IN-VITRO EXTRACELLULAR AND INTRACELLULAR ACTIVITIES OF CLAVULANIC ACID AND THOSE OF PIPERACILLIN AND CEFTRIAXONE ALONE AND IN COMBINATION WITH TAZOBACTAM AGAINST CLINICAL ISOLATES OF LEGIONELLA SPECIES

The activities of ceftriaxone, piperacillin, tazobactam, clavulanic ac id, and combinations of ceftriaxone or piperacillin with tazobactam ag ainst 22 clinical Legionella isolates were measured by broth microdilu tion and macrodilution methods and in macrophages. The broth microdilu tion MICs that inhibited 90% of strains tested were 2 and 1 mu g/ml fo r ceftriaxone and tazobactam, respectively. Broth macrodilution MICs w ere 8 and 1 mu g/ml, respectively, for the two Legionella pneumophila strains tested with piperacillin and were 0.25 and 0.5 mu g/ml, respec tively, for clavulanate. No significant intracellular anti-L. pneumoph ila activity was observed for ceftriaxone (32 mu g/ml), piperacillin ( 32 mu g/ml), tazobactam alone (16 mu g/ml), clavulanate alone (2 mu g/ ml), or tazobactam in combination with ceftriaxone (ceftriaxone/tazoba ctam at 32/3 and 16/16 mu g/ml) or piperacillin (32/4 mu g/ml). Erythr omycin (1 mu g/ml) was active against intracellular L. pneumophila in the same macrophage model of infection. It is very unlikely that tazob actam or clavulanate, alone or in combination with beta-lactam antimic robial agents, will be effective for the treatment of Legionnaires' di sease in humans.