Disk diffusion interpretive zone size criteria for use with Haemophilus test medium are proposed for five extended-spectrum cephalosporins. With cefuroxime, zones greater than or equal to 24 mm in diameter indicated susceptibility, while zones less than or equal to 20 mm implied resistance. With cefotaxime, ceftizoxime, and ceftriaxone, a single susceptible-zone size, greater than or equal to 26 mm, is proposed.
A new carbacephem analog of cefaclor, LY163892, was examined along with four other cephalosporins for chemical stability and for antibacterial activity under a variety of susceptibility test conditions. LY163892 was found to be markedly more stable than cefaclor during storage at 4 and 35 degrees C in human serum, human urine, and various bacteriological media. Under these conditions, LY163892 demonstrated stability equal or superior to the stabilities of cephalexin, cephalothin, and cefuroxime. Broth and agar dilution susceptibility tests did not reveal significant differences in LY163892 activity in a variety of test media, although LY163892 MICs were somewhat higher in Mueller-Hinton chocolate agar or Trypticase soy broth (BBL Microbiology Systems, Cockeysville, Md.) than in other media. The activity of LY163892 against selected pathogens was only slightly influenced by the increased or decreased pH of the test medium, in a manner similar to that of the other cephalosporins tested. Thus, the carbacephem structure of LY163892 appears to represent a more stable cephalosporin than cefaclor, while retaining a similar antimicrobial spectrum.
Meropenem was compared in vitro with imipenem as well as with several other contemporary beta-lactams, ciprofloxacin, and gentamicin against a group of highly antibiotic resistant members of the family Enterobacteriaceae and a collection of oxidase-positive and/or glucose-nonfermentative gram-negative bacilli. In this study, meropenem was more active than imipenem against isolates of Enterobacter, Klebsiella, Morganella, Providencia, Alcaligenes, Aeromonas, and Pasteurella.
A national surveillance study was conducted to determine trends in antimicrobial resistance patterns among three common causes of community-acquired respiratory tract infections. Fifteen participating U.S. medical centers submitted clinically significant isolates of Haemophilus influenzae, Moraxella (Branhamella) catarrhalis, and Streptococcus pneumoniae to two central laboratories for testing with a group of 12 antimicrobial agents. The majority of isolates were recovered from adult males greater than 50 years old. Overall, 84.1% of 378 M. catarrhalis and 16.5% of 564 H. influenzae (29.5% of type b strains; 15.0% of non-type b strains) produced beta-lactamase and were thus resistant to penicillin, ampicillin, and amoxicillin. Resistance in H. influenzae to other agents was 2.1% to tetracycline, 0.7% to trimethoprim-sulfamethoxazole, 1.1% to cefaclor, and 0.2% to cefuroxime and amoxicillin-clavulanate, while the M. catarrhalis isolates yielded very low MICs of these latter drugs. As demonstrated in prior studies, erythromycin showed little activity against H. influenzae. Of 487 S. pneumoniae isolates, 1 (0.2%) was penicillin resistant, while 3.8% were relatively resistant to penicillin, 4.5% were resistant to trimethoprim-sulfamethoxazole, 2.3% were resistant to tetracycline, 1.2% were resistant to chloramphenicol, and 0.2% were resistant to erythromycin. Overall, the lowest resistance rates for these common bacterial respiratory pathogens were noted with amoxicillin-clavulanate, cefuroxime, and cefaclor.
Clarithromycin is a new macrolide antibiotic which forms a microbiologically active principal in vivo metabolite, 14-OH-clarithromycin. The in vitro activities of clarithromycin and its metabolite were examined separately and in pharmacokinetically relevant fixed combinations of 4:1 and 2:1 against a group of 50 Haemophilus influenzae isolates. Broth microdilution susceptibility tests indicated that clarithromycin was less active than erythromycin against all but highly erythromycin-susceptible strains, while 14-OH-clarithromycin was generally more active than either antibiotic. An enhancement in activity against the majority of strains was demonstrated when clarithromycin and its metabolite were tested in combination.
Very little is known regarding the effects of the microgravity environment of space flight upon the action of antimicrobial agents on bacterial pathogens. This study was undertaken to develop a simple method for conducting antibacterial susceptibility tests during a space shuttle mission. Specially prepared susceptibility test research cards (bioMérieux Vitek, Hazelwood, Mo.) were designed to include 6 to 11 serial twofold dilutions of 14 antimicrobial agents, including penicillins, cephalosporins, a beta-lactamase inhibitor, vancomycin, erythromycin, tetracycline, gentamicin, ciprofloxacin, and trimethoprim-sulfamethoxazole. MICs of the drugs were determined by visual reading of color end points in the Vitek research cards made possible by incorporation of a colorimetric growth indicator (alamarBlue; Accumed International, Westlake, Ohio). This study has demonstrated reproducible susceptibility results in the testing of isolates of Staphylococcus aureus, group A Streptococcus species, Enterococcus faecalis, Escherichia coli (beta-lactamase-positive and -negative strains), Klebsiella pneumoniae, Enterobacter cloacae, and Pseudomonas aeruginosa. In some instances, the MICs were comparable to those determined by a standard broth microdilution method, while in some cases the unique test media and format yielded slightly different values that were themselves reproducible. The proposed in-flight experiment will include inoculation of the Vitek cards on the ground prior to launch of the space shuttle, storage of inoculated cards at refrigeration temperature aboard the space shuttle until experiment initiation, and then incubation of the cards for 18 to 48 h prior to visual interpretation of MICs by the mission's astronauts. Ground-based studies have shown reproducible MICs following storage of inoculated cards for 7 days at 4 to 8 degrees C to accommodate the mission's time schedule and the astronaut's activities. For comparison, ground-based control (normal gravity) MIC values will be generated by simultaneous inoculation and incubation of a second set of test cards in a laboratory at the launch site. This procedure can provide for a safe and compact experiment that should yield new information on the effects of microgravity on the biological activities of various classes of antibiotics.
A recently described medium (Haemophilus test medium [HTM]) for antimicrobial susceptibility testing of Haemophilus influenzae was evaluated in this study for broth microdilution testing of Streptococcus pneumoniae. A total of 137 clinical isolates was tested against 11 antimicrobial agents, using Mueller-Hinton broth supplemented with 3% lysed horse blood in parallel with HTM. Inocula of 5 X 10(5) CFU/ml and incubation for 20 to 24 h were used with both media. All isolates of S. pneumoniae produced acceptable growth in both media, and MICs determined in HTM agreed closely with those determined in lysed horse blood. Drugs which provided a MIC within 1 log2 concentration difference in both media included penicillin (100%), ampicillin (98.0%), amoxicillin-clavulanate (100%), ampicillin-sulbactam (100%), cephalexin (98.9%), cefaclor (96.8%), cefuroxime (99.0%), chloramphenicol (96.2%), tetracycline (96.2%), and erythromycin (100%). HTM MICs with trimethoprim-sulfamethoxazole were 1 to 2 log2 concentration increments higher in 92.0% of isolates than MICs determined in lysed horse blood. Based on the results of this study, HTM appears to represent a promising alternative medium for broth microdilution susceptibility testing of S. pneumoniae.
The E-test (PDM Epsilometer; AB Biodisk, Solna, Sweden) is an antimicrobial agent gradient-coated plastic test strip which allows MIC determinations on agar media. The test is performed in a manner similar to the agar disk diffusion procedure. A collection of Haemophilus influenzae and Streptococcus pneumoniae strains possessing various resistance mechanisms was used to evaluate the E-test method. H. influenzae strains were tested with both Haemophilus test medium (HTM) and PDM ASM II chocolate agar, while the S. pneumoniae strains were tested on Mueller-Hinton sheep blood agar. E-test MICs for a total of 10 antimicrobial agents were compared with broth microdilution MICs determined according to National Committee for Clinical Laboratory Standards methods. In general, E-test MICs for both species were quickly and easily interpreted and agreed within one log2 MIC increment in 89.8% of tests with H. influenzae and in 80.4% of pneumococcal tests. The majority of disagreements between the E-test and conventional MICs occurred with trimethoprim-sulfamethoxazole because of trailing and diffuse E-test MIC endpoints with both species. Ampicillin MICs for beta-lactamase-producing H. influenzae determined by the E-test differed at times from those determined by conventional testing because of the vagaries of interpreting colonies growing within the E-test inhibition ellipses. E-test penicillin MICs for pneumococci tended to be 1 to 2 log2 dilutions lower than those determined by using Mueller-Hinton broth supplemented with lysed horse blood. Nevertheless, strains of both species with documented resistance to the study drugs were detected by E-tests, i.e., 0.7% of the tests had very major errors with H. influenzae and 0.8% had very major errors with S. pneumoniae. Thus, the E-test represents a potential alternative method for antimicrobial susceptibility testing of these two fastidious bacterial species.
Meropenem was 8- to 32-fold more active (MIC for 90% of strains = 0.125 micrograms/ml) than imipenem against a collection of Haemophilus influenzae strains characterized as either susceptible to ampicillin or resistant to that agent by virtue of beta-lactamase or nonenzymatic mechanisms. MBCs and kinetic kill curve tests showed that meropenem (as well as imipenem, several cephalosporins, and amoxicillin-clavulanate) was bactericidal against all strains at or within four times the respective MICs. Thus, meropenem demonstrated greater inhibitory activity than imipenem and activity comparable to that of cefotaxime against these selected strains.
