The activity of
trovafloxacin against 22 clinical Legionella isolates was determined by broth microdilution susceptibility testing. The
trovafloxacin concentration required to inhibit 90% of strains tested was < or = 0.004 micrograms/ml, in contrast to 0.032 micrograms/ml for
ofloxacin. In guinea pig alveolar macrophages,
trovafloxacin achieved intracellular levels up to 28-fold over the extracellular concentration, which was similar to the levels obtained with
erythromycin.
Trovafloxacin (0.25 micrograms/ml) reduced bacterial counts of two L. pneumophila strains grown in guinea pig alveolar macrophages by > 2 log10 CFU/ml, without regrowth, under
drug-free conditions over a 3-day period;
trovafloxacin was significantly more active than
ofloxacin or
erythromycin (0.25 to 1 microgram/ml) in this assay. Single-dose (10 mg of
prodrug CP-116,517-27 per kg of
body weight given intraperitoneally [i.p.], equivalent to 7.5 mg of
trovafloxacin per kg) pharmacokinetic studies performed in guinea pigs with L. pneumophila
pneumonia revealed peak serum and lung
trovafloxacin levels to be 3.8 micrograms/ml and 5.0 micrograms/g, respectively, at 0.5 h and 4.2 micrograms/ml and 2.9 micrograms/g, respectively, at 1 h. Administration of a lower
prodrug dose (1.4 mg of
trovafloxacin equivalent per kg i.p.) gave levels in lung and serum of 0.4 microgram/g and 0.4 microgram/ml, respectively, 1 h after
drug administration. The terminal half-lives of elimination from serum and lung were 0.8 and 1.1 h, respectively. All 15 infected guinea pigs treated for 5 days with CP-116,517-27 once daily (10 mg/kg/day i.p., equivalent to 7.5 mg of
trovafloxacin per kg/day) survived for 10 days after antimicrobial
therapy, as did all 15 guinea pigs treated with
ofloxacin once daily (10 mg/kg/day i.p.) for 5 days. None of 13 animals treated with saline survived. In a second experiment with animals,
trovafloxacin (1.4 mg/kg/day i.p. for 5 days) protected all 16 guinea pigs from death, whereas all 15 animals treated with saline died.
Trovafloxacin is an effective
antimicrobial agent against Legionella in vitro and in vivo, with the ability to concentrate in macrophages and kill intracellular organisms.