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Role of environmental contamination as a risk factor for acquisition of vancomycin-resistant enterococci in patients treated in a medical intensive care unit.

BACKGROUND: Colonization pressure, proximity to another case, exposure to a nurse who cares for another case, enteral feeding, and the use of sucralfate, vancomycin hydrochloride, cephalosporins, or antibiotics are among the defined risk factors for acquisition of vancomycin-resistant enterococci (VRE) in the intensive care unit (ICU) setting. However, the role of rooms with contaminated environmental surfaces has not been well delineated. METHODS: Retrospective case-control study conducted on patients admitted to the medical ICU (MICU) of a tertiary-care, university-affiliated medical center during a 9-month period. Patients who acquired VRE (cases) were matched with 2 randomly selected control subjects who did not acquire VRE and had been in the MICU for at least the same number of days. RESULTS: Thirty cases were matched with 60 appropriate controls. Cases were more likely to have been in the hospital for longer than 7 days before MICU admission (P =.009); to have occupied a specific room with persisting contaminated surfaces (P =.06); to have had a central venous catheter (P =.05); to have received vancomycin (P =.02), cephalosporins (P =.03), and quinolones (P =.006) before MICU admission; and to have received vancomycin (P =.02) and metronidazole sodium phosphate (P =.03) after MICU admission. Multivariate analysis showed that a hospital stay of longer than 1 week before MICU admission (P =.04), use of vancomycin before or after MICU admission (P =.03), use of quinolones before MICU admission (P =.03), and placement in a contaminated room (P =.02) were the best predictors of VRE acquisition. CONCLUSIONS: Among all other factors associated with VRE transmission, VRE acquisition may depend on room contamination, even after extensive cleaning. This study underscores the need for better cleaning and the role of the environment in transmission of VRE.

Aged↗

Chlorhexidine gluconate to cleanse patients in a medical intensive care unit: the effectiveness of source control to reduce the bioburden of vancomycin-resistant enterococci.

BACKGROUND: Historically, methods of interrupting pathogen transmission have focused on improving health care workers' adherence to recommended infection control practices. An adjunctive approach may be to use source control (eg, to decontaminate patients' skin). METHODS: We performed a prospective sequential-group single-arm clinical trial in a teaching hospital's medical intensive care unit from October 2002 to December 2003. We bathed or cleansed 1787 patients and assessed them for acquisition of vancomycin-resistant enterococci (VRE). We performed a nested study of 86 patients with VRE colonization and obtained culture specimens from 758 environmental surfaces and 529 health care workers' hands. All patients were cleansed daily with the procedure specific to the study period as follows: period 1, soap and water baths; period 2, cleansing with cloths saturated with 2% chlorhexidine gluconate; and period 3, cloth cleansing without chlorhexidine. We measured colonization of patient skin by VRE, health care worker hand or environmental surface contamination by VRE, and patient acquisition of VRE rectal colonization. RESULTS: Compared with soap and water baths, cleansing patients with chlorhexidine-saturated cloths resulted in 2.5 log(10) less colonies of VRE on patients' skin and less VRE contamination of health care workers' hands (risk ratio [RR], 0.6; 95% confidence interval [CI], 0.4-0.8) and environmental surfaces (RR, 0.3; 95% CI, 0.2-0.5). The incidence of VRE acquisition decreased from 26 colonizations per 1000 patient-days to 9 per 1000 patient-days (RR, 0.4; 95% CI, 0.1-0.9). For all measures, effectiveness of cleansing with nonmedicated cloths was similar to that of soap and water baths. CONCLUSION: Cleansing patients with chlorhexidine-saturated cloths is a simple, effective strategy to reduce VRE contamination of patients' skin, the environment, and health care workers' hands and to decrease patient acquisition of VRE.

Adult↗

Antibacterial activity of Australian plant extracts against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE).

Ethanolic extracts of five traditional Australian medicinal plants, previously shown to display antibacterial activity against laboratory strains of the Gram positive bacteria Staphylococcus aureus and Enterococcus faecalis, were investigated for their abilities to inhibit clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Using plate-hole diffusion assays, the following results were obtained: (a) extract from the leaves of Eremophila alternifolia (Myoporaceae) showed activity against MRSA; (b) extract from the leaves of Acacia kempeana (Mimosaceae) showed incomplete inhibition of VRE; (c) extracts from the leaves of Amyema quandong (Loranthaceae) and Eremophila duttonii (Myoporaceae) were active against both types of bacteria; (d) extract from the stem base of Lepidosperma viscidum (Cyperaceae) was active against MRSA and exhibited incomplete inhibition of VRE. All active extracts were evaluated using time-kill assays. Most of the extracts showed bactericidal effects and reduced the number of viable cells by 4-6 logs within four hours, while the extracts from Acacia kempeana leaves and Lepidosperma viscidum stem base exhibited bacteriostatic activity against VRE. The extract from the leaves of Eremophila duttonii was the most active and reduced the number of viable cells of MRSA and VRE to undetectable levels within 1 hour.

Anti-Bacterial Agents↗

In vitro evaluation of high-level, gentamicin-resistant enterococci isolated from bacteremic patients.

We attempted to characterize the susceptibility of high-level, gentamicin-resistant (HLGR, minimum inhibitory concentration [MIC] > 2000 micrograms/ml) enterococcal blood isolates and evaluated a small subset of these isolates for bactericidal synergy. Thirteen Enterococcus faecalis and three Enterococcus faecium isolates that were HLGR were prospectively collected. Standard broth macrodilution techniques were used to determine the MICs and minimum bactericidal concentrations to a variety of antibiotics. Two isolates were evaluated for synergy by time-kill curve methods using combinations of penicillin and streptomycin, teicoplanin and rifampin, and vancomycin and ciprofloxacin. Teicoplanin was the most active antibiotic tested, with all isolates exhibiting susceptibility to this agent. Four E. faecalis isolates and one E. faecium isolate expressed only low-level resistance to streptomycin (LLSR, MICs 32-64 micrograms/ml). Penicillin and streptomycin produced bactericidal synergy in the LLSR isolate. The other antibiotic combinations did not result in bactericidal synergy in the two isolates tested. For HLGR enterococci that are only LLSR, the combination of penicillin-streptomycin appears to provide adequate bactericidal activity. Teicoplanin may potentially be useful for streptomycin-resistant HLGR isolates.

Anti-Bacterial Agents↗

Antibiotic resistant fecal isolates of Enterococci among unselected patients outside the clinical sector: an epidemiological study from Southern Germany.

PURPOSE: The aim of the study was to assess the prevalence and determinants of antibiotic-resistant Enterococci in a large group of outpatients in Southern Germany. METHODS: Stool samples were collected from 497 unselected patients aged 40-75 years attending general practitioners. Enterococcus faecium (E. faecium) and Enterococcus faecalis (E. faecalis) were cultured and minimal inhibitory concentrations of antibiotics used inside and outside the clinical sector were tested. RESULTS: E. faecium and E. faecalis could be identified and cultured in 60 (12.4%) and 205 (41.2%) of the stool samples, respectively. Under non-selective culture conditions no vancomycin-resistant Enterococcus (VRE) isolate was found. Only E. faecium isolates showed resistance to fluoroquinolones, 40% were resistant to ciprofloxacin. The prevalences of E. faecium resistance to ampicillin and doxycycline were 3.3% and 13.3%, respectively, whereas 0.5% and 29.6% of the E. faecalis isolates were resistant to ampicillin and doxycycline, respectively. Antibiotic use during the last 3 months was significantly associated with antibiotic resistance (to either ampicillin, imipenem, or doxycycline) of E. faecalis isolates (OR: 2.9; CI: 1.2-6.8). CONCLUSIONS: Prevalences of resistance were generally lower than and patterns of resistance were quite different from previous investigations in the clinical setting. Recent antibiotic use was associated with increased colonization with resistant strains.

Adult↗

Antibacterial activity of phytochemicals isolated from Erythrina zeyheri against vancomycin-resistant enterococci and their combinations with vancomycin.

Six phytochemicals were isolated from the roots of Erythrina zeyheri (Leguminosae) by repeated silica gel column chromatography using various eluting solvents. Extensive spectroscopic studies revealed that all were isoflavonoids. The antibacterial activity of the six compounds against vancomycin-resistant enterococci (VRE) was estimated by determining the minimum inhibitory concentration (MIC). Of the six isoflavonoids, erybraedin A ((6aR, 11aR)-3,9-dihydroxy-4,10-di(gamma,gamma-dimethylallyl)pterocarpan) exhibited the highest growth inhibitory potency against VRE with an MIC value of 1.56-3.13 microg/mL, followed by eryzerin C ((3R)-7,2',4'-trihydroxy-6,8-di(gamma,gamma-dimethylallyl)isoflavan) (MIC 6.25 microg/mL). These compounds also inhibited the growth of methicillin-resistant Staphylococcus aureus (MRSA) at 3.13-6.25 microg/mL. The antibacterial effects of the two compounds against VRE and MRSA were based on bacteriostatic action. When erybraedin A or eryzerin C was combined with vancomycin, the fractional inhibitory concentration (FIC) index against VRE ranged from 0.5306 to 1.0 and from 0.5153 to 0.75, respectively. The combinations also showed FIC indices of 0.6125-1.0 against MRSA. The results indicate that, depending on the case, both compounds act either synergistically or additively with vancomycin against VRE and MRSA. Erybraedin A and eryzerin C show evidence of being potent phytotherapeutic agents against infections caused by VRE and MRSA.

Anti-Bacterial Agents↗

In vitro conjugative transfer of VanA vancomycin resistance between Enterococci and Listeriae of different species.

In a study designed to gain data on the in vitro transferability of vancomycin resistance from enterococci of the VanA phenotype to listeriae of different species, three clinical Enterococcus isolates-Enterococcus faecium LS10, Enterococcus faecalis LS4, and Enterococcus faecalis A3208, all harboring a plasmid that strongly hybridized with a vanA probe-were used as donors in transfer experiments. Strains of five Listeria species were used as recipients. From Enterococcus faecium LS10, glycopeptide resistance was transferred to Listeria monocytogenes, Listeria ivanovii, and Listeria welshimeri recipients, whereas no transfer occurred to Listeria seeligeri or Listeria innocua strains. From the two Enterococcus faecalis isolates, no transfer occurred to any Listeria recipient. MICs of both vancomycin and teicoplanin were > or = 256 mg/l for all transconjugants tested. Furthermore, all transconjugants harbored a plasmid that strongly hybridized with the vanA probe, with vanA consistently located in an EcoRI fragment of about 4 kb. Exposure of Listeria transconjugants to vancomycin resulted in synthesis of a membrane protein similar in size (39 kDa) to a vancomycin-induced membrane protein of Enterococcus faecium LS10. In retransfer experiments with Listeria transconjugants used as donors, glycopeptide resistance was transferred to all Listeria recipients tested, including strains of Listeria innocua and Listeria seeligeri, which were unable to receive the resistance from Enterococcus faecium LS10. The frequency of vanA transfer to listerial recipients was greater in retransfer experiments than in the primary matings. These findings suggest that the vanA resistance determinant might spread to the established pathogen Listeria monocytogenes, both directly from a resistant enterococcus and through strains of nonpathogenic Listeria species acting as intermediate resistance vehicles.

Anti-Bacterial Agents↗

[Studies on the in vitro effects of cephalothin and gentamicin, alone and in combination, on proteus mirabilis and enterococci (author's transl)].

A combined antibiotic therapy is only useful in a few precisely defined clinical pictures where testing of the chemotherapeutics administered is required to determine their characteristics of action (antagonism, indifference, synergism) on the isolated organism. For the initial therapy of critical acute infections, simultaneous administration of cephalothin and gentamicin proved to be valuable. In the present study, the efficiency of these chemotherapeutics alone and in combination was investigated in a quantitative serial dilution test and with the membrane-filtration method. Thirty strains of Proteus mirabilis and enterococci showed only low sensitivity to the antibiotic alone. In combination, whereby gentamicin was at a constant level comparable to in vivo serum levels, an increase of bacteriostatic and bactericidal action could be demonstrated, especially for Proteus mirabilis. The antibacterial spectrum, the molecular-biological mode of action, clinical experience and possible side-effects of the cephalotin-gentamicin combination are discussed.

Cephalothin↗

Pathogenicity of enterococci outside of urinary tract and blood stream.

It is evident at this time that enterococci by themselves are able to cause infections outside the bloodstream and the urinary tract only rarely and under very special circumstances in which local defense mechanisms are severely compromised (e.g., by plastic devices). In most instances, they have been found in mixed culture and probably act synergistically with other bacteria to cause damage to the host. They could, however, be carried from their habitat into the bloodstream and eventually cause septicemia. Such a danger is probably heightened if supercolonization is fostered through antibiotics that are ineffective against them, e.g., cephalosporins.

Abdomen↗

Combination effect of meropenem with aminoglycosides and teicoplanin on Pseudomonas and enterococci.

The in vitro activity of meropenem, a new carbapenem, and the combination effect with netilmicin, tobramycin, gentamicin, and teicoplanin against Pseudomonas spp. and enterococci was studied. Meropenem showed very good in vitro activity against Pseudomonas aeruginosa (MIC90 2 mg/l) and good to moderate activity against Pseudomonas putida (MIC90 4 mg/l) and Enterococcus faecalis (MIC90 8 mg/l). Aminoglycosides were highly active against P. putida (MIC90 0.5 mg/l), but showed only moderate activity against P. aeruginosa. The synergistic effect of meropenem was shown in combination with teicoplanin against E. faecalis (40%). No Pseudomonas strains were inhibited by the synergistic effect of meropenem with aminoglycosides. No antagonism occurred with any of the combinations.

Aminoglycosides↗

Mechanisms of resistance of enterococci to beta-lactam antibiotics.

Two mechanisms are responsible for resistance of enterococci to beta-lactam antibiotics: alterations of penicillin-binding proteins and production of a beta-lactamase. The latter has been found in a few clinical isolates of Enterococcus faecalis, whereas the former appears to account for resistance in most strains. A correlation has been established between the amount of a particular penicillin-binding protein which has a low affinity for penicillin and the level of resistance. The higher activity of some penicillins, as compared to cephalosporins, has been related to the relatively higher affinity for these penicillins of the penicillin-binding protein involved in the mechanism of resistance. Alterations in the autolytic enzyme pattern have been associated with the paradoxical response to bactericidal activity of penicillin often exhibited by Enterococcus faecalis clinical isolates.

Anti-Bacterial Agents↗

Comparison of four methods for testing high-level aminoglycoside resistance in enterococci.

In a prospective study the prevalence of high-level aminoglycoside resistance (MIC greater than or equal to 2,000 micrograms/ml) among 62 clinically significant enterococci was investigated. A total of 10(5) organisms were inoculated a) onto a plate containing 2,000 micrograms/ml of gentamicin or streptomycin; b) into a microtube for dilution MIC determinations for gentamicin, amikacin, tobramycin and streptomycin; and c) into a single tube containing 500 micrograms/ml of gentamicin, amikacin, tobramycin or streptomycin in supplemented Mueller-Hinton broth. In addition, tubes containing 500 micrograms/ml of gentamicin, amikacin, tobramycin or streptomycin were inoculated with five enterococcal colonies ("crude" method). For 45 of the 62 isolates, MICs of gentamicin, amikacin and tobramycin were less than or equal to 500 micrograms/ml, while 17 (27%) showed high-level resistance. The MICs of streptomycin were less than or equal to 500 micrograms/ml for 42 of 62 isolates, and greater than or equal to 2,000 micrograms/ml for 20 (32.3%). For 8 of the 17 (47%) isolates showing high-level gentamicin resistance, MICs of streptomycin were less than or equal to 500 micrograms/ml. There was complete agreement between the results of the plate method, the microtube dilution MIC and the tube inoculated with 10(5) CFU, but the crude method gave discordant results for two isolates. It is concluded that a tube containing 500 micrograms/ml of aminoglycoside is a simple, accurate and inexpensive method for determining high-level aminoglycoside resistance.

Amikacin↗

Frequency and antimicrobial susceptibility of clinical isolates of enterococci.

A study was performed to determine the frequency and antimicrobial susceptibility of Enterococcus species in clinical specimens. Of 943 aesculin-positive isolates, 873 (92%) were identified as enterococci (737 Enterococcus faecalis, 129 Enterococcus faecium and 7 other Enterococcus species). High-level resistance to gentamicin was found in 15.2% of Enterococcus faecalis, but not in Enterococcus faecium; 58% of Enterococcus faecium were resistant to gentamicin at a concentration of 64 mg/l. None of the isolates were shown to possess vancomycin resistance.

Drug Resistance, Microbial↗

Prevalence and characterization of vancomycin-resistant enterococci in chicken intestines and humans of Korea.

The prevalence, genotype for antibiotic resistance and antibiotic susceptibility of vancomycin resistant enterococci (VRE) were determined. And molecular typings of the Enterococcus faecium isolates were analyzed. Prevalence of VRE in chickens, healthy children and intensive care unit (ICU) patients was 41.6%, 7.9%, and 20.4%, respectively. Forty out of 54 isolates from chicken intestines, and 9 out of 11 from ICU patients were identified as Enterococcus faecium. Eleven out of 13 isolates from non-hospitalized young children were E. gallinarium. Twelve strains of E. faecalis were isolated from chicken intestines. The gene for the antibiotic resistance in E. faecium, and E. faecalis was vanA, while that in E. gallinarium was vanC1. E. faecium isolates were resistant to most of antibiotics except ampicillin and gentamicin. Molecular typing of the E. faecium strains obtained by pulse field gel electrophoresis and repetitive sequence-based PCR suggest that VRE transmit horizontally from poultry to humans, especially young children, via the food chains in Korea.

Animals↗

[Septic shock due to vancomycin-resistant enterococci infection. Tigecycline monotherapy].

Adequate antimicrobial therapy is of crucial importance for the survival of critically ill patients with severe nosocomial infections. Tigecycline is an important therapeutic option for the treatment of infections caused by multi-resistant Gram-positive and Gram-negative bacteria including vancomycin-resistant enterococci (VRE). A large randomised study (patients with APACHE-II-score >30 excluded/mean APACHE-II-score 6) demonstrated that tigecycline is not inferior to imipenem/cilastatin for treatment of complicated intra-abdominal infections. However, no case has been reported with microbiological eradication and clinical cure in a patient with septic shock due to peritonitis caused by VRE and treatment with tigecycline monotherapy. Clinical details of a patient suffering from postoperative peritonitis are presented. The patient developed severe septic shock after pancreatic surgery (multiple organ failure, APACHE-II-score 34). As the site of anastomotic leakage was very small and could not be exactly identified, irrigation-suction drains were placed followed by closed postoperative continuous lavage. The pathogen responsible was identified as a vancomycin-resistant Enterococcus faecium, therefore monotherapy with tigecycline was started which resulted in microbiological response and clinical cure. Tigecycline is a new therapeutic option for the treatment of intra-abdominal infections and from an economic point of view financially rewarding when used as monotherapy.

APACHE↗

[Prevention and control of the spread of vancomycin-resistant enterococci: results of a workshop held by the German Society for Hygiene and Microbiology].

The incidence of vancomycin-resistant enterococci (VRE), especially E. faecium, is increasing in several German hospitals and some facilities have experienced VRE outbreaks. The German National Nosocomial Infection Surveillance System has also noticed a sharp increase in the incidence of nosocomial VRE infections per 10,000 patients from 0.5 in 2003 to 11.0 in 2005 accompanied by a rise in VRE-associated mortality. However, the reasons of this increase remain unknown. As VRE may cause severe nosocomial infections, transmission must be restricted. This article provides the guidelines as defined by the workshop of the German Society for Hygiene and Microbiology for the prevention of VRE transmission in both, endemic and epidemic, settings. The following topics are discussed: indication for VRE screening, microbiological diagnostics, general infection control measures (isolation precautions and use of protective clothing) and additional hygiene measures in the nosocomial VRE outbreak setting.

Cross Infection↗

Binding of extracellular matrix molecules by enterococci.

The bacterial surfaces of enterococci are not uniform. This fact is confirmed by several studies and by our results when great differences between individual strains with regard to their cell surface hydrophobicity, binding of eight ECM (extracellular matrix) molecules immobilized on latex beads and four selected ECM molecules in microtiter plates were observed. The strains expressing high binding of ECM molecules (e.g., HJ 18, HJ 23, HJ 24, HJ 26, HJ 28, HJ 36, etc.) were found among Enterococcus faecalis and E. faecium by PAA (particle agglutination assay). On the other hand, weak ECM binders (e.g., HJ 21, HJ 32, HJ 34, HJ 38, HJ 39, HJ 42, HJ 43) were also found. A direct correlation was found between porcine mucin and fetuin binding ability of eight selected strains tested in microtiter plates and by PAA. Moreover, the influence of tunicamycin treatment was different because significant (P < 0.001) blocking effect of tunicamycin was observed with two selected strains (HJ 26 and HJ 36), whereas two strains (HJ 18 and HJ 22) were not significantly affected in their fetuin binding. The treatment of six enterococcal strains with proteolytic enzymes, pronase P, and trypsin, and with sodium metaperiodate also significantly (P < 0.001) decreased their fetuin binding. This suggests that both protein and carbohydrate moieties are involved in the binding of immobilized fetuin. However, the influence of these chemicals on the fetuin binding by individual strains was different.

Agglutination Tests↗

Binding of extracellular matrix proteins by enterococci.

Forty-four enterococcal strains isolated from human clinical specimens were investigated for binding of 125I-labeled fibronectin, vitronectin, thrombospondin, lactoferrin, and collagen type I and IV, and for cell surface hydrophobicity. Most strains expressed low binding of iodine-labeled human fibronectin, collagen I and IV, and higher binding of human vitronectin, human lactoferrin, and human thrombospondin. Bacteria grown in Todd-Hewitt broth exhibited increased binding to vitronectin and thrombospondin. In particle agglutination assays (PAA), Enterococcus faecalis strains reacted strongly with coated latex beads in contrast to E. faecium strains, which generally did not react. The ability of enterococci to bind ECM proteins was affected by heating and proteolytic digestion, suggesting that some protein-binding components become surface exposed after treatment with proteases. The binding of 125I-labeled proteins to E. faecalis strain E70 was inhibited when cells were preincubated with unlabeled proteins. Preincubating cells with sulfated polymers such as dextran sulfate (Mr 5000 and 8000), pentosan sulfate and heparin decreased binding of vitronectin, lactoferrin, and thrombospondin. The binding of lactoferrin and thrombospondin was also decreased when bacteria were preincubated with galactose, fucose, and mannosamine, but not with mannose. All of 30 E. faecalis strains expressed pronounced surface hydrophobicity, but 10 of 14 E. faecium strains showed hydrophilic cell surface.

Ammonium Sulfate↗