[Show abstract][Hide abstract] ABSTRACT: This study assessed the spectrum of activity of torezolid (TR-700), the active moiety of torezolid phosphate (TR-701), and proposes tentative MIC and disk diffusion breakpoints as well as quality control ranges. The in vitro susceptibilities of 1,096 bacterial isolates, representing 23 different species or phenotypic groups, were determined for torezolid, linezolid, cefotaxime, and levofloxacin using Clinical and Laboratory Standards Institute (CLSI) broth microdilution MICs, minimum bactericidal concentrations (MBCs), agar dilution, and disk diffusion testing methods. Torezolid was very active against the majority of Gram-positive strains, including methicillin-susceptible and -resistant Staphylococcus aureus (MIC(50) = 0.25 microg/ml, MIC(90) <or= 0.5 microg/ml), coagulase-negative staphylococci (CNS; MIC(50) = 0.25 microg/ml, MIC(90) <or= 0.5 microg/ml), enterococci (MIC(50) and MIC(90) <or= 0.5 microg/ml), and streptococci (MIC(50) and MIC(90) <or= 0.25 microg/ml). Based upon MIC(90)s, torezolid was 4-fold more active than linezolid against S. aureus, coagulase-negative staphylococci, and the enterococci and 8-fold more active than linezolid against the streptococci. With the use of tentative MIC breakpoints of <or=2 microg/ml for susceptibility, torezolid disk diffusion zone diameter breakpoints are proposed using a 20-microg disk. In addition, MIC quality control ranges of torezolid were determined for three CLSI-recognized standard ATCC reference strains.
[Show abstract][Hide abstract] ABSTRACT: The spectrum of activity of ceftaroline was evaluated against 1,247 bacterial isolates representing 44 different species or
phenotypic groups. For the majority of species, the activity of ceftaroline was comparable or superior to that of ceftriaxone.
MIC and/or disk diffusion quality control ranges of ceftaroline were determined for five standard ATCC reference strains.
[Show abstract][Hide abstract] ABSTRACT: The inhibitory and bactericidal activities of daptomycin, vancomycin, and teicoplanin against a collection of 479 methicillin-resistant Staphylococcus aureus isolates were assessed. The isolates were collected from U.S. and European hospitals from 1985 to 2007 and were primarily from blood and abscess cultures. The MICs and minimum bactericidal concentrations (MBCs) of the three agents were determined, and the MBC/MIC ratios were calculated to determine the presence or absence of tolerance. Tolerance was defined as an MBC/MIC ratio of > or = 32 or an MBC/MIC ratio of > or = 16 when the MBC was greater than or equal to the breakpoint for resistance. Tolerance to vancomycin and teicoplanin was observed in 6.1% and 18.8% of the strains, respectively. Tolerance to daptomycin was not observed.
[Show abstract][Hide abstract] ABSTRACT: Retapamulin, the first pleuromutilin antimicrobial agent approved for the topical treatment of skin infections in humans,
was tested against 987 clinical isolates representing 30 species and/or resistance groups. MICs were determined along with
disk diffusion zone diameters using a 2-μg disk. Population distribution and MIC versus disk zone diameter scattergrams were
analyzed to determine microbiological MIC cutoff values and inhibition zone correlates. Minimum bactericidal concentrations
were performed on a smaller subset of key species. The retapamulin MIC90 against 234 Staphylococcus aureus isolates and 110 coagulase-negative staphylococci was 0.12 μg/ml. Retapamulin MIC90s ranged from 0.03 to 0.06 μg/ml against beta-hemolytic streptococci including 102 Streptococcus pyogenes, 103 Streptococcus agalactiae, 59 group C Streptococcus, and 71 group G Streptococcus isolates. The MIC90 against 55 viridans group streptococci was 0.25 μg/ml. Retapamulin had very little activity against 151 gram-negative bacilli
and most of the Enterococcus species tested. Based on the data from this study, for staphylococci, MICs of ≤0.5, 1, and ≥2 μg/ml with corresponding disk
diffusion values of ≥20 mm, 17 to 19 mm, and ≤16 mm can be proposed for susceptible, intermediate, and resistant microbiological
cutoffs, respectively. For beta-hemolytic streptococci, a susceptible-only MIC of ≤0.25 μg/ml with a corresponding disk diffusion
value of ≥15 mm can be proposed for susceptible-only microbiological cutoffs.
[Show abstract][Hide abstract] ABSTRACT: Of 393 isolates of Streptococcus pneumoniae from U.S. children collected in 2005-2006, nonvaccine serotypes accounted for 89.1%, with serotype 19A the most prevalent, representing 30.5% of all isolates. The MIC(90) of faropenem against serotype 19A isolates was 1 mug/ml, compared to > or =8 microg/ml against amoxicillin/clavulanate, cefdinir, cefuroxime axetil, and azithromycin.
[Show abstract][Hide abstract] ABSTRACT: Interpretive disk diffusion breakpoints for caspofungin are proposed by evaluating 762 isolates of Candida spp., representing 10 different species obtained as part of the caspofungin clinical trials. Standardized broth microdilution reference tests were compared to the zone diameters observed with 5-microg caspofungin disks produced by two different disk manufacturers. Disk diffusion breakpoints of >or=11 mm for susceptible are proposed. Compared to results from MIC testing, these zone diameters produced error rates that were <or=0.3% for all categories. In addition, an eight-laboratory disk diffusion quality control (QC) study was performed, and QC ranges are proposed for the four QC strains recommended by the CLSI.
[Show abstract][Hide abstract] ABSTRACT: Surveillance studies conducted in the United States over the last decade have revealed increasing resistance among community-acquired respiratory pathogens, especially Streptococcus pneumoniae, that may limit future options for empirical therapy. The objective of this study was to assess the scope and magnitude of the problem at the national and regional levels during the 2005-2006 respiratory season (the season when community-acquired respiratory pathogens are prevalent) in the United States. Also, since faropenem is an oral penem being developed for the treatment of community-acquired respiratory tract infections, another study objective was to provide baseline data to benchmark changes in the susceptibility of U.S. respiratory pathogens to the drug in the future. The in vitro activities of faropenem and other agents were determined against 1,543 S. pneumoniae isolates, 978 Haemophilus influenzae isolates, and 489 Moraxella catarrhalis isolates collected from 104 U.S. laboratories across six geographic regions during the 2005-2006 respiratory season. Among S. pneumoniae isolates, the rates of resistance to penicillin, amoxicillin-clavulanate, and cefdinir were 16, 6.4, and 19.2%, respectively. The least effective agents were trimethoprim-sulfamethoxazole (SXT) and azithromycin, with resistance rates of 23.5 and 34%, respectively. Penicillin resistance rates for S. pneumoniae varied by region (from 8.7 to 22.5%), as did multidrug resistance rates for S. pneumoniae (from 8.8 to 24.9%). Resistance to beta-lactams, azithromycin, and SXT was higher among S. pneumoniae isolates from children than those from adults. beta-Lactamase production rates among H. influenzae and M. catarrhalis isolates were 27.4 and 91.6%, respectively. Faropenem MICs at which 90% of isolates are inhibited were 0.5 mug/ml for S. pneumoniae, 1 mug/ml for H. influenzae, and 0.5 mug/ml for M. catarrhalis, suggesting that faropenem shows promise as a treatment option for respiratory infections caused by contemporary resistant phenotypes.
[Show abstract][Hide abstract] ABSTRACT: The in vitro spectra of activity of tigecycline and tetracycline were determined for 2,490 bacterial isolates representing 50 different species or phenotypic groups. All isolates were tested simultaneously by broth microdilution using freshly prepared Mueller-Hinton broth and by disk diffusion. Portions of these data were submitted to the Food and Drug Administration (FDA) in support of the sponsor's application for new drug approval. In a separate study, MIC and disk diffusion quality control ranges were determined. The tigecycline MICs at which 50%/90% of bacteria were inhibited were (in microg/ml) as follows: for Streptococcus spp., 0.06/0.12; for Moraxella catarrhalis, 0.06/0.12; for Staphylococcus spp., 0.12/0.25; for Enterococcus spp., 0.12/0.25; for Listeria monocytogenes, 0.12/0.12; for Neisseria meningitidis, 0.12/0.25; for Haemophilus spp., 0.25/0.5; for Enterobacteriaceae, 0.05/2.0; for non-Enterobacteriaceae, 0.5/8.0. Tigecycline was consistently more potent than tetracycline against all species studied. The data from this study confirm the FDA-approved MIC and disk diffusion breakpoints for tigecycline for Streptococcus spp. other than Streptococcus pneumoniae, enterococci, and Enterobacteriaceae. Provisional breakpoints for Haemophilus spp. and S. pneumoniae are proposed based on the data from this study. The following MIC and/or disk diffusion quality control ranges are proposed: Staphylococcus aureus ATCC 29213, 0.03 to 0.25 microg/ml; S. aureus ATCC 25923, 20 to 25 mm; Escherichia coli ATCC 25922, 0.03 to 0.25 microg/ml and 20 to 27 mm; Pseudomonas aeruginosa ATCC 27853, 9 to 13 mm, Enterococcus faecalis ATCC 29212, 0.03 to 0.12 microg/ml; S. pneumoniae ATCC 49619, 0.015 to 0.12 microg/ml and 23 to 29 mm; Haemophilus influenzae ATCC 49247, 0.06 to 0.5 microg/ml and 23 to 31 mm; and Neisseria gonorrhoeae ATCC 49226, 30 to 40 mm.
[Show abstract][Hide abstract] ABSTRACT: A multilaboratory collaborative study was performed in order to propose quality control limits for posaconazole disk diffusion susceptibility tests on Mueller-Hinton agar supplemented with 2% glucose and 0.5 microg of methylene blue per ml. Replicate tests were performed on three lots of prepared media using 5-microg posaconazole disks in each of eight laboratories to generate data to propose quality control zone diameter ranges for tests of Candida albicans ATCC 90028 (24 to 34 mm), C. parapsilosis ATCC 22019 (25 to 36 mm), C. tropicalis ATCC 750 (23 to 33 mm), and C. krusei ATCC 6258 (23 to 31 mm).
[Show abstract][Hide abstract] ABSTRACT: Daptomycin is a novel cyclic lipopeptide that is approved by the U.S. Food and Drug Administration for the treatment of complicated
skin and skin structure infections associated with Staphylococcus aureus and other gram-positive pathogens and also staphylococcal bacteremia, including right-sided endocarditis. The Clinical and
Laboratory Standards Institute (CLSI) established “susceptible-only” interpretive criteria for broth microdilution (BMD) and
disk diffusion (DD) testing of daptomycin in 2005. However, a series of S. aureus isolates have been recovered with daptomycin MICs in the nonsusceptible range (i.e., MICs of >1 μg/ml). The objective of
this study was to determine the ability of the Etest and DD methods to differentiate daptomycin-susceptible from nonsusceptible
isolates of S. aureus compared to the results of the CLSI BMD reference method. There was a good correlation between Etest MIC results and the
results of BMD among laboratories (r = 0.86 to 0.88), with 95.3% of the Etest MICs within a ±1 log2 dilution of the BMD MIC result. A total of 92 of 102 (90.2%) non-daptomycin-susceptible isolates of S. aureus identified by BMD in two participating laboratories were also classified as nonsusceptible by Etest. However, the very major
and major error rates reported by one of the participating laboratories were 13.5 and 4.0%, respectively, primarily due to
the absence of an intermediate category. The DD method, however, did not reliably differentiate daptomycin-susceptible from
non-daptomycin-susceptible isolates. In 2005, daptomycin disks were voluntarily removed from the market by Cubist Pharmaceuticals.
The disk diffusion breakpoints were subsequently removed from the CLSI M100 standard in 2006.
[Show abstract][Hide abstract] ABSTRACT: To determine the spectrum of activity of doripenem and to propose tentative MIC and disc diffusion breakpoints.
The in vitro susceptibilities of 2137 bacterial isolates, representing 28 different species, to doripenem, imipenem and meropenem were determined by the NCCLS broth microdilution and disc diffusion testing methods.
The doripenem MIC(50)s/(90)s were (in mg/L) for Enterobacteriaceae, 0.06/0.25; Pseudomonas aeruginosa, 0.25/1; Haemophilus influenzae, 0.12/0.5; streptococci, 0.016/0.5 and for staphylococci, 0.06/4. Like other carbapenems tested, doripenem MIC(50)s/(90)s were >32/>32 and 0.5/32 mg/L for the enterococci and non-fermentative Gram-negative bacilli (excluding P. aeruginosa), respectively. Against members of the Enterobacteriaceae and H. influenzae, doripenem was generally more active than imipenem and the same as or slightly less active than meropenem. Values for the non-fermentative Gram-negative bacilli excluding P. aeruginosa were comparable for all three carbapenems. Doripenem MICs increased with increasing resistance to methicillin (staphylococci), penicillin (streptococci) and strains that were beta-lactamase-negative ampicillin-resistant (Haemophilus). Doripenem exhibits excellent activity against extended-spectrum beta-lactamase-producing strains of Escherichia coli and Klebsiella spp. The NCCLS disc diffusion test was performed simultaneously on all organisms.
Assuming the MIC susceptible breakpoints for doripenem are < or =1 mg/L for the streptococci and < or =2 mg/L for all other genera, then disc diffusion zone diameter breakpoints can be proposed. In addition, MIC and/or disc diffusion quality control ranges of doripenem were determined for 10 ATCC reference strains.
[Show abstract][Hide abstract] ABSTRACT: For broth microdilution susceptibility tests of Francisella tularensis, Mueller-Hinton broth with 2% Isovitalex is recommended. Using that medium, we studied three standard control strains tested with nine antimicrobial agents potentially efficacious for treating tularemia. An eight-laboratory collaborative study generated the data needed to propose appropriate MIC control limits.
[Show abstract][Hide abstract] ABSTRACT: An international collaborative study was performed in order to propose quality control limits for voriconazole disk diffusion tests on Mueller-Hinton agar with 2% glucose and 0.5 micro g of methylene blue per ml. The supplement may be added to the agar before autoclaving, or Mueller-Hinton agar plates may be flooded with a glucose-methylene blue solution. Replicate tests on both types of agar plates with 1- micro g voriconazole disks generated data to propose zone size limits for tests of Candida parapsilosis ATCC 22019 (28 to 37 mm), Candida albicans ATCC 90028 (31 to 42 mm), and Candida krusei ATCC 6258 (16 to 25 mm). Candida tropicalis ATCC 750 was not useful for this purpose.
[Show abstract][Hide abstract] ABSTRACT: Stock solutions of telithromycin, ABT-773, azithromycin, clarithromycin, erythromycin, roxithromycin and dirithromycin were each prepared with eight different combinations of solvents and diluents. Broth microdilution trays were then prepared and frozen at -60 degrees C. Standard quality control strains were evaluated periodically during a 12-week storage time. There were no significant changes in MICs with different solvents and diluents. It was concluded that the easiest approach was to dissolve each compound in water with a small volume (< 2.5 microL/mL) of glacial acetic acid added in a dropwise fashion, followed by further dilutions in deionised water.
[Show abstract][Hide abstract] ABSTRACT: A standardized agar dilution susceptibility testing method was developed for Campylobacter that consisted of testing on Mueller-Hinton medium supplemented with 5% defibrinated sheep blood in an atmosphere of 10% CO2, 5% O2, and 85% N2. Campylobacter jejuni ATCC 33560 was identified as a quality-control (QC) strain. Minimal inhibitory concentration (MIC) QC ranges were determined for two incubation time/temperature combinations: 36 degrees C for 48 hr and 42 degrees C for 24 hr. Quality-control ranges were determined for ciprofloxacin, doxycycline, erythromycin, gentamicin, and meropenem. For all antimicrobial agents tested at both temperatures, 95-100% of the QC MIC results fell within recommended QC ranges. Twenty-one Campylobacter clinical isolates, encompassing five species of Campylobacter (C. jejuni, C. coli, C. jejuni, subsp. doylei, C. fetus, and C. lari) were tested in conjunction with the C. jejuni QC strain. While C. jejuni and C. coli could be reliably tested under both test conditions, growth of C. jejuni subsp. doylei, C. fetus, and C. lari isolates was inconsistent when incubated at 42 degrees C. Therefore, it is recommended that these species only be tested at 36 degrees C.
Microbial Drug Resistance 02/2004; 10(2):124-31. DOI:10.1089/1076629041310064 · 2.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: An international collaborative study was performed in order to propose quality control limits for fluconazole disk diffusion susceptibility tests on Mueller-Hinton agar with 2% glucose and 0.5 micro g of methylene blue per ml. The supplements may be added before autoclaving the agar, or Mueller-Hinton agar plates may be flooded with a glucose-methylene blue solution. Replicate tests on both types of agar plates generated data to propose zone size limits for tests of Candida parapsilosis ATCC 22019 (22 to 33 mm), C. tropicalis ATCC 750 (26 to 37 mm), and C. albicans ATCC 90028 (28 to 39 mm). C. krusei ATCC 6258 was not useful for this purpose.