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Biomedical subjects

L A Maher

Publications and source records attributed to L A Maher.

At least 19 recordsLinked to original sources

Development of an antimicrobial susceptibility testing method suitable for performance during space flight.

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.

Aerospace Medicine↗

Serotypes of respiratory isolates of Streptococcus pneumoniae compared with the capsular types included in the current pneumococcal vaccine.

The serotypes of 474 clinically significant Streptococcus pneumoniae respiratory isolates collected during a national surveillance study in 1987-1988 were compared to the capsular types included in the 23-valent pneumococcal polysaccharide vaccine licensed for use in the United States. Overall, 355 isolates (74.9%) belonged to types included in the current vaccine, while another 65 (13.7%) were types serologically related to vaccine types and likely to be protective by virtue of cross-reactivity. Relatively few isolates (9.1%) belonged to nonvaccine serotypes, and only 2.3% were nontypable. The mucoid serotype 3 was most frequent (13.1% of total), followed by 19F (9.3%), 23F (7.4%), 6B and 14 (5.7% each), and 4 and 6A (5.5% each). The most frequent type not included in the vaccine was type 16 (2.1% of all isolates). Thus, nearly 89% of respiratory isolates included in this study were encompassed within the antigenic spectrum of the currently marketed pneumococcal vaccine.

Adult↗

Activity of meropenem against antibiotic-resistant or infrequently encountered gram-negative bacilli.

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.

Drug Resistance, Microbial↗

Activity of a new carbapenem antibiotic, meropenem, against Haemophilus influenzae strains with beta-lactamase- and non-enzyme-mediated resistance to ampicillin.

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.

Ampicillin Resistance↗

Activity of clarithromycin and its principal human metabolite against Haemophilus influenzae.

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.

Clarithromycin↗

Quantitative antimicrobial susceptibility testing of Haemophilus influenzae and Streptococcus pneumoniae by using the E-test.

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.

Culture Media↗

Antimicrobial resistance among respiratory isolates of Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae in the United States.

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.

Adolescent↗

Use of Haemophilus test medium for broth microdilution antimicrobial susceptibility testing of Streptococcus pneumoniae.

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.

Anti-Bacterial Agents↗

Antimicrobial susceptibility testing of less commonly isolated Haemophilus species using Haemophilus test medium.

Haemophilus test medium (HTM) was developed recently for dilution and disk diffusion antimicrobial agent susceptibility testing of Haemophilus influenzae. The application of HTM to the testing of other, less frequently encountered Haemophilus species recovered from humans was evaluated in this study by using commercially prepared HTM (BBL Microbiology Systems, Cockeysville, Md.) in broth microdilution and agar disk diffusion susceptibility tests with 18 antimicrobial agents. A total of 93.3% of 90 isolates belonging to six Haemophilus species provided acceptable growth in HTM agar disk diffusion tests, while only 63.3% (57 of 90) provided acceptable growth in the broth microdilution tests. However, HTM agar dilution testing provided an alternative method for those strains (primarily H. haemolyticus) which failed to grow adequately in broth. Based on the latest National Committee for Clinical Laboratory Standards guidelines (standard M2-T4) for interpretation of HTM disk tests of H. influenzae, the overall very major, major, and minor errors for all 18 drugs and six species tested were 0.2, 0.7, and 3.4%, respectively. Thus, the use of HTM in agar or broth susceptibility tests can be recommended for testing the less commonly encountered Haemophilus species by using the same test conditions and interpretive guidelines developed for H. influenzae.

Culture Media↗

Antibacterial activity of the new glycopeptide antibiotic SKF104662.

The inhibitory activity of the new glycopeptide antibiotic SKF104662 was generally equivalent (+/- 1 concentration increment) to the activities of vancomycin, teicoplanin, and daptomycin against selected gram-positive bacteria. However, SKF104662 demonstrated greater activity against Staphylococcus epidermidis and S. haemolyticus than did teicoplanin and was more active than the other drugs against Clostridium difficile isolates. SKF104662 possessed bactericidal activity quite similar to that of vancomycin against selected isolates of Staphylococcus, Streptococcus, and Enterococcus species.

Anti-Bacterial Agents↗

Susceptibility of multiply resistant Haemophilus influenzae to newer antimicrobial agents.

One hundred and six isolates of Haemophilus influenzae from a national antimicrobial surveillance study demonstrated resistance to two or more of 10 primary antimicrobial agents by mechanisms other than or in addition to beta-lactamase. Of particular note were strains multiply resistant to ampicillin (by beta-lactamase production), chloramphenicol, trimethoprim/sulfamethoxazole, and tetracycline in various combinations. All of the aforementioned strains were shown to be highly susceptible to amoxicillin/clavulanate, the second generation cephalosporins cefuroxime and cefonicid, and the third generation cephalosporins cefotaxime, ceftizoxime, ceftriaxone, ceftazidime, moxalactam, and cefixime. However, 68 strains that demonstrated resistance or marginal susceptibility (MIC greater than or equal to 2 micrograms/ml) to ampicillin by mechanisms other than beta-lactamase, also demonstrated reduced susceptibility to amoxicillin/clavulanate (MICs up to 8 micrograms/ml) and the second generation cephalosporins (MICs up to 32 micrograms/ml). While the latter strains were susceptible to the third generation cephalosporins, MICs were often 10-fold higher than MICs of ampicillin susceptible isolates or of beta-lactamase producing isolates. All of the multiply antimicrobial-resistant strains were highly susceptible (MIC less than or equal to 0.25 micrograms/ml) to the two quinolones ciprofloxacin and pefloxacin.

Ampicillin Resistance↗

Influence of storage and susceptibility test conditions on stability and activity of LY163892 and four other cephalosporins.

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.

Bacteria↗