In vitro and in vivo antimicrobial activities of new fluoroquinolones against Pseudomonas aeruginosa

We investigated the in vitro and in vivo antimicrobial activities of new fluoroquinolones against Pseudomonas aeruginosa. The in vitro antimicrobial activities of ofloxacin (OFLX), ciprofloxacin (CPFX), tosufloxacin (TFLX), sparfloxacin (SPFX), levofloxacin (LVFX), and NM 394, the active form of prodrug NM 441, were examined against 100 clinical isolates of P. aeruginosa. The MIC ₅₀s for CPFX, TFLX and NM 394 (0.25 μg/ml) were superior to that of LVFX (1.0 μg/ml) and OFLX (2.0 μg/ml). The in vivo therapeutic efficacies of fluoroquinolones (OFLX, CPFX, LVFX, and NM 441) were evaluated by using a normal and a neutropenic murine model of P. aeruginosa pneumonia. Neutropenia was induced by the single administration of cyclophosphamide at a dose of 200 mg/kg of body weight on day 0. Experimental pneumonia was established by intratracheal inoculation of P. aeruginosa on day 3. Antibiotics were administered orally twice a day for 7 days after bacterial challenge. There was no significant difference between the therapeutic effects of CPFX, LVFX, and NM 441 when using normal ddY mice. However, when neutropenic ddY mice were infected with 9 x 10 ⁷ CFU of P. aeruginosa, the survival rates of mice were 67%, 33%, and 25% after treatment with NM 441, CPFX, and LVFX, respectively. The difference in survival rates between the NM 441-treated group and the LVFX-treated group was statistically significant (P<0.05). These results suggest that NM 441 has potent antimicrobial activity against P. aeruginosa which shows reduced susceptibility to other fluoroquinolone agents.