Interaction of Clindamycin and Gentamicin In Vitro

Abstract

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,ug 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 Mg/ml); for some strains combinations were synergistic. Sixty-two (94%) of 66 strains of Enterobacteriaceae and Pseudomonas aeruginosa were inhibited by 6.2 ,g 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 stiain of Proteus rettgeri were resistant to both clindamycin (minimal inhibitory concentration greater than 3.1 ,g/ml) and gentamicin (minimal inhibitory concentration greater than 6.2 ,g/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.

Effect of Clindamycin on Aminoglycoside Activity in a Murine Model of Invasive Escherichia coli Infection

“…These findings support the conclusion of Jawetz that "antagonism between antimicrobial drugs undoubtedly occurs .. , but with the exception of special situations, the effect is not of sufficient magnitude .to interfere with a successful outcome of treatment" (6) (3,12), or synergistic (13). Studies of antibiotic combinations in human and experimental infections are affected by additional immunological and pharmacological considerations, including phagocytic function (13), interval between infection and treatment (11), and drug distribution.…”

Susceptibilities of Gram-Negative Bacteria to Combinations of Antimicrobial Agents In Vitro

“…2). In the experimental conditions used control cultures of E. coli, containing no drug, showed detectable incorporation of radioactive amino acid beginning at 5 h and continuing to increase up to 30 h of incubation (Fig. 2).…”

“…The antibiotic combinations included gentamicin combined with either colimycin, cephalothin, tetracycline, ampicillin, or penicillin G; erythromycin com-bined with either cephalothin, ampicillin, or penicillin G; tetracycline combined with either colimycin, cephalothin, ampicillin, or penicillin G; and ampicillin or penicillin G combined with either clindamycin or colimycin. In these studies, synergy of two antimicrobial agents was defined as inhibition with a fourfold lower concentration of each antibiotic than the individual MIC of the antibiotic (5). Therefore, to screen for possible synergistic interaction between two antimicrobial agents each antimicrobial agent was added at a concentration one-fourth that of the MIC for the gram-negative organism to be tested.…”

Microdilution Transfer Plate Technique for Determining In Vitro Synergy of Antimicrobial Agents

“…The method of Kluge et al (6) requires diluting one drug in the microdilution plate, then adding the second drug (already diluted) to the wells containing the first drug. In two other methods described (3,5) Cultures and growth media. P. mirabilis (ICN 40) was used for the nalidixic acid-gentamicin combination; brain heart infusion (Difco) was the medium used for this example.…”

“…Several agar diffusion methods are also described (7,9,12). Microdilution methods have been described for determining synergy (3,5,6,15,16). Two methods (15,16) involve dilution of both drugs before pipetting each into the microdilution plate.…”