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Biomedical subjects

C Thornsberry

Publications and source records attributed to C Thornsberry.

At least 199 records · Page 11Linked to original sources

Antibacterial activity of fortimicin A compared with those of five other aminoglycosides, and factors affecting susceptibility tests.

Fortimicin A, a pseudodisaccharide aminoglycoside, was found to have broad-spectrum activity against most clinically important aerobic and facultatively anaerobic bacteria, except Pseudomonas aeruginosa, some other Pseudomonas species, and streptococci. It was comparable to amikacin in its level of activity (minimum inhibitory concentrations) and spectrum of activity (except for the lack of activity on P. aeruginosa). Fortimicin A was bactericidal and was affected by cations when tested against P. aeruginosa. Minimum inhibitory concentrations were affected by the inoculum used in the susceptibility test. The drug was resistant to most aminoglycoside-inactivating enzymes, but probably is not active against permeability mutants.

Aminoglycosides↗

Synergism, killing kinetics, and antimicrobial susceptibility of group A and B streptococci.

The susceptibility of 110 group A and 179 group B streptococci to 25 antimicrobics was tested by broth microdilution and agar disk diffusion tests. Representative strains were used in killing kinetics, penicillin-gentamicin synergy, and minimal bactericidal concentration tests. Group A streptococci were more susceptible than group B streptococci to 17 of the 25 antimicrobics tested. Group A and B streptococci were killed at the same rate if the amount of penicillin used was equivalent to their respective penicillin minimal inhibitory concentrations. Synergism was demonstrated for both group A and B streptococci when penicillin was used at concentrations equal to each respective minimal inhibitory concentration and subinhibitory concentration of gentamicin. This synergy could be demonstrated best using minimal bactericidal concentrations obtained by culturing 3- and 6-h cultures from the microdilution checkerboard tests rather than from 24-h subcultures. A greater synergistic effect was achieved by adding penicillin first and then adding gentamicin rather than in the reverse order, or simultaneously.

Anti-Bacterial Agents↗

Mezlocillin: tentative interpretive standards for disk diffusion susceptibility testing.

The susceptibility of 447 clinical bacterial isolates to mezlocillin and carbenicillin was tested by standardized agar disk diffusion and reference broth micro-dilution methods. Tentative interpretive criteria for disk susceptibility testing by using 75 micrograms mezlocillin disks are proposed: susceptible, greater than or equal to 16 mm; indeterminate, 13 to 15 mm; and resistant, less than or equal to 12 mm. These would be applicable to both Pseudomonas species and the Enterobacteriaceae, but not to Staphylococcus aureus. For S. aureus, the breakpoints for susceptible, greater than or equal to 29 mm, and resistant, less than or equal to 28 mm, hold for mezlocillin as well as for the other penicillinase-susceptible penicillins.

Bacteria↗

Cefsulodin: antibacterial activity and tentative interpretive zone standards for the disk susceptibility test.

Cefsulodin (SCE-129) is a cephalosporin with a spectrum of antibacterial activity largely limited to Pseudomonas aeruginosa and Staphylococcus aureus. Cefsulodin was compared with carbenicillin, ticarcillin, mezlocillin, and piperacillin against 779 nonenteric gram-negative bacilli and staphylococci collected from five geographically separate institutions. Against P. aeruginosa, cefsulodin was somewhat more active than piperacillin and much more active than other penicillins. In addition, cefsulodin was active against penicillinase-producing strains of S. aureus. Collaborative efforts in three laboratories led to the following tentative zone size breakpoints for 30-micrograms cefsulodin disks: susceptible greater than or equal to 18 mm (minimal inhibitory concentration) [MIC] less than or equal to 16 micrograms/ml) and resistant less than or equal to 14 mm (MIC greater than or equal to 64 micrograms/ml). These zone standards are still tentative since the dosage schedule has not yet been defined and sufficient clinical experience has not yet been gathered to support the validity of these MIC breakpoints.

Acinetobacter↗

Cefmenoxime (SCE-1365), a new cephalosporin: in vitro activity, comparison with other antimicrobial agents, beta-lactamase stability, and disk diffusion testing with tentative interpretive criteria.

The in vitro activity of cefmenoxime (SCE-1365) was evaluated in a multiphased collaborative investigation. Over 7,500 consecutive clinical isolates were tested in five laboratories, and greater than 90% of the following organisms were inhibited by cefmenoxime at the following concentrations: Enterobacteriaceae and non-enterococcal streptococci, </=0.125 mug/ml; Staphylococcus aureus, </=2.0 mug/ml; and nonfermenting gram-negative bacilli and Bacteroides fragilis group, </=32 mug/ml. Both beta-lactamase-producing and -nonproducing Haemophilus influenzae and Neisseria gonorrhoeae were inhibited by cefmenoxime at </=0.03 mug/ml. The spectrum of cefmenoxime was similar to that of other, newer cephalosporins, particularly cefotaxime. A pronounced inoculum effect was found with some species upon increasing inocula from 10(5) to 10(7) colony-forming units per ml, resulting in an approximate eightfold increase in minimum inhibitory concentrations. Cefmenoxime was bactericidal when tested with inocula of 10(5) colonyforming units per ml, and mean differences between the minimum inhibitory concentration and the minimum lethal concentration were less than one log(2) dilution. No significant hydrolysis of cefmenoxime by five different beta-lactamases was detectable, and cefmenoxime exhibited marked inhibition of type I beta-lactamases. Regression and error rate-bounded analyses of results of disk diffusion and reference broth microdilution susceptibility tests were performed on 421 bacterial isolates, and the following tentative zone size breakpoints are proposed: >/=22 mm, susceptible; </=14 mm, resistant; and 15 to 21 mm, moderately susceptible (indeterminate). These data and cross-resistance studies with other newer cephalosporins indicate marked similarity of in vitro activity within this group of drugs, particularly between cefmenoxime, moxalactam, and cefotaxime. Any one of these could serve as the representative for the disk diffusion testing of this group of drugs if comparable minimum inhibitory concentration breakpoints were used for each drug.

Bacteria↗

In vitro antimicrobial activity evaluation of cefodizime (HR221), a new semisynthetic cephalosporin.

Cefodizime (HR221) is a new alpha-methoxyimino cephalosporin developed by Hoechst-Roussel with a reported serum half-life of over 2 h. In vitro susceptibility studies showed that the cefodizime spectrum includes all those Enterobacteriaceae, staphylococci, Streptococcus spp., Haemophilus spp., and Neisseria spp. normally susceptible to cefotaxime (HR756) or ceftizoxime (FK749) or both. Cefodizime was less active (two- to eightfold) than cefotaxime or ceftizoxime against some enteric species, but was the most potent drug against some strains of Morganella spp. and Proteus vulgaris. Enterococci, methicillin-resistant Staphylococcus aureus, and most Pseudomonas spp. were resistant to cefodizime (median minimum inhibitory concentrations, greater than or equal to 64 microgram/ml). Acinetobacter spp. and Pseudomonas aeruginosa strains required cefodizime concentrations of 32 microgram/ml to inhibit 50% of tested strains. Cefodizime was very stable to hydrolysis by Richmond-Sykes type I, II, III, and IV beta-lactamases, as well as the enzyme derived from Bacillus cereus. The reference PADAC and nitrocefin substrate hydrolysis by a type I beta-lactamase was markedly inhibited (greater than 80%) by cefodizime at concentrations 0.4 to 4% of substrate concentration. Cefodizime was active against 43% of bacteria which were resistant to cephalothin and cefamandole and against 58% of those resistant to aminoglycosides.

Bacteria↗

Evaluation of the Sceptor microdilution antibiotic susceptibility testing system: a collaborative investigation.

A multiwell, dried antimicrobial agent susceptibility test system, Sceptor (BBL Microbiology Systems, Cockeysville, Md.), was tested. The system was compared directly with a reference microdilution method by using two collections of stock cultures and 305 fresh clinical isolates. Sceptor was found to be in agreement (+/- log2 dilution) with the reference microdilution method in 96.9 to 98.3% of 9,840 minimal inhibitory concentration determinations performed on stock strains and 95.0% of 7,308 minimal inhibitory concentrations obtained from the clinical isolates. The intralaboratory and interlaboratory reproducibility on stock strains was 97.6 and 97.2%, respectively. The intralaboratory reproducibility for the clinical isolates was 96.9%. Sceptor accurately categorized representative challenge strains of methicillin-resistant staphylococci, beta-lactamase-producing bacteria, organisms producing other antimicrobial agent-inactivating enzymes, and permeability mutants as resistant. Only 0.2% very major errors (false-sensitive minimal inhibitory concentrations by Sceptor) were identified among the clinical isolate test results, the majority being clinically insignificant. The product is accurate and reliable, has a long shelf life, and seems applicable for routine use in clinical laboratories.

Anti-Bacterial Agents↗

Gentamicin and amikacin disk susceptibility tests with Pseudomonas aeruginosa: definition of minimal inhibitory concentration correlates for susceptible and resistant categories.

With currently recommended disk susceptibility tests, minimal inhibitory concentration correlates for amikacin were greater than 16 micrograms/ml for resistance and less than or equal to 12 micrograms/ml (not less than or equal to 8 micrograms/ml) for susceptibility. For gentamicin, they were greater than 8 micrograms/ml for resistance and less than or equal to 6 micrograms/ml (not less than or equal to 4 micrograms/ml) for susceptibility. Minor discrepancies between disk tests and minimal inhibitory concentration determinations will occur if only doubling dilutions of drug are used for measuring minimal inhibitory concentration values.

Amikacin↗

Quality control limits for ampicillin, carbenicillin, mezlocillin, and piperacillin disk diffusion susceptibility tests: a collaborative study.

A multilaboratory in vitro study was carried out to determine disk diffusion susceptibility testing quality control limits for two new semisynthetic penicillins, mezlocillin and piperacillin. Existing limits for carbenicillin and ampicillin were reevaluated. Multiple tests (which followed standards set by the National Committee for Clinical Laboratory Standards ASM-2 revised) were performed in nine laboratories by different technologists using disks and Mueller-Hinton agar from different manufacturers. Clinically significant differences between disks produced by different manufacturers were not noted. Inhibitory zone diameter measurements from all laboratories were analyzed, and upper and lower control limits were established by using the overall median +/-0.5 the median range of the individual laboratory measurements as determining parameters. Close agreement of the data in this study with the results of national proficiency testing and quality control programs for ampicillin and carbenicillin supports the validity of our approach to making initial recommendations for quality control guidelines for new antimicrobial agents.

Ampicillin↗

Cefoperazone: spectrum of antibacterial activity and disc diffusion testing.

Cefoperazone is a new cephalosporin with a very wide spectrum of antibacterial activity, including Enterobacteriaceae, Pseudomonas aeruginosa, staphylococci, streptococci (other than serological group D strains), Neisseria and Haemophilus species (including beta-lactamase positive strains) and some anaerobes. On testing more than 8700 clinical isolates, approximately 93% were inhibited by 16 micrograms/ml of cefoperazone, 95% by 32 micrograms/ml and 98% by 64 micrograms/ml. The drug is less active on Acinetobacter and group D streptococci. We recommend that a disc containing 75 micrograms of cefoperazone be used in the diffusion test with 'breakpoints' of less than or equal to 14 mm for resistant, 15-17 mm for intermediate, and greater than or equal to 18 mm for susceptible bacteria.

Bacteria↗

The microbiology and therapy of acute pelvic inflammatory disease in hospitalized patients.

We examined microbial isolates from the endocervical and peritoneal cavity of 30 women hospitalized with acute PID. Patients were randomly assigned to one of two antibiotic regimens: amoxicillin, 6 gm by mouth every 24 hours, or aqueous penicillin G, 30 million units and gentamicin, 180 to 240 mg intravenously every 24 hours. We measured response by quantifying physical examination findings. Neisseria gonorrhoeae was isolated from the cervix of 24 patients (80%) and from the peritoneal cavity of 10 (33%). Other peritoneal isolates included Enterobacteriaceae in five patients, Ureaplasma urealyticum in five, Mycoplasma hominis in six, and Chlamydia trachomatis in three. Bacteroides melaninogenicus, the most frequent anaerobe, was isolated in 11 cases. Bacteroides fragillis was not isolated from any specimen. The cure rates were the same for both regimens: three patients failed on each. Four women required total abdominal hysterectomy and unilateral or bilateral salpingo-oophorectomy.

Adolescent↗

Sulfamethoxazole-trimethoprim synergism for Neisseria gonorrhoeae.

Sulfamethoxazole and trimethoprim are synergistic against many bacteria in sulfamethoxazole/trimethoprim concentrations of 20:1, but single-dose therapy of gonorrhea with the combination is disappointing. We used agar dilution techniques to determine minimal inhibitory concentrations of sulfamethoxazole and trimethoprim for 168 gonococci isolated from men with acute urethritis in Atlanta, Ga. The geometric mean minimal inhibitory concentrations were 5.6 microgram of sulfamethoxazole per ml and 24.3 microgram of trimethoprim per ml, a ratio of 1:4. The concentration of sulfamethoxazole inhibiting 50% of gonococcal strains dropped only from 4.7 microgram/ml to 2.9 microgram/ml with the addition of a 1/20 dilution of trimethoprim. We studied synergism with various ratios of sulfamethoxazole to trimethoprim against 20 random strains. A ratio of 1:1 was always synergistic and was the most synergistic ratio for 15 strains, whereas the 19:1 ratio was never the most syngergistic. The 19:1 ratio failed to show synergism against seven strains, but showed antagonism at this ratio with five of these seven. The sulfamethoxazole/trimethoprim ratio of 19:1 usually achieved in serum after oral administration is minimally syngergistic and is sometimes antagonistic for gonococci.

Drug Synergism↗

In vitro antimicrobial activity of cefoperazone, cefotaxime, moxalactam (LY127935), azlocillin, mezlocillin, and other beta-lactam antibiotics against Neisseria gonorrhoeae and Haemophilus influenzae, including beta-lactamase-producing strains.

Minimum inhibitory concentrations and agar disk diffusion tests were determined on clinical isolates of beta-lactamase-positive and beta-lactamase-negative Neisseria gonorrhoeae and Haemophilus influenzae with the newer beta-lactam antibiotics, cefoperazone, cefotaxime, moxalactam (LY127935), azlocillin, mezlocillin, and piperacillin, and with seven older beta-lactam antibiotics. All the drugs were active against beta-lactamase-negative strains of N. gonorrhoeae and H. influenzae. The drug most active against beta-lactamase-positive N. gonorrhoeae was cefotaxime, followed closely by cefoperazone, moxalactam, piperacillin, and mezlocillin. The drugs most active against beta-lactamase-positive strains of H. influenzae were cefotaxime, moxalactam, cefoperazone, and cefamandole.

Azlocillin↗

Rapid determination of minimum inhibitory concentrations of antimicrobial agents by the Autobac method: a collaborative study.

Four laboratories collaborated in an evaluation of the Autobac minimum inhibitory concentration (MIC) test system. The MICs of ranges of MICs determined in this system were compared with the MICs obtained with a microtube modification of the International Collaborative Study broth dilution technique. A total of 1,260 strains, mostly recent clinical isolates and including multiresistant strains, were tested by the four laboratories against 10 antibiotics; 9,360 separate MIC determinations were made. There was an overall agreement of approximately 95% between the two methods. Levels of agreement below 80% were obtained with only 4 of the 104 antibiotic-species pairs. In only one of the four major organism groups (staphylococci and penicillin G) was agreement less than 85%. There was a symmetrical distribution of MIC differences between the two methods. Tests with 56 selected strains were performed in each of four laboratories in an inter- and intra-laboratory reproducibility study. Both methods showed a standard deviation (both inter- and intra-laboratory) of one-half of a twofold dilution step. The Autobac method was actually less variable than the reference method and had equivalent reproducibility. This was particularly true when the Autobac system was operated so that the results generated permitted calculations of MICs via regression analysis.

Anti-Bacterial Agents↗

Susceptibility of Clostridium botulinum to thirteen antimicrobial agents.

A total of 224 strains of Clostridium botulinum (including isolates from 14 patients with infant botulism and 4 with wound botulism) and 15 strains of C. sporogenes were tested by agar dilution for susceptibility to tetracycline, metronidazole, erythromycin, penicillin, rifampin, chloramphenicol, clindamycin, cephalothin, cefoxitin, vancomycin, sulfamethoxazole-trimethoprim, nalidixic acid, and gentamicin. At least 90% of the C. botulinum strains tested (except for nonproteolytic strains of toxin type F with penicillin) were susceptible to all drugs except sulfamethoxazole-trimethoprim, nalidixic acid, and gentamicin. Minimal inhibitory concentrations for strains from patients with infant and wound botulism were similar to those for other C. botulinum strains.

Anti-Bacterial Agents↗

Cefotaxime: in vitro activity and tentative interpretive standards for disk susceptibility testing.

Tested against 9,412 recent clinical isolates, cefotaxime exhibited 8 to 64 times greater activity against the Enterobacteriaceae than did cephalothin and two to four times greater activity against Pseudomonas aeruginosa, but only one-half to one-eighth the activity of cephalothin against staphylococci. Using 420 different clinical isolates, but with comparable minimal inhibitory concentration (MIC) distributions, disk diffusion-MIC regression analyses were performed, using 5- and 30-micrograms cefotaxime disks. Cefotaxime MIC susceptible and resistant breakpoints of less than or equal to 8 and greater than 32 micrograms/ml are tentatively proposed. Based on the MIC breakpoints, the data showed the best discrimination among the three susceptibility categories (susceptible, indeterminate, and resistant) when the 30-micrograms cefotaxime disk was used. The zone diameter breakpoints as determined by the error rate-bounded method and regression analysis were greater than or equal to 23 mm for susceptible, 15 to 22 mm for indeterminate, and less than or equal to 14 mm for resistant.

Bacteria↗

Comparison of in vitro activity of Sch 21420, a gentamicin B derivative, with those of amikacin, gentamicin, netilmicin, sisomicin, and tobramycin.

Sch 21420 is a new aminoglycoside synthesized from gentamicin B. Susceptibility tests with Sch 21420, amikacin, gentamicin, netilmicin, sisomicin, and tobramycin were performed on a variety of bacterial species including 44 with known mechanisms of resistance to aminoglycosides. Sch 21420 and amikacin had similar effects on all except Haemophilus influenzae and Neisseria species, which were more susceptible to amikacin. Except with some strains of Serratia marcescens, the drugs used were bactericidal. Sch 21420 and amikacin were more stable than the other four aminoglycosides in the presence of the inactivating enzymes produced by some strains. Strains which were very resistant to Sch 21420 and emikacin either were permeability mutants or produced AAC (6')-I inactivating enzyme. The effect of cations on the susceptibilities of these strains to Sch 21420 and amikacin was seen mostly with Pseudomonas aeruginosa and to Sch 21420 with Acinetobacter. Cations did not affect the susceptibilities of other Pseudomonas species, Enterobacteriaceae, Staphylococcus aureus, or Streptococcus faecalis to Sch 21420 or amikacin.

Amikacin↗