Effect of calcium, magnesium, and zinc on ticarcillin and tobramycin alone and in combination against Pseudomonas aeruginosa

Abstract

Correlation between in vitro and in vivo test results for synergy between carboxypenicillins and aminoglycosides against Pseudomonas aeruginosa is poor. Although the divalent cation content of culture media is known to affect aminoglycoside susceptibility testing for P. aeruginosa, this effect of divalent cations has not been examined for synergy testing of carboxypenicillin-aminoglycoside interaction against P. aeruginosa. The minimal inhibitory concentrations (MICs) of tobramycin and ticarcillin and the interaction of these drugs in combination were studied by a microtitration method for 36 strains of P. aeruginosa in Mueller-Hinton broth with varying supplements of calcium, magnesium, and zinc. Boston, Mass., abstr. no. 1071) studied the efficacy of ticarcillin and tobramycin, singly and in combination, in a guinea pig model for P. aeruginosa bacteremia; they were unable to show an improvement in survival with combinations demonstrated to be synergistic in vitro against strains of Pseudomonas, as compared to a single-drug therapy. The results of in vitro studies examining the interaction between carboxypenicillin and aminoglycosides against P. aeruginosa are not easily compared. This is due to several reasons. First, the definition of synergy varies from study to study. Second, the divalent cation content of the culture media, which will affect aminoglycoside susceptibility (18,22,23), can also vary from study to study; unfortunately, the cation content is not even reported in a number of synergy studies of P. aeruginosa. We wondered whether some of the discrepancies in the literature concerning penicillin and aminoglycoside synergy might be due to differences in divalent cation content of the test media. To our knowledge the effect of divalent cations on the synergistic interaction of carboxypenicillins and aminoglycosides has not been systematically evaluated. We sought to do so by testing the interaction between ticarcillin and tobramycin against 36 clinical isolates of P. aeruginosa in 12 cation-defined media.

Effects of Calcium Concentrations on Antimicrobial Susceptibility Testing Against Pseudomonas aeruginosa

“…It has been reported elsewhere that the MICs of aminoglycosides and tetracyclines increased upon addition of cations to the test media of P. aeruginosa [6,7]. In the current study, we showed that the addition of calcium elicited the same effect for aminoglycosides, tetracyclines, carbapenems, quinolones, and somelactams.…”

“…The minimum inhibitory concentrations (MICs) of aminoglycosides and tetracyclines increased when P. aeruginosa growth media was supplemented with cations [6,7]. To date, there have been no reports of similar increases in MICs for other antibiotics, and to the best of our knowledge, the relationship between resistance determinants and calcium concentrations has yet to be reported.…”

Antibiotic combinations: should they be tested?

“…As with any test of antibiotic activity over time, matters of inoculum size and growth phase, medium composition, and possible in vitro drug inactivation must be considered (65,120,147,195). The last of these factors is particularly important when broad-spectrum penicillins are combined with aminoglycosides.…”

Antibiotic combinations: should they be tested?

“…Time-Kill Techniques Time-kill techniques involve repeated sampling of tubes or flasks containing the individual drugs and their combinations to determine colony counts of surviving bacteria over time (108). As with any test of antibiotic activity over time, matters of inoculum size and growth phase, medium composition, and possible in vitro drug inactivation must be considered (65,120,147,195). The last of these factors is particularly important when broad-spectrum penicillins are combined with aminoglycosides.…”