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PubMed2006

Use of streptogramin growth promoters in poultry and isolation of streptogramin-resistant Enterococcus faecium from humans.

BACKGROUND: Virginiamycin use in poultry selects for Enterococcus faecium with cross-resistance to quinupristin-dalfopristin, a drug for vancomycin-resistant E. faecium in humans. We conducted an epidemiologic study of poultry exposures as risk factors for human carriage of quinupristin-dalfopristin-resistant E. faecium. METHODS: Rectal or fecal samples for E. faecium testing were obtained from 567 newly admitted hospital patients and 100 healthy vegetarians. Participants were interviewed regarding poultry exposure. Retail poultry washes (160 conventional and 26 antibiotic free) were also tested for the presence of E. faecium. Constitutive and inducible quinupristin-dalfopristin resistance were assessed in E. faecium isolates, and resistance genes were identified by polymerase chain reaction. RESULTS: E. faecium was isolated from 105 patients, 65 vegetarians, and 77 conventional and 23 antibiotic-free poultry washes. Constitutive quinupristin-dalfopristin resistance was absent in human E. faecium, but 56% of conventional poultry isolates were quinupristin-dalfopristin resistant. Inducible quinupristin-dalfopristin resistance was more common in samples from patients than in those from vegetarians and in washes of conventional than antibiotic-free poultry. Higher poultry consumption was associated with inducible quinupristin-dalfopristin resistance. vatE was present in 38% of E. faecium isolates from patients and none from vegetarians. Touching raw poultry was associated with the presence of vatE. CONCLUSIONS: Poultry exposure is associated with a quinupristin-dalfopristin resistance gene and inducible quinupristin-dalfopristin resistance in human fecal E. faecium. The continued use of virginiamycin may increase the potential for streptogramin-resistant E. faecium infection in humans.

Adult↗
PubMed2006

What to think if the results of the National Institutes of Health randomized trial of methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococcus control measures are negative (and other advice to young epidemiologists): a review and an au revoir.

The incidence of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) infections continues to rise in National Nosocomial Infections Surveillance system hospitals, and these pathogens are reportedly causing more than 100,000 infections and many deaths each year in US healthcare facilities. This has led some to insist that control measures are now urgently needed, but several recent articles have suggested that isolation of patients does not work, is not needed, or is unsafe, or that a single cluster-randomized trial could be used to decide such matters. At least 101 studies have reported controlling MRSA infection and 38 have reported controlling VRE infection by means of active detection by surveillance culture and use of isolation for all colonized patients in healthcare settings where the pathogens are epidemic or endemic, in academic and nonacademic hospitals, and in acute care, intensive care, and long-term care settings. MRSA colonization and infection have been controlled to exceedingly low levels in multiple nations and in the state of Western Australia for decades by use of active detection and isolation. Studies suggesting problems with using such data to control MRSA colonization and infection have their own problems, which are discussed. Randomized trials are epidemiologic tools that can sometimes provide erroneous results, and they have not been considered necessary for studying isolation before it is used to control other important infections, such as tuberculosis, smallpox, and severe acute respiratory syndrome. No single epidemiologic study should be considered definitive. One should always weigh all available evidence. Infection with antibiotic-resistant pathogens such as MRSA and VRE is controllable to a low level by active detection and isolation of colonized and infected patients. Effective measures should be used to minimize the morbidity and mortality attributable to these largely preventable infections.

Cross Infection↗
PubMed1998

The role of chloramphenicol in the treatment of bloodstream infection due to vancomycin-resistant Enterococcus.

The incidence of bacteremia due to vancomycin-resistant Enterococcus (VRE) has increased markedly in recent years. We investigated the role of chloramphenicol in its treatment. All cases of VRE bacteremia occurring at our facility during a 45-month period were analyzed. The response to chloramphenicol, its effect on mortality, and the incidence of adverse effects were assessed. Fifty-one patients (65.4%) received chloramphenicol. Among patients in whom a response could be assessed, 22 (61.1%) of 36 demonstrated a clinical response, while 34 (79.1%) of 43 showed a microbiological response. Forty-two patients (53.8%) died as a result of the bacteremia. Although the mortality rate was lower for patients treated with chloramphenicol, the difference was not significant (odds ratio = 0.72; 95% confidence interval, 0.28-1.85; P = .49), nor was there an association between earlier initiation of therapy and reduced mortality (P = .45). In cases with central line-related bacteremia, there was no difference in mortality among patients treated with chloramphenicol, line removal, or both (P = .36). Although 16 patients (31.4%) had adverse effects, none could be definitely attributed to chloramphenicol. Although chloramphenicol was well-tolerated, no significant effect of its use on mortality could be demonstrated.

Adolescent↗
PubMed1998

Penicillin-binding protein 5 sequence alterations in clinical isolates of Enterococcus faecium with different levels of beta-lactam resistance.

The low-affinity penicillin-binding protein (PBP) 5 is the main beta-lactam target and is responsible for resistance to this class of antibiotics in Enterococcus faecium. The PBP 5 variants of 15 clinical isolates (including 8 resistant to vancomycin) with different levels of beta-lactam resistance were analyzed. Most of the highly beta-lactam-resistant isolates produced small quantities of PBP 5 of low affinity. This was associated with particular amino acid substitutions: an Ala or Ile for Thr-499, a Glu for Val-629, and a Pro for Ser-667. A change of Met-485 to Thr or Ala (adjacent to the conserved SDN box) was observed in isolates with MICs of ampicillin of 64 or 128 microg/mL, respectively. In the 2 most resistant isolates, with MICs of ampicillin of 256 microg/mL, an additional Ser was present just after Ser-466. Thus, particular point mutations in PBP 5 and combinations thereof may lead to high-level beta-lactam resistance in E. faecium.

Amino Acid Sequence↗
PubMed1999

Lack of efficacy of oral bacitracin plus doxycycline for the eradication of stool colonization with vancomycin-resistant Enterococcus faecium.

In a prospective observational cohort study designed to assess the role of oral bacitracin solution plus doxycycline in the eradication of intestinal carriage of vancomycin-resistant Enterococcus faecium (VREF) in patients on a renal ward, rectal swab specimens were obtained from 15 treated and 24 control patients. Cultures of the rectal swabs were negative for 15 (100%) of the antibiotic-treated vs. eight (33.3%) of the untreated patients (P < .001) on day 14. However, follow-up for a mean of 127 and 130 days revealed 9 of 15 (60%) and 15 of 24 (62.5%) in the treated and untreated cohorts (P = .86), respectively, carried VREF intermittently or persistently. Quantitative VREF stool cultures in the treated cohort revealed an initial 3.1-log10/g decrease, but there was an increase to pretreatment levels at 2-4 and 5-7 weeks post-treatment (7.8 and 7.4 log10/g). Oral bacitracin and doxycycline were not efficacious in reducing the carriage of VREF beyond the 2-week interval during which they were given.

Administration, Oral↗
PubMed1992

A cluster of vancomycin-resistant Enterococcus faecium in an intensive care unit.

OBJECTIVE: To describe the epidemiology of a cluster of vancomycin-resistant Enterococcus faecium (VAREC) in a cardiothoracic surgery intensive care unit. DESIGN: A case series of patients identified through review of surveillance data on nosocomial infections, review of microbiologic records, and culture survey of patients in the unit. RESULTS: Six patients in the cardiothoracic surgery intensive care unit had VAREC with identical antimicrobic susceptibility patterns over a 6-month period. Four patients were identified with VAREC through prospective surveillance and 2 through retrospective review. Prior vancomycin use was seen more commonly in patients with VAREC (6/6, 100%) than in those without VAREC (3/12, 25%) (Fisher's exact test, p = .01). Six of the 7 patients with prior infection developed VAREC (85.7%). A prior nosocomial infection and prior exposure to vancomycin were found to be important variables in a logistic regression analysis. VAREC also was isolated from the environment. A combination of cohorting of patients and staff, and modifications of standard contact isolation practices eliminated the presence of VAREC from the cardiothoracic surgery intensive care unit. CONCLUSIONS: The results suggest that prior administration of vancomycin, especially in the patient who develops nosocomial infection, can influence the acquisition of vancomycin-resistant enterococci and that VAREC may be transmitted from patient to patient. Using a modification of the standard infection control practice of isolation, we were able to control the spread of this resistant strain of E faecium.

Cross Infection↗
PubMed1995

Natural history of colonization with vancomycin-resistant Enterococcus faecium.

OBJECTIVE: To determine the incidence, duration, and genetic diversity of colonization with vancomycin-resistant Enterococcus faecium (VREF). SETTING: Oncology unit of a 650-bed university hospital. METHODS: Surveillance perianal swab cultures were performed on admission and weekly. The molecular relatedness of VREF isolates was determined by pulsed-field gel electrophoresis and by the hybridization pattern of the vanA resistance determinant. RESULTS: During 8 months of surveillance, the VREF colonization rate was 16.6 patients per 1,000 patient-hospital days, which was 10.6 times greater than the VREF infection rate. Eighty-six patients with VREF colonization were identified. Colonization persisted for at least 7 weeks in the majority of patients. Of 36 colonized patients discharged from the hospital and then readmitted, an average of 2 1/2 weeks later, 22 (61%) patients still were colonized with VREF. Of the 14 patients who were VREF-negative at readmission, only three patients remained culture-negative throughout hospitalizations. PFGE demonstrated that colonization with the same VREF isolate may persist for at least 1 year, and patients may be colonized with more than one strain of VREF. CONCLUSION: VREF colonization is at least 10-fold more prevalent than infection among oncology patients. Colonization often persists throughout lengthy hospitalizations and may continue for long periods following hospitalization.

Adult↗
PubMed1997

Epidemiological study of hospital-acquired infection with vancomycin-resistant Enterococcus faecium: possible transmission by an electronic ear-probe thermometer.

Clonal spread of vancomycin-resistant Enterococcus faecium among seven patients on one ward of a community teaching hospital was identified by contour-clamped homogeneous electric-field gel electrophoresis. Environmental cultures isolated the same strain from the handle of a shared electronic ear-probe thermometer. Cross-contamination of the clonal strain between two geographically separate units on this ward, sharing equipment but not personnel, suggests the possibility of an environmental source.

Case-Control Studies↗
PubMed1997

Colonization with vancomycin-resistant Enterococcus faecium: comparison of a long-term-care unit with an acute-care hospital.

OBJECTIVE: To compare the epidemiology of vancomycin-resistant Enterococcus faecium (VRE) in a long-term-care unit and an acute-care hospital. DESIGN: Point-prevalence surveys for VRE rectal colonization of patients were carried out over a 21-month period in patients in a long-term-care unit and an acute-care hospital (medical ward and intensive-care units). The environment and hands of healthcare workers also were sampled for VRE. Contour-clamped homogeneous electric field (CHEF) electrophoresis was used to evaluate possible transmission among roommates and the relatedness of patient strains to those in the environment and on the hands of healthcare workers. SETTING: A 200-bed Veterans Affairs Medical Center with an attached 90-bed long-term-care unit. RESULTS: From December 1994 to January 1996, rectal VRE colonization of patients in the long-term-care unit increased significantly from 9% to 22%. In contrast, patients on the medical ward rarely were colonized after the first survey in December 1994, and only two intensive-care-unit patients were found to be colonized during the four surveys. The environment was contaminated persistently in the long-term-care unit. In the four surveys, carriage of VRE on hands of healthcare workers varied from 13% to 41%; 65% of healthcare workers with VRE found on their hands worked in the long-term-care unit. Seven different strains were identified by CHEF typing. Although the initial survey found only vanA strains, subsequent surveys showed vanB strains also were present. CONCLUSIONS: Residents of a long-term-care unit frequently were colonized with VRE, but infections were uncommon in this population. The environment of the long-term-care unit was contaminated with VRE, and VRE was found frequently on the hands of healthcare workers in this unit. Both vanA and vanB genotypes were found in this setting.

Anti-Bacterial Agents↗
PubMed1998

Reduction in vancomycin-resistant Enterococcus and Clostridium difficile infections following change to tympanic thermometers.

OBJECTIVE: To contain a nosocomial outbreak of vancomycin-resistant Enterococcus (VRE). DESIGN: Intervention study, with comparison of incidence rates before and after intervention to assess whether changes in incidence followed the intervention and were greater than expected based on trends observed before the intervention. SETTING: A 343-bed acute-care hospital serving a predominantly elderly population referred from nursing homes, as well as patients admitted from the community. METHODS: Interventions strategies were tested on three high-risk nursing stations. These included enhanced environmental sanitation; intensive staff retraining in Universal Precautions, body substance isolation, and proper use of gloves; and the use of tympanic thermometers to avoid possible rectal or oral VRE transmission during temperature taking. RESULTS: Nosocomial VRE infections were reduced by 48% 9 months after switching to tympanic thermometers; incidence of Clostridium difficile infections also was reduced. As a result, tympanic thermometers were introduced facilitywide; additional observation for 20 months showed a risk reduction of 60% for VRE and 40% for C difficile. CONCLUSION: Cross-transmission of VRE and C difficile during temperature taking may result in bowel colonization, placing the patient at increased risk for infection. This risk may be reduced by the use of tympanic thermometers.

Anti-Bacterial Agents↗
PubMed1992

Vancomycin-resistant Enterococcus faecium in hospitalized children.

OBJECTIVE: Determine the epidemiology and risk factors for colonization with vancomycin-resistant Enterococcus faecium. DESIGN: Survey; case-control study. SETTING: Children's hospital. PATIENTS: Pediatric oncology patients. INTERVENTION: Contact isolation, restriction of vancomycin prescribing. RESULTS: There was a high prevalence of colonization with vancomycin-resistant enterococci among pediatric oncology patients. The length of hospitalization and the administration of vancomycin and other intravenous antibiotics was associated with colonization. Prevention of colonization was associated with restriction of vancomycin use and contact isolation. CONCLUSIONS: Vancomycin use may predispose to colonization with vancomycin-resistant E faecium. Vancomycin-resistant E faecium may be nosocomially spread. Contact isolation and restriction of vancomycin use may prevent spread of vancomycin-resistant E faecium.

Bacterial Typing Techniques↗
PubMed2001

Persistence of a vancomycin-resistant Enterococcus faecium in an anaerobic continuous-flow culture of porcine microflora in the presence of subtherapeutic concentrations of vancomycin.

Recombined porcine continuous-flow culture (RPCF) maintained in a continuous-flow fermentation system is effective in protecting neonatal and weaned pigs against infection by enteropathogens. In the current study, we demonstrate the effect of RPCF on vancomycin-resistant enterococci (VRE) in the presence and absence of subtherapeutic levels of vancomycin. Also examined was the ability of VRE to transfer vancomycin resistance to endogenous Enterococcus faecalis 137.1. When RPCF was challenged with VRE, the rate of VRE clearance was dependent on the method of challenge. In the control experiment, RPCF was challenged with 7.0 log10/CFU/ml VRE. Clearance of VRE from the culture was observed within 7 days at a rate of 1.44 log10/day. RPCF containing 0.001 microg/ml vancomycin cleared VRE at a slightly lower rate of 0.94 log10/day. RPCF containing 0.01 microg/ml or 0.1 microg/ml vancomycin reduced the level of VRE from 7.0 log10/CFU/ml to 2.0 log10/CFU/ml within 9 days, but failed to clear the VRE after 24 days. During the period of decline, the VRE clearance rate for the 0.01 microg/ml and 0.1 microg/ml vancomycin-treated cultures was 0.52 log10/day, and 0.53 log10/day, respectively. E. faecalis 137.1 endogenous to RPCF did not acquire the vancomycin resistance genes throughout the experiment as evidenced by direct selection, ribotyping, and pulsed-field gel electrophoresis.

Anaerobiosis↗
PubMed2002

Genetic linkage between erm(B) and vanA in Enterococcus hirae of poultry origin.

Vancomycin-resistant enterococci (VRE) have frequently been isolated from Norwegian poultry production following the prohibition of the glycopeptide growth promoter avoparcin since 1995. In the present study, a close genetic linkage between the vanA and erm(B) determinants in an Enterococcus hirae isolate of poultry origin is demonstrated, a result that indicates a mechanism for co-selection and maintenance of vancomycin resistance in absence of selective pressure from avoparcin. A total of 36 vanA-positive enterococci of poultry origin, also phenotypically resistant to erythromycin and/or tetracycline, were analyzed by PCR for identification of erm and tet resistance determinants. An E. hirae isolate harbored erm(B) and tet(K), and in this isolate vanA and erm(B) were located on a BamHI fragment of an approximately 50-kb plasmid. Approximately 3 kb of this fragment was amplified by PCR with vanA and erm(B) primers. Sequence analysis of the region between erm(B) and vanZ of Tn1546 showed a truncated IS1216V inserted downstream of the erm(B) stop codon, aligned with a conserved copy of the 3'-inverted terminal repeat of Tn1546. Mating experiments with the E. hirae isolate as donor and E. faecalis JH2-2 as recipient did not result in any transconjugants, indicating that the vanA/erm(B)-carrying plasmid was nonconjugative under the given experimental conditions.

Animals↗
PubMed2002

Streptogramin resistance among Enterococcus faecium isolated from production animals in Denmark in 1997.

The genetic background for streptogramin resistance was examined in Enterococcus faecium isolated from pigs (n = 55) and broilers (n = 207) in 1997 in Denmark. Fifty-one percent and 67%, respectively, of the isolates were resistant to streptogramins. Among streptogramin-resistant E. faecium (SREF), the genetic background for streptogramin A resistance could be determined in 96% of the isolates from broilers, compared with 14% among SREF from pigs. For broiler isolates 89% of SREF contained the vat(E) gene and 10% the vat(D) gene. Three of these isolates contained both resistance genes. Among SREF from pigs two isolates contained the vat(E) gene and two others the vat(D) gene. The genetic background for streptogramin B was most often identified as the erm(B) gene encoding macrolide, lincosamide, and streptogramin B (MLSB) resistance. Among SREF, 84% and 86% of isolates from broilers and pigs, respectively, contained the erm(B). In SREF from broilers, the erm(B) gene was physically linked to the vat(E) gene in 62% of the vat(E)-positive isolates and 79% of the isolates containing vat(D). erm(A) was detected in two SREF of broiler origin. Both isolates also contained the erm(B) gene. No SREF contained the vgb(A) gene encoding streptogramin B resistance. On the basis of genetic characterization, streptogramin-resistant isolates from broiler were divided into subgroups, according to the presence of the streptogramin A genes, to determine possible co-resistance to antimicrobials, especially glycopeptides. Twenty-five percent of the SREF from broilers were glycopeptide resistant (MIC > 16 microg/ml). None of the isolates containing the streptogramin A gene vat(D) was resistant to glycopeptide, whereas isolates containing the vat(E) gene had a lower prevalence to glycopeptide resistance than the streptogramin-sensitive isolates.

Animals↗
PubMed2003

Phenotypic and genotypic characterization of VanA Enterococcus isolated during the first nosocomial outbreak in Brazil.

We report the phenotypic and genotypic characterization of 50 VanA Enterococcus clinical isolates from infected patients and 97 isolates from colonized patients obtained during a nosocomial outbreak in a single hospital in São Paulo, Brazil during 1998. The identification of strains to the species level by conventional biochemical and phenotypic tests and by multiplex PCR assay had 100% agreement. Both E. faecalis and E. faecium were isolated from patients during this outbreak. The vanA genotype was confirmed by PCR. Antibiotic susceptibility testing showed that E. faecium isolates are generally less susceptible to antibiotics than E. faecalis. By PCR, 24 of 26 VRE strains tested carried the Tn1546 element. Pulsed-field gel electrophoresis identified five distinct patterns for E. faecalis (A, B, C, D, E) and three for E. faecium (M, N, and O). A single PFGE pattern was identified in the majority of strains of each species and does not discriminate between case and carrier isolates.

Anti-Bacterial Agents↗
PubMed2003

Recurrent episodes of shock-like syndrome caused by the same strain of vancomycin-resistant Enterococcus faecium in a pediatric patient.

We present the case of a hospitalized pediatric patient with short bowel syndrome who was dependent upon total parenteral nutrition for 17 months. Shortly after admission she became colonized with vancomycin-resistant Enterococcus faecium (VRE) and developed 12 distinct episodes of serious infection associated with it. The course of VRE colonization and infections in this patient was studied through analysis of 40 representative isolates obtained from different sites during distinct episodes of infection. Standard microbiological techniques, automated ribosomal DNA typing, polymerase chain reaction, and pulsed-field gel electrophoresis (PFGE) were used. All isolates except for the one associated with the initial episode of bacteremia were VRE, and were multidrug resistant. The last four episodes of infection were caused by isolates resistant to all tested antibiotics except for intermediate susceptibility to chloramphenicol. The vanA genotype was a source of vancomycin resistance in all VRE isolates. Both ribotyping and PFGE showed two distinct clones of VRE in clinical and stool surveillance isolates: one was associated with clinical illness and the other was not associated with infection. Recurrent VRE infections occur as a consequence of prolonged gastrointestinal colonization. Morbidity is associated with host factors, the presence of co-pathogens, and possibly intrinsically more virulent VRE strain.

DNA, Bacterial↗
PubMed2003

Linkage of erm(B) and aadE-sat4-aphA-3 in multiple-resistant Enterococcus faecium isolates of different ecological origins.

Enterococcus faecium shares its antibiotic resistance gene pool with various Gram-positive bacteria. A gene cluster aadE-sat4-aphA-3, which was first described in staphylococci, has been recently identified also in E. faecium. In staphylococci, this gene cluster was mostly integrated into the transposable element, Tn5405. We identified five different cluster types of Tn5405-like elements that were linked to erm(B) in 47 of 67 aadE-sat4-aphA-3 and erm(B) positive isolates (70.1%). Clusters differed by insertion of additional DNA between the IS1182 transposase gene and the left inverted repeat of IS1182, an integration of IS1216 between erm(B) and ORF X deleting IS1182 and the 5' end of ORF X, or a loss of the left end of Tn5405 including IS1182, ORF X, and the 5' end of ORF Y. Twenty isolates (29.8%) possessed neither a link between erm(B) and aadE-sat4-aphA-3 nor an arrangement of aadE-sat4-aphA-3 in a Tn5405-like element. A 17-kb composite cluster was identified in a single hospital isolate linking determinants for glycopeptide (vanA), macrolide-lincosamide-streptogramin B [erm(B)], and aminoglycoside-streptothricin (aadE-sat4-aphA-3) resistances.

Aminoglycosides↗
PubMed2003

In vitro activities of Daptomycin, Linezolid, and Quinupristin-Dalfopristin against a challenge panel of Staphylococci and Enterococci, including vancomycin-intermediate staphylococcus aureus and vancomycin-resistant Enterococcus faecium.

We assessed the in vitro activities of daptomycin, linezolid, and quinupristin-dalfopristin (QD) against a contemporary challenge panel of 88 staphylococcal and 90 enterococcal isolates. The staphylococci selected included vancomycin-intermediate Staphylococcus aureus (VISA), methicillin-resistant S. aureus, and coagulasenegative staphylococci. Enterococcal isolates included vancomycin-resistant Enterococcus faecium (VREF) containing either vanA, vanB1, or vanD. The MICs of daptomycin, linezolid, and QD were determined using commercial broth microdilution panels. All three VISA isolates were susceptible to daptomycin, linezolid, and QD. QD was the most active agent against staphylococcal isolates (MIC50 < or = 0.5 microg/ml and MIC90 = 1 microg/ml), including those with decreased susceptibility to vancomycin. QD was also the most active agent against VREF (MIC90 < or = 0.5 microg/ml). No differences were seen for susceptibility of vanA, vanB1, and vanD VREF strains for daptomycin, linezolid, or QD. Daptomycin was the most effective against E. faecalis. On the basis of manufacturer-suggested interpretive criteria, 92% of isolates were susceptible (MIC90 = 4 microg/ml). All isolates tested were susceptible to at least one antimicrobial agent for which interpretive criteria have been defined. Population analysis of three S. aureus isolates for which the daptomycin MICs were 8 microg/ml showed a pattern of homogeneous resistance.

Acetamides↗