Roxithromycin bioassay procedures for human plasma, urine and milk specimens [corrected and issued with original paging in Eur J Clin Microbiol 1986 Dec;5(6)].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to A L Barry.
Explore the source record for details and available documents.
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.
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.
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.
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.
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.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Tests with 52 strains of Staphylococcus aureus compared ceforanide and cefonicid. Addition of 50% human serum to the test system reduced the bacteriostatic and bactericidal activities of cefonicid, but ceforanide was not affected as greatly.
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.
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.
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).
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.
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.
Tests with 10-micrograms amdinocillin disks were performed in parallel with agar dilution tests and three different ranges of inoculum density. A resistance breakpoint of less than or equal to 13 mm and an intermediate category of 14 to 16 mm are recommended. Susceptible strains provided zones greater than or equal to 17 mm in diameter, but many appeared to be resistant by the agar dilution methods if the inoculum exceeded 10(4) CFU per spot.
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.
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.
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.