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Biomedical subjects

C Thornsberry

Publications and source records attributed to C Thornsberry.

At least 109 records · Page 6Linked to original sources

Cefpirome (HR810) disk diffusion susceptibility tests: confirmation of interpretive criteria using cefotaxime and cefoperazone-resistant strains and effects of blood supplemented media.

Cefpirome (formerly HR810) is a wide-spectrum, beta-lactamase-stable cephalosporin with antimicrobial activity against Pseudomonas species, Enterobacteriaceae, and gram-positive species. Reevaluation of the 30-microgram disk diffusion tests with commercially prepared disks using strains resistant to "third generation," cephalosporins confirms the proposed susceptibility breakpoint zone of greater than or equal to 18 mm (minimal inhibitory concentration correlate, less than or equal to 8.0 micrograms/ml) and the resistance breakpoint zone of less than or equal to 14 mm (minimal inhibitory concentration correlate, greater than or equal to 32 micrograms/ml). Major and minor interpretive errors were only 3.8%, and these errors could be further reduced (2.3%) by not testing methicillin-resistant Staphylococcus species. The addition of 5% sheep blood or chocolated blood to Mueller-Hinton agar slightly increased the cefpirome zone diameters (17.7-22.2 mm) for nearly 60% of Streptococcus faecalis strains tested.

Bacteria↗

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↗

Prevalence of antimicrobial resistance among clinical isolates of Haemophilus influenzae: a collaborative study.

The prevalence of antimicrobial resistance was assessed among a total of 3,356 clinical isolates of Haemophilus influenzae obtained from 22 medical centers distributed throughout the United States during the period July, 1983 through June, 1984. All strains were examined for beta-lactamase production with a rapid acidometric assay and for resistance to ampicillin, chloramphenicol, cephalothin, cefamandole, cefaclor, tetracycline, and erythromycin with a standardized disk diffusion procedure. The overall rate of beta-lactamase production was 15.2%, although results of disk diffusion tests suggested that the overall rate of ampicillin resistance was 19.5%. Twenty-one percent of encapsulated type b strains produced beta-lactamase; 12.1% of non-type b strains were beta-lactamase positive. Specific rates of beta-lactamase production obtained at individual study centers varied widely with no evidence of geographic clustering. The highest rates of beta-lactamase production were observed with isolates of H. influenzae recovered from infants and young children, and from blood and cerebrospinal fluid specimens. The overall rate of chloramphenicol resistance was 0.6%. The prevalence of cephalothin, cefamandole, cefaclor, tetracycline, and erythromycin resistance was 9.9%, 2.4%, 2.8%, 6.4%, and 64.2%, respectively. beta-Lactamase positive isolates of H. influenzae had higher rates of resistance to all of the cephalosporins than did strains that lacked beta-lactamase.

Adolescent↗

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↗

In vitro evaluation of A-56619 and A-56620, two new quinolones.

The in vitro activities of two new aryl-fluoroquinolones (A-56619 and A-56620) were compared with those of ciprofloxacin, ofloxacin, enoxacin, and norfloxacin. All six quinolones had broad spectra of antibacterial activity; the streptococci, Pseudomonas maltophilia, and Pseudomonas cepacia were the least susceptible. A-56619, A-56620, and chloramphenicol had similar activity against anaerobic bacteria. With both drugs, a low frequency of resistant variants (less than 10(-8)) was observed. By regression analysis, A-56619 MICs correlated best with ofloxacin MICs and A-56620 was most similar to ciprofloxacin.

Anti-Bacterial Agents↗

Microplate phosphocellulose binding assay for aminoglycoside-modifying enzymes.

We modified the phosphocellulose binding assay for aminoglycoside-modifying enzymes (AMEs) by use of microdilution plates and a multichannel micropipette. Batteries of aminoglycoside substrates for screening organisms for the presence of AMEs as well as for subclassifying enzymes were prepared and stored in microdilution plates. When tested in parallel with the conventional tube reaction assay, the microplate assay yielded comparable radioactive counts and therefore equally correct identifications of AMEs in 32 isolates representing nine bacterial species. Other modifications, such as multichannel dispensing of crude enzyme preparations and radioisotopic precursors, provided a more rapid, convenient, and less expensive means of examining large collections of organisms for AMEs.

Acetyltransferases↗

Evaluation of teicoplanin and vancomycin disk susceptibility tests.

Disk tests with two glycopeptide antibiotics, teicoplanin and vancomycin, were evaluated, and MICs were compared with those of fusidic acid and coumermycin. For tests with 30-micrograms vancomycin disks, we recommend modification of the current zone size standards to less than or equal to 10 mm for resistant and greater than or equal 15 mm for susceptible. For teicoplanin disk tests, 30-micrograms disks are recommended, with zone size interpretive standards of less than or equal to 10 and greater than or equal 14 mm. Since no resistant clinical isolates are available at this time, susceptibility testing of either drug is rarely necessary, and zone size standards are tentative.

Aminocoumarins↗

Evaluation of the MicroScan antimicrobial susceptibility system with the autoSCAN-4 automated reader.

The American MicroScan (American MicroScan, Mahwah, N.J.) identification and antimicrobial susceptibility system consists in part of an automated reading system (autoSCAN-4) with data management capabilities. We evaluated the system with 404 gram-negative and 170 gram-positive facultative anaerobic and aerobic bacteria. We compared MicroScan results read automatically and visually with each other and with the results obtained by the reference method (read visually). The overall agreement within +/- 1 log2 dilution was 94.3% when the MicroScan system (read automatically) was compared with the reference method (read visually), 96.4% when MicroScan panels (read visually) were compared with reference panels, and 97.4% when the autoSCAN-4 automated reading was compared with the visual reading of the MicroScan panels. Total discrepancies (susceptibility interpretation category changes) for the MicroScan system compared with the reference method were 7%, with 6.2% considered a minor discrepancy. The autoSCAN-4 and the complete MicroScan system yielded accurate results compared with the reference method.

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↗

The role of beta-lactamase in staphylococcal resistance to penicillinase-resistant penicillins and cephalosporins.

We showed that most Staphylococcus aureus strains that have borderline or intermediate susceptibility to the penicillinase-resistant penicillins (PRPs) react this way because of the activity of their beta-lactamase on these antimicrobial agents. These strains produced large amounts of staphylococcal beta-lactamase that rapidly hydrolyzed penicillin and partially hydrolyzed the PRPs. Susceptibility to hydrolysis was penicillin greater than oxacillin greater than cephalothin greater than methicillin. The borderline results and the hydrolysis could be prevented by the beta-lactamase inhibitors clavulanic acid and sulbactam. For intrinsically methicillin-resistant (heteroresistant) S. aureus, the inhibitors reduced the penicillin MICs, but the strains remained resistant to all the beta-lactam antimicrobial agents, including penicillin. We conclude that the borderline in vitro susceptibility or resistance to PRPs in most of these S. aureus strains is mediated by beta-lactamase and they are not heteroresistant or intrinsically resistant. We do not know whether this in vitro resistance is expressed clinically.

Cephalosporins↗

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↗

Screening pneumococci for penicillin resistance.

Eighty-four pneumococci with various MICs of penicillin (38 with MICs of less than or equal to 0.06 micrograms/ml [susceptible], 35 with MICs of 0.12 to 1.0 micrograms/ml [relatively resistant], and 11 with MICs of greater than 1.0 micrograms/ml [resistant] ) were screened by a disk diffusion test using oxacillin and methicillin to see how well they distinguished penicillin-susceptible strains from those with decreased susceptibility to penicillin. The effects of Mueller-Hinton agar plus 5% sheep blood and Trypticase soy agar plus 5% sheep blood and two atmospheres, ambient air and a candle extinction jar (increased CO2), were compared. There were no obvious differences between the effects of the two media, but zones were generally larger in ambient air than in increased CO2. Although the oxacillin test can separate penicillin-susceptible and -resistant strains, it cannot separate penicillin-resistant from relatively penicillin-resistant strains by using the breakpoint of less than 20 mm recommended by the National Committee for Clinical Laboratory Standards. When the 20-mm breakpoint was applied to methicillin, 12% of the relatively resistant strains tested were erroneously classified as susceptible. When different breakpoints were used for methicillin, there was better separation of the two classes of penicillin-resistant isolates, but a few relatively resistant strains were still classified as susceptible. We recommend that oxacillin, not methicillin, be used as the screening agent with Mueller-Hinton sheep blood agar and ambient air incubation and that the breakpoint be less than 20 mm to indicate resistance or relative resistance.

Carbon Dioxide↗

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↗

Review of in vitro activity of third-generation cephalosporins and other newer beta-lactam antibiotics against clinically important bacteria.

The third-generation cephalosporins and some newer beta-lactam compounds such as the monobactams and carbapenems, when compared with first- and second-generation cephalosporins, have an extended spectrum of activity and generally greater activity against gram-negative bacilli of clinical importance. The increased spectrum includes the Enterobacteriaceae and Pseudomonas aeruginosa. Although the third-generation cephalosporins have some activity against P. aeruginosa, of those drugs now available in the United States, ceftazidime and cefoperazone are much more active than the others, and ceftazidime is more active than cefoperazone. The activity of the third-generation compounds against Acinetobacter species and other Pseudomonas species is limited. These compounds inhibit the growth of Hemophilus and Neisseria species (including beta-lactamase-producing isolates), nonenterococcal streptococci, and anaerobic gram-positive cocci. They also inhibit the growth of methicillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci but generally are not as active against these organisms as are the first-generation cephalosporins. They do not inhibit methicillin-resistant S. aureus. The activity of third-generation cephalosporins against anaerobes varies, but moxalactam and ceftizoxime are similar in activity to cefoxitin, a second-generation compound. The third-generation cephalosporins do not inhibit the growth of Listeria. A majority of organisms resistant to cephalothin and cefamandole (first- and second-generation cephalosporins) and to aminoglycosides are inhibited by third-generation cephalosporins.

Anti-Bacterial Agents↗

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↗