Vol.53 No.S-3 December 2005
In vitro and in vivo antibacterial activity of moxifloxacin, a novel quinolone antibacterial agent
Department of Microbiology, Kyoto Pharmaceutical University, 5 Nakauchi, Misasagi, Yamashina-ku, Kyoto, Japan
Abstract
The in vitro and in vivo antibacterial activity of moxifloxacin (MFLX), a synthetic chemotherapeutic agent, was assessed by using ciprofloxacin (CPFX), sparfloxacin (SPFX), tosufloxacin (TFLX), and levofloxacin (LVFX) as comparators. The following results were obtained:
1. MFLX exhibited antibacterial activity against a broad spectrum of both gram-positive and gram-negative microorganisms.
2. The antibacterial activity of MFLX against most gram-positive clinical isolates was equivalent or superior to that of other antibacterial agents. It was also equipotent or superior to other drugs against gram-negative microorganisms except Enterobacter aerogenes, Proteus vulgaris, Morganella morganii, and Pseudomonas aeruginosa. The antibacterial activity of MFLX was lower against LVFX-resistant strains of Staphylococcus aureus and Staphylococcus epidermidis than against sensitive strains, the same as the other drugs, but its activity was 1 to 8 times greater than that of the other drugs.
3. The antibacterial activity of MFLX was unaffected by the type of medium, addition of serum, or by the size of the microorganism inoculum, but low pH of medium decrease its activity.
4. The effects of MFLX on the growth curve of S. aureus, Escherichia coli, and P. aeruginosa revealed that its action was bactericidal at concentrations above the MIC, and incubation with the drug at 4 MICs for one hour decreased the viable cell count of these bacteria to between 1/10 and less than 1/1,000 of their original values.
5. Examination of the morphology of S. aureus and E. coli with a differential interference microscope revealed swelling of S. aureus cells above 1/4 MIC, and prominent elongation of E. coli cells above 1/16 MIC. Cell lysis was also observed above the MIC.
6. The effect of MFLX on morphological changes in S. aureus and E. coli was investigated with a laser scanning microscope (LSM). MFLX induced anucleate daughter cells in S. aureus at 1/4 times the MIC. The elongated cells E. coli were multinucleate in piperacillin (cell wall synthesis inhibitor), but unicleate in MFLX at 1/2 the MIC.
7. Assessment of the therapeutic effect of MFLX on experimental generalized infection in mice demonstrated that it was less effective than the comparators against gram-negative microorganisms, but equally or more effective than SPFX and superior to CPFX and LVFX against gram-positive bacteria.
8. Assessment of the therapeutic effects of MFLX on experimental respiratory tract infection in mice yield excellent results, showing that it was almost equally as effective as SPFX and more than 3 to 5 times as effective as CPFX and LVFX.
Key word
moxifloxacin, clinical isolate, antimicrobial activity, animal model
Received
September 21, 2005
Accepted
November 24, 2005
Jpn. J. Chemother. 53 (S-3): 1-15, 2005
