Regulated interactions between partner and non-partner sensors and response regulators that control glycopeptide resistance gene expression in enterococci.
(1/967)
Transcription of the vanA and vanB glycopeptide resistance gene clusters is regulated by the VanRS and VanRBSB two-component regulatory systems, respectively. Histidine to glutamine substitutions were introduced at positions 164 of VanS and 233 of VanSB to prevent autophosphorylation of the sensor kinases and transfer of the phosphate groups to the VanR and VanRB response regulators. VanSH164Q and VanSBH233Q abolished activation of VanR and VanRB by host kinases. The phosphatase activity of VanSBH233Q was negatively modulated by vancomycin whereas VanSH164Q prevented transcription of the resistance genes under all growth conditions. Cross-talk was detected between VanRB and VanS in a vanSB null mutant. VanR is required for activation of promoters PR and PH allowing transcription of the regulatory (vanRS) and resistance (vanHAXYZ) genes, respectively. Under non-inducing conditions, activation of VanR by cross-talk was blocked by the presence of a multicopy plasmid carrying PH. Presence of the high-affinity VanR-binding sites of the regulatory region of PH on the multicopy vector probably sequestered VanR, thereby preventing autoactivation of the PR promoter. Under such circumstances, stimulation of the host kinase by glycopeptides or moenomycin was required for expression of the resistance genes. (+info)
Enterococci with glycopeptide resistance in turkeys, turkey farmers, turkey slaughterers, and (sub)urban residents in the south of The Netherlands: evidence for transmission of vancomycin resistance from animals to humans?
(2/967)
The number of vancomycin-resistant enterococci (VRE) relative to the total number of enterococci was determined in fecal samples from turkeys and three human populations in 1996, each with a different level of contact with turkeys, i.e., turkey farmers, turkey slaughterers, and (sub)urban residents. The percentage of VRE relative to the total enterococcal population (i.e., the degree of resistance) was low (2 to 4%) in all groups (except in six samples). No difference was observed between farmers who used avoparcin and those who did not. The pulsed-field gel electrophoresis (PFGE) patterns of the VRE isolates from the different populations were quite heterogeneous, but isolates with the same PFGE pattern were found among animal and human isolates, in addition to the isolates which were described previously (A. E. van den Bogaard, L. B. Jensen, and E. E. Stobberingh, N. Engl. J. Med. 337:1558-1559, 1997). Detailed molecular characterization of vanA-containing transposons from different isolates showed, that in addition to a previously reported strain, similar transposons were present in VRE isolates from turkeys and turkey farmers. Moreover, similar VanA elements were found not only in isolates with the same PFGE pattern but also in other strains from both humans and animals. (+info)
The efficacy and safety of quinupristin/dalfopristin for the treatment of infections caused by vancomycin-resistant Enterococcus faecium. Synercid Emergency-Use Study Group.
(3/967)
A progressive increase in the incidence of vancomycin resistance in strains of Enterococcus faecium (VREF) has severely constrained treatment options for patients with infection caused by this emerging pathogen. Quinupristin/dalfopristin (Synercid), the first injectable streptogramin antibiotic, is active in vitro against VREF, with an MIC90 of 1.0 mg/L. We studied the clinical efficacy and safety of quinupristin/dalfopristin in the treatment of VREF infection. Two prospective studies were conducted simultaneously. The first enrolled only patients with VREF infection; the second included patients with infection caused by other gram-positive bacterial pathogens in addition to VREF. Patients were enrolled if they had signs and symptoms of active infection and no appropriate alternative antibiotic therapy. The recommended treatment regimen of quinupristin/dalfopristin was 7.5 mg/kg i.v. every 8 h for a duration judged appropriate by the investigator. A total of 396 patients with VREF infection were enrolled. The most frequent indications for treatment included intra-abdominal infection, bacteraemia of unknown origin, urinary tract infection, catheter-related bacteraemia, and skin and skin structure infection. This patient population had a high prevalence of severe underlying illness, including a history of diabetes mellitus, transplantation, mechanical ventilation, dialysis, chronic liver disease with cirrhosis and oncological disorders. The mean (+/- S.D.) duration of treatment was 14.5 +/- 10.7 days (range: 1-108). The majority of patients (82.1%) were treated every 8 h, as assessed on day 2 of treatment, while 15.9% were treated every 12 h. The clinical success rate was 73.6% [142/193 clinically evaluable patients; 95% confidence interval (CI): 67.4%, 79.8%], the bacteriological success rate 70.5% (110/156 bacteriologically evaluable patients; 95% CI: 63.4%, 77.7%) and the overall success (both clinical and bacteriological success) rate 65.8% (102/156 bacteriologically evaluable patients; 95% CI: 57.9%, 72.9%). VREF bacteraemia at entry, mechanical ventilation and laparotomy were associated with a worse outcome. Quinupristin/dalfopristin was generally well tolerated. The most common systemic adverse events related to treatment were arthralgias (9.1%) and myalgias (6.6%). Related laboratory abnormalities were infrequent. In these severely ill patients with VREF infection and no other clinically appropriate therapeutic alternatives, quinupristin/dalfopristin demonstrated substantial efficacy and a good nervous system, cardiovascular, gastrointestinal, renal and hepatic tolerability. (+info)
A cluster of VanD vancomycin-resistant Enterococcus faecium: molecular characterization and clinical epidemiology.
(4/967)
VanD-mediated glycopeptide resistance has been reported for an isolate of Enterococcus faecium, BM4339. Three clinical isolates of vancomycin-resistant E. faecium collected from 3 patients during a 6-week period in 1993 had agar dilution MICs of vancomycin and teicoplanin of 128 and 4 microg/mL, respectively. Polymerase chain reaction (PCR) using degenerate primers complementary to genes encoding d-Ala-d-X ligases yielded a 630-bp product that was similar to the published partial sequence of vanD. By use of inverse PCR, vanD, vanHD, and two partial flanking open-reading frames were sequenced. The deduced amino acid sequence of VanD showed 67% identity with VanA and VanB. vanD appeared to be located on the chromosome and was not transferable to other enterococci. The 3 isolates were indistinguishable by pulsed-field gel electrophoresis and differed from BM4339. No other isolates carrying vanD were found in a subset of 875 recent US isolates of vancomycin-resistant enterococci. (+info)
Quinupristin/dalfopristin: therapeutic potential for vancomycin-resistant enterococcal infections.
(5/967)
Vancomycin-resistant Enterococcus faecium (VREF) is an opportunistic pathogen, which causes infections among severely ill, hospitalized patients, in whom it is likely to increase the risk of progressive local or systemic disease and to worsen the prognosis. Because these organisms are often highly resistant to penicillin, ampicillin and many other antimicrobials including the glycopeptides, there are few proven therapeutic alternatives for the treatment of infection caused by VREF. Quinupristin/dalfopristin is highly active against VREF in vitro. A prolonged post-antibiotic effect, good polymorphonuclear leucocyte/macrophage penetration and slow release, and active metabolites allow this agent to be used with an 8 or 12 h dosing interval. The combined results from a Phase III non-comparative study and an emergency-use study of quinupristin/dalfopristin for the treatment of VREF infection produced a clinical response rate (cure or improvement) in 142 (73.6%) of 193 clinically evaluable patients. The baseline pathogen was eradicated or presumed eradicated from 110 of 156 (70.5%) bacteriologically evaluable patients. Fifty-two per cent of the severely ill patients in these two studies died, but no death was attributed to quinupristin/dalfopristin therapy. The most common adverse event was arthralgia (9.1%). Quinupristin/dalfopristin has demonstrated efficacy for the treatment of serious VREF infections, including those that have failed conventional therapy. (+info)
Costs of treating infections caused by methicillin-resistant staphylococci and vancomycin-resistant enterococci.
(6/967)
Infection with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus faecium (VREF) increases the risk of mortality and results in prolonged hospitalization and high utilization of costly treatment modalities. Measures to prevent the spread of MRSA (and possibly VREF) include patient isolation and decontamination, hygiene measures, ward closure, and screening of patients and staff for carriage. In seriously ill patients, the increased use of vancomycin for the treatment of MRSA can lead to the emergence of VREF colonization/infection. Quinupristin/dalfopristin is effective in the treatment of MRSA infections, including nosocomial pneumonia, skin and soft tissue infection, and septicaemia. In the treatment of nosocomial pneumonia, clinical success rates were equivalent between quinupristin/dalfopristin and vancomycin. In the context of a hospital policy which emphasizes effective hygiene measures and the prudent use of antibacterials, quinupristin/dalfopristin is an effective antimicrobial that can help to control the high costs associated with multiresistant MRSA and VREF infections. (+info)
Near absence of vancomycin-resistant enterococci but high carriage rates of quinolone-resistant ampicillin-resistant enterococci among hospitalized patients and nonhospitalized individuals in Sweden.
(7/967)
Rates of colonization with enterococci with acquired resistance to vancomycin (vancomycin-resistant enterococci [VRE]) and ampicillin (ampicillin-resistant enterococci [ARE]) were determined by using fecal samples from 670 nonhospitalized individuals and 841 patients in 27 major hospitals. Of the hospitalized patients, 181 (21.5%) were carriers of ARE and 9 (1.1%) were carriers of VRE. In univariate analyses, length of hospital stay (odds ratio [OR], 4.6; 95% confidence interval [CI], 2.5 to 8.9) and antimicrobial therapy (OR, 4.7; 95% CI, 3.3 to 6.7) were associated with ARE colonization, as were prior treatment with penicillins (OR, 3.1; 95% CI, 1.8 to 5. 5), cephalosporins (OR, 2.9; 95% CI, 1.7 to 5.0), or quinolones (OR, 2.7; 95% CI, 1.5 to 4.7). In logistic regression analysis, antimicrobial therapy for at least 5 days was independently associated with ARE carriage (adjusted OR, 3.8; 95% CI, 2.6 to 5.4). Over 90% of the ARE isolates were fluoroquinolone resistant, whereas 14% of the ampicillin-susceptible Enterococcus faecium isolates were fluoroquinolone resistant. ARE carriage rates correlated with the use of fluoroquinolones (P = 0.04) but not with the use of ampicillin (P = 0.68) or cephalosporins (P = 0.40). All nine VRE isolates were E. faecium vanB and were found in one hospital. Seven of these isolates were related according to their types as determined by pulsed-field gel electrophoresis. Among the nonhospitalized individuals, the ARE carriage rate was lower (6%; P < 0.05), and only one person, who had recently returned from Africa, harbored VRE (E. faecium vanA). The absence of VRE colonization in nonhospitalized individuals reflects an epidemiological situation in Sweden radically different from that in countries in continental Europe where glycopeptides have been widely used for nonmedical purposes. (+info)
Glycopeptide-intermediate Staphylococcus aureus: evaluation of a novel screening method and results of a survey of selected U.S. hospitals.
(8/967)
Isolates of Staphylococcus aureus with decreased susceptibilities to glycopeptide antimicrobial agents, such as vancomycin and teicoplanin, have emerged in the United States and elsewhere. Commercially prepared brain heart infusion agar (BHIA) supplemented with 6 microg of vancomycin per ml was shown in a previous study to detect glycopeptide-intermediate S. aureus (GISA) with high sensitivity and specificity; however, this medium, when prepared in-house, occasionally showed growth of vancomycin-susceptible control organisms. This limitation could significantly impact laboratories that prepare media in-house, particularly if they wished to conduct large surveillance studies for GISA. Therefore, a pilot study to detect GISA was performed with vancomycin-containing Mueller-Hinton agar (MHA) prepared in-house in place of commercially prepared BHIA. MHA was selected for this study because this medium is widely available and well standardized. The results of the pilot study showed that supplementation of MHA with 5 microg of vancomycin per ml was both a sensitive and a specific method for screening for GISA isolates. This method was used to screen for GISA among 630 clinical isolates of methicillin-resistant S. aureus collected during 1997 from 33 U.S. hospitals. Although 14 S. aureus isolates grew on the screening agar, all were vancomycin susceptible (MICs were +info)