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Biomedical subjects

R L Perkins

Publications and source records attributed to R L Perkins.

At least 37 records · Page 2Linked to original sources

In vitro activity of gentamicin and minocycline alone and in combination against bacteria associated with intra-abdominal sepsis.

The minimal inhibitory concentrations of gentamicin and minocycline alone and in combination were determined by a broth microdilution method for 100 aerobic, facultative, and anaerobic isolates representative of pathogens recovered from patients with intra-abdominal sepsis. Gentamicin inhibited all strains of Klebsiella, Enterobacter, and Pseudomonas aeruginosa in concentrations of 0.4 to 3.1 mug/ml and all strains of Escherichia coli and Proteus mirabilis in concentrations of 0.8 to 12.5 mug/ml. Whereas minocycline did not consistently inhibit these organisms in concentrations of 1.6 mug or less/ml, it did act synergistically with gentamicin against 43% of the Enterobacteriaceae tested in clinically achievable concentrations; significant synergy was most common with E. coli (60%). Minocycline inhibited 62% of Bacteroides fragilis, 71% of Clostridium, 40% of anaerobic cocci, and 40% of enterococci tested in concentrations of 1.6 mug or less/ml. Whereas gentamicin rarely inhibited these organisms in concentrations of 6.2 mug or less/ml, it did act synergistically with minocycline against 20% of B. fragilis, 67% of Clostridium, 22% of anaerobic cocci, and 22% of enterococci (which had minimal inhibitory concentrations of minocycline within the range tested) at clinically achievable concentrations. Although only four (13%) of the 30 isolates resistant to both gentamicin and minocycline alone were inhibited by clinically achievable concentrations of the combination, the observed synergy, particularly against strains of E. coli, was considered to be of potential clinical usefulness. Antagonism between gentamicin and minocycline was not observed at the concentrations tested.

Abdomen↗

Treponema pallidum infection in subcutaneous polyethylene chambers in rabbits.

Male New Zealand white rabbits with subcutaneous polyethylene chambers in place for at least 3 months were inoculated by one of the following three methods: (i) "intra-chamber" (IC) inoculation with "normal" chamber fluid: (ii) intratesticular inoculation with Treponema pallidum; or (iii) IC inoculation with T. pallidum. Rabbits given dexamethasone only, oxisuran only, both drugs, or no drug were observed serially after inoculation. T. pallidum survived and temporarily multiplied to significant numbers within subucutaneous chambers after IC inoculation in rabbits given dexamethasone. In rabbits not treated with dexamethasone, T. pallidum counts in chamber fluid decreased rapidly and remained at low levels for 30 days after IC inoculation. Oxisuran appeared to have little or no effect on T. pallidum multiplication. All rabbits studied had a nonreactive serum and chamber fluid serological test for syphilis before inoculation. All rabbits inoculated with T. pallidum eventually developed reactive serum and chamber fluid serological tests. The IC route of inoculation was associated with a delay in the development of serum serological reactivity and with earlier chamber fluid reactivity as compared with the intratesticular route of inoculation. An immediate but transent influx of polymorphonuclear leukocytes was associated with IC inoculation of T. pallidum. Chamber fluid total protein content declined very slightly in all groups of rabbits during the month after inoculations. Successful cultivation of T. pallidum in an in vivo setting suggests that this animal model may be useful in further studies of the biology of the organism of the pathogenesis, immunology, and treatment of syphilis.

Animals↗

Microdilution technique for antimicrobial susceptibility testing of anaerobic bacteria.

A microdilution technique using commercially available media and materials was developed and used to determine the minimal inhibitory concentrations (MICs) of clindamycin, chloramphenicol, tetracycline, minocycline, ampicillin, carbenicillin, cephalothin, and gentamicin for 101 anaerobic isolates. Representative strains of Bacteroides, Clostridium, Fusobacterium, Peptococcus, and Peptostreptococcus were tested. The use of Schaedler broth at pH 7.2, an inoculum of 10(5) to 10(7) colony-forming units per ml, and incubation at 35 C in an anaerobic glove box with an atmosphere of 80% nitrogen, 10% hydrogen, and 10% carbon dioxide resulted in good growth and easily interpretable results. After 48 h of incubation, 97% of strains tested were inhibited by 3.1 mug or less of clindamycin per ml and 98% were inhibited by 12.5 mug or less of chloramphenicol per ml. Tetracycline and minocycline inhibited 81 and 88% of strains tested in concentrations of 1.6 mug or less per ml and 1.6 mug or less per ml, respectively. Ampicillin inhibited all strains other than B. fragilis in concentrations of 3.1 mug or less per ml. Excluding certain strains of Bacteroides and Clostridium, carbenicillin in concentrations of 12.5 mug or less per ml and cephalothin in concentrations of 6.2 mug or less per ml inhibited all strains tested. Gentamicin was inactive although some strains of anaerobic cocci and Bacteroides were inhibited by 3.1 mug or less per ml. After 18 to 24 h of incubation, eight of the 101 strains had not grown sufficiently for MICs to be determined; for the 93 strains which had grown sufficiently, 93% of 744 MICs were the same or one concentration lower than the 48-h MICs.

Anaerobiosis↗

Fluid and penicillin G dynamics in polyethylene chambers implanted subcutaneously in rabbits.

Chemical and cellular characteristics of fluid within subcutaneously implanted polyethylene chambers in rabbits were studied over a 3-month period. The fluid attained a relatively stable protein and cellular composition which was consistent with a mononuclear exudate. After a single dose of intramuscular penicillin G, the antibacterial activity of chamber fluid was found to be dynamic and similar to the serum antibacterial activity. This animal model may be useful for in vivo studies of the interaction of microorganisms with antimicrobial agents.

Animals↗

Cephacetrile: clinical evaluation in 27 patients.

Cephacetrile, a new derivative of 7-aminocephalosporanic acid, was evaluated in 27 patients. Soft tissue infections due primarily to gram-positive cocci were treated in 16 patients; 12 had bacteriological and clinical cure, and 4 improved but the lesions resolved incompletely or cultures remained positive. Seven of eight patients with respiratory tract infections were cured, including three with pneumococcal pneumonia; the eighth proved to have a noninfectious process and failed to respond. Two patients with acute urinary tract infections due to Escherichia coli had prompt clinical and bacteriological improvement, but follow-up was incomplete. One patient with sepsis due to Staphylococcus aureus expired. Laboratory abnormalities observed during cephacetrile therapy included mild eosinophilia in four patients, thrombocytosis in nine, direct Coombs' test positivity in four, and an elevated serum glutamic pyruvic transaminase in eight patients. No evidence of nephrotoxicity was detected. Severe superinfection due to Enterobacter species was observed in one patient. Mean peak serum concentrations of cephacetrile were 22, 69, and 104 mug/ml after 1 g intramuscularly, 1 g intravenously, and 1.5 g intravenously, respectively. Thus, in early studies cephacetrile was efficacious for selected bacterial infections, but determination of its comparative value within the cephalosporin group of antibiotics requires further clinical investigation.

Bacterial Infections↗

Surface manifestations of antibiotic-induced alterations in protein synthesis in bacterial cells.

Scanning electron microscopy of changes in bacteria induced by antimicrobial agents which interfere with cell wall synthesis revealed morphological alterations which correlated well with their mechanism of action. The present studies were undertaken to investigate the presence and characteristics of alterations in surface morphology resulting from the action of antibiotics known to interfere with intracellular protein synthesis. Strains of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa were exposed to kanamycin, chloramphenicol, and tobramycin during various phases of bacterial growth. A spectrum of morphological changes related to concentration of drug and duration of exposure was observed which was similar to those induced by penicillin or cephalothin. Cells were also exposed to sulfamethoxazole with similar results. The morphological abnormalities observed may be surface reflections of specific abnormalities of intracellular protein synthesis or may represent a final common pathway of druAg-induced injury at many sites within or on bacterial cells.

Anti-Bacterial Agents↗