The activities of ceftriaxone, piperacillin, tazobactam, clavulanic acid, and combinations of ceftriaxone or piperacillin with tazobactam against 22 clinical Legionella isolates were measured by broth microdilution and macrodilution methods and in macrophages. The broth microdilution MICs that inhibited 90%o of strains tested were 2 and 1 ,ug/ml for ceftriaxone and tazobactam, respectively. Broth macrodilution MICs were 8 and 1 ,ug/ml, respectively, for the two LegioneUla pneumophila strains tested with piperacillin and were 0.25 and 0.5 ,ug/ml, respectively, for clavulanate. No significant intracellular anti-L. pneumophila activity was observed for ceftriaxone (32 ,ug/ml), piperacillin (32 ,ug/ml), tazobactam alone (16 ,Ig/ml), clavulanate alone (2 ,ig/ml), or tazobactam in combination with ceftriaxone (ceftriaxone/tazobactam at 32/4 and 16/16 ,ug/ml) or piperacillin (32/4 ,ig/ml). Erythromycin (1 ,ug/ml) was active against intracellular L. pneumophila in the same macrophage model of infection. It is very unlikely that tazobactam or clavulanate, alone or in combination with f-lactam antimicrobial agents, will be effective for the treatment of Legionnaires' disease in humans.Contrary to expectations, the ,-lactamase inhibitor clavulanic acid has been shown to be active against extracellular and intracellular Legionella pneumophila and in murine models of L. pneumophila infection (28, 33-36, 38, 39). This has led to the evaluation of the activities of other P-lactamase inhibitors against L. pneumophila. Recently, Collins and colleagues (1) reported that tazobactam, with or without piperacillin, is active against extracellular Legionella species. We tested tazobactam alone and in combination with either ceftriaxone or piperacillin to confirm the findings of Collins and colleagues and to determine whether these antimicrobial agents were active against intracellular L. pneumophila. The activity of clavulanic acid alone was also determined. We demonstrate that both tazobactam and clavulanic acid are active against extracellular, but not intracellular, L. pneumophila.
MATERIALS AND METHODSBacteria and growth media. All legionellae studied were clinical isolates. These strains were identical to those used in prior studies and comprised 2 strains each of Legionella dumoffli, Legionella longbeachae, Legionella micdadei, 1 strain of Legionella bozemanii, and 15 strains of L. pneumophila (9,12