Synergism between aminoglycosides and cephalosporins with antipseudomonal activity: interaction index and killing curve method

Abstract

Combinations of gentamicin with cefotaxime, moxalactam, and ceftazidime were tested against 43 bacterial strains, most of them blood isolates. With an interaction index of 0.5 as borderline, synergism was demonstrated against 30 to 40% of the strains by the fractional inhibitory concentration index and against 50 to 70% by the fractional bactericidal concentration index. The reproducibility of the index was within ±0.2 for two-thirds of 40 repetitive assays and within ±0.4 to 0.5 for all of these assays. Similar results were obtained when netilmicin was substituted for gentamicin. The killing curve system for studying antibiotic synergism was standardized to give results comparable to those obtained with the interaction index. This was achieved when one-half of a previously determined minimum bactericidal concentration was used for single drugs and the amount of antibiotic was at least halved again when drugs were used in combination. An initial bacterial concentration of 105 to 106 colony-forming units per ml is recommended. Given these conditions, synergism could be defined as a 2-log10 or more decrease in viable count given by both drugs together, as compared with the more active of the pair after 24 h. Prediction of killing curve results could then be obtained with the fractional bactericidal concentration index. When cephalosporins and gentamicin were combined from the start, the beta-lactam antibiotics were less susceptible to inactivation, as demonstrated in time-killing assays. If one of the antibiotics were added after 24 h, synergism was not demonstrable. The results indicate that the new cephalosporins may be advantageously combined with aminoglycosides.

In vitro susceptibility of Mycobacterium avium complex to the new fluoroquinolone sparfloxacin (CI-978; AT-4140) and comparison with ciprofloxacin

“…The FIC index is the sum of the FIC for each drug in combination, and the FBC index is the sum of the FBC of each drug in combination (3). Synergism was defined as an FIC or FBC index of c0.5 for combinations involving two drugs (3,11), and an FIC or FBC index of 0.75 for combinations of three drugs (11), based on the definition of Berenbaum (1). FIC and FBC indices of sparfloxacin in combination with ethambutol or rifampin or both are shown in Table 2.…”

“…The FIC was calculated as the MIC of drug in combination divided by the MIC of drug alone, and the FBC was calculated as the MBC(AFB) of drug in combination divided by the MBC(AFB) of drug alone (3). The FIC index is the sum of the FIC for each drug in combination, and the FBC index is the sum of the FBC of each drug in combination (3).…”

Antibacterial Interaction of Crude Methanol Extract of <i>Garcinia kola</i> Seed with Gatifloxacin

“…A recent study indicated that the ethanolic extract of G. kola seed did not affect the activity of some fluoroquinolone antibioticsnorfloxacin and pefloxacin -in vitro 12 . It was demonstrated, however, in a recent in vivo study that the interaction between an aqueous seed extract of G. kola and ciprofloxacin hydrochloride against Staphylococcus aureus showed a biphasic effect of an antagonistic effect at an earlier stage and a potentiative (additive) effect at a later stage 10 .…”

“…A probable explanation of this enhanced activity in combination is that the gatifloxacin and the antimicrobial principles in methanol extract of G. kola seed may possibly have different mechanisms of action or may be inhibiting two different steps in the same biosynthetic pathway of the organism resulting in an overall synergy at certain combinations. Gatifloxacin is known to act by preventing bacterial replication through inhibition of DNA gyrase while the mechanism of action of G. kola seed extract is yet to be completely elucidated 10 . However, it has been noted that two antimicrobial agents may interact antagonistically if one is bacteriostatic and the other is bactericidal 11 .…”

Antibiotic Resistance and the Prospects of Medicinal Plants in the Treatment of Salmonellosis

“…Although the introduction of new compounds into clinical use has helped to curtail the spread of resistant pathogens, resistance to such new drugs, has developed in some cases. It has been observed by several studies that antibiotic combinations can have synergistic benefits and interactions between existing antibiotics (Bayer et al, 1980;Hallander et al, 1982;Hooton et al, 1984;Cottagnoud et al, 2000; instaed of Bayer et al, 1980;Hooton et al, 1984;Cottagnoud et al, 2000;Hallander et al, 1982.). Several current therapeutic regimes are based on synergistic interactions between antibiotics with different target sites.…”