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PubMed1990

Differential rates of digestion of bacteria by freshwater and marine phagotrophic protozoa.

Differential decreases over time of two bacterial species, Escherichia coli and Enterococcus faecalis, in a freshwater and a marine ecosystem were observed and explained by a differential rate of digestion of these bacteria by phagotrophic flagellates and ciliates. For this purpose, fluorescence-labeled bacteria (FLB) were used and prepared from the two species cited above. The number of FLB was observed for 5 days in fresh and marine waters in the presence or absence (0.2-mum-pore-size-filtered water) of natural microbiota. These experiments showed a longer persistence of Enterococcus faecalis FLB as opposed to Escherichia coli FLB in the presence of natural microbiota. Removal of FLB was due to protozoan grazing because no decrease of FLB number was observed in the absence of natural microbiota. In short-term (about 40 min) ingestion experiments, we found similar clearance rates of Escherichia coli and Enterococcus faecalis FLB by assemblages of flagellates from the freshwater and the marine ecosystem and by cultured assemblages of ciliates from the marine ecosystem. Clearance rates of Enterococcus faecalis FLB were greater than those of Escherichia coli FLB for assemblages of ciliates from the freshwater ecosystem. Comparison of rates of ingestion and digestion of FLB by protozoa showed that Escherichia coli FLB were digested and ingested at similar rates. However, Enterococcus faecalis FLB were digested slower than they were ingested. These results suggest that a longer persistence of Enterococcus faecalis as opposed to Escherichia coli can be explained by a differential digestion by flagellates and ciliates in aquatic ecosystems. Moreover, rates of ingestion and digestion were strongly correlated for both FLB types.

Journal Article↗

PubMed2004

Lack of correlation between phenotypic techniques and PCR-based genotypic methods for identification of Enterococcus spp.

A total of 123 genetically-unrelated strains of Enterococcus spp. strains (51 Enterococcus faecalis, 57 Enterococcus faecium, 10 Enterococcus gallinarum, and 5 Enterococcus casseliflavus) were phenotypically identified by biochemical profiles and by using an automated method. The strains were also analyzed by a PCR assay to assess the accuracy of the phenotypically-based methods for identification of Enterococcus spp. With this aim, a PCR assay using different cell targets, which allows simultaneous detection of glycopeptide-resistant genotypes as well as identification to the species level by means of different gene targets, was used as the gold standard method. All 51 strains of E. faecalis were correctly identified, whereas 48 of 57 strains (84.2%) of E. faecium, were correctly identified. All of the strains of E. gallinarum and 3 out of 5 strains of E. casseliflavus were also correctly identified. The overall results showed that it is possible to identify Enterococcus spp. at the molecular level in less than 30 hours, compared with the 48-96 hours required for the phenotypically-based methods. The excellent accuracy of the PCR assay in identifying these species, particularly E. faecium, must also be emphasized. These findings may have implications for the routine clinical identification of enterococci species.

Bacterial Typing Techniques↗

PubMed1999

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↗

PubMed2004

[The study of the pro-nucleating activity of bacteria identified in cholesterol gallstones in model bile systems].

OBJECTIVE: To explore the relationship of bacteria identified in cholesterol gallstones and gallstone formation. METHODS: Observe the bacteria activity in model bile and the influence of bacteria on the cholesterol nucleation time (NT). RESULTS: (1) Model bile were suitable for the growth of E. coli, Pseudomonas aeruginosa, staphylococcus aureus, enterococcus faecalis, clostridium difficile and Clostridium. Propionibacterium acne grew weakly and the growth of Bacteroides fragilis was restrained in model bile. (2) Only pseudomonas aeruginosa and enTerococcus faecalis could ly shorten the cholesterol nucleation time. (3) With pseudomonas aeruginosa or enTerococcus faecalis added in model bile, the formation of cholesterol crystals presented a progressive course of evolution. CONCLUSIONS: Pseudomonas aeruginosa and enterococcus faecalis, not propionibacterium acne, have pro-nucleating ability in model bile.

Bile↗

PubMed1992

Detection of vancomycin resistance in Enterococcus species.

Enterococcus faecalis and Enterococcus faecium isolates that are resistant to vancomycin have recently been identified in North America and Europe. Of 155 clinical isolates of enterococci (113 E. faecium and 42 E. faecalis), we found that 98 were resistant, 52 were moderately susceptible, and 5 had intermediate susceptibilities to vancomycin by using broth microdilution susceptibility testing according to the National Committee for Clinical Laboratory Standards (NCCLS) (Approved Standard M7-A2). Using NCCLS disk diffusion methodology (Approved Standard M2-A4), we evaluated the NCCLS supplemental M100-S3 revisions for zone diameter interpretive standards and incubation conditions and found 5.8% minor errors. A total of 234 isolates, which included an additional 79 E. faecium isolates that were moderately susceptible to vancomycin, were used to evaluate the Vitek GPS-TA card (bioMerieux, Inc., Hazelwood, Mo.) and the Pos MIC type 6 panel (MicroScan; Baxter Health Care Corp., West Sacramento, Calif.) for the detection of vancomycin resistance. The Vitek card was 100% specific and 72% sensitive, whereas the MicroScan panel with the Walk/Away system was 98% specific, with a sensitivity of 93% which increased to 99% when readings were performed manually. An agar screen plate method was evaluated with vancomycin concentrations of 6, 8, 10, or 12 micrograms/ml; plates were inoculated so as to obtain a final concentration of 10(5) CFU per spot. This method was found to be 100% sensitive and specific at all concentrations.

Drug Resistance, Microbial↗

PubMed1993

In vitro activity of RP59500, an injectable streptogramin antibiotic, against vancomycin-resistant gram-positive organisms.

The in vitro activity of RP59500, a streptogramin antibiotic, against 146 clinical isolates of vancomycin-resistant gram-positive bacteria was examined. Five strains of the species Enterococcus casseliflavus and Enterococcus gallinarum, for which the MIC of vancomycin was 8 micrograms/ml, were also studied. Twenty-eight vancomycin-susceptible strains of Enterococcus faecalis and Enterococcus faecium were included for comparison. The drug was highly active against Leuconostoc spp., Lactobacillus spp., and Pediococcus spp. (MICs, < or = 2 micrograms/ml). RP59500 was more active against vancomycin-susceptible strains of E. faecium than E. faecalis (MICs for 90% of the strains [MIC90s], 1.0 versus 32 micrograms/ml). Vancomycin-resistant strains of E. faecalis were as resistant to RP59500 as vancomycin-susceptible strains (MIC90, 32 micrograms/ml), but some vancomycin-resistant E. faecium strains were relatively more resistant to the new agent (MIC90, 16; MIC range, 0.5 to 32 micrograms/ml) than were vancomycin-susceptible organisms of this species.

Drug Resistance, Microbial↗

PubMed1995

DNA hybridization and contour-clamped homogeneous electric field electrophoresis for identification of enterococci to the species level.

In this study, 113 Enterococcus faecium, 37 Enterococcus faecalis, 24 Enterococcus gallinarum, 15 Enterococcus raffinosus, and 13 Enterococcus casseliflavus clinical isolates and American Type Culture Collection (ATCC) strains were evaluated by contour-clamped homogeneous electric field electrophoresis. Thirty-one of the E. faecium, 22 of the E. faecalis, 24 of the E. gallinarum, 15 of the E. raffinosus, and 13 of the E. casseliflavus isolates were also evaluated by DNA-DNA hybridization. Genomic DNAs from type strains E. faecalis ATCC 19433, E. faecium ATCC 19434, E. gallinarum ATCC 49573, E. raffinosus ATCC 49427, and E. casseliflavus ATCC 25788 were labeled with biotin for use as probes. E. faecalis differed from all other species in always having a largest fragment of > 400 kb. E. gallinarum was different from all other species in having all SmaI fragments of < 200 kb. Biotin-labeled probes showed a high degree of hybridization with genomic DNA from the same species and a low degree of hybridization when hybridized to genomic DNA from different species for all isolates tested except for four isolates identified as E. faecium by conventional biochemical methods. The DNA from these four isolates hybridized strongly to DNA from E. gallinarum ATCC 49573 and weakly to E. faecium ATCC 19434 DNA and had all SmaI fragments of < 200 kb in size. These data suggest that these isolates are nonmotile E. gallinarum. DNA from each ATCC type strain hybridized strongly with itself and had only a low degree of hybridization with DNA from other ATCC type strains tested. These results suggest that contour-clamped homogeneous electric field electrophoresis patterns and DNA-DNA hybridization with biotin-labeled probes may be of use for species differentiation of some enterococci.

Blotting, Southern↗

PubMed2001

Bile salt hydrolase activity of Enterococci isolated from food: screening and quantitative determination.

One hundred seventeen enterococcal strains isolated from food (47 Enterococcus faecium, 48 Enterococcus faecalis, 16 Enterococcus durans, 2 Enterococcus gallinarum, 3 Enterococcus casseliflavus, and 1 Enterococcus malodoratus) were screened for bile salt hydrolase (BSH) activity on de Man, Rogosa, and Sharpe agar medium containing taurocholic acid and calcium chloride. The highest incidence of BSH-active strains was observed for E. faecalis (81%) followed by E. faecium (50%) and E. durans (44%). Isolates were grouped into four putative activity groups (no, low, medium, and high activity) based on the size of precipitation zones observed in the screening experiment. Our results showed that assumptions on BSH activity based on the size of bile precipitation zones in screening experiments did not correlate with actual activity as quantified by high-pressure liquid chromatography, but the screening assay is useful for assessing the presence or absence of BSH activity.

Amidohydrolases↗

PubMed2001

Resuscitation rate in different enterococcal species in the viable but non-culturable state.

AIMS: The viable but non-culturable (VBNC) state is a survival strategy adopted by bacteria when exposed to environmental stress. When in this state bacteria are no longer culturable on conventional growth media, but cells display metabolic activity and maintain pathogenicity factors/genes and, in some cases, resuscitation from the VBNC state has been shown. This state has been described for both human pathogens and faecal pollution indicators. In this study, we present evidence for entry of different enterococcal species into the VBNC state in an oligotrophic microcosm. METHODS AND RESULTS: The duration of the viability of the cells in the VBNC state was measured either by detecting the presence of pbp5 mRNA or by quantifying their resuscitation capability. Enterococci showed different behaviours. Enterococcus faecalis and Enterococcus hirae entered into the VBNC state within 2 weeks and remained in that state for 3 months. In the experiments described the resuscitation rate was 1:10 000 cells as soon as the cells entered the VBNC state and decreased gradually to undetectable levels over the following 3 months. Enterococcus faecium, however, remained culturable up to 4 weeks. After this time period, when the population was totally unculturable, the cells were far less resuscitable than other enterococci and only over a narrow time interval (2 weeks). CONCLUSIONS: These results suggest that Ent. faecalis and Ent. hirae enter the VBNC state but that Ent. faecium, in an oligotrophic laboratory environment, tends to die instead of entering the VBNC state. SIGNIFICANCE AND IMPACT OF THE STUDY: These experiments may mimic what happens when enterococci are released by humans and animals in natural environments.

Bacterial Proteins↗

PubMed2002

Comparison of susceptibility to antimicrobials of the enterococcal species isolated from pigeons (Columba livia).

Antimicrobial resistance profiles were assessed in Enterococcus faecium, Enterococcus faecalis, and Enterococcus columbae strains isolated from racing pigeons (Columba livia). E. columbae is the most prevalent enterococcal species in the intestines of pigeons. Acquired resistance against the antimicrobials bambermycin, vancomycin, monensin, narasin, virginiamycin (cross-resistant with quinupristin/dalfopristin), avilamycin (cross-resistant with evernimicin), and ampicillin was not seen. Only for the antimicrobials tetracycline and tylosin was a frequent occurrence of resistance found in all three enterococcal species tested. Resistance to the fluoroquinolone antimicrobial enrofloxacin was present in E. columbae. Bacitracin resistance was seen in the species E. faecalis and E. faecium but not in E. columbae. High-level streptomycin resistance was found in E. columbae and in one E. faecium strain, whereas high-level gentamicin resistance was mainly associated with E. faecalis. The differences noted between the different species illustrate the difficulties related to the choice of indicator bacteria for antimicrobial resistance in the intestinal flora.

Animals↗

PubMed1996

Vancomycin-resistant enterococci.

OBJECTIVE: To review vancomycin resistance in enterococci (Enterococcus faecalis and Enterococcus faecium) with respect to history, epidemiology, mechanism of resistance, and management. DATA SOURCES: A MEDLINE, IDIS, and current journal search of English-language articles on vancomycin-resistant enterococci (VRE) published between 1982 and 1994 was conducted. STUDY SELECTION: Studies and reports pertaining to vancomycin-resistant E. faecalis and E. faecium were evaluated. Case reports, cohort, epidemiologic, in vitro and in vivo studies were evaluated. DATA EXTRACTION: Reports in which vancomycin minimum inhibitory concentrations were 32 micrograms/mL or more were evaluated. DATA SYNTHESIS: Large outbreaks of VRE infection have occurred as a result of nosocomial spread. Such outbreaks have required intensive infection control procedures to limit the spread of VRE. Vancomycin resistance in E. faecalis and E. faecium has been subdivided into phenotypes, VanA and VanB. The mechanism of vancomycin resistance is caused by the production of depsipeptide D-Ala-D-Lac, which replaces D-Ala-D-Ala in the peptidoglycan pathway, thereby preventing the binding of vancomycin to D-Ala-D-Ala in the peptidoglycan cell wall. The vanA gene is associated with a transpositional element (Tn1546) that can be transferred via conjugation while most data suggest that vanB has an endogenous origin. Education, aggressive infection control practices. surveillance programs, and appropriate use of vancomycin are necessary to respond to the VRE problem. CONCLUSIONS: The prevalence of VRE has increased significantly in recent years and has become a worldwide problem. Several factors, such as prior exposure to vancomycin and antibotics (e.g., cephalosporins, antianaerobic agents), physical location in the hospital, immunosuppression, prolonged hospital stay, and VRE gastrointestinal colonization are associated with VRE infection and colonization. Antibiotic treatment of serious VRE infection depends on the phenotype. Optimal treatment of the VanA phenotype is unknown; the VanB phenotype may be treated with teicoplanin and an aminoglycoside.

Animals↗

PubMed2005

Contribution of enterococci to the spread of antibiotic resistance in the production chain of swine meat commodities.

Thirty-six samples, including fecal specimens, dry feedstuffs, raw and processed pork meat products, and dry fermented sausages, were collected from two production chains of swine meat commodities and analyzed for the presence of 11 antibiotic resistance (AR) genes. Specific PCR assays carried out on DNA extracted directly from the samples revealed a high incidence of the genes tet(K) (80.5%), ermB (66.7%), and tet(M) (66.7%). Feces and feedstuffs gave the largest number of positive amplifications. To elucidate the contribution of enterococci to the occurrence and spread of AR, 146 resistant enterococci were isolated, and their identity, genetic fingerprints, and AR gene profiles were determined by means of molecular techniques. Enterococcus faecalis and Enterococcus faecium were the predominant isolated species (43.8 and 38.4%, respectively); Other Enterococcus species identified were E. durans (8.9%), E. hirae (2.7%), E. gallinarum (2.1%), E. mundtii (2.1%), and E. casseliflavus (2.1%). A number of isolates displayed a complex AR gene profile comprising up to four different resistance determinants. The genes tet(M) and ermB were highly diffused, being present in 86.9 and 84.9%, respectively, of the isolates. The application of amplified fragment length polymorphism fingerprinting was particularly valuable to monitor the resistant enterococcal isolates along the production chain and to individuate steps in which contamination might occur. In fact, isolates of E. faecalis and E. faecium showing the same amplified fragment length polymorphism profile and AR gene pattern were detected in samples taken at different steps of the food chain suggesting three cases of bacterial clonal spread.

Animals↗

PubMed1995

A survey of antimicrobial susceptibility of clinical isolates of Enterococcus spp. from Irish hospitals.

Nosocomial enterococcal infections are increasing. In order to establish the species distribution and antibiotic resistance patterns of enterococci in clinical specimens from hospitalized patients, we undertook a survey of 23 Irish hospitals. One thousand and five viable enterococcal strains were studied. Nine different species of enterococci were identified, including Enterococcus faecalis (84%); Enterococcus faecium (9%); and Enterococcus hirae (3%). The most common sites of isolation were the urinary tract (66%), wound and soft tissues (23%) and blood stream (3%). Many of the isolates were multiply antibiotic resistant. Ampicillin resistance was detected in 16%. Neither beta-lactamase production, nor high level penicillin resistance was detected. High level gentamicin resistance was evident in 7% of isolates and varied among species, e.g. 4% E. faecalis, 24% E. faecium, and 34% E. hirae. A number of isolates (23%) were also highly resistant to streptomycin. No clinically significant glycopeptide resistance was detected. The species distribution and incidence of multiple resistance was geographically widespread. This emphasizes the need for detailed speciation and in-vitro susceptibility testing along with the evaluation of alternative combination chemotherapeutic regimens for the management of serious enterococcal infection.

Anti-Bacterial Agents↗

PubMed2005

An active surveillance study of vancomycin-resistant Enterococcus in Queen Elizabeth Hospital, Hong Kong.

OBJECTIVE: To assess the rate of faecal vancomycin-resistant Enterococcus colonisation in high-risk patients in a regional hospital. DESIGN: Prospective observational surveillance study. SETTING: Queen Elizabeth Hospital, Hong Kong. PATIENTS: From September 2001 to December 2002, stool samples from patients in the intensive care unit and patients in whom Clostridium difficile testing was requested were used for study using a broth enrichment method. MAIN OUTCOME MEASURES: Number of faecal vancomycin-resistant Enterococcus colonisation. RESULTS: A total of 2414 cultures from 1792 patients were tested for vancomycin-resistant Enterococcus using a broth enrichment method. Only one (0.06%) patient was found to harbour a vancomycin-resistant Enterococcus faecalis in the gastro-intestinal tract. Surveillance cultures from contacts of the case revealed another six with vancomycin-resistant Enterococcus faecalis. Vancomycin-resistant Enterococcus faecalis was also later reported from a clinical specimen (catheterized urine) of another patient. They were all epidemiologically linked to the index case. Mean inhibitory concentrations of vancomycin and teicoplanin were determined to be higher than 256 and 0.5 microgram/mL, respectively by E-test for all the vancomycin-resistant Enterococcus isolates. Polymerase chain reaction analysis confirmed the presence of vanB genes and the result was in line with the phenotype. Pulsed-field gel electrophoresis confirmed a monoclonal vancomycin-resistant Enterococcus outbreak. Strict infection control measures recommended by the Centers for Disease Control and Prevention were followed and the outbreak was successfully controlled. CONCLUSION: Vancomycin-resistant Enterococcus colonisation is rare, but present among high-risk patients in our hospital. A routine surveillance programme should be implemented that will enable early case detection and prompt initiation of infection control measures to prevent the emergence of an endemic situation.

Enterococcus faecalis↗

PubMed2005

In vitro activity of linezolid against key gram-positive organisms isolated in the united states: results of the LEADER 2004 surveillance program.

Since the approval of linezolid in 2000, sporadic reports of resistance have been given and a greater understanding of the underlying mechanisms of resistance has been gained. However, since these developments, an updated status of the in vitro activity of linezolid against gram-positive organisms from the United States has not been reported. The LEADER 2004 surveillance initiative was undertaken to obtain current and representative data on the activity of linezolid against key species, including isolates with significant resistance phenotypes. Organisms were isolated during 2004 and included 2,872 Staphylococcus aureus, 496 coagulase-negative staphylococcus (CNS), 428 Enterococcus faecalis, 196 Enterococcus faecium, and 422 Streptococcus pneumoniae isolates. All S. aureus isolates (54.2% oxacillin resistant) were susceptible to linezolid (MIC90 = 2 microg/ml); MIC distributions were consistent, regardless of oxacillin or multidrug resistance status. For CNS, one nonsusceptible isolate was encountered (Staphylococcus epidermidis; MIC = 32 microg/ml), but overall, the MIC(90) (1 microg/ml) was lower than that obtained with S. aureus. For E. faecalis and E. faecium, 99.5% and 96.4% of isolates, respectively, were linezolid susceptible. Both species had an MIC90 of 2 microg/ml, and MIC distributions did not vary with the vancomycin susceptibility status of the populations analyzed. Linezolid nonsusceptibility was not encountered among the S. pneumoniae isolates. These findings indicate that linezolid nonsusceptibility has remained rare among staphylococci and uncommon and sporadic among enterococci. Nonetheless, careful and ongoing monitoring of the in vitro effectiveness of linezolid will be needed so that any changes to the current status may be detected as soon as possible.

Acetamides↗

PubMed2001

Use of preclinical data for selection of a phase II/III dose for evernimicin and identification of a preclinical MIC breakpoint.

One of the most challenging issues in the design of phase II/III clinical trials of antimicrobial agents is dose selection. The choice is often based on preclinical data from pharmacokinetic (PK) studies with animals and healthy volunteers but is rarely linked directly to the target organisms except by the MIC, an in vitro measure of antimicrobial activity with many limitations. It is the thesis of this paper that rational dose-selection decisions can be made on the basis of the pharmacodynamics (PDs) of the test agent predicted by a mathematical model which uses four data sets: (i) the distribution of MICs for clinical isolates, (ii) the distribution of the values of the PK parameters for the test drug in the population, (iii) the PD target(s) developed from animal models of infection, and (iv) the protein binding characteristics of the test drug. In performing this study with the new anti-infective agent evernimicin, we collected a large number (n = 4,543) of recent clinical isolates of gram-positive pathogens (Streptococcus pneumoniae, Enterococcus faecalis and Enterococcus faecium, and Staphylococcus aureus) and determined the MICs using E-test methods (AB Biodisk, Stockholm, Sweden) for susceptibility to evernimicin. Population PK data were collected from healthy volunteers (n = 40) and patients with hypoalbuminemia (n = 12), and the data were analyzed by using NPEM III. PD targets were developed with a neutropenic murine thigh infection model with three target pathogens: S. pneumoniae (n = 5), E. faecalis (n = 2), and S. aureus (n = 4). Drug exposure or the ratio of the area under the concentration-time curve/MIC (AUC/MIC) was found to be the best predictor of microbiological efficacy. There were three possible microbiological results: stasis of the initial inoculum at 24 h (10(7) CFU), log killing (pathogen dependent, ranging from 1 to 3 log(10)), or 90% maximal killing effect (90% E(max)). The levels of protein binding in humans and mice were similar. The PK and PD of 6 and 9 mg of evernimicin per kg of body weight were compared; the population values for the model parameters and population covariance matrix were used to generate five Monte Carlo simulations with 200 subjects each. The fractional probability of attaining the three PD targets was calculated for each dose and for each of the three pathogens. All differences in the fractional probability of attaining the target AUC/MIC in this PD model were significant. For S. pneumoniae, the probability of attaining all three PD targets was high for both doses. For S. aureus and enterococci, there were increasing differences between the 6- and 9-mg/kg evernimicin doses for reaching the 2 log killing (S. aureus), 1 log killing (enterococci), or 90% E(max) AUC/MIC targets. This same approach may also be used to set preliminary in vitro MIC breakpoints.

Aminoglycosides↗

PubMed2005

Daptomycin: a new drug class for the treatment of Gram-positive infections.

Daptomycin is the first member of a new class of bactericidal antibiotics, the cyclic lipopeptides. In September 2003, daptomycin was approved for the treatment of Gram-positive infections associated with complicated skin and skin structure infections. A key feature of daptomycin is its rapid, concentration-dependent bactericidal activity against significant Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus, glycopeptide-intermediate and -resistant S. aureus and vancomycin-resistant Enterococcus faecalis and Enterococcus faecium (VRE). Daptomycin also has a unique mechanism of action, no cross-resistance with any other class of antibiotic and a relatively prolonged concentration-dependent postantibiotic effect in vitro. In the United States, daptomycin has been approved for use at a dose of 4 mg/ kg once daily in the treatment of S. aureus (including methicillin-resistant strains), three beta-hemolytic streptococci (S. pyogenes, S. agalactiae and S. dysgalactiae subsp. equisimilis) and E. faecalis associated with complicated skin and skin structure infections. In addition, daptomycin is undergoing a phase III evaluation for the treatment of bacteremia and endocarditis due to S. aureus. With its once-daily dosing, favorable safety profile and low potential for resistance, daptomycin is a powerful new antibiotic therapy against Gram-positive infections.

Anti-Bacterial Agents↗

PubMed1989

The enterococci: evidence of species-specific clinical and microbiologic heterogeneity.

Investigations of the clinical role of enterococci have been limited largely to enterococcal bacteremia and endocarditis and have not distinguished between the various species of enterococci. To characterize the full spectrum of enterococcal disease and to determine whether clinically important differences exist among infections and/or instances of colonization (infections/colonizations) by the various enterococcal species, cases of enterococcal infection/colonization diagnosed at the Dallas Veterans Administration Medical Center (DVAMC) in 1986 were reviewed. During this period, 220 Enterococcus faecalis, 21 Enterococcus faecium, 12 Enterococcus avium, and no Enterococcus durans isolates were identified in clinical specimens (other than stool) submitted to the DVAMC microbiology laboratory. Clinical characteristics of cases of infection/colonization by the three species of enterococci were similar and did not vary significantly when blood stream invasion occurred. Nevertheless, mortality data and therapeutic response rates suggested differences in virulence of the three enterococcal species. Enterococcal infections/colonizations (including bacteremia) frequently were polymicrobial. Although Enterobacteriaceae were the most common copathogens identified overall, Staphylococcus aureus was the most common copathogen in bloodstream infections. E. avium was more resistant than E. faecalis or E. faecium to penicillin G and ampicillin and less resistant to most other antimicrobial agents. The results of this investigation suggest that enterococci are a heterogeneous group of bacteria that should not be treated as a single entity in clinical investigations.

Anti-Bacterial Agents↗