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PubMed1985

In-vitro evaluation of cefpirome (HR 810), teicoplanin and four other antimicrobials against enterococci.

In-vitro activities of cefpirome (HR 810), a fourth generation cephalosporin, and teicoplanin were compared with those of ampicillin, piperacillin, and vancomycin against 56 clinical isolates of enterococci. Cefpirome had good activity with the MIC90 and MBC90 being 4 and 16 mg/l. Ampicillin and piperacillin had MBC90 of 4 and 16 mg/l. Teicoplanin was extremely active with the MIC90 being 1.6 mg/l while vancomycin had poor cidal activity with the MBC90 being 16 mg/l. A decrease in activity of cefpirome was noted when the inoculum size was increased from 10(3) to 10(7) organisms per ml. Synergy was demonstrated against most Streptococcus faecium isolates with a combination of cefpirome and gentamicin or piperacillin. Against Str. faecalis, with a similar combination, synergy was seen in less than 50% isolates. No antagonism was noted with any of the antibiotic combinations.

Ampicillin↗

PubMed1986

Bactericidal activity of netilmicin compared with gentamicin and streptomycin, alone and in combination with penicillin, against penicillin tolerant viridans streptococci and enterococci.

Netilmicin was compared with gentamicin and streptomycin for in-vitro activity against 30 strains of penicillin-tolerant streptococci including 16 strains of enterococci. Both netilmicin and gentamicin tested alone at 4 mg/l caused 99.9% kill of more than half of the 13 strains of viridans streptococci tested, whereas streptomycin, 4 mg/l, had no bactericidal effect against these strains. Netilmicin, gentamicin and streptomycin tested alone at 8.0 mg/l against 10 strains of Streptococcus faecalis resulted in 99.9% kill of six, one and zero strains respectively. Combinations of penicillin with 2 mg/l of either netilmicin or gentamicin resulted in bactericidal synergy against 12 of 13 strains of viridans streptococci and all 10 strains of S. faecalis after 18 to 24 h incubation. Parallel experiments showed that higher concentration of penicillin were required to obtain 99.9% kill of 10 streptococcal strains when 4 mg/l streptomycin was compared with 2 mg/l of the other aminoglycosides. Killing curves showed similar bactericidal synergy for netilmicin-penicillin and gentamicin-penicillin combinations against most streptococci tested after 24 h incubation but there was sometimes a greater bactericidal effect noted with netilmicin after only 6 h incubation of the broth or after 48 h incubation. The results of this in-vitro study suggest that netilmicin is at least as effective as gentamicin as a bactericidal synergic agent with penicillin against penicillin-tolerant viridans streptococci and S. faecalis strains isolated from patients with endocarditis. Neither gentamicin or netilmicin were effective as bactericidal synergic agents with penicillin against 4 of 6 strains of S. faecium tested.

Drug Synergism↗

PubMed1990

Modification of penicillin-binding proteins of penicillin-resistant mutants of different species of enterococci.

Mutants resistant to penicillin G were selected in a stepwise manner from nine different species of enterococci. Mutants with the highest level of resistance showed cross-resistance to all beta-lactams tested. For eight of the nine species, resistance correlated with increased production of a low molecular weight penicillin-binding protein (PBP). Two of these species produced a new PBP of low molecular weight, while two other species produced an additional PBP of high molecular weight. With the exception of Enterococcus faecium, no difference was observed in terms of lysis or bactericidal effect when the sensitive strains and their resistant mutants were tested at ten times their respective MICs of penicillin G. With E. faecium an increased lytic and bactericidal effect was observed for the resistant mutant.

Bacterial Proteins↗

PubMed1992

Comparison of LY264826-gentamicin with vancomycin-gentamicin against enterococci from blood cultures.

The combination of the new glycopeptide LY264826 and gentamicin was compared with the combination of vancomycin and gentamicin against 30 strains of enterococci, comprising 20 strains of Enterococcus faecalis, five strains of Enterococcus faecium and five strains of Enterococcus avium, isolated from blood cultures. LY264826 plus gentamicin was synergic against E. faecalis and E. faecium, but not against E. avium.

Anti-Bacterial Agents↗

PubMed1992

The in-vitro antibacterial activity of a combination of cefpirome or cefoperazone with vancomycin against enterococci and Staphylococcus aureus.

Cefpirome, cefoperazone and ceftazidime were tested for their in-vitro activity against Enterococcus faecalis and methicillin-resistant Staphylococcus aureus (MRSA) isolates. Cefpirome was the most active cephalosporin followed by cefoperazone. Ceftazidime had only very limited activity against these strains. In experiments with cefpirome/vancomycin and cefoperazone/vancomycin combinations, synergy was detected against most MRSA strains and some enterococci. Antagonism did not occur.

Cefoperazone↗

PubMed1993

Antimicrobial susceptibility testing of enterococci: results of a survey conducted by the United Kingdom National External Quality Assessment Scheme for Microbiology.

Six strains of enterococci were distributed to participants in the United Kingdom National External Quality Assessment Scheme for Microbiology with a request that they be tested for susceptibility to ampicillin/penicillin and vancomycin and for high-level resistance to gentamicin. More than 98% of laboratories correctly reported the resistant strains as resistant to penicillin and ampicillin. However, there was a poorer correlation for the susceptible strains, with only 1-6% and 69-83% of laboratories reporting the strains as susceptible to penicillin and ampicillin respectively. Those laboratories which used 5-25 micrograms ampicillin discs or breakpoint methods reported proportionally more results correctly for the susceptible strains than those using 2 micrograms discs. Participants using Escherichia coli or an enterococcus as a control and those not using a control at all were more likely to report ampicillin-susceptible strains correctly than those using Staphylococcus aureus NCTC 6571 (Oxford strain). For vancomycin-susceptible and high-level vancomycin-resistant strains, 93-96% and 96-99% of reports respectively were correct. For the low-level vancomycin-resistant strains, only 50-54% of reports were correct. Participants using a 5 micrograms vancomycin disc reported proportionally more of the low-level resistant strains correctly than those using 10, 20, 25, 30 or 100 micrograms discs. Participants not using controls were proportionally more likely to report the low-level resistant strains as susceptible than those using an enterococcus or S. aureus NCTC 6571 as a control. For the high-level gentamicin-resistant (HLGR) strains, 96-98% of reports were correct. Depending on the strain, between 12% and 41% of participants also reported high-level resistance for the strains which were not HLGR. Those using low-content discs (< or = 30 micrograms) and breakpoint or MIC methods were more likely to report strains which were not HLGR as HLGR than those using high-content discs. Those using an enterococcus as a control were less likely to report strains which were not HLGR as HLGR than those using either S. aureus NCTC 6571 or E. coli as a control and those not using a control.

Ampicillin Resistance↗

PubMed1995

Susceptibility of enterococci, methicillin-resistant Staphylococcus aureus and Streptococcus pneumoniae to the glycylcyclines.

The in-vitro activities of two glycylcyclines, DMG-MINO and DMG-DMDOT, and several comparative agents were determined against 263 enterococci, 102 methicillin-resistant Staphylococcus aureus and 55 Streptococcus pneumoniae recent clinical isolates. The glycylcyclines and teicoplanin were the most active agents against the enterococcal isolates. All methicillin-resistant S. aureus were susceptible to the glycylcyclines. Only DMG-DMDOT, ciprofloxacin, teicoplanin and vancomycin exhibited comparable activity against penicillin-susceptible, -intermediate and -resistant S. pneumoniae strains.

Anti-Bacterial Agents↗

PubMed1996

Efficacy of ABT-719, a 2-pyridone antimicrobial, against enterococci, Escherichia coli, and Pseudomonas aeruginosa in experimental murine pyelonephritis.

ABT-719 is a 2-pyridone antimicrobial which inhibits DNA gyrase activity. It has considerable subcutaneous (sc) and oral efficacy in the treatment of experimental pyelonephritis induced in carrageenan-treated mice by clinical isolates of Enterococcus faecalis, Enterococcus faecium, Escherichia coli, and Pseudomonas aeruginosa. Therapeutic ED50s, defined here as producing a 2 log10 reduction in kidney bacterial burden, provide a reliable end point for comparison of drug efficacy in this experimental infection. Therapeutic ED50s for ABT-719 against these infections were equal to or up to ten-fold lower than those for ciprofloxacin, used as a reference because of similarity in mode of action. Against E. faecalis, the therapeutic ED50s for ABT-719 were 4.5-13.6 mg/kg.day for sc administration and 6.8-8.9 mg/kg.day for oral administration. ABT-719 was more potent than ciprofloxacin and vancomycin against the E. faecalis strains, which showed ciprofloxacin and vancomycin resistance covering a range of MICs. Against E. faecium, the therapeutic ED50s for ABT-719 were 8.8 mg/kg.day (sc) and 9.4 mg/kg.day (oral). Against an isolate of E. faecium showing ciprofloxacin and vancomycin resistance the ED50 for ABT-719 to achieve a 1 log10 reduction in kidney bacterial burden was 17.9 mg/kg.day by sc administration. While ABT-719 had lower efficacy against this isolate than against others, ciprofloxacin and vancomycin failed to show efficacy. Against E. coli, the therapeutic ED50 for ABT-719 was 1.1 mg/kg.day (oral), and against P. aeruginosa, this value was 2.7 mg/kg.day (oral) with values against both of these pathogens similar to those for ciprofloxacin. ABT-719, which represents the new 2-pyridone compound class, has promise for the treatment of urinary tract infections, as suggested by the significant efficacy seen against experimental pyelonephritis caused by E. coli, P. aeruginosa and susceptible and resistant enterococci.

Animals↗

PubMed1997

In-vitro study of the synergy between beta-lactam antibiotics and glycopeptides against enterococci.

The synergy between glycopeptides and beta-lactams was studied using different techniques such as broth macrodilution, killing curves and agar dilution combined with agar diffusion. Two glycopeptide-resistant enterococci isolated from different clinical samples were used. Results showed different effects with significant changes in MICs. Antibacterial activity was related to the concentration of glycopeptide and beta-lactam for Enterococcus faecalis 8253, while for Enterococcus faecium 8072 a paradoxical effect was observed. With this strain, the best synergic effect was detected at teicoplanin concentrations of 1-4 mg/L, but antibacterial activity was reduced at concentrations of 8, 16 and 32 mg/L. No synergic effect was observed with vancomycin. The combination of agar dilution with agar diffusion techniques may constitute a simple method for routine detection of synergic effects between glycopeptides and beta-lactams.

Anti-Bacterial Agents↗

PubMed1999

In-vitro activity of fosfomycin against vancomycin-resistant enterococci.

The effect of fosfomycin against 69 vancomycin-resistant isolates of Enterococcus faecium (VanA), five of E. faecium (VanB), 11 of Enterococcus faecalis (VanA), three of E. faecalis (VanB), 10 of Enterococcus gallinarum (VanC1) and two of Enterococcus casseliflavus (VanC2) and glycopeptide-sensitive E. faecium (n = 8) and E. faecalis (n = 10) was tested in vitro. Fosfomycin inhibited 97%, 94% and 96% of the vancomycin-resistant strains, according to results of agar dilution, broth microdilution, and a disc diffusion method (DIN 58940). The disc diffusion test by the NCCLS method does not include fosfomycin; using breakpoints suggested by Andrews et al. (< or = 11 mm, resistant; > or = 18 mm, susceptible), 5% of the vancomycin-resistant strains tested would have been considered fosfomycin resistant. Minimal inhibitory concentrations of most vancomycin-resistant isolates were in the intermediate sensitivity range, yielding an MIC50 of 32 mg/L and an MIC90 of 64 mg/L. Moreover the majority of inhibitory zone sizes by the disc diffusion method (DIN 58940) corresponded to intermediate susceptibility. These results suggest that fosfomycin at a high dosage and possibly used in combination with other drugs could be a potentially useful drug for the treatment of infections caused by vancomycin-resistant enterococci.

Anti-Bacterial Agents↗

PubMed1999

Inducible or constitutive expression of resistance in clinical isolates of streptococci and enterococci cross-resistant to erythromycin and lincomycin.

Thirty-five of 40 clinical isolates of enterococci and streptococci cross-resistant to erythromycin and lincomycin and harbouring erm genes were inducibly resistant to these drugs, suggesting that ribosomal methylation is predominantly inducibly expressed in these bacterial genera. Regulatory regions located upstream of the erm genes of four inducible and three constitutive strains were amplified and sequenced. Expression of constitutive resistance in two strains of Streptococcus pneumoniae and Enterococcus faecalis could be accounted for by a large deletion or a DNA duplication within the regulatory regions, respectively.

Anti-Bacterial Agents↗

PubMed1999

The prevalence and clonal expansion of high-level gentamicin-resistant enterococci isolated from blood cultures in a Dutch university hospital.

We studied the prevalence and clonality of high-level gentamicin-resistant enterococci (HLGRE) in a Dutch university hospital. Of 238 enterococcal strains isolated from blood cultures between 1991 and 1997, 57 were HLGRE. Genomic analysis of these strains revealed 19 different genotypes, two of which were encountered more frequently [type A (12/57), type B (23/57)]. The spread of these types largely explained the rise in HLGRE incidence from 14% in 1991 to 31% in 1997. However, the contribution of unique strains to the total HLGRE burden also increased from 4% to 16%. We conclude that both clonal expansion and the emergence of unique HLGRE have contributed significantly to the increasing incidence of HLGRE.

Anti-Bacterial Agents↗

PubMed2000

Susceptibility to quinupristin/dalfopristin and other antibiotics of vancomycin-resistant enterococci from the UK, 1997 to mid-1999.

Susceptibility to quinupristin/dalfopristin and other antibiotics was studied for clinical isolates of vancomycin-resistant enterococci (VRE) referred by UK hospitals between January 1997 and June 1999. Single isolates of VRE from 858 patients in 136 hospitals were received, of which 76% were Enterococcus faecium and 21% were Enterococcus faecalis, the remainder comprising minor species. Most isolates were multi-resistant. After allowing for the effect of blood, which raised the MICs of quinupristin/dalfopristin four-fold, 98.3% of E. faecalis isolates and all the Enterococcus avium, Enterococcus casseliflavus and Enterococcus gallinarum appeared resistant to quinupristin/dalfopristin, whereas 98.8% of the E. faecium isolates and the single Enterococcus raffinosus isolate were susceptible.

Drug Therapy, Combination↗

PubMed2000

Influence of different medium components on the in vitro activity of the growth-promoting antibiotic flavomycin against enterococci.

The growth-promoting antibiotic flavomycin (also called bambermycin, flavophospholipol and moenomycin) has a complex spectrum of activity against enterococci, with some species being naturally resistant and others susceptible. In this study, proteins added to Mueller-Hinton II medium had a strong deleterious effect on the activity of flavomycin, glucose had no effect and starch decreased the activity of flavomycin. The fatty substances Tween 80 and tributyrin increased the activity of flavomycin for several enterococcal species. Slight differences in the composition of the susceptibility test medium affected the MIC results obtained, indicating that strict standardization of the test medium is necessary.

Animals↗

PubMed2002

Nisin, alone and combined with peptidoglycan-modulating antibiotics: activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci.

OBJECTIVE: We have sought ways to circumvent resistance, by combining nisin with other antibiotics known to target bacterial cell wall biosynthesis. METHODS: Twenty strains each of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) were tested in vitro by standardized methods against nisin alone and combined with bacitracin, ramoplanin and chloramphenicol. RESULTS: Ramoplanin was the most potent compound, and bacitracin had the least activity. Two-way synergy was observed with nisin and ramoplanin. However, chloramphenicol was clearly antagonistic to the activity of nisin. CONCLUSIONS: Observations of synergy between nisin and ramoplanin against MRSA and VRE offer a promising approach to the concept of combining nisin with inhibitors of cell wall peptidoglycan. Further investigations are needed in order to develop this approach as a clinical possibility.

Anti-Bacterial Agents↗

PubMed2002

The in vitro and in vivo antibacterial characterization of vancomycin and linezolid against vancomycin-susceptible and -resistant enterococci.

The present study was designed to compare in vitro antibacterial activities of linezolid and vancomycin against vancomycin-susceptible Enterococcus faecalis (VSEF) and vancomycin-resistant enterococci (VRE) isolated in Japan with those of quinupristin-dalfopristin, teicoplanin and minocycline, and the in vitro short time bactericidal activity and the in vivo activities of linezolid and vancomycin against vancomycin-susceptible and -resistant E. faecalis. The MIC90s of linezolid, quinupristin-dalfopristin, vancomycin, teicoplanin and minocycline for VSEF and VRE were both 2 mg/L, both 2 mg/L, 2 and >128 mg/L, 0.25 and >128 mg/L, and both 32 mg/L, respectively. The efficacy of linezolid for mice with bacteraemia caused by VSEF was similar to that of vancomycin, but the elimination ratio of viable organisms from the blood of mice treated with vancomycin was significantly higher than in linezolid-treated and untreated mice at 2 h post-administration, and those of the two groups at 4 and 6 h were significantly higher than in untreated mice. Moreover, linezolid was highly active in mice with bacteraemia caused by vancomycin-resistant E. faecalis because this drug had potent in vitro activity against the organisms. Our results indicate that linezolid is suitable for the treatment of VRE and VSEF bacteraemia, and vancomycin is suitable for VSEF bacteraemia.

Acetamides↗

PubMed2002

Linezolid-resistant enterococci: report of the first isolates in the United Kingdom.

Linezolid, the first oxazolidinone antibacterial agent to be developed for clinical use, was licensed in the UK in early 2001. We report the first three examples of resistant enterococci (two isolates of Enterococcus faecium and one Enterococcus faecalis) isolated in the UK, which were obtained from patients who had received linezolid. The linezolid MICs for the resistant isolates were 64 mg/L. Pulsed-field gel electrophoresis (PFGE) analysis of the linezolid-susceptible and -resistant isolates from two of the patients, combined with sequence analysis of rRNA, indicated that resistance developed in previously susceptible strains, most probably via a point mutation in the 23S rRNA.

Acetamides↗

PubMed2003

European survey of vancomycin-resistant enterococci in at-risk hospital wards and in vitro susceptibility testing of ramoplanin against these isolates.

A survey in eight European countries, including 13 hospitals, of vancomycin-resistant enterococci (VRE) in at-risk hospital wards (such as the ICU and the haematology ward) was performed in 2001, and the in vitro susceptibility of the isolates ramoplanin and other drugs was tested. A total of 1314 non-duplicate clinical enterococcal isolates were collected, and 38 (2.9%) were vancomycin resistant: 27 Enterococcus faecium and 11 Enterococcus faecalis; 35 VanA and three VanB phenotypes. Rates of VRE among clinical enterococcal isolates varied between 0 and 1.7% for the participating countries, except the UK (10.4%) and Italy (19.6%). One hundred and twenty-three (3.5%) VRE were found among 3499 stool samples tested for the presence of these organisms: 111 (3.2%) E. faecium and 12 (0.3%) E. faecalis; 114 (3.3%) VanA and nine (0.3%) VanB phenotypes. Rates of intestinal colonization with VRE varied between 0 and 1.2% for the participating countries, except Italy (7.5%) and the UK (32.6%). In vitro susceptibility testing showed that the Italian and UK VRE are multi-resistant (including resistance to ampicillin and high-level resistance to gentamicin and streptomycin), and that ramoplanin was active against all strains of VRE, with an MIC90 of 0.5 mg/L for clinical isolates. Pulsed-field gel electrophoresis showed that the high prevalence of VRE in the Italian and UK centres was related to the monoclonal emergence and spread of three centre-specific clones. This survey suggests that in some centres in Europe, a similar situation may be encountered to that in the USA (monoclonal spread of multi-resistant VRE in at-risk wards).

Anti-Bacterial Agents↗