Vancomycin-resistant Bacillus circulans carrying the vanA gene responsible for vancomycin resistance in enterococci.
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Anti-Bacterial Agents↗
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Genetic characterization of vanG, a novel vancomycin resistance locus of Enterococcus faecalis.
Enterococcus faecalis strain WCH9 displays a moderate level of resistance to vancomycin (MIC = 16 microgram/ml) and full susceptibility to teicoplanin but is negative by PCR analysis using primers specific for all known enterococcal vancomycin resistance genotypes (vanA, vanB, vanC, vanD, and vanE). We have isolated and sequenced a novel putative vancomycin resistance locus (designated vanG), which contains seven open reading frames, from this strain. These are organized differently from those of all the other enterococcal van loci, and, furthermore, the individual vanG gene products exhibit less than 50% amino acid sequence identity to other van gene products.
Amino Acid Sequence↗
Methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci: therapeutic realities and possibilities.
During the past decade much effort has been devoted worldwide to limiting the spread of methicillin-resistant Staphylococcus aureus. However, the recent emergence of almost untreatable vancomycin-resistant enterococci has led to a new and unexpected public health problem in hospitals and the community. Moreover, the threat of transfer of glycopeptide resistance to S aureus means that development of alternative antimicrobial strategies has become urgent. Whereas major advances have been made in our understanding of methicillin and vancomycin resistance mechanisms, we still need to identify the sources and reservoirs of the genetic determinants of resistance and to discover how they disseminate in the environment. The outcome of the battle between antimicrobials and bacteria is still uncertain, but the challenge is worth meeting.
Anti-Bacterial Agents↗
Toxin-antitoxin systems are ubiquitous and plasmid-encoded in vancomycin-resistant enterococci.
Vancomycin-resistant enterococci (VRE) are common hospital pathogens that are resistant to most major classes of antibiotics. The incidence of VRE is increasing rapidly, to the point where over one-quarter of enterococcal infections in intensive care units are now resistant to vancomycin. The exact mechanism by which VRE maintains its plasmid-encoded resistance genes is ill-defined, and novel targets for the treatment of VRE are lacking. In an effort to identify novel protein targets for the treatment of VRE infections, we probed the plasmids obtained from 75 VRE isolates for the presence of toxin-antitoxin (TA) gene systems. Remarkably, genes for one particular TA pair, the mazEF system (originally identified on the Escherichia coli chromosome), were present on plasmids from 75/75 (100%) of the isolates. Furthermore, mazEF was on the same plasmid as vanA in the vast majority of cases (>90%). Plasmid stability tests and RT-PCR raise the possibility that this plasmid-encoded mazEF is indeed functional in enterococci. Given this ubiquity of mazEF in VRE and the deleterious activity of the MazF toxin, disruption of mazEF with pharmacological agents is an attractive strategy for tailored antimicrobial therapy.
Antitoxins↗
Intrinsically vancomycin-resistant gram-positive organisms: clinical relevance and implications for infection control.
Intrinsic resistance to vancomycin in gram-positive bacteria presumably predates acquired vancomycin resistance in enterococci but it has only recently generated interest. Intrinsically resistant enterococci possessing the vanC gene and the non-enterococcal genera Leuconostoc, Lactobacillus, Pediococcus and Erysipelothrix are known to cause human infection. This review examines the available data on their identification, resistance mechanisms, epidemiology, clinical infections and antimicrobial susceptibility. Intrinsically vancomycin-resistant gram-positives are usually opportunistic pathogens. Although serious infections may occur, treatment options remain available. No additional infection control measures for the intrinsically resistant genera appear justified with currently available evidence, although vigilance should be maintained to detect future changes in susceptibility patterns.
Anti-Bacterial Agents↗
Epidemiology of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus in a rural state.
BACKGROUND: Most data on methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) isolates come from large tertiary care centers. Infection control personnel need to understand the epidemiology of MRSA and VRE across the continuum of care, including small rural hospitals, to develop effective control strategies. OBJECTIVE: To describe the epidemiology of MRSA and VRE in Iowa. SETTING: Fifteen hospitals in Iowa. Methods Between July 1998 and June 2001, a total of 1,968 S. aureus isolates and 1,845 Enterococcus isolates from patients infected with these pathogens were examined. Multivariate models were developed to evaluate patient and institutional risk factors for MRSA infection and VRE infection. RESULTS: The proportion of S. aureus isolates resistant to methicillin was 31%, and the proportion of Enterococcus isolates resistant to vancomycin was 6%. Independent risk factors for MRSA infection included residence in a long-term care facility, age of more than 60 years, hospitalization in a hospital with less than 200 short-term care beds, and acquiring the infection in the hospital. Independent risk factors for VRE infection included use of a central venous catheter, residence in a long-term care facility, acquisition of infection in the hospital, and hospitalization in a hospital with more than 200 short-term care beds. CONCLUSIONS: In Iowa, the epidemiology of MRSA differ from those of VRE. MRSA has become established in small rural hospitals. Effective MRSA control strategies may require inclusion of all hospitals in a state or region.
Aged↗
Association between antecedent intravenous antimicrobial exposure and isolation of vancomycin-resistant enterococci.
Vancomycin-resistant enterococci (VRE) have become important causes of nosocomial infections. This study evaluated the association between a variety of intravenous antimicrobial exposures and the isolation of VRE using two control groups: (1) a vancomycin-susceptible enterococci (VSE) group, to assess factors associated with development of VRE, and (2) a nonenterococci control group, to assess factors associated with positive cultures for enterococci without regard to vancomycin resistance. After adjusting for the effect of other antimicrobials, time at risk, and patient morbidity, compared to vancomycin-susceptible enterococci controls, exposures to imipenem (OR = 4.9, 95% CI = 1.6-14.1) and ceftazidime (OR = 2.6, 95% CI = 1.1-6.1) were significant predictors of VRE. When compared to nonenterococci controls, exposures to ampicillin (OR = 20.1, 95% CI = 1.5-263.1) and imipenem (OR = 5.1, 95% CI = 1.5-17.1) were significantly associated with VRE. Neither piperacillin nor vancomycin was associated with VRE compared to either control group. This study offers further evidence that the replacement of broad-spectrum cephalosporins by extended-spectrum penicillins, specifically piperacillin, may be effective in reducing VRE.
Adult↗
Reducing the spread of antimicrobial-resistant microorganisms. Control of vancomycin-resistant enterococci.
Strategies to reduce the spread of hospital-acquired microorganisms resistant to multiple antimicrobial agents are discussed. Because hospitals have experienced a rapid increase in the incidence of infection and colonization with vancomycin-resistant enterococci (VRE) in the past 5 years, the Hospital Infection Control Practices Advisory Committee of the Centers for Disease Control and Prevention has issued recommendations for preventing the spread of vancomycin resistance. Controlling VRE dissemination in pediatric patients requires prompt detection of VRE by microbiology laboratories, education of staff and families about VRE, use of infection control measures to prevent person-to-person VRE transmission, and prudent vancomycin use.
Child↗
[Hospital infection control measures for methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci].
Methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci are major hospital pathogens in hospital settings. These organisms are mainly transmitted by direct skin contact with infected/colonized patients. Air borne transmission may rarely occur in MRSA positive cases with upper respiratory infections. Contamination in immediate environment requires proper disinfection after contact. Screening patients for MRSA and VRE can be restricted against those in/from the high risk areas. The clinical pictures, methods for screening and the precautions were also discussed based on the nature of communicability in both pathogens.
Cross Infection↗
Selective digestive tract decontamination--will it prevent infection with multidrug-resistant gram-negative pathogens but still be applicable in institutions where methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci are endemic?
The purposes of selective decontamination of the digestive tract are to treat infections that may be incubating at the time a patient is admitted to an intensive care unit (ICU), by intravenous administration of antibiotics during the first days of a stay in the ICU, and to prevent ICU-acquired infections, by topical application of antibiotics in the oropharynx and the gastrointestinal tract. Despite multiple trials in which a considerable reduction in the incidence of ventilator-associated pneumonia was demonstrated, major objections against the routine use of selective decontamination of the digestive tract have included a lack of demonstrated reductions in mortality rates and in length of stay (in individual trials), a lack of cost-efficacy data, and the threat of selection of multidrug-resistant bacteria. Recently, 2 controlled, randomized studies reported significant reductions in mortality rates among patients in ICUs who underwent selective decontamination of the digestive tract in combination with reduced selection of antibiotic-resistant pathogens. However, those studies were performed in settings where levels of antibiotic resistance are low, and some methodological issues remain unresolved. If these beneficial results are confirmed, the question of how to balance these benefits against the expected enhanced selection of methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and, possibly, multidrug-resistant gram-negative bacteria will emerge.
Anti-Bacterial Agents↗
Molecular epidemiology of hospital-acquired vancomycin-resistant enterococci.
Vancomycin-resistant Enterococcus faecium strains are a significant cause of nosocomial infections in predisposed patients. Multiple-locus variable-number tandem repeat analysis (MLVA) has been validated recently by use of a global strain collection. In this report, we applied MLVA together with multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) to type 14 isolates from three clusters of patients colonized or infected with vancomycin-resistant Enterococcus faecium and another 10 epidemiologically unrelated isolates from the same hospital. The clusters could be distinguished by all three typing methods, which proved to be concordant. PFGE patterns provided the highest resolution. We observed seven sequence types (ST), six MLVA types (MT), and nine distinct ST/MT combinations. The combination of MLST and MLVA may be an alternative to PFGE in hospital epidemiology, providing the benefits of high accuracy, reproducibility, and portability.
Bacterial Typing Techniques↗
Overproduction of a 37-kilodalton cytoplasmic protein homologous to NAD+-linked D-lactate dehydrogenase associated with vancomycin resistance in Staphylococcus aureus.
We previously reported the isolation of a laboratory-derived Staphylococcus aureus mutant, 523k, that has constitutive low-level resistance to vancomycin (MIC = 5 micrograms/ml) and teicoplanin (MIC = 5 micrograms/ml) and elaborates a ca. 39-kDa cytoplasmic protein that was not detected in the parent strain 523 (MIC = 1 micrograms/ml). We have now detected the protein in strain 523 by immunoblotting with antiserum raised against the protein. Consistent with our initial observations, densitometric analysis of the immunoblots revealed an increased production of the protein in 523k compared with that of the susceptible parent 523. The 5' region of the gene encoding the protein of interest was identified by nucleotide sequencing a PCR product amplified from the genome of 523k with degenerate primers designed to encode the amino acid sequence of proteolytic peptides obtained from the protein. The remainder of the gene was identified by library screening, PCR, and nucleotide sequencing. The gene encodes a 36.7-kDa protein with homology to a family of bacterial NAD+-dependent, D-specific 2-hydroxyacid dehydrogenases which includes both D-lactate dehydrogenase and the enterococcal vancomycin resistance protein VanH and is therefore designated ddh. Increased production of the product of ddh, Ddh, was associated with increased D-lactate dehydrogenase activity in 523k, a finding which suggested that Ddh is likely to be the D-lactate dehydrogenase previously identified in S. aureus. The increased D-lactate dehydrogenase activity in strain 523k and the structural similarities among Ddh, D-lactate dehydrogenase, and VanH suggest that overproduction of Ddh might play a role in vancomycin resistance in this strain.
Alcohol Oxidoreductases↗
Comparison of linezolid activities under aerobic and anaerobic conditions against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium.
Methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium were exposed to linezolid (MIC of 2 mg/liter) under aerobic or anaerobic conditions in an in vitro pharmacodynamic model. Drug concentration and half-life were adjusted to simulate clinical dosing (600 mg twice daily) of linezolid. Linezolid produced a 2-log(10) killing at 24 h, and rates of killing against each of these facultative organisms as measured by mean survival time appeared similar under aerobic and anaerobic conditions.
Acetamides↗
Vancomycin resistance in Staphylococcus aureus.
Vancomycin resistance in enterococci, predominantly Enterococcus faecium, developed in the latter half of the 1980s, and the long anticipated development of vancomycin resistance in Staphylococcus aureus has now occurred. A number of vancomycin-intermediate strains have been described, and these strains have abnormal, thickened cell walls in the presence of vancomycin. Two mechanisms of resistance have been described in the strains: affinity trapping of vancomycin molecules by cell wall monomers and clogging of the outer layers of peptidoglycan by bound vancomycin molecules, and change in the structure or metabolism of teichoic acids. Of more serious concern has been the description in 2002 of two patients with vancomycin-resistant S aureus infections. In one instance, the patient had skin lesions coinfected with vancomycin resistant, vanA genotype, E faecalis, and the vanA resistance genes could have been transferred to the S aureus strain. Expression of resistance was high in one S aureus strain and low in the other, making detection more challenging in the latter instance. These developments are of great concern, and every effort should be made to prevent further development and spread of vancomycin resistance in staphylococci.
Anti-Bacterial Agents↗
Inducible carboxypeptidase activity in vancomycin-resistant enterococci.
Vancomycin was found to coinduce DD-carboxypeptidase activity, together with resistance, in eight low- or high-level glycopeptide-resistant strains of enterococci. The constitutively resistant mutant (MT10) of a low-level-resistant strain of Enterococcus faecium (D366) spontaneously expressed a level of carboxypeptidase similar to that of the induced strain D366. Pentapeptide, UDP-MurNac-pentapeptide, as well as D-alanyl-D-alanine were in vitro substrates for the carboxypeptidase which was not inhibited by penicillin. The level of vancomycin resistance correlated roughly with the level of carboxypeptidase activity. We infer from these results that the carboxypeptidase is one component of the glycopeptide resistance mechanism.
Anti-Bacterial Agents↗
Impact of alcohol-based, waterless hand antiseptic on the incidence of infection and colonization with methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci.
OBJECTIVE: Colonized and infected inpatients are major reservoirs for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), and transient carriage of these pathogens on the hands of healthcare workers remains the most common mechanism of patient-to-patient transmission. We hypothesized that use of alcohol-based, waterless hand antiseptic would lower the incidence of colonization and/or infection with MRSA and VRE. METHODS: On June 19, 2001, alcohol hand antiseptic was introduced at the University campus and not the nearby Memorial campus of the University of Massachusetts Medical School (Worcester, MA), allowing us to evaluate the impact of this antiseptic on the incidence of MRSA and VRE colonization and infection. From January 1 through December 31, 2001, the incidence of MRSA colonization or infection was compared between the 2 campuses before and after the hand antiseptic was introduced. Its effect on VRE colonization and infection was only studied in the medical intensive care unit at the University campus. RESULTS: At the University campus, the incidence of MRSA colonization or infection decreased from 1.26 cases/1,000 patient-days before the intervention to 0.75 cases/1,000 patient-days after the intervention, for a 1.46-fold decrease (95% confidence interval, 1.04-2.58; P = .037). At the Memorial campus, the incidence of MRSA colonization or infection remained virtually unchanged, from 0.34 cases/1,000 patient-days to 0.49 cases/1,000 patient-days during the same period. However, a separate analysis of the University campus data that controlled for proximity to prevalent cases did not show a significant improvement in the rates of infection or colonization. The incidence of nosocomial VRE colonization or infection before and after the hand antiseptic decreased from 12.0 cases/1,000 patient-days to 3.0 cases/1,000 patient-days, a 2.25-fold decrease (P = .018). Compliance with rectal surveillance for detection of VRE was 86% before and 84% after implementation of the hand antiseptic intervention. The prevalences of VRE cases during these 2 periods were 25% and 29%, respectively (P = .017). CONCLUSIONS: Alcohol hand antiseptic appears to be effective in controlling the transmission of VRE. However, after controlling for proximity to prevalent cases (ie, for clustering), it does not appear to be more effective than standard methods for controlling MRSA. Further controlled studies are needed to evaluate its effectiveness.
Alcohols↗
Vancomycin-resistant enterococci.
Vancomycin-resistant enterococci (VRE) are gaining much attention in the West, chiefly because of the lack of available antimicrobial therapy for VRE infections as most VRE are also resistant to drugs previously used to treat such diseases (e.g. aminoglycosides and ampicillin), the possibility that the vancomycin-resistant genes present in VRE can be transferred to methicillin-resistant Staphylococcus aureus (MRSA), and increasing reports of VRE and the trend towards endemicity in North America. There are three case reports and a study showing stool carriage of more than 10% from Singapore. One of the case reports is notable as the VRE isolated from the urinary tract is community-acquired. In Europe, there is a strong association between the use of avoparcin (a glycopeptide) in animal feeds and the emergence of VRE. Clonal dissemination resulting in nosocomial transmission is also demonstrated. Prior vancomycin use is a risk factor for the subsequent development of VRE bacteraemia. The laboratory plays an important role, namely, a) detection of VRE, and b) determination of susceptibilities of antimicrobials whereby possible therapeutic options may be instituted when antimicrobial intervention is indicated. There is a need to evaluate existing infection control measures against VRE to prevent it from becoming endemic in Singapore as had happened in North America.
Anti-Bacterial Agents↗
Colonial variation in vancomycin resistant Enterococcus faecium.
Vancomycin resistant enterococci are increasingly being isolated from inpatients. This report describes the colonial variation present in most isolates of vancomycin resistant Enterococcus faecium obtained at this hospital. Colonial variants within the same culture were indistinguishable by antimicrobial susceptibility, biochemical reactions, and ribotyping. Failure to appreciate this colonial variation will lead to pure cultures being regarded as contaminated or mixed.
Cross Infection↗