Progresses on the prevalence and mechanism of vancomycin- resistant bacteria.

Controlling the spread of vancomycin-resistant enterococci. Is active screening worthwhile?

Long term Impact of a Disinfectant with Residual Activity on Suppression of Bacteria on Fomites in Hospital Waiting Rooms

In the past 20 years, vancomycin and other glycopeptide antibiotics have been administered to patients with Streptococcal and Staphylococcal infections that were resistant to all other antibiotics or to patients who were allergic to penicillins and cephalosporins. After extensive use of vancomycin and other glycopeptide antibiotics in humans, several strains of Enterococcus have developed high-level vancomycin resistance (collectively called VRE, vancomycin-resistant Enterococcus), and this resistance phenotype has spread to other organisms. The spread of vancomycin resistance to other pathogens and, potentially, to bacterial strains on the CDC's bioterrorism watch list is a major biomedical concern. Bacteria most often become resistant to vancomycin by acquiring a transposon containing genes that encode for a number of proteins, five of which are essential for the high-level resistance phenotype. The five essential gene products are called VanR, VanS, VanH, VanA, and VanX. Previous studies have shown that the inactivation of VanX results in an organism that is sensitive to vancomycin and that VanX is an excellent inhibitor target. In this review the known inhibitors and structural and mechanistic properties of VanX will be discussed. These data will be used to offer suggestions for novel, rationally-designed or -redesigned inhibitors, which could potentially be used in combination with existing glycopeptide antibiotics as a treatment for vancomycin-resistant bacterial infections.

Evidence that contaminated surfaces contribute to the transmission of hospital pathogens and an overview of strategies to address contaminated surfaces in hospital settings

Occurrence of glycopeptide resistance among Enterococcus faecium isolates from conventional and ecological poultry farms.

Introduction

<i>In Vitro</i> Activity of Fidaxomicin (OPT-80) Tested against Contemporary Clinical Isolates of <i>Staphylococcus</i> spp. and <i>Enterococcus</i> spp

Vancomycin remains the drug of choice for resistant gram positive infections caused by Enterococcus spp and Methicillin resistant Staphylococcus aureus (MRSA). Increased use of vancomycin has led to frank resistance and increase in MIC (MIC creep). Vancomycin intermediate Staphylococcus aureus (VISA), Vancomycin resistant Staphylococcus aureus (VRSA) & Vancomycin resistant Enterococci (VRE) are important emerging nosocomial pathogens resulting in treatment failures. This study was undertaken to detect vancomycin resistance among clinical isolates of Staphylococcus aureus and Enterococcus faecalis by phenotypic and genotypic methods. The study was conducted in a 1850 bedded university teaching hospital from November 2013 to April 2014. Non-repetitive, consecutive clinically significant Staphylococcus aureus (109) and Enterococcus faecalis (124) were included in this study. They were identified up to species level by conventional and automated methods. Susceptibility to various antibiotics was tested by disc diffusion method. MIC of vancomycin was determined by agar dilution method. Inducible resistance to clindamycin was detected by the D test. Methicillin resistance in Staphylococcus aureus (MRSA) was screened using cefoxitin disc. All isolates were subjected to polymerase chain reaction (PCR) to detect van A and van B genes. Out of 109 Staphylococcus aureus isolates, 54 were MRSA. By MIC there was no resistance observed to vancomycin.MIC50 was 1μg/ml. None of the isolates harboured van A and van B. Among Enterococcus faecalis, sixteen isolates (12.9%) and four isolates (3.2%) exhibited resistance to vancomycin and teicoplanin by disc diffusion respectively. All isolates were susceptible to linezolid. Van A was detected in 2, van B in 7 and one had both van A and van B. PCR remains the gold standard for diagnosis of vancomycin resistance. There was no resistance observed to vancomycin among Staphylococci though the MIC creep detected is a cause for concern. Eight percent of Enterococci were vancomycin resistant.

For 3 decades, vancomycin has been a favored therapy for serious penicillinand cephalosporin-resistant Gram-positive bacterial infections. Development of vancomycin resistance may have been restrained by the requirement for intravenous administration, which limited its use and lessened exposure to the gastrointestinal flora. Nevertheless, physicians are increasingly encountering children and adults infected with vancomycin-resistant Gram-positive organisms. Resistance to vancomycin has been encountered in all commonly occurring, clinically significant Gram-positive bacterial species except Streptococcus pyogenes, Streptococcus pneumoniae, and Streptococcus agalactiae. Although therapeutic options are usually guided by the antimicrobial susceptibilities of individual isolates, recommended infection-control measures vary with the specific species and the mechanism of resistance. VANCOMYCIN-RESISTANT STAPHYLOCOCCUS AUREUS Vancomycin-resistant Staphylococcus aureus (VRSA) were first recognized in Japan in 1996; the first case of infection due to VRSA in the United States was reported in 2002. Since then, at least 8 additional cases of VRSA infection have been identified in the United States, with more than half of these cases occurring in Michigan. Isolates often seem to have evolved independently in settings where patients were previously colonized with vancomycin-resistant enterococcus (VRE) and methicillin-resistant S. aureus (MRSA). Environments that promote biofilm formation may facilitate transmission of resistance from VRE to MRSA. VRSA isolates (vancomycin MIC 16 g/mL) are fundamentally different from vancomycin-intermediate S. aureus (VISA) isolates (vancomycin MIC 4 – 8 g/mL). Resistance in VISA isolates is typically mediated via mechanisms that develop in the presence of vancomycin and are not readily transferrable to other strains. The potential for spread of these isolates is low in the absence of vancomycin therapy. In contrast, VRSA isolates uniformly contain the vanA gene derived from enterococcus (discussed below). The VanA phenotype is transferable to other MRSA strains and across microbial species, with a much greater potential for spread, even in the absence of vancomycin therapy. Thus far, VRSA outbreaks have not occurred; however, because of the potential for spread with dire consequences, a case of VRSA infection warrants a more rigorous infection-control response than a case of infection with MRSA, VISA, or VRE. Infection-control measures should be implemented urgently according to a written plan, if VRSA is suspected. The local health department and the Centers for Disease Control and Prevention should be consulted immediately. Management of contacts should occur according to contact categorization. Attempts to decolonize individuals who are found to be colonized should be considered on a case-by-case basis. Infections with S. aureus isolates that have vancomycin MICs 4 g/mL typically do not respond clinically to vancomycin therapy. To date, all VRSA have also been found to be resistant to methicillin. Fortunately, all VRSA and VISA isolates have been susceptible to one or more commercially available antibiotics. Recommended antibiotics for VRSA and VISA, according to susceptibilities and other clinical considerations, are listed in Table 1. Secondary agents include teicoplanin (not available in the United States), trimethoprim-sulfamethoxazole, tetracycline, rifampin (usually in combination therapy), and chloramphenicol.

The objectives of this study were to determine the presence and antimicrobial resistance of Methicillin Resistant Staphylococcus aureus (MRSA) and Vancomycin Resistant Enterococci (VRE) on beef and chicken carcasses and meat, and workers hands’ at processing time from a cattle and a poultry slaughterhouse, and beef and chicken meat at retail level. Disk diffusion method was used to determine the antimicrobial resistance profile of the Enterococcus spp. and S. aureus isolates. Minimum Inhibitory Concentration (MIC) values were determined for vancomycin and oxacillin resistance. Finally, conventional PCR was performed to determine the presence of the mecA and vanA resistance genes in isolates classified resistant to oxacillin and vancomycin according to MIC values. S. aureus and Enterococcus faecium isolated from 17 (17%) and eight (8%) samples, respectively. E. faecalis was not detected in any sample. The highest resistance rates were to ampicillin (3/5, 60 %) and penicillin G (5/5, 100 %) in MRSA and tetracycline (4/5, 80 %) in VRE isolates. While the mecA gene was detected in all MRSA isolates, vanA gene was not detected in any of the phenotypically vancomycin resistant E. faecium isolates. The present study provides data for multiple antimicrobial resistance and presence of VRE and MRSA isolated from an ongoing surveillance in humans, livestock and poultry in Turkey.

Healthcare Utilization and Serious Infection Prevalence Associated With Penicillin “Allergy” In Hospitalized Patients: A Cohort Study

The rise in antibiotic resistance limits the availability of antibiotics to treat bacterial infections. Despite this, antibiotic development pipelines remain sparse which makes using adjuvants to reverse antibiotic resistance a promising therapeutic strategy. The use of vancomycin, a frontline antibiotic used to treat hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA) infections, is complicated by high rates of treatment failure. Vancomycin binds to the D-ala-D-ala terminus of the nascent peptidoglycan precursor lipid II, preventing cell wall biosynthesis. Vancomycin-resistant strains of S. aureus and Enterococci typically express a van gene cluster that is induced in response to vancomycin and results in the synthesis of an alternative lipid precursor with a peptide chain ending in D-ala-D-lac. Vancomycin has low affinity for the D-ala-D-lac terminus, and the bacteria can resume growth even in the presence of an otherwise lethal dose of vancomycin. We previously showed that palmitoleic acid, a host-produced monounsaturated fatty acid, combined with vancomycin led to an accumulation of large fluid patches in the bacterial membrane, resulting in membrane destabilization and cell death. In this study, we observed that palmitoleic acid increases the rate of vancomycin killing by more than 50-fold, compared to vancomycin alone. This rapid bactericidal activity by the combined treatment sensitized vancomycin-resistant S. aureus (VRSA) and vancomycin-resistant Enterococcus (VRE) to vancomycin, likely by outpacing the expression of vancomycin resistance genes. This study represents an important step in the ongoing effort to mitigate antibiotic resistance.IMPORTANCEThe development of antibiotics has transformed medicine, reducing the incidence and severity of bacterial infections and allowing for advancements in healthcare, including invasive surgeries and organ transplants. However, the rise of antibiotic resistance poses a significant threat to these medical advancements, leading to treatment failures that result in increased patient morbidity and mortality, as well as substantial healthcare costs. Vancomycin-resistant Enterococcus (VRE) species are prevalent in hospital settings and chronic infections. Although high-level vancomycin resistance in S. aureus is rare, S. aureus can acquire plasmids expressing vancomycin resistance genes from resistant Enterococcal species during infection, further complicating treatment. In this study, we find that palmitoleic acid increases the rate of vancomycin killing and restores sensitivity to vancomycin-resistant S. aureus (VRSA) and VRE isolates.

The increase in vancomycin use in the 1980s to treat antibiotic-associated colitis and methicillin-resistant Staphylococcus aureus (MRSA) is largely responsible for the appearance of vancomycin-resistant enterococcus, which in turn spawned isolated cases of vancomycin-resistant S. aureus. Perhaps most worrisome to clinicians are strains of MRSA that are heteroresistant to vancomycin; these isolates are difficult to detect. Appropriate use of vancomycin coupled with awareness of infection control measures is paramount to abrogating the emergence of new vancomycin-resistant MRSA organisms and preserving its future efficacy. The continued reliance on vancomycin for the treatment of MRSA infections will depend on whether vancomycin resistance can be minimized. Newer antibacterial agents, particularly those with activity toward MRSA and vancomycin-resistant enterococcus, such as linezolid, quinupristin/dalfopristin, daptomycin, and tigecycline, may take a more prominent clinical role when gram-positive bacteria resistance to vancomycin further escalate.

To assess whether use of oral vancomycin for treatment during an outbreak of Clostridium difficile infection (CDI) was associated with increased rates of colonization with vancomycin-resistant enterococci (VRE). A retrospective analysis of hospital databases. The Jewish General Hospital in Montreal, Quebec, Canada. We collected data regarding VRE colonization and CDI from November 1, 2000, through September 30, 2007, during which policies of preferential oral metronidazole or vancomycin treatment were implemented to control an outbreak of CDI. Four periods were considered: period 1, the preoutbreak period when metronidazole was used; period 2, the CDI outbreak period when metronidazole was used; period 3, the postoutbreak period when vancomycin was used; and period 4, the postoutbreak period when metronidazole was used. A total of 2,412 cases of CDI and 425 cases of VRE colonization were identified. The rate of CDI increased significantly during period 2 and decreased to preoutbreak levels during period 3. The rate of VRE also increased during period 2 and decreased during the first 18 months of period 3. A clonal outbreak of cases of VRE (VanA) colonization was observed toward the end of period 3 and into period 4. Excluding the period of the clonal outbreak, there was a strong correlation between the number of cases of CDI and VRE colonization (r=0.736; P=.001) and a negative association between VRE colonization and vancomycin use (r=-0.765; P=.04). Increased vancomycin use was not associated with an increase in VRE colonization over a 2-year period. Restriction of vancomycin use during CDI outbreaks because of the fear of increasing VRE colonization may not be warranted.

IntroductionScandinavian countries have traditionally had a low prevalence of resistant organisms, but have in recent years experienced a change in their epidemiology. We aim to describe the epidemiology of carbapenemase-producing organisms (CPOs), vancomycin-resistant enterococci (VRE) and methicillin-resistant S. aureus (MRSA) in Norway, measure the importance of infections contracted abroad, and assess the morbidity and mortality associated with these resistant bacteria in Norway.Methods and materialsWe used data from the Norwegian surveillance system for communicable diseases covering all findings of the selected resistant bacteria including both infections and colonisation, in the period 2006–2017. Annual trends were assessed using negative binomial regression. For MRSA, we were able to calculate the Morisita-Horn index and transmission numbers following importation in order to assess the effect this had on further domestic transmission.ResultsThe incidence rates (per 100,000 personyears) of the three groups of resistant bacteria have increased during the period. In 2017 the incidence rates were 0.82 for CPOs, 7.09 for VRE and 43.8 for MRSA. 81% of CPO cases were diagnosed in hospitals, but 73% were infected abroad. Most VRE cases were infected in Norwegian hospitals, 85% were associated with hospitals outbreaks. MRSA was predominantly diagnosed in the community, only 21% were diagnosed in hospitals. Of all MRSA cases, 35% were infected in other countries. Most MRSA spa-types were not identified again after introduction, resulting in a transmission of MRSA equivalent to a mean of 0.30 persons infected from each spa-type identified (range: 0–22). The proportion of infections among all notified cases within each diagnose was 44% for MRSA, 9% for VRE and 45% for CPOs. Among persons notified with bacteraemia, the 30 days all-cause mortality were 20%, 16% and 50% for MRSA, VRE and CPOs respectively.DiscussionThe incidence rates of CPOs, VRE and MRSA in Norway are low, but increasing. The continuing increase of notified resistant bacteria highlights the need for a revision of existing infection prevention and control guidelines.