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In vitro activities of an investigational quinolone, glycylcycline, glycopeptide, streptogramin, and oxazolidinone tested alone and in combinations against vancomycin-resistant Enterococcus faecium.

We evaluated the in vitro activities of clinafloxacin, CL331,002, LY333328, quinupristin dalfopristin, and eperezolid (formerly known as U-100,592) against four strains of enterococci. All regimens tested resulted in the growth inhibition of each isolate. Against the three clinafloxacin-susceptible strains, clinafloxacin tested alone was the most active treatment, decreasing the bacterial inoculum by more than 3 log10 CFU/ml after 24 h in time-kill curve studies.

4-Quinolones↗

Combined antimicrobial resistance in Enterococcus faecium isolated from chickens.

Nineteen E. faecium strains isolated from chicken caecum samples, collected in slaughterhouses and highly resistant to vancomycin or gentamicin, were coresistant to erythromycin, and/or tetracyclines, and/or streptogramins, and/or avilamycin. Multiple antibiotic resistance was related to the presence in various combinations of aac(6')-aph(2"), erm(B), emtA, mef(A), tet(L), tet(M), and vanA genes.

Animals↗

Optimization of bacteriocin ST311LD production by Enterococcus faecium ST311LD, isolated from spoiled black olives.

Bacteriocin ST311LD is approximately 2.3 kDa in size. Low levels of bacteriocin activity were recorded in BHI and M17 broth (800 AU/ml) and in 10% (w/v) soy milk (3,200 AU/ml). No bacteriocin production was recorded in 10% (w/v) molasses, despite good growth. Optimal levels (12,800 AU/ml) were detected in MRS broth which had been supplemented with tryptone (20.0 g/l), saccharose (5.0 or 10.0 g/l) or vitamin C (1 ppm). Increased potassium levels did not result in higher levels of activity, and glycerol (1.0 g/l) inhibited the production of bacteriocin ST311LD.

Bacteriocins↗

The effect of a probiotic Enterococcus faecium product in diets of healthy dogs on bacteriological counts of Salmonella spp., Campylobacter spp. and Clostridium spp. in faeces.

An experiment was conducted to determine the effects of a probiotic on selected faecal bacteria of healthy dogs under different feed and environmental conditions. For the study 12 dogs kept in households were used for an 18-day supplementation with a patented commercially available strain of E. faecium NCIB 10415 (Enteroferm). In order to minimize losses the probiotic product was orally applicated once a day before meals at a dose of 2 g per dog (9.2 x 10(9) CFU). The faeces were collected before the beginning of the supplementation and at the end of the 18-day application period. In order to exclude contamination, all faeces were taken rectally. Before and at the end of the experimental period total Salmonella spp., Campylobacter spp. and Clostridium spp. counts were determined in fresh faeces using selective media. It was demonstrated that the 18-day application of the probiotic E. faecium product induced modifications on the gastrointestinal microflora in all dogs. While Salmonella spp. and Campylobacter spp. counts were in majority of the dogs higher than before the application. Clostridium spp. counts were significantly reduced in 10 of 12 dogs. According to the guidelines for the evaluation of the efficiency of microorganisms in dogs a relevant efficacy effect was supported by this data. However, a beneficial effect of the probiotic product on healthy dogs remains questionable.

Administration, Oral↗

Infections due to vancomycin-resistant Enterococcus faecium resistant to linezolid.

Linezolid is a new oxazolidinone antibiotic used to treat infections caused by vancomycin-resistant enterococci (VRE). In early clinical trials, emergence of resistance occurred rarely. We report clinical details and antibiotic susceptibility from five patients treated with linezolid for VRE infections who had resistant organisms isolated during therapy. Four were transplant patients receiving protracted courses of the drug; three cases were associated with treatment failure. One of 45 linezolid-treated patients developed resistance during therapy. Susceptibility testing should be done in all cases on starting therapy.

Acetamides↗

Induction signals for vancomycin resistance encoded by the vanA gene cluster in Enterococcus faecium.

The induction of vancomycin resistance in enterococci containing the vanA gene cluster is thought to be controlled by a two-component sensor-response regulator system encoded by vanR and vanS. Eight inducing compounds were identified by screening a panel of more than 6,800 antibiotics and synthetic compounds including the three tested glycopeptides (vancomycin, avoparcin, and ristocetin), two other cell wall biosynthesis inhibitors (moenomycin and bacitracin), two cyclic peptide antibiotics (antibiotic AO341 beta and polymyxin B), and a macrocyclic lactone antibiotic (moxidectin). Induction activity by structurally unrelated antibiotics suggests that the induction signal is not a structural feature of vancomycin.

Bacterial Proteins↗

In vitro susceptibility of Enterococcus faecium isolated from food to growth-promoting and therapeutic antibiotics.

A total of 76 E. faecium strains, isolated at retail level from raw poultry meat, cheese, raw pork, and preparations of cheese and raw pork, were tested for their susceptibility and resistance to growth-promoting antibacterials used in animals and antibiotics used therapeutically in humans. All strains were uniformly susceptible to the growth promoters bambermycin and avilamycin. Resistance against bacitracin, virginiamycin and narasin was high among strains from poultry meat. With tylosin, a macrolide antibiotic used therapeutically and for growth promotion, resistance was mainly detected in strains originating from poultry meat, though also in some strains from pork and from pork and cheese preparations. The therapeutic antibiotic dalfopristin/quinupristin did not show full cross-resistance with the growth-promoting antibiotic virginiamycin. With dalfopristin/quinupristin two different levels of resistance were found. Only one E. faecium strain isolated from poultry was resistant to the glycopeptides avoparcin and vancomycin. Only one poultry meat strain was highly resistant to ampicillin. However, nearly all poultry meat strains showed decreased sensitivity. Only 3 out of 24 poultry strains were susceptible to minocycline, while all strains from other origins were susceptible to this tetracycline antibiotic. High-level streptomycin resistance was seen in strains of all origins, though infrequently. High-level gentamicin resistance was not found.

Animal Husbandry↗

The vanZ gene of Tn1546 from Enterococcus faecium BM4147 confers resistance to teicoplanin.

A five-gene cluster from Tn1546 confers resistance to the glycopeptide antibiotics vancomycin (Vm) and teicoplanin (Te) by synthesis of pentadepsipeptide peptidoglycan precursors terminating in D-lactate, which replaces D-alanine in the same position of precursors utilized by susceptible enterococci. Cloning and nucleotide sequencing indicated that Tn1546 contains an additional gene, designated vanZ, which confers low-level Te resistance, in the absence of the genes required for pentadepsipeptide synthesis. Analysis of cytoplasmic peptidoglycan precursors, accumulated in the presence of ramoplanin, showed that VanZ-mediated Te resistance does not involve incorporation of a substituent of D-alanine into the precursors.

Amino Acid Sequence↗

Characterization of glycopeptide-resistant enterococcus faecium (GRE) from broilers and pigs in Denmark: genetic evidence that persistence of GRE in pig herds is associated with coselection by resistance to macrolides.

Glycopeptide-resistant enterococci (GRE) from broilers and pigs were characterized to investigate the background for the persistence of GRE in pig herds. All porcine isolates belonged to closely related pulsed-field gel electrophoretic (PFGE) types, with the ermB and vanA genes located on the same transferable genetic element. Broiler isolates belonged to different PFGE types. The persistence of GRE in Danish pig herds after the ban of glycopeptides may be explained by the genetic link between ermB and vanA and coselection by use of macrolides for treatment and growth promotion.

Animals↗

Intramucosal bacteria in colon cancer and their elimination by probiotic strain Enterococcus faecium M-74 with organic selenium.

Intraepithelial bacteria were isolated by the gentamicin protection assay (GPA) from biopsy samples obtained at colonoscopy (colon cancer, n = 10 patients; colonic adenoma, n = 20; control group, n = 20; cancer patients without gastrointestinal tract GIT malignancy, n = 10). After a three-month administration of E. faecium M-74 to patients with positive GPA biopsies, 172 biopsy specimens from 60 patients were examined with the GPA. The number of biopsies with intracellular bacteria was significantly higher in adenoma and carcinoma group than in control group (26 vs. 10%; p = 0.004); in cancer patients without GIT malignancy the difference was nonsignificant. E. faecium M-74 was also administered to 5 patients with colonic adenoma; according to a control colonoscopy the number of biopsies with intracellular bacteria was significantly lower after probiotic administration (48 vs. 16%; p = 0.03). A striking prevalence of intraepithelial bacteria was also showed in patients with large bowel adenoma and carcinoma. The administration of probiotic strain M-74 can thus be considered to be an effective and promising method for elimination of pathogenic bacteria in the case of inflammatory bowel disease and colon cancer.

Adenoma↗

[Antagonistic activity of the rumen bacteria, Enterococcus faecium and Staphylococcus warneri].

The bacterial strains E. faecium and S. warneri were tested for their antagonistic activities, and/or for the antimicrobial spectrum of bacteriocin-like substances produced by these bacteria. Isolates of rumen and non-rumen origin were used as indicator strains (Tab. I). All the isolates (except the strains SW48 and EF24c as indicators of rumen origin) produced bacteriocin-like substances inhibiting the growth of at least one of the series of the nine indicators used while clear inhibition zones 2-10 mm prevailed (Tabs. II, III). Among the enterococci, the inhibition of non-rumen indicators was more intensive in comparison with the indicators of rumen origin, but the inhibition zones were only 2-5 mm. In general, the staphylococci showed the antagonistic activity with the lower antimicrobial spectrum in comparison with the enterococci. None of the tested strains inhibited the growth of the indicator E. faecium A26. The summary results show that the growth of both gram-positive and gram-negative bacteria was inhibited. The prolonged cultivation time did not influence the antagonistic activity of the tested strains. In the strains EF35, SW34 and SW98, the antagonistic activity was maintained after trypsin treatment. But in the other strains, this treatment led to the loss of the antagonistic activity. The use of pronase P resulted in the loss of the activity in the strains SW24, EF35 and EF26/142. The use of pronase P did not lead to the loss of the activity in the other tested isolates (Tab. IV).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Multidrug-resistant Enterococcus faecium. An untreatable nosocomial pathogen.

The prevalence of enterococci and nosocomial pathogens has increased over the past 15 years. They have become increasingly resistant to agents traditionally useful in the treatment of invasive diseases due to enterococci. Vancomycin resistance, first described in clinical isolates in 1988, has disseminated worldwide. It is usually associated with high-level resistance to penicillins and aminoglycosides rendering the treatment of patients with vancomycin-resistant enterococci very difficult. Several investigators have reported mortality rates greater than 50% for vancomycin-resistant enterococcal bacteraemia. Risk factors associated with vancomycin-resistant enterococcal bacteraemia include prolonged hospital stay, neutropenia, prior oral or parenteral vancomycin use, and broad spectrum antibiotics. Since there is no uniformly effective antimicrobial therapy for patients infected with vancomycin-resistant enterococci, preventing of the spread of infection with the rigorous application of barrier precautions and other infectious control techniques is of paramount importance.

Animals↗

[Infection outbreak due to resistant Enterococcus faecium to glycopeptides in a Hospital of Rosario, Argentina].

Enterococci causes serious illness in immunocompromised patients and in severely ill, hospitalized patients. They are commonly isolated from the human gastrointestinal tract, and resistance to vancomycin has increased in frequency during the past few years. We report three cases of nosocomial vancomycin resistant Entrococcus faecium (VRE) infections from September to December of 2000. A 54-year-old man presented post surgical wound infection due to VRE after 2 months of hospitalization. The second is a 65-year-old neutropenic patient with a medical history of acute myeloid leukemia and esophageal carcinoma. In this case, central venous catheter was colonized with EVR. The third, a 65-year-old woman who received therapy with ceftriaxone, ciprofloxacin and clindamicin had a urinary tract infection due to EVR. The three isolates were resistant to vancomycin (MIC value > 256 micrograms/ml). The DNA amplification pattern obtained by OD-PCR were similar in the three cases.

Aged↗

Role of transposon Tn5482 in the epidemiology of vancomycin-resistant Enterococcus faecium in the pediatric oncology unit of a New York City Hospital.

During a 36-month period between 1993 and 1995 in the Pediatric Oncology Unit of Memorial Sloan Kettering Cancer Center, 74 patients experienced episodes of infection or colonization caused by vancomycin-resistant enterococci (VRE). Characterization of the 74 bacterial isolates by microbiological and molecular techniques (pulsed-field gel electrophoresis and hybridization with DNA probes specific for the vanA and vanB genes and for IS1251) identified 73 Enterococcusfaecium and one Enterococcusfaecalis (vanB) among the primary VRE isolates. Most (69/73) of the E. faecium isolates carried vanA and four isolates, the vanB gene complex. The overwhelming majority (67/69) of the vanA -positive isolates also gave hybridization signal for IS1251, indicating the presence of the newly described conjugative transposon Tn5482. No hybridization with IS1251 was obtained with the four vanB-carrying isolates. About 30% of the vanA-positive strains (23/69) were represented by PFGE subtype variants of a single clone, most isolates of which were recovered during a 4-month period between April to June of 1994. The larger portion of the vanA-carrying VRE represented by close to 70% of the isolates (46/69) belonged to as many as 37 different clonal types, indicating tremendous genetic diversity. Among 67 of the 69 vanA-carrying isolates, the localization of the Tn5482-associated vanA gene complex could be unequivocally identified either on the chromosome (40/69) or in plasmids (27/69). Transconjugants recovered from filter mating experiments using either a chromosomally located or plasmid-borne vanA donor strain and a single vancomycin-susceptible strain of either E. faecium or E. faecalis were analyzed by molecular typing techniques. Seven out of 10 independent transconjugants recovered from the same cross showed extensive differences in PFGE pattern and also in the localization of the vanA hybridizing DNA fragment transferred from the common VRE donor with chromosomally located vanA. The observations suggest that the extensive genetic diversity observed among the clinical isolates of VRE may be generated during conjugation between vancomycin-resistant and -susceptible enterococcal isolates. The observations also suggest that the epidemic spread of VRE in the United States may be linked to the frequent presence of Tn5482 among the American isolates.

Anti-Bacterial Agents↗

Community dissemination of vancomycin-resistant Enterococcus faecium.

BACKGROUND AND OBJECTIVE: In the United States, vancomycin-resistant enterococci (VRE) are predominantly acquired in the hospital. The extent of dissemination of VRE into the community in the United States has not been examined. Our objective was to determine the prevalence of VRE among nonhospitalized patients. METHODS: We conducted a cross-sectional surveillance study in an ambulatory care clinic. One hundred ambulatory patients participated in the study. Measurements included a written questionnaire on patient demographics, clinical data, and prior exposure to health care settings and antibiotics; rectal swabs; pulsed-field gel electrophoresis; and polymerase chain reaction genotyping. RESULTS: Three of 100 subjects (3%) were colonized with VRE, including one person who did not have any exposure to a health care setting or antibiotics. CONCLUSIONS: VRE was recovered from nonhospitalized patients. Physicians should be alert to the potential of VRE transmission in the ambulatory care setting.

Adult↗

Genesis of methicillin-resistant Staphylococcus aureus (MRSA), how treatment of MRSA infections has selected for vancomycin-resistant Enterococcus faecium, and the importance of antibiotic management and infection control.

We extensively studied the epidemiology and time course of endemic methicillin-resistant Staphylococcus aureus (MRSA) in the Millard Fillmore Hospital, a 600-bed teaching hospital in Buffalo. The changeover from methicillin-susceptible S. aureus to MRSA begins on the first hospital day, when patients are given cefazolin as presurgical prophylaxis. Under selective antibiotic pressure, colonizing flora change within 24 to 48 hours. For patients remaining hospitalized, subsequent courses of third-generation cephalosporins further select and amplify the colonizing MRSA population. Therefore, managing antibiotic selective pressure might be essential. Other strategies include attention to dosing, so that serum concentrations of drug exceed the minimum inhibitory concentration, and antibiotic cycling. Although there are some promising new antibiotics on the horizon, it is necessary to deal with many resistance patterns by using the combined strategies of infection control and antibiotic management.

Anti-Bacterial Agents↗

Replacement of the essential penicillin-binding protein 5 by high-molecular mass PBPs may explain vancomycin-beta-lactam synergy in low-level vancomycin-resistant Enterococcus faecium D366.

The mechanism of synergy between vancomycin and penicillin, as well as other beta-lactam antibiotics, was examined in a penicillin-resistant E. faecium (D366) expressing an inducible low-level resistance to vancomycin. It was demonstrated that penicillin per se was not able to reduce the inducible expression of the 39.5-kDa protein (VANB) or the carboxypeptidase activity which are involved in the mechanism of vancomycin resistance of this strain. Assays of competition between 3H-benzylpenicillin and diverse beta-lactam antibiotics suggested as the most likely explanation of the synergy that, once vancomycin resistance has been induced, the high-molecular mass penicillin-binding proteins (PBPs), and possibly PBP1 in particular, which have a high affinity for beta-lactam antibiotics, take over the role of the low-affinity PBP5 which is, in the non-induced strain, responsible for beta-lactam resistance.

Bacterial Proteins↗

Daptomycin in the treatment of vancomycin-resistant Enterococcus faecium bacteremia in neutropenic patients.

OBJECTIVE: Vancomycin resistant enterococcal (VRE) blood stream infection (BSI) in neutropenic patients is associated with poor outcome. We report our experience in treating VRE BSI in febrile, neutropenic patients with daptomycin, a recently licensed lipopeptide with bactericidal activity against VRE. PATIENTS AND METHODS: Patients with fever, neutropenia and VRE BSI were treated with more than one dose of daptomycin (either 6 mg/kg/day or 4 mg/kg/day) in an open label, emergency-use trial. Patients were then assessed for clinical and microbiological cures and survival. MIC's of isolates to daptomycin were determined. RESULTS: Nine febrile, neutropenic patients with VRE BSI received daptomycin. Four of 9 courses (44%) had clinical and/or microbiologic cure. Two of the 5 who failed cure died within 3 days of initiation of daptomycin. Five subjects survived to 30 days after the onset of BSI. CONCLUSIONS: Use of daptomycin in neutropenic patients with VRE BSI deserves further study as a treatment for VRE BSI in neutropenic patients.

Adult↗