Factors influencing the vitek gram-positive susceptibility system's detection of vanB-encoded vancomycin resistance among enterococci

Jett, Bradley D.; Free, L; Sahm, Daniel F.

doi:10.1128/jcm.34.3.701-706.1996

Cited by 26 publications

(7 citation statements)

References 19 publications

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“…Differences were smaller but still apparent for vancomycin-resistant isolates. We noted that most of our enterococcal isolates grew relatively poorly in Mueller-Hinton broth, and several clinical isolates had to be excluded from the (12). Glycopeptide antibiotics act by binding of the peptidoglycan precursor lipid-linked N-acetylglucosamine-N-muramylpentapeptide at the D-alanine-D-alanine terminus (24,29).…”

mentioning

confidence: 99%

Semisynthetic glycopeptide antibiotics derived from LY264826 active against vancomycin-resistant enterococci

Nicas

Mullen

Flokowitsch

et al. 1996

Antimicrob Agents Chemother

107

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Certain derivatives of the glycopeptide antibiotic LY264826 with N-alkyl-linked substitutions on the epivancosamine sugar are active against glycopeptide-resistant enterococci. Six compounds representing our most active series were evaluated for activity against antibiotic-resistant, gram-positive pathogens. For Enterococcus faecium and E. faecalis resistant to both vancomycin and teicoplanin, the MICs of the six semisynthetic compounds for 90% of the strains tested were 1 to 4 micrograms/ml, compared with 2,048 micrograms/ml for vancomycin and 256 micrograms/ml for LY264826. For E. faecium and E. faecalis resistant to vancomycin but not teicoplanin, the MICs were 0.016 to 1 micrograms/ml, compared with 64 to 1,024 micrograms/ml for vancomycin. The compounds were highly active against vancomycin-susceptible enterococci and against E. gallinarum and E. casseliflavus and showed some activity against isolates of highly vancomycin-resistant leuconostocs and pediococci. The MICs for 90% of the strains of methicillin-resistant Staphylococcus aureus tested were typically 0.25 to 1 micrograms/ml, compared with 1 microgram/ml for vancomycin. Against methicillin-resistant S. epidermidis MICs ranged from 0.25 to 2 micrograms/ml, compared with 1 to 4 micrograms/ml for vancomycin and 4 to 16 micrograms/ml for teicoplanin. The spectrum of these new compounds included activity against teicoplanin-resistant, coagulase-negative staphylococci. The compounds exhibited exceptional potency against pathogenic streptococci, with MICs of < or = 0.008 microgram/ml against Streptococcus pneumoniae, including penicillin-resistant isolates. In in vivo studies with a mouse infection model, the median effective doses against a challenge by S. aureus, S. pneumoniae, or S. pyogenes were typically 4 to 20 times lower than those of vancomycin. Overall, these new glycopeptides, such as LY307599 and LY333328, show promise for use as agents against resistant enterococci, methicillin-resistant S. aureus, and penicillin-resistant pneumococci.

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confidence: 99%

Semisynthetic glycopeptide antibiotics derived from LY264826 active against vancomycin-resistant enterococci

Nicas

Mullen

Flokowitsch

et al. 1996

Antimicrob Agents Chemother

107

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“…The reasons for these variations in reported susceptibilities are not clear, but the importance of different medium cation concentrations has been noted previously in reports evaluating antimicrobial susceptibilities of Pseudomonas aeruginosa to aminoglycosides and imipenem (8,19). It has been noted that susceptibility results for vancomycin may depend on the media used, the method employed, and the physicochemical characteristics of the drug, independent of the growth rate of the microorganism (15).…”

Section: Discussionmentioning

confidence: 99%

Comparison of Inhibitory and Bactericidal Activities and Postantibiotic Effects of LY333328 and Ampicillin Used Singly and in Combination against Vancomycin-Resistant Enterococcus faecium

Baltch

Smith

Ritz

et al. 1998

Antimicrob Agents Chemother

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One hundred ninety-five individual vancomycin-resistant Enterococcus faecium (VRE) isolates from five upstate New York hospitals were studied for antimicrobial susceptibilities to LY333328, quinupristin-dalfopristin, teicoplanin, ampicillin, and gentamicin. LY333328 was the most active antibiotic against VRE. The effect of media and methods on the antibacterial activity of LY333328, its synergy with ampicillin, and the postantibiotic effects (PAE) of LY333328 and ampicillin were evaluated. In microdilution tests, the MIC of LY333328 at which 90% of the isolates were inhibited (MIC 90 ) was 2 g/ml in Mueller-Hinton II (MH II) broth and 1 g/ ml in brain heart infusion (BHI) broth. In contrast, on MH II agar the MIC 90 was 4 g/ml and on BHI agar it was >16 g/ml. Bactericidal activity was observed for most strains at concentrations from 8 to >133 times the MIC of the tube macrodilution in MH II broth. A bactericidal effect of LY333328 plus ampicillin was demonstrated in time-kill studies, but there was great strain-to-strain variability. By the MH II agar dilution method, bacteristatic synergy (defined as a fractional inhibitory concentration of <0.5) with LY333328 and ampicillin was demonstrated for 61% of the strains tested. Under similar conditions, there was synergy with LY333328 and quinupristin-dalfopristin or gentamicin for 27 and 15% of the strains tested, respectively. The PAE of LY333328 was prolonged (23.0 h at 10 times the MIC). However, 50% normal pooled human serum decreased the PAE to 12.2 h at 10 times the MIC. Test conditions and media had a considerable effect on VRE susceptibilities to LY333328. The prolonged PAE of LY333328, a potent new bactericidal glycopeptide, and its synergy with ampicillin in a large proportion of strains suggest that further evaluation of this drug in pharmacokinetic studies and experimental infections, including those with VRE, is warranted.

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“…Accurate detection of resistant strains is important for microbiologists and clinicians in guiding optimal therapy for enterococcal infections and in implementing interventions to control and prevent nosocomial outbreaks (5). However, several studies have reported that some susceptibility testing methods, especially commercial automated systems and the commonly used disk diffusion test, are unable to detect resistance to key aminoglycosides and glycopeptides (2,7,9,23,30,34,36).…”

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confidence: 99%

Use of Molecular and Reference Susceptibility Testing Methods in a Multicenter Evaluation of MicroScan Dried Overnight Gram-Positive MIC Panels for Detection of Vancomycin and High-Level Aminoglycoside Resistances in Enterococci

Chen¹,

Marshall²,

Winokur

et al. 1998

J Clin Microbiol

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Modified MicroScan gram-positive MIC no. 8 panels (PM-8) were analyzed for their improved ability to detect vancomycin resistance (VR) and high-level aminoglycoside resistance (HLAR) in enterococci. A validation study design that utilized selected challenge strains, recent clinical isolates, and reproducibility experiments in a multicenter format was selected. Three independent medical centers compared the commercial panels to reference broth microdilution panels (RBM) and Synergy Quad Agar (QA). Resistance was verified by demonstration of VR and HLAR genes by PCR tests. The study was conducted in three phases. (i) In the challenge phase (CP), two well-characterized sets of enterococci were obtained from the Centers for Disease Control and Prevention; one set contained 50 isolates for VR testing and one contained 48 isolates for HLAR testing. In addition, a set of 47 well-characterized isolates representing diverse geographic areas, obtained from earlier national surveillance studies, was tested at the University of Iowa College of Medicine (UICM). (ii) In the efficacy phase (EP), each laboratory tested 50 recent, unique clinical isolates by all methods. (iii) In the reproducibility Phase (RP), each laboratory tested the same 10 strains by all methods in triplicate on three separate days. All isolates from the EP were sent to the UICM for molecular characterization of vanA, -B, -C 1 , -C 2-3 , and HLAR genes. In the CP, the ranking of test methods by error rates (in parentheses; very major and major errors combined, versus PCR results) were as follows: for high-level streptomycin resistance (HLSR), QA (12.0%) > PM-8 (5.2%) > RBM (1.6%); for high-level gentamicin resistance (HLGR), RBM (3.7%) > PM-8 (3.1%) > QA (2.6%); and for VR, RBM ‫؍‬ QA (3.0%) > PM-8 (1.2%). In the EP, agreement between all methods and the reference PCR result was 98.0% for HLSR, 99.3% for HLGR, and 98.6% for VR. In the RP, the percentages of results ؎ 1 log 2 dilution of the all-participant mode were as follows: for VR, 100% (PM-8), 98.9% (QA), and 90.0% (RBM); for HLSR, 99.6% (RBM), 98.5% (PM-8), and 82.2% (QA); and for HLGR, 99.6% (RBM), 99.3% (PM-8), and 98.1% (QA). The ability of the PM-8 to detect VR and HLAR in enterococci was comparable to those for reference susceptibility and molecular PCR methods and was considered acceptable for routine clinical laboratory use.

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Factors influencing the vitek gram-positive susceptibility system's detection of vanB-encoded vancomycin resistance among enterococci

Cited by 26 publications

References 19 publications

Semisynthetic glycopeptide antibiotics derived from LY264826 active against vancomycin-resistant enterococci

Semisynthetic glycopeptide antibiotics derived from LY264826 active against vancomycin-resistant enterococci

Comparison of Inhibitory and Bactericidal Activities and Postantibiotic Effects of LY333328 and Ampicillin Used Singly and in Combination against Vancomycin-Resistant Enterococcus faecium

Use of Molecular and Reference Susceptibility Testing Methods in a Multicenter Evaluation of MicroScan Dried Overnight Gram-Positive MIC Panels for Detection of Vancomycin and High-Level Aminoglycoside Resistances in Enterococci

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