Therapeutic considerations in using combinations of newer β-lactam antibiotics

Abstract

The in vitro activity, pharmacokinetic interactions, and clinical efficacy of newer beta-lactam antibiotic combinations are reviewed. Combinations of beta-lactam antibiotics offer an antimicrobial spectrum similar to that of aminoglycoside-beta-lactam combinations without the renal or eighth cranial nerve toxicity of aminoglycosides. Synergistic activity with beta-lactam combinations is demonstrable in vitro against a wide variety of aerobic gram-negative bacilli, but the frequency, with which it is found is substantially less than for aminoglycoside-beta-lactam combinations. Also, in vitro antagonism can be demonstrated, particularly with combinations containing an agent capable of inducing beta lactamase. Substantial alterations in the pharmacokinetics of cefotaxime and desacetylcefotaxime have been demonstrated by the concomitant administration of mezlocillin or azlocillin. In addition, the clearance of moxalactam has been shown to be reduced by concomitant administration of piperacillin, and the clearance of oxacillin is reduced by concomitant mezlocillin therapy. Dosage reductions of these drugs may be appropriate in certain situations. Several clinical trials comparing therapy with beta-lactam combinations versus aminoglycoside-containing regimens in neutropenic patients have shown no difference in overall efficacy between the two regimens, with the possible exception of infections in persistently granulocytopenic patients and perhaps in patients with Pseudomonas aeruginosa infections. beta-lactam combinations are generally less nephrotoxic, but potentially more costly when newer compounds are included, than amino-glycoside-containing regimens. These beta-lactam combinations should be reserved for use in patients at high risk for aminoglycoside toxicity.