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Biomedical subjects

P C Fuchs

Publications and source records attributed to P C Fuchs.

At least 163 records · Page 9Linked to original sources

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↗

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↗

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↗

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↗

CI-934, a new difluoroquinolone: in vitro antibacterial activity and proposed disk diffusion test interpretive criteria.

The susceptibility of 7,763 clinical isolates at four medical centers to CI-934 and three comparative quinolones was tested. CI-934 was the most active compound against Gram-positive isolates, such as staphylococci (MIC 90 = 0.25 microgram/ml), and enterococci (MIC 90 = 0.5 microgram/ml). CI-934 was the least active of these drugs against Pseudomonas spp. (MIC 90 = greater than 8.0 micrograms/ml). Against all other organisms CI-934 was very effective, being most comparable with enoxacin. With a selected group of isolates, CI-934 demonstrated high activity against Haemophilus influenzae (MIC 90 = 0.06 microgram/ml), Neisseria meningitidis and N. gonorrhoeae (MIC 90 = 0.13 microgram/ml), Listeria monocytogenes (MIC 90 = 1.0 microgram/ml), methicillin-resistant staphylococci (MIC 90 = 0.13 microgram/ml), and modest activity against anaerobes. Disk diffusion susceptibility testing of CI-934 was evaluated using 3-, 5-, and 10-micrograms disks. Because of its lower interpretive error rate, the 3-micrograms disk is tentatively recommended. With less than or equal to 2 micrograms/ml and greater than 4 micrograms/ml as the susceptible and resistant MIC breakpoints, the corresponding 3-micrograms disk zone diameters breakpoints are greater than or equal to 15 mm and less than or equal to 11 mm. Because most isolates of Pseudomonas spp. are not susceptible to CI-934 and the zone size interpretive error rate is particularly high (33%) with Pseudomonas spp., we suggest that isolates of this genus not be tested for clinical purposes.

Anti-Bacterial Agents↗

Antimicrobial activity of Ro 19-5247 (T-2525), a new oral cephalosporin, tested against 7,745 recent clinical isolates.

The susceptibility testing of 7,745 recent clinical isolates from four medical centers showed Ro 19-5247 to be eight- to greater than 64-fold more active than cephalexin against the Enterobacteriaceae. Ro 19-5247 was comparable with cephalexin in anti-staphylococcal activity (MIC50, 4.0 micrograms/ml) and fourfold more active than cefixime. None of the oral cephalosporins were effective (MIC50, greater than 32 micrograms/ml) against enterococci, Pseudomonas aeruginosa and P. maltophilia. beta-lactamase hydrolysis experiments failed to demonstrate significant Ro 19-5247 inactivation by ten commonly encountered chromosomal- or plasmid-mediated enzymes (P99, K1, K14, TEM, CARB, OXA).

Bacteria↗

Effect of beta-lactamase inhibitors on the antimicrobial activity of cefoperazone, cefotaxime, and ceftizoxime against aerobic and anaerobic beta-lactamase producing bacteria.

Clavulanic acid (2.0 micrograms/ml) lowered the minimal inhibitory concentrations (MICs) of ceftizoxime and cefotaxime against 49 strains of the Bacteroides fragilis group by a mean of 4.0 and 3.4 log2 concentrations, respectively. Sulbactam plus ceftizoxime gave almost identical results. Sulbactam lowered cefoperazone MICs by a mean of 2 log2 concentrations. Against 52 aerobic and facultative isolates producing a variety of beta-lactamase types, the use of beta-lactamase inhibitors (sulbactam) was most effective in reducing the MICs of cefoperazone.

Bacteria, Aerobic↗

RO 23-6240 (AM-833), a new fluoroquinolone: in vitro antimicrobial activity and tentative disk diffusion interpretive criteria.

The susceptibility of over 7000 recent clinical bacterial isolates to RO 23-6240, a new trifluorinated quinolone, was determined at four medical centers. Over 99% of Enterobacteriaceae and 97% of staphylococci were inhibited by less than or equal to 2.0 micrograms/ml of RO 23-6240. Only 71% of Pseudomonas spp. were inhibited by this concentration. Streptococci and enterococci were resistant to RO 23-6240. Clinical isolates of Haemophilus spp., pathogenic Neisseria spp., and Branhamella catarrhalis were inhibited by less than or equal to 0.25 micrograms/ml of RO 23-6240. This drug's antibacterial activity was comparable with that of enoxacin and norfloxacin, but was less than that of ciprofloxacin against most species. Using less than or equal to 2.0 micrograms/ml and greater than or equal to 8.0 micrograms/ml as the susceptible and resistant MIC breakpoints for RO 23-6240, the regression analysis-derived disk diffusion zone diameter breakpoints for the 5 micrograms disk are: Susceptible greater than or equal to 19 mm intermediate 16-18 mm, and resistant less than or equal to 15 mm.

Anti-Bacterial Agents↗

Quality control limits for microdilution susceptibility tests with aztreonam, imipenem, ceftriaxone, ceftazidime, ceftizoxime, cefuroxime, and cefonicid.

A six-laboratory collaborative study was performed in order to define quality control limits for microdilution tests with seven new beta-lactams (aztreonam, imipenem, ceftriaxone, ceftazidime, ceftizoxime, cefuroxime, and cefonicid). Four standard control strains were tested and the expected MIC limits for each of the appropriate drug-microorganism combinations were defined.

Anti-Bacterial Agents↗

Ceftizoxime and cefoxitin susceptibility testing against anaerobic bacteria: comparison of results from three NCCLS methods and quality control recommendations for the reference agar dilution procedure.

Ceftizoxime and cefoxitin (control) were tested against 99 anaerobic bacteria using three commonly used susceptibility testing methods. The cefoxitin MIC results with the National Committee for Clinical Laboratory Standards (NCCLS) reference agar dilution (RAD) method and the broth microdilution (BMD) method did not differ by more than one log2 dilution step. However, the ceftizoxime BMD MIC results were 2- to 4-fold lower than those produced by the RAD procedure. Broth disk elution (BDE) tests for both cephalosporins (ceftizoxime and cefoxitin) had very high rates of false-susceptible and false-resistant error when compared to the RAD MICs: the BDE tests are not recommended for either cephalosporin. Findings indicate that because of method and possible medium or technical variability, ceftizoxime MICs should be determined only by the NCCLS RAD method. Also, cefoxitin susceptibility should be assessed primarily by RAD or BMD procedures. This should minimize confusion related to ceftizoxime's spectrum and activity against anaerobic bacteria compared to similar beta-lactam drugs. Ceftizoxime quality control guidelines were established for Bacteroides fragilis (ATCC 25285): mode, 64 micrograms/ml, range 32-128 micrograms/ml. Other control strains were not reliable.

Agar↗

Quality control limits for microdilution susceptibility tests with norfloxacin.

A multilaboratory study was designed to define quality control limits for microdilution susceptibility tests with norfloxacin. The following limits were proposed: for Escherichia coli ATCC 25922, 0.03 to 0.125 micrograms/ml; for Pseudomonas aeruginosa ATCC 27853, 1.0 to 4.0 micrograms/ml; for Staphylococcus aureus ATCC 29213, 0.5 to 2.0 micrograms/ml; and for Streptococcus faecalis ATCC 29212, 2.0 to 8.0 micrograms/ml. The latter represents a change in the previously recommended control limits.

Enterococcus faecalis↗

Antimicrobic susceptibility and plasmid profile analysis as identity tests for multiple blood isolates of coagulase-negative staphylococci.

We compared a disk diffusion antimicrobic susceptibility panel with plasmid DNA profiles as tests for identity of 106 isolates of coagulase-negative staphylococci cultured from the blood of 45 patients on multiple occasions. The antimicrobic panel included penicillin, oxacillin, clindamycin, trimethoprim-sulfamethoxazole, chloramphenicol, tetracycline, tobramycin, kanamycin, and gentamicin. Nineteen patterns of antimicrobic susceptibility were found. The most common pattern was present in 25% of the isolates, and at least one isolate from 31% of the patients had this pattern. Forty-seven distinct plasmid DNA profiles were found. The most common plasmid profile was present in 8.5% of the isolates, and at least one isolate from 15% of the patients had this profile. Twenty-eight patients had multiple isolates that were identical by plasmid profile analysis. Twenty-seven (96%) of these patients had isolates that were also identical by antimicrobic susceptibility. Nineteen patients had multiple isolates that were different by plasmid profile analysis. In 18 (95%) of these patients, the isolates were also different by antimicrobic susceptibility. Although plasmid DNA profile analysis is a more discriminating tool, these data confirm that a selected disk diffusion antimicrobic susceptibility panel may be used to screen multiple blood isolates of coagulase-negative staphylococci for identity or differences.

Anti-Bacterial Agents↗

In vitro activity of carumonam (RO 17-2301), BMY-28142, aztreonam, and ceftazidime against 7,620 consecutive clinical bacterial isolates.

For 45-60 days four geographically separate clinical laboratories tested routine clinical bacterial isolates for susceptibility to carumonam, aztreonam, BMY-28142, and ceftazidime by the broth microdilution method. All four drugs were highly active against Enterobacteriaceae, inhibiting greater than 96% of the 4887 strains tested at less than or equal to 8.0 microgram/ml. The minimal inhibitory concentration at which 50% of the isolates were inhibited for each drug was less than or equal to 0.125 micrograms/ml. Ceftazidime was the most active against nonenteric gram-negative bacilli (86% inhibited at less than or equal to 8.0 micrograms/ml), followed by BMY 28142 (82%), carumonam (75%), and aztreonam (68%). The two monobactams exhibited no activity against gram-positive cocci at the concentrations tested, whereas BMY-28142 had excellent activity against nonenterococcal streptococci and good activity against staphylococci.

Anti-Bacterial Agents↗

In vitro activity of DJ-6783 (a keto carboxylic acid) compared with six other orally administered antimicrobial agents.

DJ-6783 is a new keto carboxylic acid having an expanded antimicrobial activity when compared with nalidixic acid or cinoxacin. Its usable activity includes the following: Enterobacteriaceae (MIC90, less than or equal to 0.06-4.0 micrograms/ml), Acinetobacter species (MIC90, 0.25-1.0 microgram/ml), Pseudomonas species (MIC90, 1.0-2.0 micrograms/ml), P. aeruginosa (MIC90, 16 micrograms/ml), Staphylococcus species (MIC90, 1.0-32 micrograms/ml), Haemophilus influenzae (MIC900, less than or equal to 0.06 microgram/ml), and Neisseria species (MIC90 less than or equal to 0.06 microgram/ml). The Streptococcus species were resistant to DL-6783 with MIC50 ranging from 16 to greater than 32 micrograms/ml. The drug appears to be bactericidal, minimally influenced by increasing inocula, but resistant mutants can be selected by serial subinhibitory concentration passages of strains in DJ-6783. The resulting resistant organisms also have higher MICs to related drugs such as norfloxacin, cinoxacin, and nalidixic acid. DJ-6783 was the most active organic acid not having structural characteristics of the fluorinated 4-quinolones.

Anti-Bacterial Agents↗

In vitro evaluation of cefixime (FK027, FR17027, CL284635): spectrum against recent clinical isolates, comparative antimicrobial activity, beta-lactamase stability, and preliminary susceptibility testing criteria.

Cefixime, a new orally absorbed cephalosporin, was compared by in vitro testing with other oral beta-lactams, including cephalexin, cefaclor, cefuroxime, amoxicillin, and amoxicillin + clavulanate. Enterobacteriaceae were inhibited by lower concentrations of cefixime than any of the reference drugs; 90% and 95% were inhibited by less than or equal to 1.0 and less than or equal to 8.0 micrograms/ml, respectively. Cefixime was the least active among these drugs against staphylococci, with only 31% of 1106 strains inhibited by less than or equal to 8.0 micrograms/ml and less than 1% by less than or equal to 1.0 microgram/ml. Enterococci and pseudomonads were not susceptible to any of the drugs tested. Penicillin-resistant pneumococci were relatively resistant to cefixime, but penicillin-susceptible pneumococci were very susceptible to cefixime. Other streptococci were generally susceptible to all compounds tested, with relative activities of amoxicillin greater than cefaclor and cefuroxime greater than cefixime greater than cephalexin. Cefixime was inactive against Bacteroides species. A slight inoculum effect occurred with cefixime with inocolum concentrations varying from 10(5) to 10(6) colony forming units per milliliter, but this was more marked at 10(7) colony forming units per milliliter. Cefixime was resistant to hydrolysis by seven common beta-lactamases. It inhibited the hydrolysis of nitrocefin only by type 1 cephalosporinases. The disk diffusion zone diameter breakpoints for the 30-micrograms cefixime disk were determined by regression analysis to be greater than or equal to 27 mm (susceptible) and less than or equal to 23 mm (resistant), respectively corresponding to minimal inhibitory concentration breakpoints of less than or equal to 1.0 and greater than or equal to 4.0 micrograms/ml. Because of the high interpretive error rate (13.8%) and the occurrence of these breakpoints on the parabolic portion of the regression curve, we recommend further evaluation of cefixime disks with lower potencies.

Amoxicillin↗

The anti-microbial activity, beta-lactamase stability, and disk diffusion susceptibility testing of carumonam (RO 17-2301, AMA-1080), a new monobactam.

Carumonam, a new monobactam, was found to have an anti-microbial spectrum similar to aztreonam. Its spectrum includes Enterobacteriaceae, Haemophilus influenzae, pathogenic Neisseria species, Pseudomonas aeruginosa, and some streptococci. Staphylococcus species, enterococci, and many other nonenteric gram-negative bacilli were not inhibited. Enterobacteriaceae resistant to cefoperazone (minimum inhibitory concentrations [MICs] greater than or equal to 32 mg/L) were more likely inhibited by carumonam (52% at less than or equal to 8.0 mg/L) than aztreonam (39%) or ceftazidime (35%). Dilution test methods on agar or in Mueller-Hinton broth produced similar results. Carumonam minimum bactericidal concentrations were usually the same or one dilution above the MIC. Carumonam and aztreonam were very stable to most chromosomal (P99, K1, K14) and plasmid-mediated beta-lactamases (TEM, OXA, PSE). The Klebsiella oxytoca enzymes hydrolyzed aztreonam at rates greater than or equal to fivefold higher than carumonam but at a rate less than 1% that of cephaloridine. The aztreonam MICs for these Klebsiella stains were greater than or equal to 32 mg/L, but the hydrolysis rates do not fully explain the high-grade resistance to aztreonam. In vitro susceptibility tests with 30-micrograms carumonam disks were found to be very predictive. Similar regression statistics were observed for aztreonam and cefotaxime. Recommendations for carumonam susceptibility testing are susceptible greater than or equal to 21 mm (less than or equal to 8.0 mg/L) and resistant less than or equal to 14 mm (greater than or equal to 32 mg/L). Cross-resistance analysis favors the independent testing of carumonam or aztreonam against gram-negative species other than Enterobacteriaceae and P. aeruginosa.

Anti-Bacterial Agents↗