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Biomedical subjects

P C Fuchs

Publications and source records attributed to P C Fuchs.

At least 181 records · Page 10Linked to original sources

LY164846 in vitro antimicrobial activity testing, including disk diffusion susceptibility tests using 30-microgram disks.

A new oral cephalosporin, LY164846 (Eli Lilly & Co., Indianapolis, Ind.), was found to have a unique antimicrobial spectrum confined to methicillin-susceptible Staphylococcus spp., streptococci (except Enterococcus spp.), Haemophilus influenzae, Branhamella catarrhalis, and some anaerobes. Cephalothin in vitro tests (30-microgram disks or dilution) can represent LY164846 for laboratory testing if comparable interpretive breakpoints are applied to strains within the spectrum of LY164846. Organisms not inhibited by LY164846 (MICs greater than or equal to 32 micrograms/ml) were members of the family Enterobacteriaceae, Pseudomonas spp., Acinetobacter spp., enterococci, and some strains of Staphylococcus haemolyticus and of the Bacteroides fragilis group.

Anti-Bacterial Agents↗

Antimicrobial activity of Ro 15-8074, active metabolite of a new oral cephalosporin (Ro 15-8075), against 7,775 recent clinical isolates.

Susceptibility testing of 7,775 recent clinical isolates from four medical centers showed Ro 15-8074 to be 2-to greater than 8-fold more active than either cefaclor or cefuroxime against the Enterobacteriaceae. Ro 15-8074 MICs for 50% of the strains tested were greater than or equal to 32 micrograms/ml for Staphylococcus spp., enterococci, Pseudomonas aeruginosa, and Pseudomonas maltophilia. beta-Lactamase hydrolysis experiments failed to demonstrate significant Ro 15-8074 inactivation by commonly encountered chromosomal or plasmid-mediated enzymes (P99, K1, K14, TEM, and CARB).

Anti-Bacterial Agents↗

Tentative disk diffusion susceptibility interpretive criteria for BMY-28142, a new cephalosporin.

A total of 750 bacterial isolates, including 37 different species, were tested for susceptibility to BMY-28142 by standardized broth microdilution and disk diffusion tests. The zone diameter interpretive criteria tentatively suggested for the 30-micrograms BMY-28142 disk are as follows: susceptible = greater than or equal to 18 mm (MIC less than or equal to 8.0 micrograms/ml), resistant = less than or equal to 14 mm (MIC greater than or equal to 32 micrograms/ml), and indeterminate = 15 to 17 mm.

Bacteria↗

Selection of a reference lot of Mueller-Hinton agar.

A collaborative study was undertaken to evaluate the performance of currently marketed Mueller-Hinton agars from seven manufacturers by replicate disk diffusion tests with standard quality control strains. Identification of the manufacturers was concealed, and the resulting data were evaluated for the selection of a physical reagent standard against which the performance of future production lots would be tested and made to conform. A medium was selected which was sufficiently close to existing National Committee for Clinical Laboratory Standards quality control limits that current interpretive criteria would require minimum modification. Two of the seven lots were eliminated from further consideration because the final pHs were outside acceptable limits. The remaining four lots had 96% of mean zone diameters less than or equal to 2 mm from those of the chosen lot and 65% of the means were less than or equal to 1 mm from those of the chosen lot for all 28 antimicrobial agent-organism combinations. Manufacturers then attempted to produce new lots of Mueller-Hinton agar which performed within the prescribed limits of the chosen lot. One lot performed in close conformity with the selected standard, but the overall performance of the media was essentially the same as that of the randomly chosen lots in the initial study. It was concluded that one of the original seven lots demonstrated properties which made it a tentative candidate for a physical reagent standard and that the use of a physical reagent standard in evaluating production lots might aid in stabilizing the performance of Mueller-Hinton agar.

Agar↗

Disk diffusion susceptibility testing of two macrolide antimicrobial agents: revised interpretive criteria for erythromycin and preliminary guidelines for roxithromycin (RU 965).

The 15-micrograms erythromycin disk was twice evaluated for interpretive accuracy against 417 and then 266 strains of gram-positive cocci, Neisseria meningitidis, and Haemophilus influenzae by using the criteria suggested by the National Committee for Clinical Laboratory Standards. These studies suggest a revision of streptococcal and Staphylococcus sp. interpretive guidelines to criteria (greater than or equal to 23 mm = susceptible, less than or equal to 13 mm = resistant) that are more compatible with in vivo erythromycin concentrations. It is also recommended that zone diameters be modified for H. influenzae (greater than or equal to 23 mm = susceptible, less than 22 mm = resistant) and that meningococci not be tested. A wide moderately susceptible category (1.0 to 4.0 micrograms/ml) would primarily include enterococcus strains and those organisms that would then respond only to parenteral administration of erythromycin. Roxithromycin (RU 965 or RU 28965), a new oxime ether erythromycin derivative, was also evaluated by investigator-prepared 15-micrograms disks and later with 30- and 60-micrograms commercial disks. Although roxithromycin was comparable to erythromycin in activity and regression line statistics, changes in the susceptible disk criteria were necessary because of superior roxithromycin serum concentrations and a longer serum half-life. Preliminary susceptible breakpoint criteria were greater than 21 mm = susceptible, 10 to 20 mm = indeterminate, and less than or equal to 9 mm = resistant. By using the recommended interpretive criteria for both macrolides, less than 98% absolute agreement was obtained, therefore suggesting the application of a spectrum class concept.

Erythromycin↗

Tentative disk diffusion susceptibility interpretive criteria for pefloxacin.

Standardized broth microdilution and disk diffusion susceptibility tests for pefloxacin were performed on 585 clinical isolates. The 5-micrograms pefloxacin disk is recommended, and the following breakpoints are proposed: susceptible, greater than or equal to 19 mm (MIC, less than or equal to 2.0 micrograms/ml); resistant, less than or equal to 15 mm (MIC, greater than 4.0 micrograms/ml); and intermediate, 16 to 18 mm.

Bacteria↗

Cefixime disk susceptibility test criteria.

A total of 583 bacterial isolates was tested for susceptibility to cefixime by broth microdilution and by disk agar diffusion with 5-, 10-, and 30-microgram disks. At MIC breakpoints of less than or equal to 1.0 and greater than or equal to 4 micrograms/ml for susceptible and resistant, respectively, the 5-microgram disk showed slightly better discrimination. The 5-microgram cefixime disk is recommended with proposed interpretive breakpoint criteria of: less than or equal to 17 mm, resistant; 18 to 20 mm, intermediate; and greater than or equal to 21 mm, susceptible.

Bacteria↗

Antimicrobial activity of cefmetazole (CS-1170) and recommendations for susceptibility testing by disk diffusion, dilution, and anaerobic methods.

Cefmetazole, formerly CS-1170, was found to have antimicrobial activity slightly superior to that of cefoxitin but a clinically usable antimicrobial spectrum that should be considered identical to that of cefoxitin. Disk diffusion and dilution test methods with cefmetazole correlated highly (r, greater than or equal to 0.95) with cefoxitin results. The recommended 30-micrograms cefmetazole disk interpretive breakpoints for susceptibility and resistance were greater than or equal to 18 mm (MIC, less than or equal to 8.0 micrograms/ml) and less than or equal to 14 mm (MIC, greater than or equal to 32 micrograms/ml), respectively. Cefmetazole and cefoxitin should be considered to be in the same antimicrobial spectrum class, requiring separate testing for other cephalosporins such as cephalothin, cefamandole, cefuroxime, and cefotetan. Recommended interpretive criteria performed well for fastidious organisms (Haemophilus influenzae, Neisseria meningitidis, and Branhamella catarrhalis) and for broth microdilution tests with anaerobes. Cefmetazole and cefoxitin broth disk elution tests for anaerobic bacteria produced higher rates of false susceptibility results.

Bacteria↗

Interpretive criteria for temocillin disk diffusion susceptibility testing.

The susceptibility of 677 clinical bacterial isolates to temocillin was determined by broth microdilution and disk diffusion methods for the purpose of evaluating disks with three different temocillin concentrations and determining the temocillin disk diffusion interpretive criteria. The 60 microgram temocillin disk provided the highest interpretive accuracy (96.2%), although the 30 microgram disk differed by having only three (1.2%) additional minor interpretive errors. Based on available temocillin pharmacokinetics and recommended dosage schedules, the minimum inhibitory concentration breakpoints chosen were: greater than or equal to 32 micrograms/ml = resistant and less than or equal to 16 micrograms/ml = susceptible. The corresponding disk diffusion zone diameter breakpoints for the 60 microgram disk were less than or equal to 17 mm and greater than or equal to 21 mm; zone diameters of 18-20 mm were considered intermediate. For the 30 microgram disk these were less than or equal to 15 mm, greater than or equal to 19 mm and 16-18 mm respectively.

Bacteria↗

Evaluation of in vitro antibacterial activity of enoxacin: comparison with other orally absorbed antimicrobial agents, proposed disk diffusion test interpretive criteria, and quality control limits.

The antibacterial activity of enoxacin was assessed by a standard microdilution susceptibility test method against 6,096 consecutive clinical isolates at four clinical laboratories and compared with that of norfloxacin and cefaclor. Its activity was comparable to that of norfloxacin; both inhibited over 90% of Enterobacteriaceae at 0.5 micrograms/ml. Resistance to enoxacin [minimum inhibitory concentration (MIC) greater than 4 micrograms/ml] was observed in only 18 of 4,076 Enterobacteriaceae (0.5%, 36 of 650 nonfermentative gram-negative bacilli (5.5%), and 6 of 836 staphylococci (0.7%). Relatively poor activity was observed against streptococci. An additional 618 selected clinical isolates were tested with enoxacin and were compared with nine other orally absorbed antimicrobial agents. The greatest activity was observed with enoxacin, norfloxacin, and cotrimoxazole, but some difference were noted with individual species. Results of enoxacin disk diffusion susceptibility testing of 487 isolates were correlated with the MICs, analyzed, and interpretive criteria were determined. With MIC breakpoints of: susceptible = less than or equal to 2.0 micrograms/ml, intermediate = 4.0 micrograms/ml, and resistant = greater than 4.0 micrograms/ml, the corresponding preliminary disk diffusion zone diameter breakpoints for the 10-micrograms enoxacin disk are: susceptible greater than or equal to 18 mm, intermediate 15-17 mm, and resistant less than or equal to 14 mm. Quality control zone diameter limits were determined for three standard QC organisms.

Anti-Bacterial Agents↗

In-vitro evaluation of Sch 34343: antimicrobial activity, beta-lactamase stability and inhibition.

Sch 34343 was compared with representative parenteral beta-lactams including monobactams (aztreonam), 1-oxa-beta-lactams (latamoxef), carbapenems (imipenem) and cephalosporins (cefamandole, cefoperazone, cefotaxime, cefsulodin and ceftazidime). Sch 34343 was active against the Enterobacteriaceae (MIC50 range, 0.12-4.0 mg/l) and the facultative Gram-positive cocci (MIC50 range, 0.03-4.0 mg/l), and was comparable to the third-generation cephalosporins and imipenem. Pseudomonas aeruginosa and other Pseudomonas spp. were not susceptible to Sch 34343. Haemophilus influenzae and Neisseria spp. were all susceptible to less than or equal to 2.0 mg/l of Sch 34343. Methicillin-resistant staphylococci (MIC90, 32 mg/l) appear to be insusceptible to Sch 34343. Sch 34343 inhibited the majority of cefotaxime- and gentamicin-resistant bacteria (MICs less than or equal to 8.0 mg/l). The new penem was stable to hydrolysis by 11 beta-lactamase preparations (both plasmid- and chromosomally-mediated types). Sch 34343 inhibited beta-lactamases as did other newer cephalosporins.

Anti-Bacterial Agents↗

Cefpiramide: comparative in-vitro activity and beta-lactamase stability.

Cefpiramide is a new Pseudomonas-active cephalosporin with a broad spectrum of antibacterial activity. Like cefoperazone, cefpiramide was moderately susceptible to hydrolysis by a variety of beta-lactamases from Gram-negative bacilli. Tests with 6552 bacterial isolates in five separate medical centres documented cefpiramide's effectiveness against the more commonly encountered bacterial pathogens. Additional studies with 761 selected isolates, representing 35 species, demonstrated similarities between cefpiramide and cefoperazone; cefpiramide was more active against Acinetobacter spp. and Pseudomonas spp. Like most other cephalosporins, cefpiramide inhibited methicillin-susceptible staphylococci, non-enterococcal streptococci, Neisseria gonorrhoeae, N. meningitidis and beta-lactamase-negative Haemophilus influenzae. Cefpiramide was marginally active against Streptococcus faecalis (MIC 50, 8.0 mg/l).

Bacteria↗

Evaluation of the in vitro activity of BMY-28142, a new broad-spectrum cephalosporin.

The in vitro activity of BMY-28142, a new cephalosporin, was tested by a broth microdilution system and compared with those of cefotaxime, ceftazidime, cefoperazone, moxalactam, and HR 810 against 747 bacterial isolates, one-third of which were resistant to one or more third-generation cephalosporins. BMY-28142 was the most active drug tested against 326 Enterobacteriaceae with an MIC for 90% of the organisms tested (MIC90) of 1.0 micrograms/ml. Against these Enterobacteriaceae the relative activities were: BMY-28142 greater than HR 810 greater than moxalactam and ceftazidime greater than cefotaxime greater than cefoperazone. For cefotaxime- and cefoperazone-resistant strains, the MIC90 of BMY-28142 was 4.0 micrograms/ml (compared with 0.13 micrograms/ml for susceptible strains). BMY-28142, with an MIC90 of 8.0 micrograms/ml for Pseudomonas aeruginosa, was about half as active as ceftazidime. The relative activities against P. aeruginosa were: ceftazidime greater than BMY-28142 greater than HR 810 greater than cefoperazone greater than moxalactam and cefotaxime. The MIC90 of BMY-28142 against staphylococci was 2.0 micrograms/ml, which was fourfold less active than HR 810, slightly less active than cefotaxime and cefoperazone, and fourfold more active than ceftazidime and moxalactam. BMY-28142 was very active against beta-lactamase-positive and -negative Haemophilus influenzae (MIC90, 0.06 micrograms/ml), Neisseria gonorrhoeae (MIC90, 0.015 micrograms/ml),aand nonenterococcal streptococci. Its activity against Streptococcus faecalis was poor (MIC90, 64 micrograms/ml). BMY-28142 was stable against the several beta-lactamases tested but exhibited little beta-lactamase inhibitory effect.

Bacteria↗

Proposed disk diffusion susceptibility criteria for ofloxacin.

Disk diffusion zone diameter breakpoint criteria for ofloxacin were tentatively established by correlating MICs with 1-, 3-, and 5-micrograms disk inhibitory zone diameters for 638 bacterial isolates representing 36 species. We recommend use of 5-micrograms disks with the following breakpoints: susceptible (MIC, less than or equal to 2.0 micrograms/ml), greater than or equal to 16 mm; intermediate (MIC, 4.0 micrograms/ml), 13 to 15 mm; and resistant (MIC, greater than or equal to 8.0 micrograms/ml), less than or equal to 12 mm.

Anti-Bacterial Agents↗

Cefotiam susceptibility testing criteria.

Interpretive zone size breakpoints for diffusion tests with 30-micrograms cefotiam disks are diameters of greater than or equal to 18 mm for susceptible and less than or equal to 14 mm for resistant strains. The standard control strains Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923 should both give zones 27 to 33 mm in diameter. Tests with 579 clinical isolates yielded an unacceptably high rate of very major discrepancies between disk tests and microdilution tests; such discrepancies were especially common among Enterobacter spp. Additional studies support the concept that standard microdilution tests and standard disk diffusion tests may fail to detect a potential for resistance among some microorganisms.

Cefotaxime↗

Cerebellar toxicity following high-dose cytosine arabinoside.

A patient with acute cerebellar toxicity following systemic high-dose cytosine arabinoside (ara-C) 3 g/m2/12 h for secondary acute nonlymphocytic leukemia is reported. Initial symptoms of ataxia and dysarthria emerged at 30 g/m2 cumulative dose and persisted without improvement over a ten-week period. Recurrence and worsening of cerebellar symptoms followed further consolidation treatment with high-dose ara-C. Subsequent autopsy showed extensive Purkinje's cell damage in the lateral cerebellar hemispheres. Persistent severe toxicity can occur at total doses less than those generally recognized.

Ataxia↗

Antimicrobial prophylaxis in elective colon surgery. Experience of 1,035 operations in a community hospital.

An 11 year study of 1,035 elective colon resections reaffirmed the value of oral antibiotic prophylaxis. Five antibiotic regimens were used in 88 percent of the patients. The most effective and most frequently used regimen was the combination of parenteral cephalosporin with oral erythromycin and an aminoglycoside. The overall infection rate with this regimen was 11 percent and the wound sepsis rate was 2.5 percent. The use of parenteral cephalosporins alone was not effective. Furthermore, resistant bacteria were cultured from the wound infections of parenteral cephalosporin patients. A nondirective annual review of these data and each surgeon's infection rate resulted in a change in the antibiotic ordering practices and decreased infection rates. It is no longer acceptable surgical practice to omit antibiotic prophylaxis in colon operations.

Abscess↗