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PubMedDate not supplied

Inhibitory and bactericidal effects of telithromycin (HMR 3647, RU 56647) and five comparative antibiotics, used singly and in combination, against vancomycin-resistant and vancomycin-susceptible enterococci.

The inhibitory and bactericidal effects of telithromycin (HMR 3647, RU 66647) were compared with those of gentamicin, ampicillin, erythromycin, azithromycin and vancomycin against 74 strains of enterococci (34 Enterococcus faecalis and 40 Enterococcus faecium) by agar dilution, broth dilution, time kill assays and postantibiotic effect (PAE). The telithromycin MIC(90) for vancomycin-sensitive (VSE) E. faecalis strains tested using the agar dilution method was 8 microg/ml. For a different group of VSE E. faecalis strains tested using the broth dilution method it was 0.06 microg/ml The telithromycin MIC(90)s for vancomycin-resistant (VRE) and VSE E. faecium strains, determined using the agar dilution method, were 4 and 8 microg/ml, respectively, while for a different set of VRE and VSE E. faecium strains tested using the broth macrodilution method, they were 32 and 16 microg/ml, respectively. Telithromycin MBC(90)s for E. faecalis were 4-6 tubes higher and for E. faecium 3-5 tubes higher, respectively, than the MIC(90)s. In time kill assays, telithromycin had bactericidal activity against only 1 of 7 E. faecium strains; for all other E. faecium and E. faecalis strains, only inhibitory activity was demonstrated. Neither synergy nor drug interference was observed when telithromycin was used in combination with ampicillin, vancomycin or gentamicin. At 10 times the MIC, the PAE of telithromycin against E. faecalis was 2.8 h, while for E. faecium it was 1.6 h. Telithromycin should be evaluated for therapy of enterococcal infections, including those caused by VRE organisms. However, because of the strain-to-strain variability in susceptibility to telithromycin, MIC determinations are important, especially for erythromycin-resistant strains.

Anti-Bacterial Agents↗
PubMed1999

Antimicrobial susceptibility patterns of enterococci causing infections in Europe. The European VRE Study Group.

In vitro susceptibilities of 4,208 enterococci (83% Enterococcus faecalis isolates, 13.6% Enterococcus faecium isolates, and 3.4% isolates of other species) from patients in 27 European countries towards 16 antibiotics were determined. High-level resistance to gentamicin varied by country (range, 1 to 49%; mean, 22.6% +/- 12. 3%) and per species (19.7% E. faecalis isolates, 13.6% E. faecium isolates, 3.4% by other species). Vancomycin resistance was detected in 0.06% E. faecalis, 3.8% E. faecium, and 19.1% isolates of other species. All enterococci were susceptible to LY 333328 and everninomicin, and 25% of E. faecalis isolates and 85% of other enterococci were susceptible to quinupristin-dalfopristin. The MIC of moxifloxacin and trovafloxacin for ciprofloxacin-susceptible E. faecalis at which 90% of the isolates were inhibited was 0.25 to 0.5 microg/ml.

Anti-Bacterial Agents↗
PubMed2000

Diversity among high-level aminoglycoside-resistant enterococci.

A total of 55 Enterococcus faecalis and 21 Enterococcus faecium non-replicate isolates were obtained from routine clinical specimens, during a 1 year period, in a tertiary care hospital in Athens, Greece. The most common isolation site was the urinary tract (44% of E. faecalis and 33% of E. faecium isolates). No vancomycin resistance was detected. Ampicillin-resistant isolates did not produce beta-lactamase. High-level gentamicin resistance was detected in 22% and 0% of E. faecalis and E. faecium isolates, respectively. The corresponding figures for high-level streptomycin resistance were 40% and 33%. The aminoglycoside-modifying enzyme gene aac(6')+aph(2") was detected by PCR in 10 of 12 high-level gentamicin-resistant E. faecalis isolates, and the ant(6)-I gene in all high-level streptomycin-resistant isolates of both species. DNA fingerprinting by PFGE grouped 31 of 55 E. faecalis isolates into 10 clusters, and 10 of 21 E. faecium isolates into two clusters, containing two to seven isolates each. Two E. faecalis PFGE types, comprising isolates expressing high-level aminoglycoside resistance, and not observed among non-high-level aminoglycoside-resistant strains, were disseminated in building A of the hospital. In contrast, high-level aminoglycoside resistance seemed to have been acquired nosocomially by a number of genotypically different E. faecium types. Molecular typing was therefore instrumental in understanding the differences in the mode of spread and acquisition of high-level aminoglycoside resistance among these two different enterococcal species.

Aminoglycosides↗
PubMed1990

Characterization of a class of nonformylated Enterococcus faecalis-derived neutrophil chemotactic peptides: the sex pheromones.

Bacteria produce a heterogeneous mixture of neutrophil chemotactic agents in culture filtrates. Formylmethionyl peptides have been shown to comprise a significant portion of the chemotactic activity in bacterial culture filtrates; however, not all of the chemotactic agents in bacterial culture filtrates are formylated peptides. To examine whether nonformylated peptides derived from bacteria could act as chemotactic agents, we studied several nonformylated hepta- and octapeptide Enterococcus faecalis-derived sex pheromones, their modified derivatives, and their competitive inhibitors for activation of rat peritoneal neutrophils. Several of these peptides, in particular cAM373 and cPD1, proved to be potent chemotactic agents in submicromolar concentrations as well as inducers of lysosomal granule enzyme secretion. Moreover, the more biologically active peptides were able to compete with fMet-Leu-[3H]Phe for binding to the formyl peptide receptor. These studies demonstrate that the formylmethionyl moiety may be an absolute requirement only for the binding of di- and tripeptides to the formyl peptide receptor. Larger peptides that may have or that may allow for additional contact points between the peptide and receptor may require N-formylation only relatively. Indeed, by removing this structural restraint, the formyl peptide receptor may interact with an unlimited number of peptide fragments of both infectious and host origins to then modulate neutrophil responses to infection and inflammation.

Amino Acid Sequence↗
PubMed1997

Active efflux of antimicrobial agents in wild-type strains of enterococci.

Enterococci are intrinsically resistant to numerous antimicrobial agents. We examined the energy-dependent efflux of radiolabeled drugs from four reference strains of Enterococcus faecalis and a strain of Enterococcus faecium and found that most strains pumped out norfloxacin and chloramphenicol. Efflux of tetracycline was detected only in certain strains.

Anti-Bacterial Agents↗
PubMedDate not supplied

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↗
PubMed2004

Substantially increased faecal carriage of vancomycin-resistant enterococci in a tertiary Greek hospital after a 4 year time interval.

OBJECTIVES: In a tertiary Greek hospital with no documented vancomycin-resistant enterococci (VRE) infections, a cross-sectional study was conducted in order to determine the degree of VRE faecal carriage among adult patients hospitalized in high-risk units. METHODS: Specimens for the surveillance were collected from separate patients in two periods (January-May 1999 and January-May 2003); 258 specimens were submitted during the first period and 149 during the second period. RESULTS: Three patients (1.2%) were colonized with VRE during the first period, whereas 52 (34.9%) were colonized during the second period. Two VRE isolates of the first period were Enterococcus faecalis and one Enterococcus faecium, whereas those of the second period were E. faecium except for three E. faecalis and two Enterococcus gallinarum. All VRE isolates apart from the two E. gallinarum isolates were positive for the vanA gene. The 48 vancomycin-resistant E. faecium were classified into eight clonal types, one of those predominating with 29 isolates; the remaining included one to nine isolates. The five vancomycin-resistant E. faecalis formed four distinct clonal types. CONCLUSIONS: The study reports a substantially higher prevalence of VRE carriage when the surveillance was repeated after a 4 year time interval. Urgent infection control measures are needed to prevent emergence of VRE outbreaks in our hospital setting.

Bacterial Proteins↗
PubMed1991

Species identification and antibiotic resistance patterns of the enterococci.

One hundred and forty isolates were identified using the GPI Card (Vitek Systems) and a conventional biochemical scheme. Agar dilution susceptibility testing was performed and isolates were screened for beta-lactamase production. The GPI Card was accurate in identifying Enterococcus faecalis, but discrepant results were obtained for seven (29.1%) of the 24 non-Enterococcus faecalis isolates. Ampicillin resistance was present in 2.9% of isolates and there were no beta-lactamase producers. There was no vancomycin resistance but 12.1% of isolates showed high-level resistance to gentamicin.

Ampicillin Resistance↗
PubMed1990

Species identities of enterococci isolated from clinical specimens.

Conventional tests and commercially available systems were used to determine the species identities of clinical isolates of enterococci. Strict adherence to the conventional test scheme of Facklam and Collins (R. R. Facklam and M. D. Collins, J. Clin. Microbiol. 27:731-734, 1989) resulted in the misidentification of lactose-negative Enterococcus faecalis isolates as Enterococcus solitarius, but this problem was overcome by the application of additional tests. The commercially available systems tested were unable to recognize some of the more recently described enterococcal species. E. faecalis accounted for 87.1% of 302 consecutive isolates. Enterococcus faecium (8.6%), Enterococcus avium (0.7%), Enterococcus durans (0.3%), Enterococcus gallinarum (1.0%), Enterococcus casseliflavus (1.0%), Enterococcus hirae (0.3%), and Enterococcus raffinosus (0.3%) isolates were also identified. None of the isolates produced beta-lactamase, but 15.4% of 235 isolates tested, including 1 strain of E. gallinarum, displayed high-level resistance to gentamicin.

Culture Media↗
PubMed1994

Clinical and molecular epidemiology of enterococcal bacteremia in a pediatric teaching hospital.

An apparent increase in the incidence of enterococcal bacteremias from 7 to 48/1000 bacteremias during 1986 to 1991 (p < 0.01) prompted this descriptive clinical and molecular epidemiologic study of 83 episodes occurring in 80 children between 1986 and 1992. Most community-acquired cases were in infants, in comparison with nosocomial episodes (24/26 and 34/57; p < 0.01); many of them were neonates (10/26 and 6/57; p < 0.01). Nosocomial cases were associated with underlying conditions including major surgery 56%, immunosuppression 49%, organ and tissue transplants 30%, and cardiac 32%, pulmonary 25%, renal 21%, and hepatic 21% disorders. Nosocomial episodes developed after a median of 32 days. There were 58 primary and 25 secondary bacteremias. Thirty-two episodes were polymicrobial and 44 organisms were involved. Twenty-six percent of the patients died. In 15%, death was preceded by septic shock, disseminated intravascular coagulation, and polymicrobial bacteremia (p < 0.01). Of 75 isolates, 82% were Enterococcus faecalis and 14% were Enterococcus faecium. Fourteen E. faecalis strains produced hemolysin; none produced beta-lactamase. Three had high-level resistance to gentamicin and 13 to streptomycin; two E. faecium and none of the E. faecalis strains were vancomycin resistant at a low level (p < 0.01) and one was ampicillin resistant. Pulsed-field gel electrophoresis of whole-cell DNA digested with restriction enzymes Sma I and Eag I showed five isolates with a homogeneous pattern, two with another homogeneous pattern, and 68 with distinct heterogeneous patterns. The increase in enterococcal bacteremias was not due to a clonal strain dissemination but to an increase in cases of heterogeneous enterococcal strains. We conclude that enterococcal septicemia is now an important cause of serious morbidity and death in critically ill children.

Anti-Bacterial Agents↗
PubMed1996

Antimicrobial activity of carbene complexes of rhodium(I) and ruthenium(II).

Twenty-four carbene-rhodium(I), carbene-ruthenium(II) complexes and related compounds were evaluated for their in vitro antimicrobial activity against the Gram-positive bacteria Enterococcus faecalis (ATCC 29212) and Staphylococcus aureus (ATCC 29213) and Gram-negative bacteria Escherichia coli (ATCC 25922), Pseudmonas aeruginosa (ATCC 27853). The compounds 1, 2, 3, 5, 7, 8, 9, 16, 18 and 19 were found very effective to inhibit the growth of Enterococcus faecalis and Staphylococcus aureus at the minimum inhibitory concentrations (MICs) of 5, 25, 5, 50, 25, 24, 24, 24, 6.25and 12.5 micrograms/ml, respectively. The compounds 6, 10, 12, 14, 15 and 17 were significantly effective against Enterococcus faecalis and Staphylococcus aureus with MIC values of 100-200 micrograms/ml. The compounds 2, 6 and 11 were also significantly effective against Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa with MIC values of 200-400 micrograms/ml.

Ampicillin↗
PubMed2004

Assessment of the role of antibiotics and enterococcal virulence factors in a mouse model of extraintestinal translocation.

OBJECTIVE: To study the relative contribution of antibiotics and bacterial virulence factors in the process of translocation of Enterococcus faecalis from the gut to extraintestinal organs. DESIGN: Prospective controlled animal study. SETTING: Animal experimental laboratory at a university medical center. SUBJECTS: Fifty-two female Balb/c mice. INTERVENTIONS: We developed a mouse model to study the translocation of Enterococcus faecalis from the intestinal tract. Balb/c mice received sterile drinking water or antibiotic combinations to deplete their indigenous intestinal microflora. The animals subsequently were fed genetically engineered enterococci expressing different combinations of the putative enterococcal virulence factors aggregation substance and binding substance. Animals were killed, and their livers, spleens, and mesenteric lymph nodes were aseptically removed and cultured along with fecal samples for enumeration of bacteria. MEASUREMENTS AND MAIN RESULTS: All animals were colonized with the test strains at 2-6 x 109 colony forming units/g of feces; in the antibiotic-treated animals, feces were free from anaerobes and Enterobacteriaceae. In animals fed the identical bacterial mutant, the colony counts in mesenteric lymph nodes were significantly lower in mice not treated with antibiotics than in those treated with antibiotics (p =.016). Multigroup analysis of variance revealed no significant differences of the translocation frequencies for the different mutant strains; however, the differences were statistically significant for all groups receiving antibiotics vs. the group not receiving antibiotics (p <.05-.01). There was a trend (although not statistically significant) for a higher proportion of positive cultures from either spleen or liver in mice that had enterococci recovered from their mesenteric lymph nodes (28%) relative to those that did not have enterococci isolated from the lymph nodes (12%; rate ratio 2.39, p =.30 by logistic regression analysis). CONCLUSIONS: Oral antibiotics can select for extraintestinal translocation of Enterococcus faecalis, and neither aggregation substance nor binding substance seems to be required for this process. The experiments encourage further exploration of host and microbial factors contributing to translocation and may provide a better understanding of the pathogenesis of enterococcal infections in patients in intensive care units.

Animals↗
PubMed2002

[Enterococcal endophthalmitis following cataract surgery].

BACKGROUND: Postoperative endophthalmitis can be subdivided into acute and chronic forms which are typically caused by different organisms. Enterococcus faecalis is an organism which normally causes an acute form of endophthalmitis. PATIENTS AND METHODS: We report on four cases of different forms of endophthalmitis following cataract extraction and intraocular lens (IOL) implantation who had been referred to our institution between 1998 and 2001. Enterococcus faecalis was the causative organism in all of them. RESULTS: Two patients presented with an acute form and were immediately treated in our hospital after symptom onset utilizing pars plana vitrectomy with and without IOL explantation. The two other patients were initially treated with subconjunctival and/or systemic antibiotics and steroids over a period of about two months before referral to our hospital. After initial improvement the inflammation exacerbated in these two patients and vitrectomy with or without IOL and capsular bag explantation was performed. The explanted IOL and capsular bag of one patient were examined using scanning electron microscopy and it was shown that the enterococci were adherent to the IOL and the capsular bag. CONCLUSION: Enterococcus faecalis can be the causative organism both of an acute and of a recurrent form of postoperative endophthalmitis. The recurrent form may be caused by organisms which tend to adhere to the IOL and the capsular bag. This should be kept in mind when considering different treatment options.

Acute Disease↗
PubMed2006

Importance of the structure of vancomycin binding pocket in designing compounds active against vancomycin-resistant enterococci (VRE).

16-Membered meta, para-cyclophanes mimicking the vancomycin binding pocket (D-O-E ring) are designed and synthesized. The structural features of these biaryl ether containing macrocycles are: a) the deletion of the carboxyl group of vancomycin's central amino acid (amino acid D); b) the elongation of the N-terminal; c) the presence of lipidated aminoglucose at the D-ring. Cycloetherification by way of an intramolecular nucleophilic aromatic substitution reaction (S(N)Ar) is used as a key step for the construction of the macrocycle. Minimum inhibitory concentrations for all of the derivatives are measured using a standard microdilution assay. Compounds 2a-2c and 3a-3c displayed weak activities against resistant strain Enterococcus faecalis L560 and were inactive against Enterococcus faecium resistant strain L2215.

Anti-Bacterial Agents↗
PubMed1997

Why does Staphylococcus aureus secrete an Enterococcus faecalis-specific pheromone?

The long known fact that Staphylococcus aureus can secrete a peptide (staph-cAM373) which acts as a sex pheromone for strains of E. faecalis carrying the sex pheromone plasmid pAM373 was studied in detail. 85 of 100 independent isolates of S. aureus produced an activity inducing the pAM373 encoded adhesin resulting in a clumping reaction of E. faecalis (i.e. secreted staph-cAM373), but not a single one of 100 independent isolates of coagulase-negative Staphylococci possessed this activity. The production of peptides acting as sex pheromone for E. faecalis was observed only for sex pheromone plasmid pAM373, but not for sex pheromone plasmids pAD1 and pPD1. It was shown that the amount of staph-pAM373 produced during growth paralleled cell mass, therefore this peptide should not be used as a cell density indicator by S. aureus (i.e. has no quorum sensing function). The potential function of staph-cAM373 to trigger gene transfer from Escherichia faecalis to S. aureus is discussed.

Bacterial Adhesion↗