation of rational antimicrobial stewardship as a routine part of COVID-19 management.

scholarly journals The history of healthcare facilities management services: a UK perspective on infection control

Facilities ◽  
2018 ◽  
Vol 36 (7/8) ◽  
pp. 369-385 ◽  
Author(s):  
Stanley Njuangang ◽  
Champika Liyanage ◽  
Akintola Akintoye
Keyword(s):  
Health Care ◽  
Roman Empire ◽  
Infection Control ◽  
Care Facility ◽  
Facility Management ◽  
Convincing Evidence ◽  
Epidemiological Evidence ◽  
Content Type ◽  
Wide Range ◽  
History Of

Purpose The history of the development of non-clinical services in infection control (IC) dates back to the pre-modern era. There is evidence of health-care facility management (HFM) services in Roman military hospitals. With the fall of the Roman Empire, Christian beliefs and teaching shaped the development of HFM in monastic hospitals. It was not until the late Victorian era that the link between HFM services and diseases caused by “miasma”, or bad air, became established. The discovery of bacteria in the modern scientific era reduced the level of importance previously attached to non-clinical causes of infections. Today, in the NHS, HFM services continue to be treated as though they had no real role to play in IC. This paper aims to collate historical and epidemiological evidence to show the link between HFM and IC. Design/methodology/approach The evidence gathered in this research paper is primarily based on an in-depth review of research from a wide range of sources. A “within-study literature analysis” was conducted to synthesise the research materials. This involved the application of “between-source triangulation” to verify the quality of the information contained in the studies, and “between-source complementarity” to provide an in-depth elaboration of the historical facts. Findings Historical and epidemiological evidence shows that HFM services such as cleaning, waste management, catering, laundry and maintenance continue to play a crucial role in IC. This is corroborated by evidence gathered from the work of renowned pioneers in the field of IC. However, reforms in the NHS have failed to consider this, as HFM services have been largely fragmented through different partnership arrangements. Practical implications Among many other things, this research raises the profile of HFM staff in relation to the issue of IC in hospitals. It presents convincing evidence to show that the relationship between the clinical and non-clinical domains in controlling infections in hospitals has a long history. The findings of this research give HFM staff invaluable information about the significant role of their profession in the control of infections in hospitals. Originality/value This is one of the few studies examining the historical development of HFM services, as well as their contribution to IC. Other work in this area has mainly been framed from a clinical health-care perspective.

scholarly journals A Phenotypically Silent vanB2 Operon Carried on a Tn1549-Like Element in Clostridium difficile

mSphere ◽  
2016 ◽  
Vol 1 (4) ◽  
Author(s):  
Daniel R. Knight ◽  
Grace O. Androga ◽  
Susan A. Ballard ◽  
Benjamin P. Howden ◽  
Thomas V. Riley
Keyword(s):  
Health Care ◽  
Clostridium Difficile ◽  
Resistance Genes ◽  
Vancomycin Resistance ◽  
Content Type ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant ◽  
Emergence Of Resistance ◽  
First Time

ABSTRACT In an era when the development of new antimicrobial drugs is slow, vancomycin remains the preferred antimicrobial therapy for Clostridium difficile infection (CDI), the most important health care-related infection in the world today. The emergence of resistance to vancomycin would have significant consequences in relation to treating patients with CDI. In this paper, we describe for the first time a complete set of vancomycin resistance genes in C. difficile. The genes were very similar to genes found in vancomycin-resistant enterococci (VRE) that were associated with the emergence and global dissemination of this organism. Fortunately, the C. difficile strain did not show any reduced susceptibility to vancomycin in vitro (MIC, 1 mg/liter), possibly because of a small difference in one gene. However, this observation signals that we may be very close to seeing a fully vancomycin-resistant strain of C. difficile. In the last decade, Clostridium difficile infection (CDI) has reached an epidemic state with increasing incidence and severity in both health care and community settings. Vancomycin is an important first-line therapy for CDI, and the emergence of resistance would have significant clinical consequences. In this study, we describe for the first time a vanB2 vancomycin resistance operon in C. difficile, isolated from an Australian veal calf at slaughter. The operon was carried on an ~42-kb element showing significant homology and synteny to Tn1549, a conjugative transposon linked with the emergence and global dissemination of vancomycin-resistant enterococci (VRE). Notably, the C. difficile strain did not show any reduced susceptibility to vancomycin in vitro (MIC, 1 mg/liter), possibly as a result of an aberrant vanRB gene. As observed for other anaerobic species of the animal gut microbiota, C. difficile may be a reservoir of clinically important vancomycin resistance genes. IMPORTANCE In an era when the development of new antimicrobial drugs is slow, vancomycin remains the preferred antimicrobial therapy for Clostridium difficile infection (CDI), the most important health care-related infection in the world today. The emergence of resistance to vancomycin would have significant consequences in relation to treating patients with CDI. In this paper, we describe for the first time a complete set of vancomycin resistance genes in C. difficile. The genes were very similar to genes found in vancomycin-resistant enterococci (VRE) that were associated with the emergence and global dissemination of this organism. Fortunately, the C. difficile strain did not show any reduced susceptibility to vancomycin in vitro (MIC, 1 mg/liter), possibly because of a small difference in one gene. However, this observation signals that we may be very close to seeing a fully vancomycin-resistant strain of C. difficile.

Impact of Contact and Droplet Precautions on the Incidence of Hospital-Acquired Methicillin-Resistant Staphylococcus aureus Infection

2007 ◽  
Vol 28 (11) ◽  
pp. 1261-1266 ◽  
Author(s):  
Ed Mangini ◽  
Sorana Segal-Maurer ◽  
Janice Burns ◽  
Annette Avicolli ◽  
Carl Urban ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Control Strategies ◽  
Baseline Period ◽  
Clinical Microbiology Laboratory ◽  
Methicillin Resistant ◽  
Contact Precautions ◽  
Clinical Culture ◽  
Surgical Icu ◽  
Mrsa Infection ◽  
Hospital Acquired

Objective.To evaluate the efficacy of contact and droplet precautions in reducing the incidence of hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections.Design.Before-after study.Setting.A 439-bed, university-affiliated community hospital.Methods.To identify inpatients infected or colonized with MRSA, we conducted surveillance of S. aureus isolates recovered from clinical culture and processed by the hospital's clinical microbiology laboratory. We then reviewed patient records for all individuals from whom MRSA was recovered. The rates of hospital-acquired MRSA infection were tabulated for each area where patients received nursing care. After a baseline period, contact and droplet precautions were implemented in all intensive care units (ICUs). Reductions in the incidence of hospital-acquired MRSA infection in ICUs led to the implementation of contact precautions in non-ICU patient care areas (hereafter, “non-ICU areas”), as well. Droplet precautions were discontinued. An analysis comparing the rates of hospital-acquired MRSA infection during different intervention periods was performed.Results.The combined baseline rate of hospital-acquired MRSA infection was 10.0 infections per 1,000 patient-days in the medical ICU (MICU) and surgical ICU (SICU) and 0.7 infections per 1,000 patient-days in other ICUs. Following the implementation of contact and droplet precautions, combined rates of hospital-acquired MRSA infection in the MICU and SICU decreased to 4.3 infections per 1,000 patient-days (95% confidence interval [CI], 0.17-0.97; P = .03). There was no significant change in hospital-acquired MRSA infection rates in other ICUs. After the discontinuation of droplet precautions, the combined rate in the MICU and SICU decreased further to 2.5 infections per 1,000 patient-days. This finding was not significant (P = .43). In the non-ICU areas that had a high incidence of hospital-acquired MRSA infection, the rate prior to implementation of contact precautions was 1.3 infections per 1,000 patient-days. After the implementation of contact precautions, the rate in these areas decreased to 0.9 infections per 1,000 patient-days (95% CI, 0.47-0.94; P = .02).Conclusion.The implementation of contact precautions significantly decreased the rate of hospital-acquired MRSA infection, and discontinuation of droplet precautions in the ICUs led to a further reduction. Additional studies evaluating specific infection control strategies are needed.

scholarly journals Multicenter Study of High-Dose Daptomycin for Treatment of Enterococcal Infections

2013 ◽  
Vol 57 (9) ◽  
pp. 4190-4196 ◽  
Author(s):  
Anthony M. Casapao ◽  
Ravina Kullar ◽  
Susan L. Davis ◽  
Donald P. Levine ◽  
Jing J. Zhao ◽  
...  
Keyword(s):  
Clinical Success ◽  
Clinical Success Rate ◽  
High Dose ◽  
Content Type ◽  
Hospital Acquired Infections ◽  
Median Dosage ◽  
All Cause Mortality ◽  
Vancomycin Resistant ◽  
Hospital Acquired ◽  
Enterococcal Infections

ABSTRACTEnterococci are among the leading pathogens isolated in hospital-acquired infections. Current antimicrobial options for vancomycin-resistant enterococci (VRE) are limited. Prior data suggest that daptomycin at >6 mg/kg of body weight/day may be used to treat enterococcal infections. We retrospectively evaluated the effectiveness and safety of high-dose daptomycin (HD-daptomycin) therapy (>6 mg/kg) in a multicenter cohort of adult patients with enterococcal infections to describe the characteristics and outcomes. Two hundred forty-five patients were evaluated.Enterococcus faeciumwas identified in 175 (71%), followed byEnterococcus faecalisin 49 (20%) andEnterococcusspp. in 21 (9%); overall, 204 (83%) isolates were VRE. Enterococcal infections included bacteremia (173, 71%) and intra-abdominal (35, 14%) and bone and joint (25, 10%) infections. The median dosage and duration of HD-daptomycin were 8.2 mg/kg/day (interquartile range [IQR], 7.7 to 9.7) and 10 days (IQR, 6 to 15), respectively. The overall clinical success rate was 89% (193/218), and microbiological eradication was observed in 93% (177/191) of patients. The median time to clearance of blood cultures on HD-daptomycin was 3 days (IQR, 2 to 5). The 30-day all-cause mortality rate was 27%, and 5 (2%) patients developed daptomycin-nonsusceptible enterococcal strains while on HD-daptomycin. Seven patients (3%) had creatine phosphokinase (CPK) elevation, yet no HD-daptomycin regimen was discontinued due to an elevated CPK and all patients were asymptomatic. Overall, there was a high frequency of clinical success and microbiological eradication in patients treated with HD-daptomycin for enterococcal infections, even in patients with complicated and difficult-to-treat infections. No adverse event-related discontinuation of HD-daptomycin was noted. HD-daptomycin may be an option for the treatment of enterococcal infections.

scholarly journals Chlorhexidine Induces VanA-Type Vancomycin Resistance Genes in Enterococci

2016 ◽  
Vol 60 (4) ◽  
pp. 2209-2221 ◽  
Author(s):  
Pooja Bhardwaj ◽  
Elizabeth Ziegler ◽  
Kelli L. Palmer
Keyword(s):  
Resistance Genes ◽  
Venous Catheter ◽  
Vancomycin Resistance ◽  
Chlorhexidine Gluconate ◽  
Content Type ◽  
Hospital Acquired Infections ◽  
Chlorhexidine Bathing ◽  
Vancomycin Resistant ◽  
Species Specific ◽  
Hospital Acquired

ABSTRACTChlorhexidine is a bisbiguanide antiseptic used for infection control. Vancomycin-resistantE. 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 thatvanAupregulation was not strain or species specific by querying other VanA-type VRE. VanB-type genes were not induced. ThevanHpromoter was found to be responsive to subinhibitory chlorhexidine gluconate in VREfm, as was production of the VanX protein. UsingvanHreporter experiments withBacillus subtilisand deletion analysis in VREfm, we found that this phenomenon is VanR dependent. Deletion ofvanRdid not result in increased chlorhexidine susceptibility, demonstrating thatvanHAXinduction 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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