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Beta-lactam antibiotics and gastrointestinal colonization with vancomycin-resistant enterococci.

We studied the effect of different subcutaneously administered beta-lactam antibiotics on the establishment of gastrointestinal colonization by vancomycin-resistant Enterococcus faecium C68 in a mouse model. Aztreonam, cefazolin, cefepime, and, to a lesser extent, ceftazidime, which neither have significant antienterococcal activity nor are secreted into human bile at high concentrations, did not promote significant vancomycin-resistant enterococci (VRE) colonization. Piperacillin-tazobactam, which has antienterococcal activity and is secreted in human bile at high concentrations, inhibited colonization after limited exposure to the inoculum but was associated with progressively increased VRE colony counts in stool samples after repeated exposure to the VRE inoculum. Ceftriaxone and cefotetan, which lack antienterococcal activity but are secreted into human bile at high concentrations, were associated with rapid and high-level colonization. These data suggest that the risk of VRE colonization varies during exposure to different beta-lactam antimicrobial agents and that the risk is related to biliary concentration and antienterococcal activity of the specific beta-lactam.

Animals↗

Projected benefits of active surveillance for vancomycin-resistant enterococci in intensive care units.

Hospitals use many strategies to control nosocomial transmission of vancomycin-resistant enterococci (VRE). Strategies include "passive surveillance," with isolation of patients with known previous or current VRE colonization or infection, and "active surveillance," which uses admission cultures, with subsequent isolation of patients who are found to be colonized with VRE. We created a mathematical model of VRE transmission in an intensive care unit (ICU) using data from an existing active surveillance program; we used the model to generate the estimated benefits associated with active surveillance. Simulations predicted that active surveillance in a 10-bed ICU would result in a 39% reduction in the annual incidence of VRE colonization when compared with no surveillance. Initial isolation of all patients, with withdrawal of isolation if the results of surveillance cultures are negative, was predicted to result in a 65% reduction. Passive surveillance was minimally effective. Using the best available data, active surveillance is projected to be effective for reducing VRE transmission in ICU settings.

Anti-Bacterial Agents↗

Preventing the influx of vancomycin-resistant enterococci into health care institutions, by use of a simple validated prediction rule.

BACKGROUND: The goal of this study was to develop a validated prediction rule for identification of patients harboring vancomycin-resistant enterococci (VRE) at hospital admission. METHODS: A model for the prediction of patients harboring VRE at admission was created and validated by assigning weighted point values to independent risk factors associated with harboring VRE at admission, in 2 different cohorts of patients from 2 tertiary care hospitals in Boston, Massachusetts. Patients with VRE isolated from clinical culture samples collected within 48 h of hospital admission were compared with patients not harboring VRE. To assess the diagnostic accuracy of the prediction rule, the main outcome measures were patient demographic characteristics, comorbid illnesses, hospitalizations, and antibiotic exposure. RESULTS: A total of 412 patients were enrolled. A risk index score was derived by using the following 6 independent risk factors associated with VRE recovery within 48 h of hospital admission: previous isolation of methicillin-resistant Staphylococcus aureus (MRSA), whether the patient was receiving long-term hemodialysis, transfer from a long-term care facility, antibiotic exposure, prior hospitalization, and age >60 years. On the basis of a point score >or=10, the sensitivity, specificity, and positive and negative predictive values of this prediction rule were 44%, 98%, 81%, and 90%, respectively. CONCLUSIONS: This validated clinical prediction rule provides a novel strategy for the identification of patients at high risk of harboring VRE at hospital admission. Implementation of this rule may reduce the influx of VRE into health care institutions and the overall prevalence of VRE, by targeting VRE-screening measures and contact isolation precautions for these high-risk patients.

Adult↗

Control of vancomycin-resistant enterococci: one size fits all?

Infection caused by vancomycin-resistant enterococci (VRE) is associated with high morbidity and mortality rates; it poses a serious threat, in particular, to immunosuppressed patients. It generates high costs and challenges infection-control programs. Here, we look at the insights that mathematical models offer into the epidemiology of VRE colonization and infection, the potential benefits of various infection-control interventions, and the possibility of designing a tailored approach to controlling VRE. Models show that epidemics of VRE infection in diverse institutions may differ in the relative contributions of cross-transmission and the influx of new cases, as well as in the various mechanisms of local transmission. They also highlight the phenomenon of decreasing returns associated with many interventions and, hence, the need to identify the most important routes of transmission, to break the weakest links in the chain of transmission, and to contain the influx of cases of VRE infection. These observations also provide insights into the management of infection with other antibiotic-resistant nosocomial pathogens.

Anti-Bacterial Agents↗

Endocarditis due to vancomycin-resistant enterococci: case report and review of the literature.

BACKGROUND: Endocarditis due to vancomycin-resistant enterococci (VRE) is rare, and the literature consists almost exclusively of reports of single cases. METHODS: We report a case of VRE prosthetic valve endocarditis and review 18 cases of native and prosthetic valve VRE endocarditis reported in the literature. RESULTS: The majority of cases were due to Enterococcus faecium. Nearly all of these infections were hospital acquired, and the vast majority of patients had significant underlying disease processes, including dialysis and transplantation. More than three-quarters of cases were left-sided, and the aortic valve was most commonly involved. Peripheral stigmata of endocarditis were not reported in any of the cases. Approximately 40% of patients developed cardiac complications. Nearly three-quarters of patients survived, despite the difficulties associated with providing bactericidal antimicrobial therapy, and only 4 patients underwent valve replacement. CONCLUSIONS: VRE endocarditis is an uncommon nosocomial infection that affects patients with significant comorbid conditions. Most cases are due to E. faecium, and the aortic valve is involved in at least one-half of cases. One-third of patients require surgical treatment. Optimal antimicrobial therapy remains undefined, but an attempt to identify bactericidal combination therapy should be sought.

Adult↗

A mathematical model quantifying the impact of antibiotic exposure and other interventions on the endemic prevalence of vancomycin-resistant enterococci.

BACKGROUND: Mathematical modeling can be used to describe the interdependent and dynamic interactions that contribute to the transmission dynamics of vancomycin-resistant enterococci (VRE). A model was developed to quantify the contribution of antibiotic exposure and of other modifiable factors to the dissemination of VRE in the hospital setting. METHODS: The model consists of 4 compartments: patients colonized with VRE receiving and not receiving antibiotics and uncolonized patients receiving and not receiving antibiotics. A series of differential equations describe the movement between these compartments. Baseline parameter estimates were obtained from pharmacy, infection-control, and clinical databases. RESULTS: The main predictions of this model are that (1) preventing the initiation or enhancing the discontinuation of unnecessary antimicrobial therapy will have a greater impact if it is targeted to patients who are not colonized with VRE; (2) increasing the number of patients harboring VRE at the time of hospital admission substantially increases the endemic prevalence of VRE; and (3) eliminating the influx of VRE results in the eradication of this pathogen from the hospital. A decrease in the endemic prevalence of VRE also occurs with a decrease in the length of hospital stay of colonized patients, increased hand hygiene compliance, and a lower ratio of health-care workers : patients. CONCLUSION: This mathematical model provides a framework to assist in targeting necessary interventions aimed at limiting the spread of VRE.

Anti-Bacterial Agents↗

Molecular epidemiology of vancomycin-resistant enterococci: a 2-year perspective.

OBJECTIVE: To determine the molecular epidemiology of vancomycin-resistant enterococci (VRE) at our medical center in order to identify the extent of strain clonality and possible transmission patterns of this pathogen. DESIGN: An important facet of our infection control program includes molecular typing of all clinical and surveillance isolates of VRE to determine transmission patterns in the hospital. Molecular strain typing is performed by restriction endonuclease analysis (REA) of genomic DNA. REA patterns are visually compared to categorize VRE strains into type and subtype designations. SETTING: A 588-bed, university-affiliated, tertiary-care hospital and a neighboring 155-bed rehabilitation facility. RESULTS: From January 1995 through December 1996, 379 VRE isolates were collected from 197 patients. Thirty-three genotypes were determined by REA typing; 15 genotypes were implicated in 29 instances of potential nosocomial transmission. Three major clusters of VRE involving patients on multiple nursing units and two adjacent hospitals were identified. The remaining instances of nosocomial transmission occurred in small patient clusters. CONCLUSIONS: In conclusion, the VRE epidemic at this medical center is polyclonal. VRE transmission patterns are complex, and, while large clusters do occur, the usual pattern of nosocomial acquisition of this pathogen occurs in the setting of "mini-clusters".

Bacterial Typing Techniques↗

Reporting of vancomycin-resistant enterococci in Connecticut: implementation and validation of a state-based surveillance system.

OBJECTIVE: To assess state-based surveillance for isolation from a sterile site of vancomycin-resistant enterococci (VRE) in Connecticut. DESIGN: Clinical laboratory reporting (passive surveillance) of VRE isolates to the Connecticut Department of Public Health (CDPH) was followed by state-initiated validation, laboratory proficiency testing, and review of hospital demographic characteristics. SETTINGS: All 45 clinical laboratories and all 37 (36 for 1995 and 1996) acute-care hospitals in Connecticut were included in the study. MAIN OUTCOME MEASURES: The outcome measures included determination of the statewide incidence of VRE and the accuracy of passive reporting, determination of clinical laboratory proficiency in detecting VRE, and analysis of hospital characteristics that might be associated with an increased incidence of VRE. RESULTS: During 1994 through 1996, 29 (78%) of 37 hospital-affiliated clinical laboratories and 1 (11%) of 9 commercial or other laboratories in Connecticut reported to the CDPH the isolation of VRE from sterile sites; 158 isolates were reported for these 3 years. Based on verification, we discovered that these laboratories actually detected 58 VRE isolates in 1994, 104 in 1995, and 104 in 1996 (total, 266). The age-standardized incidence rate of VRE was 14.1 cases per million population in 1994 and 26.8 cases per million population for both 1995 and 1996. Laboratory proficiency testing revealed that high-level vancomycin resistance was identified accurately and that low- and moderate-level resistance was not detected. The incidence of VRE isolates was three times greater in hospitals with over 300 beds compared with categories of hospitals with fewer beds. Increases in the number of VRE isolates were at least twice as likely in hospitals located in areas with a higher population density, or with a residency program or trauma center in the hospital. CONCLUSIONS: Passive reporting of VRE isolates from sterile sites markedly underestimated the actual number of iso lates, as determined in a statewide reporting system. Statewide passive surveillance systems for routine or emerging pathogens must be validated and laboratory proficiency ensured if results are to be accurate and substantial underreporting is to be corrected.

Adolescent↗

Recovery of high-level streptomycin-resistant enterococci from hemodialysis water and dialysate in 85 Greek renal units.

In the 85 renal units of Greece, enterococci were recovered from 10 samples of tap water, 6 of treated hemodialysis water, and 21 of dialysate. Eleven isolates were Enterococcus faecium, and 8 were Enterococcus raffinosus; 6 other additional enterococcal species were found. Twenty-two strains exhibited high-level resistance to streptomycin, 16 were resistant to rifampicin, and one to erythromycin. In our hemodialysis units, treated water and dialysate raise concern regarding transfer to patients of uncommon enterococcal species exhibiting high-level streptomycin resistance.

Cross Infection↗

Emergence of vancomycin-resistant enterococci at a university hospital in Taiwan: persistence of multiple species and multiple clones.

OBJECTIVES: To describe the epidemiology of vancomycin-resistant enterococci (VRE) in a university hospital in Taipei, Taiwan. DESIGN: Retrospective review over a 27-month period, from March 1996 to May 1998. SETTING: A tertiary-care teaching hospital in Taiwan. PARTICIPANTS: Patients with VRE isolated from any body site. METHODS: Patients were identified through hospital microbiology and infection control records. Patient charts were reviewed for clinical and epidemiology data, including age, gender, previous hospital admissions, underlying diseases, types of infection, and recent antibiotic use. VRE isolates were characterized by their typical biochemical reactions, cellular fatty acid profiles, and the presence of van genes. Antibiotypes using the E-test and randomly amplified polymorphic DNA (RAPD) patterns of these isolates were used to determine the clonality. RESULTS: Twenty-five isolates of VRE recovered from 12 patients were identified. One patient with a perianal abscess had 12 isolates of VRE (4 Enterococcus faecalis, 7 Enterococcus faecium, and 1 Enterococcus casseliflavus) recovered from perianal lesions. Among 3 patients who were hospitalized in the same room, 1 had a community-acquired cellulitis over the left leg caused by E. faecalis, and the other 2 patients both had anal colonization with 2 isolates of E. faecalis. The other 8 patients had 1 E. faecalis isolate each from various clinical specimens. All isolates possessed vanA resistance phenotype and vanA genes. Different antibiotypes and RAPD patterns of the isolates from different patients excluded the possibility of nosocomial spread at the hospital. CONCLUSIONS: Multiple species of VRE (E. faecalis, E. faecium, and E. casseliflavus) and multiple clones of E. faecium could colonize or infect hospitalized patients. In addition, clones of VRE can persist long-term in patients' lower gastrointestinal tracts. These results extend our knowledge of the coexistence and the persistence of multiple species and multiple clones of VRE in hospitalized patients.

Cross Infection↗

Control of vancomycin-resistant enterococci at a community hospital: efficacy of patient and staff cohorting.

OBJECTIVE: To evaluate the efficacy of patient and staff cohorting to control vancomycin-resistant enterococci (VRE) at an Indianapolis community hospital. DESIGN: To interrupt transmission of VRE, a VRE point-prevalence survey of hospital inpatients was conducted, and VRE-infected or -colonized patients were cohorted on a single ward with dedicated nursing staff and patient-care equipment. To assess the impact of the intervention, staff compliance with contact isolation procedures was observed, and the VRE point-prevalence survey was repeated 2 months after the cohort ward was established. RESULTS: Following the establishment of the cohort ward, VRE prevalence among all hospitalized inpatients decreased from 8.1% to 4.7% (25 positive cultures among 310 patients compared to 13 positive cultures among 276 patients, P=.14); VRE prevalence among patients whose VRE status was unknown before cultures were obtained decreased from 5.9% to 0.8% (18 positive cultures among 303 patients compared to 2 positive cultures among 262 patients, P=.002); and observed staff-patient interactions compliant with published isolation recommendations increased (5 [22%] of 23 interactions compared to 36 [88%] of 41 interactions, P<.0001). CONCLUSIONS: Our data suggest that, in hospitals with endemic VRE or continued VRE transmission despite implementation of contact isolation measures, establishing a VRE cohort ward may be a practical and effective method to improve compliance with infection control measures and thereby to control epidemic or endemic VRE transmission.

Adult↗

Comparison of three methods to recover vancomycin-resistant enterococci (VRE) from perianal and environmental samples collected during a hospital outbreak of VRE.

OBJECTIVE: To establish an efficient and sensitive technique for recovering vancomycin-resistant enterococci (VRE) from perianal and environmental samples collected during implementation of control measures for an outbreak of VRE. DESIGN: Perianal and environmental samples were collected in triplicate on sterile swabs. One swab was used to inoculate a selective broth medium containing 6 pg of vancomycin and 8 pg of ciprofloxacin per mL, one to inoculate Campylobacter agar containing 10 microg/mL of vancomycin, and one to inoculate Enterococcosel agar containing 8 microg/mL of vancomycin. SETTING: Samples were collected in the intensive care units of a 600-bed university hospital over a period of 2 months. SAMPLE SELECTION: Patients and their immediate environment were sampled if they resided in a ward with a patient known to be colonized or infected with VRE. RESULTS: Of the 88 perianal samples obtained from 63 patients, 37 were positive for VRE by broth culture, with 36 also recovered on both types of solid media (sensitivity, 97.3%; negative predictive value, 98.1%). Of the initial samples collected from each of the 63 patients, 20 were positive for VRE by all methods. Of the 500 environmental samples cultured, 139 were positive for VRE in broth, with only 33 recovered on Campylobacter agar (sensitivity, 23.7%; negative predictive value, 77.2%) and 22 on Enterococcosel agar (sensitivity, 15.8%; negative predictive value, 75.2%). CONCLUSIONS: Our data indicate that, when performing surveillance cultures during an outbreak of VRE, use of an enrichment broth medium is required to recover VRE contaminating environmental surfaces; however, direct inoculation to selective solid medium is adequate to recover VRE in patient perianal specimens.

Agar↗

Outbreak of vancomycin-resistant enterococci in a burn unit.

OBJECTIVE: To investigate and control an outbreak of colonization and infection caused by vancomycin-resistant enterococci (VRE) in a burn intensive care unit (BICU). DESIGN: Epidemiological investigation, including multiple point-prevalence culture surveys of patients and environment, cultures from hands of healthcare workers (HCWs), pulsed-field gel electrophoresis (PFGE) typing of patient and environmental isolates, case-control study, and institution and monitoring of control measures. SETTING: BICU in an 800-bed university medical center in Galveston, Texas. RESULTS: Between June 6, 1996, and July 14, 1997, 21 patients were colonized by VRE, and 4 of these patients developed bacteremia. Of 2,844 environmental cultures, 338 (11.9%) were positive, but all hand cultures from HCWs were negative. PFGE typing indicated that the outbreak was clonal, with VRE isolates from patients differing by < or =4 bands from the index case. Thirteen of 14 environmental isolates varied by < or =4 bands from the pattern of the index case. A case-control study analyzed by exact logistic regression identified diarrhea (odds ratio [OR], 43.9; 95% confidence interval [CI95], 5.5-infinity; P=.0001) and administration of an antacid (OR, 24.2; CI95, 2.9-infinity; P=.002) as independent risk factors for acquisition of VRE. During a 5-week period in October and November 1996, all patient and 317 environmental cultures were negative for VRE. The outbreak recurred from a contaminated electrocardiogram lead that had not been identified during the prior 5 weeks. VRE were finally eradicated from the BICU in July 1997, using barrier isolation and a very aggressive environmental decontamination program. CONCLUSIONS: A VRE outbreak in a BICU over 13 months was caused by a single clone. After apparent eradication of VRE from a BICU, recrudescence of the outbreak occurred, evidently from a small inapparent source of environmental contamination. Changes in gastrointestinal (GI) tract function (motility) and administration of medications, other than antibiotics, that have an effect on the GI tract may increase the risk of GI tract colonization by VRE in burn patients. Application of barrier isolation and an aggressive environmental decontamination program can eradicate VRE from a burn population.

Adult↗

Risk factors for colonization with vancomycin-resistant enterococci in a Melbourne hospital.

OBJECTIVE: To determine risk factors for colonization with vancomycin-resistant enterococci (VRE) in a hospital outbreak. DESIGN: Outbreak investigation and case-control study. SETTING: A referral teaching hospital in Melbourne, Australia. PARTICIPANTS: Cases were inpatients colonized (with or without clinical disease) with VRE between July 26 and November 28, 1998; controls were hospitalized patients without VRE. METHODS: Five cases of VRE were identified between July 26 and November 8, 1998, by growth of VRE from various sites. Active case finding by cultures of rectal swabs from patients surveyed in wards was commenced on July 26, after the first isolate of VRE. RESULTS: There were 19 cases and 66 controls. All the VRE identified were vanB, and all were Enterococcus faecium. One molecular type predominated (18/19 cases). In a logistic-regression model, being on the same ward as a VRE case was the highest risk factor (odds ratio [OR], 82; 95% confidence interval [CI95], 5.7-1,176; P=.001). Having more than five antibiotics (OR, 11.9; CI95 1.1-129.6; P<.05), use of metronidazole (OR, 10.9; CI95, 1.7-69.8; P=.01), and being a medical patient (OR, 8.1; CI95, 1.4-47.6; P<.05) also were significant. Intensive care unit admission was associated with decreased risk (OR, 0.1; CI95, 0.01-0.8; P<.05). CONCLUSION: Our findings are consistent with an acute hospital outbreak. Monitoring and control of antibiotic use, particularly metronidazole, may reduce VRE in our hospital. Ongoing surveillance and staff education also are necessary.

Case-Control Studies↗

Laboratory-based surveillance for vancomycin-resistant enterococci: utility of screening stool specimens submitted for Clostridium difficile toxin assay.

OBJECTIVE: To study vancomycin-resistant enterococci (VRE) gastrointestinal colonization prevalence in high-risk hospitalized patients and to assess the cost and utility of this laboratory-based surveillance. SETTING: Large university teaching hospital. DESIGN: Quarterly prevalence culture survey of 50 stool specimens submitted for Clostridium difficile toxin A assay from October 1996 through June 1999 (n=526). Screening culture survey of all C difficile-positive stool specimens from July 1998 through June 1999 (n=140). PATIENTS: Specimens for analysis were collected from patients who were admitted to the hospital and who had C difficile toxin A testing ordered. Patient samples were excluded from analysis if they were obtained from patients not hospitalized at UCLA Medical Center, if the C difficile toxin assay result was indeterminate, or if the patient was known to have previous VRE colonization or infection. RESULTS: During quarterly surveillance, VRE was detected in 19.8%, C difficile toxin A in 9.5%, and both VRE and C difficile toxin A in 3.2% of stool specimens submitted for C difficile toxin assay. Patients whose stool specimens were positive for C difficile toxin A were significantly more likely than those whose specimens were negative to have VRE detected (odds ratio, 2.3; 95% confidence interval, 1.2-4.5). Based on these findings, in July 1998, we began routine screening of all C difficile-positive stool specimens for VRE. From July 1998 through June 1999, 58 (41.4%) of 140 patients with C difficile-positive specimens had VRE newly detected in the stool. The combined cost of the two laboratory-based surveillance strategies was approximately $62 per VRE-positive patient identified and $5,800 per year. CONCLUSION: Quarterly surveillance of stool submitted for C difficile assay combined with screening all C difficile-positive stools is a cost-effective and efficient strategy for detecting VRE stool colonization among high-risk hospitalized patients. Such a laboratory-based surveillance should be included as part of a comprehensive program to limit nosocomial VRE transmission.

Bacterial Toxins↗

Management of an outbreak of vancomycin-resistant enterococci in the medical intensive care unit of a cancer center.

Between November 1996 and February 1997, 17 episodes of vancomycin-resistant enterococci (VRE) infection or colonization (9 infections, 8 colonizations), all with the same or a similar genomic DNA pattern, were identified in the medical intensive care unit (MICU) of a tertiary-care cancer hospital. The cases were genotypically traced to a patient who was admitted to the hospital in September 1996 and who, by December 1996, had four different admissions to the MICU. Multifaceted infection control measures, including decontamination of the environment and of nondisposable equipment, halted the nosocomial transmission of VRE in the MICU.

Cancer Care Facilities↗

Costs and savings associated with infection control measures that reduced transmission of vancomycin-resistant enterococci in an endemic setting.

OBJECTIVE: To determine the costs and savings of a 15-component infection control program that reduced transmission of vancomycin-resistant enterococci (VRE) in an endemic setting. DESIGN: Evaluation of costs and savings, using historical control data. SETTING: Adult oncology unit of a 650-bed hospital. PARTICIPANTS: Patients with leukemia, lymphoma, and solid tumors, excluding bone marrow transplant recipients. METHODS: Costs and savings with estimated ranges were calculated. Excess length of stay (LOS) associated with VRE bloodstream infection (BSI) was determined by matching VRE BSI patients with VRE-negative patients by oncology diagnosis. Differences in LOS between the matched groups were evaluated using a mixed-effect analysis of variance linear-regression model. RESULTS: The cost of enhanced infection control strategies for 1 year was $116,515. VRE BSI was associated with an increased LOS of 13.7 days. The savings associated with fewer VRE BSI ($123,081), fewer patients with VRE colonization ($2,755), and reductions in antimicrobial use ($179,997) totaled $305,833. Estimated ranges of costs and savings for enhanced infection control strategies were $97,939 to $148,883 for costs and $271,531 to $421,461 for savings. CONCLUSION: The net savings due to enhanced infection control strategies for 1 year was $189,318. Estimates suggest that these strategies would be cost-beneficial for hospital units where the number of patients with VRE BSI is at least six to nine patients per year or if the savings from fewer VRE BSI patients in combination with decreased antimicrobial use equalled $100,000 to $150,000 per year.

Adult↗