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Biomedical subjects

A L Barry

Publications and source records attributed to A L Barry.

At least 181 records · Page 10Linked to original sources

Antimicrobial activity of Ro 23-9424, a novel ester-linked codrug of fleroxacin and desacetylcefotaxime.

Ro 23-9424 is a novel ester-linked codrug of fleroxacin (Ro 23-6240; AM-833) and the cefotaxime metabolite desacetylcefotaxime. Its potency was determined against over 1,000 organisms and found to be intermediate between those of the two components. More than 99% of members of the family Enterobacteriaceae were inhibited by greater than or equal micrograms of Ro 23-9424 per ml; its MIC for 50% of strains tested ranged from greater than or equal to 0.06 to 1 micrograms/ml. Staphylococci, streptococci, Branhamella catarrhalis, Corynebacterium jeikeium, Bacillus spp., Haemophilus influenzae, Listeria monocytogenes, and the pathogenic Neisseria spp., including oxacillin-resistant Staphylococcus aureus, beta-lactamase-producing strains, and penicillin-resistant pneumococci, were also inhibited by Ro 23-9424. Pseudomonas aeruginosa, Enterococcus spp., and Bacteroides fragilis group isolates were more refractory to Ro 23-9424 (the MIC for 90% of strains tested was less than or equal to 32 micrograms/ml). Overall, Ro 23-9424 inhibited 97% of the aerobic strains, compared with 90% for ceftazidime and 92% for cefoperazone. Ro 23-9424 was bactericidal, was relatively stable to inoculum effects on MICs at 10(7) CFU/ml, and was determined to be highly active against organisms resistant to fluoroquinolones or ceftazidime. Preliminary quality control guidelines were determined, and a 30-micrograms disk concentration appears to be the most usable form.

Anti-Infective Agents↗

Quality control guidelines for testing cefotetan in the reference agar dilution procedure for susceptibility testing of anaerobic bacteria.

Reference values for quality control of in vitro susceptibility tests with cefotetan against anaerobic bacteria were determined in two independent multilaboratory studies with the approved National Committee for Clinical Laboratory Standards agar dilution method and three control strains (Bacteroides fragilis ATCC 25285, Bacteroides thetaiotaomicron ATCC 29741, and Clostridium perfringens ATCC 13124). The results of the two studies were in agreement. The recommended MIC control limits for B. fragilis ATCC 25285 and B. thetaiotaomicron ATCC 29741 are 4.0 to 16 micrograms/ml and 32 to 128 micrograms/ml, respectively. MICs for C. perfringens ATCC 13124 were too variable to be useful for controlling tests with cefotetan.

Bacteria, Anaerobic↗

Quality control limits for the standard anaerobic reference agar dilution susceptibility test procedure of the National Committee for Clinical Laboratory Standards.

Multilaboratory studies were performed to develop MIC quality control limits for the National Committee for Clinical Laboratory Standards reference agar dilution method for anaerobic susceptibility tests. Acceptable MICs were defined as those which include greater than 95% of all 100 MICs generated by the study. Most MIC control limits included either 2- or 3-dilution intervals rather than the more traditional 3-dilution intervals that are described as the mode +/- 1 doubling dilution.

Amoxicillin↗

Ofloxacin susceptibility testing quality control parameters for microdilution and disk diffusion, and confirmation of disk diffusion interpretive criteria.

The susceptibilities of 221 clinical isolates to ofloxacin were tested simultaneously by broth microdilution and disk diffusion methods with commercially prepared 5-micrograms ofloxacin disks. The acceptability of the following previously proposed zone diameter breakpoints was confirmed: greater than or equal to 16 mm, susceptible; 13 to 15 mm, intermediate; less than or equal to 12 mm, resistant. On the basis of a multilaboratory collaborative study, the following are proposed as acceptable ofloxacin MIC ranges for quality control organisms: Escherichia coli ATCC 25922, 0.03 to 0.06 micrograms/ml; Staphylococcus aureus ATCC 29213, 0.12 to 0.5 micrograms/ml; Pseudomonas aeruginosa ATCC 27853 and Enterococcus faecalis ATCC 29212, 1.0 to 4.0 micrograms/ml. Ofloxacin quality control zone diameter ranges for the disk diffusion test are tentatively proposed, but variations in the performance of different lots of Mueller-Hinton agar may prove to be a serious problem for users.

Bacteria↗

Reassessment of susceptibility test interpretive criteria for ticarcillin and ticarcillin-clavulanic acid.

There are at least four different existing or proposed interpretive criteria for the disk diffusion susceptibility testing of ticarcillin and ticarcillin plus clavulanic acid (T/C). To assess these criteria, 570 gram-negative bacillary isolates were tested for susceptibility to ticarcillin and T/C by both disk diffusion and broth microdilution methods. These included 53 strains of the family Enterobacteriaceae selected for ticarcillin resistance and high-level beta-lactamase production. The broth microdilution test results were more influenced by increased beta-lactamase production than were disk diffusion results. In the absence of published data indicating which of the two standardized test methods better predicts clinical response, we conclude that until such data are available the more conservative National Committee for Clinical Laboratory Standards tentative criteria for tests with members of the Enterobacteriaceae are appropriate. Our data do not support the use of separate T/C interpretive criteria for Pseudomonas spp. and members of the Enterobacteriaceae. The appropriateness of different interpretive criteria needs further evaluation.

Anti-Bacterial Agents↗

Temafloxacin disk potency and tentative interpretive criteria for susceptibility tests.

Temafloxacin disk susceptibility test criteria were evaluated by testing 697 bacterial isolates. Either 5- or 10-micrograms disks could be used satisfactorily. A 5-micrograms temafloxacin disk with zone size breakpoints of less than or equal to 12 mm for resistance (MIC, greater than 4.0 micrograms/ml) and greater than 16 mm for susceptibility (MIC, less than or equal to 2.0 micrograms/ml) is recommended.

Anti-Infective Agents↗

Comparison of cefadroxil and cephalothin disk susceptibility test results.

Diffusion susceptibility tests with 30-micrograms cefadroxil disks and 30-micrograms cephalothin disks were evaluated. For both agents, the same zone size interpretive criteria were recommended (less than or equal to 14 mm for resistance and greater than or equal to 18 mm for susceptibility). Tests were performed with 904 bacterial isolates, and the data were examined to determine whether the two cephalosporins might be used interchangeably for purposes of in vitro susceptibility testing. When Haemophilus influenzae, Listeria monocytogenes, and methicillin-resistant staphylococci were evaluated, the two agents differed significantly. For testing other species, a cephalothin disk or cephalothin MIC could be used for predicting susceptibility or resistance to cefadroxil.

Bacteria↗

Standardization of antimicrobial susceptibility testing.

In summary, methods for measuring bacterial susceptibility to antimicrobial agents in vitro were initially developed with little direction or coordinated effort. When a need appeared, most laboratory workers simply devised a method that would solve their own immediate problem. That resulted in a chaotic array of testing procedures that were being used in different laboratories and most of those procedures were not carefully controlled. Standardization of methods being used in the United States was brought about under the guidance of Dr. John C. Sherris and many others. As a result of the efforts that occurred in the late 1950s and early 1960s, susceptibility testing in the United States has reached a fairly sophisticated level of maturity. The National Committee for Clinical Laboratory Standards has accepted the challenge of maintaining the level of standardization that we have learned to expect.

Microbial Sensitivity Tests↗

Criteria for in vitro susceptibility testing of cefotetan. Correlations with clinical and bacteriologic responses.

Standardized in vitro susceptibility testing criteria and quality-control guidelines for cefotetan have been well documented in the scientific literature. Cefotetan and cefoxitin differ in their in vitro spectrums of activity and cannot be used interchangeably for in vitro tests. In vitro susceptibility information failed to correlate with clinical or bacteriologic responses of treated patients when 314 anaerobic bacteria from 145 patients were evaluated. All cefotetan-resistant anaerobic bacteria were eradicated by cefotetan therapy, and 93 percent of patients with resistant strains were clinically curved. Most members of the Bacteroides distasonis-ovatus-thetaiotaomicron group of pathogens were resistant in vitro, but only one strain persisted after cefotetan therapy for a 96.6 percent cure rate. There was better correlation when 2,336 aerobic bacteria from 1,630 infected body sites were considered. Microorganisms susceptible or moderately susceptible by in vitro tests were equally responsive to therapy (95 percent of patients clinically cured and 94 percent of isolates eradicated). However, strains that were resistant by in vitro test criteria were less likely to respond clinically. Development of resistance during therapy or superinfections (1.7 percent) were not found to be clinically important problems with cefotetan chemotherapy.

Bacteria, Aerobic↗

In vitro activity of FCE 22101, imipenem, and ceftazidime against over 6,000 bacterial isolates and MIC quality control limits of FCE 22101.

Six geographically separate laboratories within the USA tested 6,198 bacterial isolates against FCE 22101 (a penem), imipenem (a carbapenem) and ceftazidime (a third-generation cephalosporin). Ninety-three percent of 2,749 Enterobacteriaceae were inhibited by FCE 22101, while 95% were susceptible to ceftazidime and 99% were susceptible to imipenem. FCE 22101 had little activity against Pseudomonas spp. but was active against most gram-positive pathogens, including enterococci. FCE 22101 MICs for standard quality control strains were defined as 0.5-2.0 micrograms/ml for Escherichia coli ATCC 25922, 2-8 micrograms/ml for Enterococcus faecalis ATCC 29212 and 0.06-0.25 microgram/ml for Staphylococcus aureus ATCC 29213.

Anti-Bacterial Agents↗

Ceftibuten (7432-S, SCH 39720): comparative antimicrobial activity against 4735 clinical isolates, beta-lactamase stability and broth microdilution quality control guidelines.

The antimicrobial activity of ceftibuten, a new oral cephalosporin, was evaluated using 4735 clinical bacterial isolates processed at four medical centers. Ceftibuten inhibited nearly 92% of all Enterobacteriaceae (less than or equal to 8.0 micrograms/ml), thereby being markedly superior to cefixime which inhibited 78.7% at less than or equal to 1.0 microgram/ml and cefuroxime which inhibited 45.1% at less than or equal to 2.0 micrograms/ml. Pseudomonads and staphylococci were not within the spectrum of activity of ceftibuten. Ceftibuten was found to be very stable in the presence of five commonly occurring beta-lactamases of both the chromosomal-mediated (P99, K1) and plasmid-mediated (CARB-2, OXA-1, TEM-1) types. Only Type Ia (P99) beta-lactamase was significantly inhibited by ceftibuten. On the basis of results of a ceftibuten MIC quality control study conducted in five laboratories, a quality control range of 0.12 to 0.5 microgram/ml is recommended for the Escherichia coli ATCC 25922 strain.

Anti-Bacterial Agents↗

In vitro interaction between the penem FCE 22101 and ceftazidime.

FCE 22101, a penem antimicrobial agent, was found to resist hydrolysis by bacterial beta-lactamases and to have a strong affinity for Type Ia enzymes. Like imipenem, FCE 22101 was shown to be capable of inducing resistance to a wide range of beta-lactam antibiotics. FCE 22101 antagonized the in vitro activity of ceftazidime against enteric bacilli that commonly produce inducible enzymes. This penem should not be combined with other beta-lactams for chemotherapeutic purposes.

Anti-Bacterial Agents↗

Antimicrobial activity of MDL 19,592: an oral cephalosporin.

MDL 19,592, a semisynthetic oral cephalosporin, has an antimicrobial spectrum principally directed against Gram-positive cocci (MIC50, 0.25-4 micrograms/ml), Branhamella catarrhalis (MIC50, 1-2 micrograms/ml), and pathogenic Neisseria spp. such as meningococci (MIC50, 4 micrograms/ml). Enterobacteriaceae, enterococci, Pseudomonas spp., Corynebacterium jeikeium, and Acinetobacter calcoaceticus strains had MDL 19,592 MIC50 of greater than or equal to 32 micrograms/ml. Although MDL 19,592 generally had a spectrum most similar to cefadroxil, it could not be represented by the cephalothin susceptibility test because of low predictive values and MIC correlations.

Acinetobacter↗

BMY-28100, a new oral cephalosporin: antimicrobial activity against nearly 7,000 recent clinical isolates, comparative potency with other oral agents, and activity against beta-lactamase producing isolates.

The antimicrobial activity of BMY-28100 was tested against approximately 7,000 bacterial pathogens in a multicenter, multiphased collaborative investigation. The BMY-28100 spectrum and antimicrobial potency was most similar to that of cefaclor and superior to that of cephalexin among currently available cephalosporins. Species that had greater than or equal to 90% of clinical strains inhibited by BMY-28100 (less than or equal to 8.0 micrograms/ml) were: Citrobacter diversus, Escherichia coli, Klebsiella spp., Proteus mirabilis, Salmonella spp., Branhamella catarrhalis, Haemophilus influenzae, Neisseria gonorrhoeae, N. meningitidis, methicillin-susceptible Staphylococcus supp., Streptococcus pneumoniae, S. pyogenes, S. agalactiae, S. bovis, serogroup C and G streptococci, Listeria monocytogenes and gm-positive anaerobes. BMY-28100 inhibited 9% more of the 6286 fresh clinical isolates at less than or equal to 8.0 micrograms/ml than cefaclor at the same concentration. BMY-28100 was generally bactericidal, but MICs for some species were markedly increased when an inoculum concentration of 10(7) CFU/ml was used. Strains producing plasmid-mediated beta-lactamases (TEM, OXA, SHV, HMS) were susceptible to BMY-28100, cefaclor, and cefuroxime. BMY-28100 was less active against strains producing chromosomal-mediated beta-lactamases (Types I and IV). BMY-28100 was not hydrolyzed significantly by the tested plasmid-mediated beta-lactamases, but was destroyed by Type I cephalosporinases and Klebsiella K1 enzymes.

Administration, Oral↗

Effect of clavulanic acid on the susceptibility of clinical anaerobic bacteria to ticarcillin: a multicenter study.

Over 2,000 recent clinical isolates of anaerobic bacteria were tested at five medical centers for susceptibility to ticarcillin, ticarcillin plus clavulanic acid, clindamycin, and metronidazole. At 64 micrograms/ml, ticarcillin inhibited 92% of all isolates, but 98% were inhibited at this concentration when 2 micrograms/ml of clavulanic acid was added. With different Bacteroides species, clavulanic acid reduced ticarcillin MICs 2- to 32-fold; other anaerobic species were not significantly affected.

Bacteria, Anaerobic↗

Antimicrobial activity of U-76,252 (CS-807), a new orally administered cephalosporin ester, including recommendations for MIC quality control.

U-76,253A (R-3746), the active metabolite of the new cephalosporin ester, U-76,252 (CS-807), was tested against 4,742 fresh clinical isolates from four large medical centers. U-76,253A was very active against nearly all species of Enterobacteriaceae (87.7% inhibited at less than or equal to 4.0 micrograms/ml). Staphylococcus spp., and the streptococci. The U-76,253A spectrum was superior to the comparison orally administered cephalosporins (cephalexin, cephradine, cefaclor). Pseudomonas spp., Acinetobacter spp., and the enterococci were resistant to U-76,253A and the other tested drugs. Broth microdilution MIC quality control (QC) limits were established for U-76,253A in a multilaboratory investigation using a minimum of 125 MIC determinations per organism. The following MIC QC ranges were recommended; Escherichia coli (ATCC 25922) = 0.25-1.0 micrograms/ml, Staphylococcus aureus (ATCC 29213) = 2.0-4.0 micrograms/ml and Pseudomonas aeruginosa (ATCC 27853) = greater than 32 micrograms/ml.

Administration, Oral↗

An in vitro evaluation of HRE 664, a novel penem antibiotic.

HRE 664 is a novel parenteral penem with a broad antimicrobial spectrum. In this study, HRE 664 inhibited 90% of Enterobacteriaceae at less than or equal to 2.0 micrograms/ml, Haemophilus influenzae and Neisseria gonorrhoeae at less than or equal to 0.5 microgram/ml, oxacillin-susceptible staphylococci at less than or equal to 0.13 microgram/ml, oxacillin-resistant staphylococci at less than or equal to 8.0 micrograms/ml, enterococci at less than or equal to 8.0 micrograms/ml, and streptococci at less than or equal to 0.13 microgram/ml. All strains of Pseudomonas aeruginosa were resistant (MICs were greater than 32 micrograms/ml). HRE 664 exhibited a minimal inoculum effect and good bactericidal activity with all organisms tested except an oxacillin-resistant Staphylococcus aureus. With the latter, there was a marked inoculum effect and no on-scale bactericidal endpoints. No measurable hydrolysis of HRE 664 occurred with any of the five Gram-negative bacterial beta-lactamases tested. When stored at -20 degrees C, HRE 664 showed no significant loss of activity for up to 6 wk, but detectable deterioration occurred thereafter. At -60 degrees C, no loss in HRE 664 potency was observed for up to 12 wk. Proposed HRE 664 MIC quality control parameters are: 0.03-0.13 microgram/ml for S. aureus ATCC 29213, 0.25-1.0 micrograms/ml for Escherichia coli 25922, and 2.0-8.0 micrograms/ml for Enterococcus faecalis ATCC 29212.

Anti-Bacterial Agents↗