Clindamycin and gentamicin for aerobic and anaerobic sepsis.

Thirty-eight adult patients with serious pleuropulmonary, soft-tissue, bone, and intra-abdominal infections caused by combinations of aerobic, facultative, and anaerobic bacteria were treated with parenterally given clindamycin phosphate and gentamicin sulfate and surgery when appropriate. Nine had associated bacteremia. In 29, infections failed to respond to other therapeutic regimens, which included penicillins, cephalosporins, aminoglycosides, and chloramphenicol. Results with clindamycin and gentamicin were excellent and were attributed primarily to the activity of clindamycin against anaerobes, particularly Bacteroides fragilis. Serum concentrations of clindamycin surpassed by manyfold the minimal inhibitory concentrations (MICs) for anaerobes. Serum concentrations of gentamicin did not consistently surpass the MICs for Enterobacteriaceae and Pseudomonas aeruginosa, although those organisms were consistently gentamicinsusceptible by disk diffusion susceptibility tests. Persistent colonization with Enterobacteriaceae, P aeruginosa, enterococci, or Candida were common, and occasionally they were significant in prolonging the clinical courses of patients with extensive infections.

Simplified method for antimicrobial susceptibility testing of anaerobic bacteria.

A simple, abbreviated broth dilution test (tube test) utilizing a commercially available medium and inexpensive disposable materials, and which could be performed entirely in room air, was developed and used to test the susceptibility of 100 strains of anaerobic bacteria to clindamycin, chloramphenicol, ampicillin, and tetracycline. Results are reported in categories of susceptibility: susceptible to concentrations surpassed in vivo with usual dosage, susceptible to concentrations surpassed in vivo with high dosage, and resistant to concentrations achievable in vivo. Results are compared to minimal inhibitory concentrations which were determined simultaneously by using a microdilution method in an anaerobic glove box. Twenty strains of Bacteroides fragilis, 10 strains of Fusobacterium, 20 strains of Clostridium, 10 strains of gram-positive non-sporeforming bacilli, and 30 strains of cocci grew to visible turbidity within 1 day of incubation. Of the 360 antibiotic-organism combinations tested, 98% were in a susceptibility category that corresponded (within one concentration) to the actual minimal inhibitory concentration as determined by the microdilution method. After 2 days of incubation, growth was more abundant, but results often indicated inappropriate degrees of resistance. Variation in inoculum size had little effect on results. Ten strains of B. melaninogenicus did not grow enough for susceptibility to be categorized accurately. The tube test could be used in any clinical microbiology laboratory for a limited number of susceptibility tests on anaerobic bacteria other than B. melaninogenicus without preparation of special media or purchase of special equipment.

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.

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.

Interaction of clindamycin and gentamicin in vitro.

The minimal inhibitory concentrations of clindamycin and gentamicin alone and in combinations were determined by a microdilution method for 163 aerobic, facultative, and anaerobic clinical isolates. All 77 strains of Staphylococcus aureus, Diplococcus pneumoniae, Streptococcus pyogenes, and anaerobic bacteria (except for three strains of Clostridium) were inhibited by 1.6 mug or less of clindamycin per ml. Gentamicin did not interfere with the activity of clindamycin within the range of concentrations tested (0.1 to 100 mug/ml); for some strains combinations were synergistic. Sixty-two (94%) of 66 strains of Enterobacteriaceae and Pseudomonas aeruginosa were inhibited by 6.2 mug or less of gentamicin per ml. Combinations of clindamycin and gentamicin were indifferent for 29 strains and synergistic for 33 strains. All 20 strains of enterococcus, three strains of Clostridium, three strains of Escherichia coli, and one strain of Proteus rettgeri were resistant to both clindamycin (minimal inhibitory concentration greater than 3.1 mug/ml) and gentamicin (minimal inhibitory concentration greater than 6.2 mug/ml). Combinations of clindamycin and gentamicin were indifferent for 16 and synergistic for 11 of the resistant strains. Except for clindamycin-sensitive isolates, synergy was usually observed only at concentrations of one or both drugs which are not readily obtainable in vivo. Antagonism was never observed.