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Biomedical subjects

A L Barry

Publications and source records attributed to A L Barry.

At least 199 records · Page 11Linked to original sources

Multicenter in vitro evaluation of lomefloxacin (NY-198, SC-47111), including tests against nearly 7,000 bacterial isolates and preliminary recommendations for susceptibility testing.

Lomefloxacin (NY-198 or SC-47111) is a difluoro-quinolone derivative having a C-methyl at the 3-position of the piperazine ring, thus minimizing its metabolic alteration in vivo. In our research, its antimicrobial activity was most similar to that of difloxacin, enoxacin, fleroxacin, and norfloxacin but usually less than that of ciprofloxacin and ofloxacin against most species. Lomefloxacin shared cross-resistance with other 4-quinolones but remained very active against ceftazidime-resistant organisms, including stably derepressed beta-lactamase producing Gram-negative bacilli. Lower pH increased the lomefloxacin MICs. MBCs were usually identical to the measured MIC, and the lomefloxacin MICs were not significantly increased by high inoculum concentrations. The Enterobacteriaceae were found to have a very low rate of spontaneous mutation to lomefloxacin resistance (10(-8)-10(-9). In vitro tests by 5-micrograms and 10-micrograms lomefloxacin disks and dilution methods were correlated, and the 10-micrograms disk was recommended for clinical trials using a less than or equal to 4 micrograms/ml susceptible breakpoint. The quality assurance guidelines for dilution tests were determined by a multilaboratory study.

4-Quinolones↗

Antimicrobial activity of LY163892, an orally administered 1-carbacephem.

LY163892 was found to be similar to cefaclor and slightly superior to cephalexin in antimicrobial activity and spectrum. Bacteria with MIC50 less than or equal to 8.0 mg/l included Escherichia coli, Klebsiella spp., Proteus mirabilis, Citrobacter diversus, Haemophilus influenzae, Branhamella catarrhalis, pathogenic Neisseria spp., oxacillin-susceptible staphylococci, and Streptococcus spp. Strains that produced plasmid-mediated beta-lactamases generally remained susceptible to LY163892. LY163892 was found to be bactericidal in general, but its MICs for some bacterial strains were adversely affected by increased inocula.

Bacteria↗

Interpretative criteria for the agar diffusion susceptibility test with azithromycin.

Azithromycin (CP-62,993) is a macrolide with a tendency to concentrate in various body tissues. Difficulties that arise when establishing tentative minimum inhibitory concentration (MIC) breakpoints for such a drug include the question of whether MICs should be compared with the achievable concentrations in blood or in tissue. Pending clinical experience with this drug, we recommend the following tentative criteria for interpreting tests with 15 micrograms azithromycin discs: susceptible greater than or equal to 18 mm (MIC less than or equal to 2 mg/l) and resistant less than or equal to 13 mm (MIC greater than or equal to 8 mg/l).

Agar↗

In vitro evaluation of DuP 105 and DuP 721, two new oxazolidinone antimicrobial agents.

DuP 105 and DuP 721 are two members of the oxazolidinones, a new class of synthetic antimicrobial agents with activity against gram-positive bacteria. In vitro tests compared the two new drugs with five other antimicrobial agents against 216 gram-positive isolates representing 4 genera and 10 species. DuP 721 MICs for 50% of the strains tested (MIC50s) ranged from 2.0 to 8.0 micrograms/ml, DuP 105 MIC50S ranged from 4.0 to 16 micrograms/ml, and vancomycin MIC50S ranged from 0.25 to 1.0 microgram/ml. Methicillin-resistant and -susceptible staphylococci were susceptible to ciprofloxacin, vancomycin, and DuP 721.

Ampicillin↗

Antimicrobial activity, spectrum, and recommendations for disk diffusion susceptibility testing of ceftibuten (7432-S; SCH 39720), a new orally administered cephalosporin.

The antimicrobial activity and spectrum of ceftibuten (7432-S; SCH 39720) was determined on a wide variety of bacterial species selected for resistance to oral and parenteral beta-lactam antimicrobial agents. Ceftibuten was found to be the most active beta-lactam tested against members of the family Enterobacteriaceae, inhibiting 81.6% of strains at less than or equal to 8.0 micrograms/ml compared with 75.0 and 54.8% of strains inhibited by cefixime and cefuroxime, respectively. All strains of Haemophilus influenzae (MIC for 90% of strains [MIC90], less than or equal to 0.06 microgram/ml), Branhamella catarrhalis (MIC90, 3.0 micrograms/ml), and pathogenic Neisseria spp. (MIC90, less than or equal to 0.06 and 0.019 microgram/ml) were susceptible to ceftibuten. Beta-hemolytic Streptococcus spp. (serogroups A, B, C, and G) were also inhibited by ceftibuten, but penicillin-resistant pneumococci were generally resistant to cefixime and ceftibuten. The activity and spectrum of ceftibuten seem most applicable to infections of the respiratory and urinary tract plus those infections caused by pathogenic Neisseria spp. Ceftibuten disks (30 micrograms) were evaluated and found to have an acceptable correlation (r = 0.88) with ceftibuten MICs. Preliminary zone size interpretive criteria for MIC breakpoints of less than or equal to 4.0 and less than or equal to 8.0 micrograms/ml were calculated.

Administration, Oral↗

In vitro antimicrobial activity of tigemonam, a new orally administered monobactam.

At five geographically separate medical centers, over 6,000 clinical bacterial isolates were tested for their susceptibility to tigemonam by the broth microdilution method. The antimicrobial spectrum of tigemonam was similar to that of aztreonam, but with two differences. Aztreonam was more active against Pseudomonas spp., and tigemonam was more active against some streptococci. Tigemonam was highly resistant to hydrolysis by the eight beta-lactamase enzymes tested. A significant (greater than a fourfold increase in the MICs of tigemonam) inoculum effect occurred when 3 of 13 isolates were tested with inocula of 5 X 10(5) and 1 X 10(7) CFU/ml. Tigemonam was bactericidal for all but 1 of the 13 isolates. Of the four quality-control strains recommended by the National Committee for Clinical Laboratory Standards, only Escherichia coli ATCC 25922 provided on-scale results. The proposed MIC quality-control range of tigemonam for E. coli ATCC 25922 is 0.13 to 0.5 micrograms/ml.

Aztreonam↗

Antimicrobial activity and disk diffusion susceptibility testing of U-76,253A (R-3746), the active metabolite of the new cephalosporin ester, U-76,252 (CS-807).

Compound U-76,253A (R-3746), the active metabolite sodium salt of the prodrug ester U-76,252 (CS-807), was demonstrated to be active against members of the family Enterobacteriaceae with 82 and 85% of strains inhibited by less than or equal to 2.0 and less than or equal to 4.0 micrograms/ml, respectively. In addition, U-76,253A inhibited all strains of Branhamella catarrhalis, Haemophilus influenzae, pathogenic Neisseria spp., oxacillin-susceptible Staphylococcus aureus, beta-hemolytic streptococci, and pneumococci at less than or equal to 4.0 micrograms/ml. Pseudomonas spp., Acinetobacter spp., enterococci, and oxacillin-resistant staphylococci were resistant to U-76,253A. This U-76,253A antimicrobial activity and spectrum was generally superior to that of comparison orally administered cephems (cefaclor, cefuroxime, and cefixime) and the amoxicillin-clavulanic acid combination. Tests with beta-lactamase-producing isolates indicated that U-76,253A was bactericidal and that its MICs were only influenced by high inoculum concentrations (10(7) CFU/ml) against type Ia and IVc enzyme-producing strains. Preliminary disk diffusion interpretive zone criteria were calculated for 10- and 30-micrograms U-76,253A disks and several possible susceptible MIC breakpoints. The absolute interpretive agreement between MICs and zone diameters ranged from 87.8 to 95.6%. Final selection of interpretive criteria awaits further U-76,252 pharmacokinetic information.

Anti-Bacterial Agents↗

In vitro activities of azithromycin (CP 62,993), clarithromycin (A-56268; TE-031), erythromycin, roxithromycin, and clindamycin.

The in vitro activity of azithromycin (CP 62,993 or XZ-450) against Haemophilus influenzae was greater than that of three other macrolides. However, azithromycin was four- to eightfold less active than erythromycin against the gram-positive cocci and against Listeria monocytogenes. Erythromycin and azithromycin were similar in their activity against Legionella pneumophila, Neisseria gonorrhoeae, Neisseria meningitidis, and Branhamella catarrhalis.

Azithromycin↗

Criteria for disk susceptibility tests and quality control guidelines for the cefoperazone-sulbactam combination.

For in vitro susceptibility tests with cefoperazone and sulbactam (a beta-lactamase inhibitor), 75/30-micrograms disks may be used with the interpretive zone size breakpoints that are currently used for 75-micrograms cefoperazone disks. For dilution tests, a 2:1 ratio of cefoperazone to sulbactam is recommended. For quality control purposes, MIC limits that are used to monitor cefoperazone tests were also applied to tests with the combination of drugs. For gram-negative control strains, zone size limits were calculated to be 1 mm smaller than those used for cefoperazone disks. To monitor the sulbactam portion of the combination, Acinetobacter calcoaceticus subsp. anitratus ATCC 43498 was selected; zones with 75/30-micrograms disks were 26 to 32 mm in diameter, and broth microdilution MICs ranged from 1.0/0.5 to 8.0/4.0 micrograms/ml. With cefoperazone alone, MICs for Acinetobacter calcoaceticus subsp. anitratus were 16 to 64 micrograms/ml and zones ranged from 14 to 18 mm in diameter. For anaerobic dilution tests, only Bacteroides thetaiotaomicron ATCC 29741 is recommended for cefoperazone-sulbactam; MICs ranged from 8.0/4.0 to 32/16 micrograms/ml.

Bacteria, Anaerobic↗

Variability of clarithromycin and erythromycin susceptibility tests with Haemophilus influenzae in four different broth media and correlation with the standard disk diffusion test.

Four separate laboratories performed antimicrobial susceptibility tests with 40 Haemophilus influenzae isolates, each tested in triplicate. Erythromycin and a new macrolide, clarithromycin (A-56268; TE-031), were tested by the disk diffusion method, by the agar dilution procedure in two different media, and by broth microdilution tests in four different media. Erythromycin MICs for 90% of the strains were 16 micrograms/ml in Mueller-Hinton broth with 3% lysed horse blood and NAD, 4.0 micrograms/ml in hemophilus test medium, and 2.0 micrograms/ml in supplemented Schaedler broth or in the fastidious broth medium from Beckman Instruments, Inc. Clarithromycin MICs were generally 1 doubling dilution greater than erythromycin MICs in each of the media. Erythromycin disk tests corresponded best with MICs determined in the fastidious broth medium. In that same medium, clarithromycin MICs were about 1 doubling dilution greater than what would be expected from the results of disk tests. Because there were fewer growth failures, hemophilus test medium is recommended for microdilution tests with H. influenzae. Incubation of all tests for a full 24 h without an increased CO2 atmosphere was needed to achieve maximal precision of the tests. Interlaboratory and intralaboratory reproducibility of all tests was satisfactory.

Clarithromycin↗

Proposed changes in interpretive criteria and potency of ampicillin and ampicillin-sulbactam disks for susceptibility tests.

The accuracy of disk susceptibility tests with ampicillin and ampicillin-sulbactam was not improved when the amount of ampicillin was increased from 10 to 20 or 30 micrograms per disk. For testing members of the family Enterobacteriaceae, ampicillin disk tests correlated better with broth microdilution tests when the zone size standards were altered from greater than or equal to 14 greater than or equal to 17 mm for susceptible and from less than or equal to 11 to less than or equal to 13 mm for resistant. The same zone size breakpoints apply to tests with ampicillin-sulbactam disks (10/10 micrograms). When Staphylococcus, Branhamella, and Haemophilus species are tested against ampicillin, interpretive breakpoints are those separating beta-lactamase-producing strains from nonproducing strains. However, when ampicillin-sulbactam is tested, beta-lactamase enzymes are efficiently inhibited by the sulbactam component, and thus zone size standards for ampicillin do not apply: zone size standards for the Enterobacteriaceae can be used for testing the combination against Staphylococcus, Branhamella, and Haemophilus species. For Streptococcus, Enterococcus, and Listeria species, only ampicillin disks need be tested, since ampicillin-sulbactam disks give essentially identical results.

Ampicillin↗

Disk diffusion susceptibility testing for LY163892 (KT-3777), a new orally administered 1-carbacephem.

LY163892, a new orally administered 1-carbacephem, was found to have a spectrum of antimicrobial activity very similar to that of cefaclor. Diffusion tests with 30-micrograms LY163892 disks produced acceptable interpretive error rates with greater than or equal to 22 mm as the susceptibility zone diameter. This was required to reduce potential false-susceptibility results, particularly among Enterobacter spp. and Providencia stuartii: both species included strains that produce beta-lactamases capable of hydrolyzing Ly163892. Preliminary recommendations for LY163892 disk tests are presented, but the continued use of the 30-micrograms cephalothin "class representative" disk might be the best procedure to minimize LY163892 interpretive errors for clinical trials. A separate LY163892 disk for testing Haemophilus influenzae strains should be seriously considered.

Bacteria↗

Evaluation of in vitro methods for testing ceftriaxone against anaerobic bacteria, including quality control guidelines.

Tests with 100 anaerobic bacterial isolates demonstrated comparability between ceftriaxone MICs obtained with the reference agar dilution procedure and those obtained with a broth microdilution susceptibility testing procedure. The aerobically incubated thioglycolate disk elution test was also evaluated. Six 30-micrograms ceftriaxone disks in 5 ml of thioglycolate separated strains for which MICs were less than or equal to 32 micrograms/ml from those for which MICs were greater than or equal to 64 micrograms/ml (6% overall discrepancies). Quality control limits for ceftriaxone agar dilution tests were determined to be as follows: Bacteroides fragilis ATCC 25285, 32 to 128 micrograms/ml; and Bacteroides thetaiotaomicron ATCC 29741, 64 to 256 micrograms/ml.

Bacteria, Anaerobic↗

Evaluation of in vitro methods for testing susceptibility of anaerobes to ampicillin-sulbactam and amoxicillin-clavulanic acid.

A total of 97 anaerobic bacteria were tested for susceptibility to ampicillin, ampicillin-sulbactam, and amoxicillin-clavulanic acid by broth microdilution and disk elution methods, the results of which were compared with those of the reference agar dilution method. With the broth microdilution method, approximately 95% of MICs were within 1 dilution of those of the reference agar method, with a definite (0.6 to 0.7 dilution) trend toward lower MICs. The disk elution test performed satisfactorily, but additional anaerobic isolates resistant to ampicillin-sulbactam and/or amoxicillin-clavulanic acid (currently rare) are needed to assure the predictability of resistance by the disk elution test.

Amoxicillin↗

In vitro evaluation of ceftibuten (7432-S, SCH 39720), a novel orally administered cephalosporin.

7432-S (SCH 39720) was the most active beta-lactam tested against the Enterobacteriaceae, inhibiting 92% of strains at less than or equal to 8.0 micrograms/ml compared to 82%, 65% and 39% of strains inhibited by cefixime, cefuroxime and cefaclor, respectively. 7432-S was also very effective against Haemophilus influenzae (MIC90, less than or equal to 0.25 microgram/ml), Branhamella catarrhalis (MIC90, 4.0 micrograms/ml) and Neisseria meningitidis (MIC90, less than or equal to 0.25 microgram/ml). Serogroup B streptococci and the penicillin-resistant pneumococci were generally less susceptible to 7432-S and comparison cephems than Streptococcus pyogenes or penicillin-susceptible S. pneumoniae isolates. Pseudomonas spp., enterococci, Acinetobacter spp. and Staphylococcus spp. were routinely resistant to 7432-S (MIC50s, greater than or equal to 32 micrograms/ml).

Administration, Oral↗

In vitro activity of ciprofloxacin against gram-positive cocci.

In vitro studies compared the activities of ciprofloxacin, vancomycin, and fusidic acid against staphylococci, streptococci, and enterococci. Against 111 methicillin-resistant and 162 methicillin-susceptible staphylococcal strains, fusidic acid was the most potent of the three drugs (minimal inhibitory concentration [MIC] for 90 percent of the strains was 0.06 microgram/ml). Ciprofloxacin and vancomycin were also effective anti-staphylococcal drugs (MIC of ciprofloxacin for 90 percent of the strains was 0.5 microgram/ml and of vancomycin was 1.0 microgram/ml). Ciprofloxacin had a more rapid bactericidal effect against staphylococci than did vancomycin. Neither vancomycin nor ciprofloxacin alone had useful bactericidal activity against enterococci. Streptococci were only marginally susceptible to ciprofloxacin (MIC for 90 percent of the strains was 1.0 to 4.0 micrograms/ml for different species). Vancomycin was superior to ciprofloxacin in its anti-streptococcal activity (MIC for 90 percent of the strains was 0.25 to 0.5 microgram/ml). The promising in vitro anti-staphylococcal activity of ciprofloxacin deserves further consideration in clinical trials.

Ciprofloxacin↗