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Biomedical subjects

A L Barry

Publications and source records attributed to A L Barry.

At least 109 records · Page 6Linked to original sources

Antibacterial activity of PD 131628 and proposed disc diffusion susceptibility test criteria.

The antibacterial activity of PD 131628 was compared with that of ciprofloxacin against 401 clinical isolates. The two drugs had comparable MICs for most Gram-negative species. PD 131628 was two to eight times more active against Gram-positive species and against Xanthomonas maltophilia. Both drugs were bactericidal, Among Gram-positive isolates, resistant mutants were not detected in vitro. Among Gram-negative bacilli, spontaneously occurring mutants resistant to PD 131628 were readily demonstrated more frequently than for ciprofloxacin. Resistance to PD 131628 was more readily induced by serially transferring the Gram-negative species, and resistant organisms emerged more rapidly on prolonged incubation in time-kill studies. Correlating the PD 131628 5 micrograms disc diffusion zone diameters with PD 131628 MICs, the following breakpoints are tentatively proposed: susceptible, MIC < or = 1 mg/L or zone > or = 19 mm; intermediate, MIC 2.0 mg/L or zones 16-18 mm; and resistant, MIC > or = 4.0 mg/L or zones < or = 15 mm.

Anti-Infective Agents↗

In vitro activities of 12 orally administered antimicrobial agents against four species of bacterial respiratory pathogens from U.S. Medical Centers in 1992 and 1993.

Clinical isolates of Haemophilus influenzae, Streptococcus pneumoniae, Streptococcus pyogenes, and Moraxella catarrhalis were gathered from 19 different clinical laboratories throughout the continental United States. The in vitro activities of 12 orally administered antimicrobial agents were compared by broth microdilution tests with 3,151 bacterial isolates. Among 890 H. influenzae isolates, 30% were capable of producing beta-lactamase enzymes (12 to 41% in different medical centers). Most of the 619 beta-lactamase-negative H. influenzae strains were susceptible to ampicillicin (MIC, < or = 1.0 micrograms/ml): 5 strains were intermediate in susceptibility (MIC, 2.0 micrograms/ml) and 1 strain was ampilicillin resistant (MIC, 4.0 micrograms/ml). Ninety-two percent of 698 M. catarrhalis strains were beta-lactamase positive. Of 799 S. pneumoniae isolates, 15% were intermediate in susceptibility to penicillin and 7% were resistant to penicillin. The prevalence of penicillin-susceptible pneumococci in different institutions ranged from 63 to 95%. Only 1% of 764 S. pyogenes isolates were resistant to the macrolides, but 5% of S. pneumoniae isolates were macrolide resistant. Only 71% of 58 penicillin-resistant S. pneumoniae isolates were erythromycin susceptible, whereas 97% of the 622 penicillin-susceptible strains were erythromycin susceptible. Penicillin-resistant pneumococci were also relatively resistant to the cephalosporins and amoxicillin. Penicillin-susceptible pneumococci were susceptible to amoxicillin-clavulanic acid (MIC for 90% of isolates tested [MIC90], < or = 0.12/0.06 microgram/ml), cefixime (MIC90, 0.25 microgram/ml), cefuroxime axetil (MIC90, < or = 0.5 microgram/ml), cefprozil (MIC90, < or = 0.5 micrograms/ml), cefaclor (MIC90, 0.5 microgram/ml), and loracarbef (MIC90, 1.0 microgram/ml). Most strains of the other species remained susceptible to the study drugs other than amoxicillin.

Administration, Oral↗

Interpretive criteria for susceptibilities of Haemophilus influenzae to ampicillin, amoxicillin, and amoxicillin-clavulanic acid.

One hundred fifty isolates of Haemophilus influenzae (including 30 beta-lactamase-positive strains and 23 beta-lactamase-negative, ampicillin-resistant strains) were tested for susceptibilities to ampicillin, amoxicillin, and amoxicillin-clavulanic acid (A/C) by the broth microdilution method in Haemophilus test medium (HTM) and in Mueller-Hinton medium with lysed horse blood and by the disk diffusion method on HTM agar. Our results support the use of HTM for susceptibility testing of H. influenzae but raise a number of questions regarding the interpretive criteria currently in use, particularly with respect to the fourfold difference in MIC susceptibility breakpoints for ampicillin and A/C and a resulting high proportion of A/C-susceptible beta-lactamase-negative, ampicillin-resistant strains.

Amoxicillin↗

Evaluation of a novel colorimetric broth microdilution method for antifungal susceptibility testing of yeast isolates.

A comparative evaluation of two broth microdilution methods for antifungal susceptibility testing of 600 clinical yeast isolates (Candida spp., Torulopsis glabrata, and Cryptococcus neoformans) against amphotericin B, fluconazole, and flucytosine (5FC) was conducted. Microdilution testing was performed according to National Committee for Clinical Laboratory Standards (NCCLS) recommendations (NCCLS document M27-P). By using the growth control for comparison, reference microdilution MIC endpoints for amphotericin B were scored as the lowest concentration at which a score of 0 (complete absence of growth) was observed, and those for 5FC and fluconazole were scored at the lowest concentration at which a score of 2 (prominent decrease in turbidity) (MIC-2) was observed. The second microdilution method employed a colorimetric endpoint using an oxidation-reduction indicator (Alamar Biosciences, Inc., Sacramento, Calif.) and was assessed independently of the reference microdilution MICs. The MICs for the two microdilution test systems were read after 24 and 48 h of incubation. Excellent agreement between the reference and colorimetric microdilution MICs was observed. Overall agreement was > or = 95% for all three drugs at 24 h. At 48 h, agreement was > or = 98% for amphotericin B and 5FC but dropped to 84% for fluconazole. Given these results it appears that the colorimetric microdilution approach to antifungal susceptibility testing may be viable alternative to the NCCLS reference method for testing yeasts.

Amphotericin B↗

Comparison of broth macrodilution, broth microdilution, and E test antifungal susceptibility tests for fluconazole.

A comparison of the E test, the broth microdilution test, and the reference broth macrodilution susceptibility test of the National Committee for Clinical Laboratory Standards for fluconazole susceptibility testing was performed with 238 clinical isolates of Candida species and Torulopsis (Candida) glabrata. An 80% inhibition endpoint MIC was determined by the reference broth macrodilution method after 48 h of incubation. The MICs obtained by the two study methods were read after 24 and 48 h of incubation. Overall, excellent agreement within 2 doubling dilutions was obtained between the broth microdilution and the broth macrodilution methods for the combined results for all species at both 24 h (93%) and 48 h (94%). The correlation of 24-h MIC endpoints between the E test and the broth macrodilution methods was 37% for T. glabrata, 56% for Candida tropicalis, 93% for Candida albicans, and 90% for other Candida species. The percent agreement at 48 h ranged from 34% for T. glabrata to 97% for Candida species other than C. albicans and C. tropicalis. These initial results support the further evaluation of the E test as an alternative method for fluconazole susceptibility testing of Candida species.

Candida↗

Selection of a fluoroquinolone-class disk for susceptibility tests.

A study was conducted to select a fluoroquinolone disk that could be used to represent other members of the fluoroquinolone class of drugs for routine susceptibility testing in the laboratory. Eight different fluoroquinolone agents were tested by disk diffusion and broth microdilution methods using 185 bacterial isolates, including 60 Enterobacteriaceae, 50 Pseudomonas species, 45 other gram-negative bacilli, and 30 Staphylococcus aureus. False-susceptible and false-resistant test results occurred at rates of 0-10% when disks containing different agents were tested against this unusually resistant collection of isolates. Much lower error rates would be expected with the type of microorganisms routinely encountered in clinical laboratories. Pefloxacin, enoxacin, or ciprofloxacin disks were not useful as class representatives. However, amifloxacin, lomefloxacin, ofloxacin, temafloxacin, or fleroxacin disks could be used to represent the other fluoroquinolones for routine susceptibility testing with a minimal chance of incurring serious errors.

Anti-Infective Agents↗

In vitro activity of ceftriaxone and other cephalosporins against 602 clinical isolates of staphylococci from geographically diverse medical centers.

The in vitro activity of ceftriaxone and six additional antimicrobial agents (ceftizoxime, cefoperazone, cefuroxime, fleroxacin, ciprofloxacin, and trimethoprim/sulfamethoxazole) was assessed or 602 recent clinical isolates of staphylococci from six geographically distinct medical centers in North America. All seven antimicrobial agents were active (90-100% of strains susceptible) against oxacillin-susceptible (OS) strains of Staphylococcus aureus (OSSA) and coagulase-negative staphylococci (OSCNS) but had limited activity against oxacillin resistant (OR) staphylococci. Our assessment of the in vitro antistaphylococcal activity of ceftriaxone against contemporary isolates of Staphylococcus aureus and coagulase-negative staphylococci indicates that the activity versus OS staphylococci has not changed over the past decade despite widespread use of the drug. It appears that these agents will continue to be useful for empiric therapy in those centers in which OR strains are uncommon.

Academic Medical Centers↗

Interpretive criteria and quality control parameters for determining bacterial susceptibility to fosfomycin tromethamine.

Studies with fosfomycin tromethamine disks containing 200 micrograms of fosfomycin and 50 micrograms of glucose-6-phosphate confirmed the following zone diameter criteria for the NCCLS method: < or = 12 mm for resistant (MIC > or = 256 micrograms/ml), 13-15 mm for intermediate (MIC 128 micrograms/ml) and > or = 16 mm for susceptible (MIC < or = 64 micrograms/ml). Additional studies defined acceptable MIC and zone diameter ranges for the following quality control strains: Escherichia coli ATCC 25922, MIC 0.5 to 4.0 micrograms/ml, zone diameter 23 to 29 mm; Staphylococcus aureus ATCC 25923, zone diameter 26 to 32 mm; Pseudomonas aeruginosa ATCC 27813, MIC 2.0 to 8.0 micrograms/ml; and Enterococcus faecalis, ATCC 29212, MIC 16 to 64 micrograms/ml.

Bacteria↗

Comparison of fixed concentration and fixed ratio options for dilution susceptibility testing of gram-negative bacilli to ampicillin and ampicillin/sulbactam.

Ampicillin combined with sulbactam was tested at both fixed ratio (2:1 and 1:1) and fixed sulbactam concentrations (4 micrograms/ml, 8 micrograms/ml and 16 micrograms/ml) against 2440 consecutively isolated gram-negative bacilli. Sulbactam significantly enhanced the spectrum of ampicillin activity. Overall, at 8 micrograms/ml ampicillin inhibited 50% of the Enterobacteriaceae isolates, whereas 69% to 84% of the isolates were inhibited by the various sulbactam combinations. The widest spectrum of activity for ampicillin/sulbactam was achieved by testing at a fixed sulbactam concentration of 16 micrograms/ml, followed by the 1:1 ratio and the fixed 8 micrograms/ml (84%, 76% and 74% inhibited, respectively). The amount of sulbactam at the susceptible breakpoint concentrations of ampicillin markedly affected the percentage of susceptible strains. Combinations that include 8 micrograms/ml of sulbactam are suggested for consideration.

Ampicillin↗

Haemophilus test medium versus Mueller-Hinton broth with lysed horse blood for antimicrobial susceptibility testing of four bacterial species.

Studies were undertaken to determine whether broth microdilution susceptibility tests could be standardized by using a single medium for testing fastidious respiratory pathogens. Mueller-Hinton broth with lysed horse blood and the broth version of Haemophilus Test Medium (HTM) were directly compared. Ten orally administered agents were found to give essentially identical results in both media but minor differences were noted. Because the test are easier to read when HTM broth is used, that medium is to be preferred for routine testing of Haemophilus influenzae, Streptococcus pneumoniae, Streptococcus pyogenes and Moraxella catarrhalis isolates by the microdilution procedure.

Anti-Bacterial Agents↗

Evaluation of disk susceptibility testing of fosfomycin tromethamine.

Fosfomycin tromethamine is an orally administered fosfomycin that may be used for single-dose therapy of uncomplicated urinary tract infections. At breakpoint concentrations [< or = 128 micrograms/ml plus 25 micrograms/ml glucose-6-phosphate (G-6-P)], fosfomycin tromethamine inhibited > 90% of the 350 bacterial isolates tested. When testing Escherichia coli, Klebsiella spp., and Enterobacter spp., we note that the performance of fosfomycin disks improved when G-6-P was added to the disks. The interpretive error rates were minimized when 200-micrograms fosfomycin disks were supplemented with either 50 or 100 micrograms G-6-P. Using < or = 128 and > or = 256 micrograms/ml as the susceptible and resistant MIC breakpoints, respectively, the regression-analysis-derived disk diffusion zone diameter breakpoints for the 200-micrograms fosfomycin disk supplemented with 50 micrograms of G-6-P are as follows: susceptible, > or = 16 mm; intermediate, 13-15 mm; and resistant, < or = 12 mm.

Bacteria↗

RO 23-9424, a new cephalosporin 3'-quinolone: in-vitro antimicrobial activity and tentative disc diffusion interpretive criteria.

The susceptibility of 410 clinical bacterial isolates to RO 23-9424, a novel cephalosporin 3'-quinolone, was determined. Overall, 97% of Enterobacteriaceae and 100% of staphylococci were inhibited by < or = 8.0 mg/L of RO 23-9424. Only 60% of Pseudomonas aeruginosa and 80-90% of Pseudomonas spp. and Xanthomonas maltophilia were inhibited by this concentration. Enterococci and Listeria monocytogenes were resistant to RO 23-9424. Clinical isolates of Moraxella catarrhalis, Streptococcus spp., and Corynebacterium jekeium were all susceptible to < or = 8.0 mg/L of RO 23-9424. This drug's antimicrobial activity was superior to that of its two components fleroxacin and desacetylcefotaxime against the organisms tested. Using < or = 8.0 mg/L and > or = 32 mg/L respectively as the susceptible and resistant MIC breakpoints for RO 23-9424, the regression analysis-derived disc diffusion zone diameter breakpoints for the 30 micrograms disc are: susceptible > or = 19 mm, intermediate 16-18 mm, and resistant < or = 15 mm.

Anti-Infective Agents↗

Methods for testing the susceptibility of anaerobic bacteria to two fluoroquinolone compounds, PD 131628 and clinafloxacin.

The susceptibility of anaerobic bacteria to two new fluoroquinolones, PD 131628 (the bioactive form of PD 131112 or CI-990) and clinafloxacin (CI-960 or PD 127391), was determined with the agar dilution procedures and two media, and one broth microdilution procedure. Sparfloxacin and ciprofloxacin were also tested by the broth microdilution method. One hundred anaerobic isolates and four control strains were tested by the three methods which gave minimum inhibitory concentrations (MICs) that were essentially comparable, but not identical. With the broth microdilution method, the relative potency of the four fluoroquinolones was: clinafloxacin > PD 131628 > sparfloxacin > ciprofloxacin. For the latter three drugs but not clinafloxacin, the MIC values were often near the proposed interpretive breakpoint concentrations, and thus minor methodological differences frequently influenced the interpretive categories. Replicate agar dilution tests in five laboratories established MIC control limits for each of four control strains: those MIC limits could also be used to define the expected performance of the two alternative methods.

Anti-Infective Agents↗

Dirithromycin disc susceptibility tests: interpretative criteria and quality control parameters.

Dirithromycin and its bioactive metabolite (erythromycylamine) were compared in vitro to erythromycin against 450 bacterial isolates. Dirithromycin and erythromycylamine did not differ in their in-vitro activity and the two compounds were additive when combined in equal proportions. Both compounds were active against erythromycin-susceptible bacteria but erythromycin was two to four times more potent on a weight-to-weight basis. Interpretive criteria for dirithromycin were not based on achievable blood concentrations since tissue concentrations may be 20-30 times greater than peak serum levels. Dirithromycin-susceptible strains were those with zones > or = 19 mm in diameter (15 micrograms dirithromycin disc) or MIC < or = 2.0 mg/L and resistance was defined as a zone < or = 15 mm or MIC > or = 8.0 mg/L. Interpretive criteria for testing Haemophilus influenzae on Haemophilus Test Medium (HTM) agar were not defined because of the drug's poor activity in the test system used. Two multi-laboratory studies were also undertaken, one to define quality control limits for disc diffusion tests and the other to define broth microdilution MIC control limits for tests with dirithromycin.

Anti-Bacterial Agents↗

Susceptibilities of beta-lactamase-producing and -nonproducing ampicillin-resistant strains of Haemophilus influenzae to ceftibuten, cefaclor, cefuroxime, cefixime, cefotaxime, and amoxicillin-clavulanic acid.

In in vitro studies we evaluated the susceptibilities of beta-lactamase-producing and -nonproducing, ampicillin-resistant strains of Haemophilus influenzae and compared them with those of ampicillin-susceptible strains. Ampicillin, amoxicillin-clavulanic acid, ceftibuten, cefaclor, cefuroxime, cefixime, and cefotaxime were evaluated by broth microdilution tests and disk diffusion tests. The disk diffusion tests accurately categorized beta-lactamase-producing strains and ampicillin-susceptible strains as being susceptible to the study drugs other than ampicillin. Ampicillin-resistant, beta-lactamase-nonproducing strains were relatively resistant to all seven study drugs, but the disk diffusion test did not always predict that resistance. The clinical relevance of the decreased susceptibility to various agents remains unclear, but to be conservative, all ampicillin-resistant, beta-lactamase-nonproducing strains might be assumed to be resistant to other beta-lactams. After excluding that small group of isolates, reliable susceptibility test results were obtained with lots of Haemophilus Test Medium that met quality assurance criteria.

Amoxicillin↗

Antimicrobial activity and disk diffusion susceptibility testing of Ro 40-6890, the active metabolite of the new cephalosporin ester, Ro 41-3399.

Ro 40-6890, the active metabolite of Ro 41-3399, was tested against 391 gram-negative and gram-positive clinical isolates. Ro 40-6890 was active against members of the family Enterobacteriaceae, Moraxella catarrhalis, pneumococci, other Streptococcus spp., and methicillin-susceptible staphylococci. Preliminary disk diffusion interpretive zone criteria were calculated for 5-, 10-, and 30-micrograms Ro 40-6890 disks and several possible MIC susceptibility breakpoints. We recommend the use of the 5-micrograms disk and suggest that the following zone diameters be used as breakpoints in clinical trials: susceptible, > or = 21 mm (MIC, < or = 1 microgram/ml); intermediate, 18 to 20 mm (MIC, 2 micrograms/ml); and resistant, < or = 17 mm (MIC, > or = 4 micrograms/ml).

Anti-Bacterial Agents↗

Susceptibility of Haemophilus influenzae to piperacillin-tazobactam combinations: interpretive criteria and quality control limits for standardized tests.

In vitro studies evaluated methods for testing the susceptibility of Haemophilus influenzae to piperacillin-tazobactam combinations. Ampicillin-resistant beta-lactamase-nonproducing strains of H. influenzae may be presumed to be relatively resistant to combinations of piperacillin-tazobactam, even though they frequently appear to be susceptible by disk diffusion methods. Other ampicillin-resistant or -susceptible strains were predictably susceptible; i.e., 130 such strains gave zones of inhibition > or = 26 mm in diameter, and MICs for these strains were < or = 0.125/4.0 micrograms/ml (< or = 1.0/0.12 micrograms/ml when an 8:1 ratio was tested). A resistant category has yet to be defined. For quality control purposes, H. influenzae ATCC 49247 should give zones of inhibition 32 to 38 mm in diameter, and broth microdilution MICs should be 0.12/4.0 to 0.5/4.0 micrograms/ml.

Ampicillin Resistance↗