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The epidemiology of fecal carriage of vancomycin-resistant enterococci.

An outbreak of vancomycin-resistant enterococci (VRE) began at the University of Massachusetts Medical Center in May 1993. As of September 1995, we had a total of 253 patients infected or colonized with VRE, with consequent increasing demand for private rooms. We analyzed results of surveillance cultures for VRE of 49 patients known to be colonized or infected with VRE. Of these, 34 (70%) were classified as persistent carriers, defined as patients with at least three consecutively positive cultures from any site taken over at least a 2-week period. The length of carriage varied from 19 to 303 days (median, 41 days); 11 patients were converters, defined as patients with three consecutive negative cultures from all previously colonized sites taken over a 3-week period. These patients were free of VRE for 39 to 421 days (median, 142 days). Four were recolonizers after they were documented to be clear of VRE for 33 to 106 days. VRE carriage tends to be prolonged, and hospitalization of patients with VRE will require continued isolation and contact precautions for control of transmission.

Carrier State↗

Managing vancomycin-resistant enterococci. A winning team approach.

Antibiotics have been the treatment of choice for a broad range of bacterial infections for decades. In recent years, however, concern has been growing over the increasing incidence of infections that are resistant to known antibiotics. A 1995 outbreak of ampicillin- and vancomycin-resistant enterococci (VRE) at the 3Y site of the McMaster University Medical Centre brought this concern home to us and resulted in the development of outbreak-management guidelines for VRE.

Ampicillin Resistance↗

Vancomycin-resistant enterococci: an emerging health problem.

Since 1995, KePRO has worked with the peer review organization for 13 other states/commonwealths and the District of Columbia, as well as the Boston Regional Office of the Health Care Financing Administration, in the implementation of the largest study ever conducted involving Vancomycin-resistant enterococci (VRE). Fifteen Pennsylvania hospitals volunteered to participate in the study, designed to identify and assess the appropriateness of vancomycin use, contributing 19 percent of the total records used in the baseline study. This article, the first of two, describes VRE and its increasing prevalence. In the second installment, we will describe patterns of vancomycin use identified in KePRO's study of participating Pennsylvania hospitals, as well as the steps these hospitals are taking to control antibiotic use. Since all data gathered by KePRO are protected by federal confidentiality guidelines, the facilities that graciously agreed to pioneer KePRO's vancomycin utilization project will not be identified or identifiable.

Anti-Bacterial Agents↗

Vancomycin-resistant enterococci: improving treatments.

Recent issues of Morbidity and Mortality Weekly Report (MMWR), a publication of the Centers for Disease Control and Prevention (CDC), described clinical isolates of Staphylococcus aureus with intermediate resistance to vancomycin in patients in Michigan and New Jersey. As described last month in the first installment of this article, vancomycin has been the only approved antibiotic to which S. aureus had been uniformly sensitive. Media coverage of this latest example of increasing antibiotic resistance included the September 4, 1997, issue of The Wall Street Journal, which carried a report of a large study of the appropriateness of vancomycin use being coordinated by the Health Care Financing Administration (HCFA). The article reported study findings that "63 percent of orders for the drug vancomycin violated guidelines from the Centers for Disease Control and Prevention." In this report, we provide additional details about that study, as well as results specific to the Pennsylvania hospitals that participated in this project. The journal article failed to point out that each of the hospitals volunteered to participate in this 15-state study, beginning in late 1995, as part of their strategy to prevent and control the spread of vancomycin-resistant enterococci (VRE). These facilities agreed with experts that optimizing vancomycin use was an important part of this strategy, in addition to traditional infection control measures such as appropriate handwashing practices, prompt and accurate identification of resistant organisms, and isolation of infected and colonized patients when indicated.

Aged↗

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↗

[Vancomycin-resistant enterococci in pediatric hematology: don't panic!].

Do immunocompromised children, carrying vancomycin-resistant enterococci (VRE) need to be treated? For 3 years, 230 children with chemotherapy and/or bone-marrow transplantation (BMT) received amikacin for gut decontamination and rinsed their mouth with solutions including vancomycin or not, according to the duration and severity of neutropenia. Some patients were isolated, others were at home with ambulatory treatment. The first-line antibio-therapy was piperacillin-amikacin-vancomycin in the chemotherapy unit, imipenem-vancomycin in the BMT unit. Once-a-week, the laboratory used to check the efficiency of decontamination procedures and look for emerging resistant bacteria. Four patients were identified as VRE carriers in their gut flora. The fecal carriage was long-lasting in a single patient, for whom attempts of eradication failed. No patient underwent VRE bacteremia. From our experience, it seems reasonable to neglect enterococcal eradication, provided that hygienic measures are strictly applied.

Amikacin↗

Investigation into the efficacy of disinfectants against MRSA and vancomycin-resistant enterococci.

In the study reported here, several disinfectants for surfaces, instruments, hands and mucous membrane were tested for their effectiveness against methicillin-resistant strains of S. aureus and vancomycin-resistant enterococci. The results show that after use of the recommended concentrations with the recommended contact times, which were determined on the basis of the criteria for disinfectants according to the DGHM guideline for the testing and evaluation of chemical disinfection procedures, an adequate effect was able to be proved. Increased resistance of the methicillin-resistant S. aureus and vancomycin-resistant E. faecium strains to the tested disinfectants was not found. Only after use of diluted solutions differences in the bacterial count reductions were observed. In further studies it is to be investigated whether these differences are due to resistance to antibiotics or to intrinsic resistance.

Disinfectants↗

Design and synthesis of simple macrocycles active against vancomycin-resistant enterococci (VRE).

16-membered meta,para-cyclophanes mimicking the vancomycin binding pocket (D-O-E ring) were designed and synthesized. The structural key features of these biaryl ether containing macrocycles are (1) the presence of beta-amino-alpha-hydroxy acid or alpha,beta-diamino acid as the C-terminal component of the cyclopeptide and (2) the presence of a hydrophobic chain or lipidated aminoglucose at the appropriate position. Cycloetherification by an intramolecular nucleophilic aromatic substitution reaction (S(N)Ar) is used as the key step for the construction of the macrocycle. The atropselectivity of this ring-closure reaction is found to be sensitive to the peptide backbone and chemoselective cyclization (phenol versus primary amine) is achievable. Glycosylation of phenol was realized with freshly prepared 3,4,6-tri-O-acetyl-2-N-lauroyl-2-amino-2-deoxy-alpha-D-glucopyranosyl bromide under phase-transfer conditions. Minimum inhibitory concentrations for all of the derivatives are measured by using a standard microdilution assay, and potent bioactivities against both sensitive and resistant strains are found for some of these compounds (MIC (minimum inhibitory concentration) = 4 microg mL(-1) against VRE). From these preliminary SAR studies, it was anticipated that both the presence of a hydrophobic substituent and an appropriate structure of the macrocycle were required for this series of compounds to be active against VRE.

Amides↗

Growth characteristics of enterococci isolated from Laban Rayeb.

Eleven strains of Enterococcus (Streptococcus) faecalis isolated from Laban Rayeb, a type of fermented milk, had been studied when grew in milk. Enterococcus (Streptococcus) faecalis strains 19 and 22 were the most active strains in the production of lactic acid, acetaldehyde and diacetyl. Both strains exhibited a high proteolytic activity besides a good clean flavour. Based on the obtained results, Enterococcus (Streptococcus) faecalis 19 and 22 could be used to bring about the lactic fermentation during the manufacture of some cultured dairy products.

Acetaldehyde↗

Studies on excision of conjugative transposons in enterococci: evidence for joint sequences composed of strands with unequal numbers of nucleotides.

We determined the nucleotide sequence of polymerase chain reaction products resulting from amplification of joint regions created after excision of transposons Tn5381 and Tn916 from a single site within plasmid pAD1. For both transposons, two joint sequences were observed. One (ATAGAT) was six nucleotides in length and identical to one of the junction sequences flanking the integrated transposon. This sequence also represents the original target sequence within pAD1. The other (TATGT (Tn5381) or TAGTT (Tn916)) was five nucleotides in length and identical to the junction sequence at the other end of the integrated transposons. These results suggest that excision of conjugative transposons from some insertion sites in gram-positive bacteria results in the formation of a joint region heteroduplex mismatched in nucleotide number as well as complementarity.

Base Sequence↗

Conjugal transfer of plasmid DNA from Escherichia coli to enterococci: a method to make insertion mutations.

Shuttle vector pAT18 was transferred by conjugation from Escherichia coli S17-1 to Enterococcus faecalis OG1RF and Enterococcus faecium SE34. Transfer was mediated by the transfer functions of plasmid RK2 in E. coli S17-1 and the origin of conjugal transfer (oriT) located on pAT18. The oriT sequence was then inserted into two plasmids to generate vectors pTEX5235 and pTEX5236. These two vectors cannot replicate in gram-positive bacteria and can be used to make insertion mutants in gram-positive bacteria. An internal sequence from an autolysin gene of E. faecalis OG1RF was cloned into pTEX5235 and transferred by conjugation from E. coli S17-1 to E. faecalis OG1RF. The plasmid was found to integrate into the chromosome of OG1RF by a single crossover event, resulting in a disrupted autolysin gene. A cosmid carrying the pyrimidine gene cluster from E. faecalis, with a transposon insertion in pyrC, was also transferred from E. coli S17-1 to E. faecalis OG1RF. After selection for the transposon, it was found to have recombined into the recipient chromosome by a double crossover between the cosmid and the chromosome of OG1RF. This resulted in a pyrC knockout mutant showing an auxotrophic phenotype.

Conjugation, Genetic↗