Effect of Highly Potent Antipseudomonal β-Lactam Agents Alone and in Combination with Aminoglycosides Against Pseudomonas aeruginosa

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Abstract
The activities of ticarcillin, cefsulodin, ceftazidime, aztreonam, and imipenem, formerly known as N-formimidoyl thienamycin, were evaluated alone and in combination with aminoglycosides against 56 clinical isolates of Pseudomonas aeruginosa, which were characterized by aminoglycoside susceptibility and content of aminoglycoside-modifying enzymatic activities. All β-lactam agents were highly active against aminoglycoside-susceptible isolates, and with few exceptions the aminoglycoside-resistant isolates were susceptible to all of the β-lactam agents except ticarcillin. Combinations of the β-lactam agents with aminoglycosides frequently acted synergistically, but the effect of different β-lactam agents in combination with an aminoglycoside against individual strains was unpredictable. The presence or absence of an aminoglycoside-modifying enzymatic activity had no observed effect on synergism with tobramycin. Killing-curve experiments with strains in the presence of concentrations of a β-lactam and an aminoglycoside that were not bactericidal alone (one-fourth the minimal bactericidal concentration) showed synergistic bactericidal action against four strains that were tested. The results demonstrate the great activity of these newer antipseudomonal β-lactam agents and their potential for synergism with aminoglycosides.

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