Bactericidal Activities of Methoxyfluoroquinolones Gatifloxacin and Moxifloxacin against Aerobic and Anaerobic Respiratory Pathogens in Serum

Abstract

Gatifloxacin (Bristol-Myers Squibb) and moxifloxacin (Bayer) are new methoxyfluoroquinolones with broadspectrum activity against aerobic and anaerobic pathogens of the respiratory tract. In this investigation, we analyzed the bactericidal activity in serum over time of these antimicrobials against three aerobic (Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus) and four anaerobic (Peptostreptococcus micros, Peptostreptococcus magnus, Fusobacterium nucleatum, and Prevotella melaninogenica) bacteria associated with respiratory tract infections. Serum samples were obtained from 11 healthy male subjects following a single 400-mg oral dose of gatifloxacin and moxifloxacin. These samples were collected prior to and at 2, 6, 12, and 24 h after the dose of each drug. Gatifloxacin exhibited bactericidal activity for a median of 12 h against Streptococcus pneumoniae (MIC ‫؍‬ 0.5 g/ml), Peptostreptococcus micros (MIC ‫؍‬ 0.25 g/ml), and F. nucleatum (MIC ‫؍‬ 0.5 g/ml) and 24 h against H. influenzae (MIC ‫؍‬ 0.03 g/ml), Staphylococcus aureus (MIC ‫؍‬ 0.125 g/ml), Peptostreptococcus magnus (MIC ‫؍‬ 0.125 g/ml), and Prevotella melaninogenica (MIC ‫؍‬ 0.5 g/ml). Moxifloxacin exhibited bactericidal activity for a median of 24 h against Streptococcus pneumoniae (MIC ‫؍‬ 0.125 g/ml), H. influenzae (MIC ‫؍‬ 0.015 g/ml), Staphylococcus aureus (MIC ‫؍‬ 0.06 g/ml), F. nucleatum (MIC ‫؍‬ 0.5 g/ml), Prevotella melaninogenica (MIC ‫5.0؍‬ g/ml), Peptostreptococcus magnus (MIC ‫؍‬ 0.125 g/ml), and Peptostreptococcus micros (MIC ‫؍‬ 0.25 g/ml). The results from this pharmacodynamic study suggest that these fluoroquinolones would have prolonged killing activity against these organisms in vivo and may have clinical utility in the treatment of mixed aerobic-anaerobic respiratory tract infections.Gatifloxacin (Bristol-Myers Squibb) and moxifloxacin (Bayer) are new 8-methoxyfluoroquinolones with broad-spectrum antimicrobial activity which includes anaerobic bacteria (29). Both compounds have comparable in vitro activity against common aerobic and anaerobic respiratory pathogens (3). Moreover, they exhibit similar serum pharmacokinetics and penetration into respiratory tissues (9, 24). The ability of gatifloxacin and moxifloxacin to eradicate aerobic respiratory pathogens, such as Streptococcus pneumoniae and Haemophilus influenzae, has been well documented in pharmacodynamic models and clinical trials (9, 24). Their effectiveness in the treatment of anaerobic infections is unknown.In contrast to studies with aerobic bacteria, where concentration-dependent killing has been observed, concentrationindependent killing was discovered against Bacteroides thetaiotaomicron with various fluoroquinolones in an in vitro pharmacodynamic model (27). This model further discovered that resistant strains of Bacteroides fragilis emerged when the area under the concentration-time curve from 0 to 24 h (AUC 24 )-to-MIC ratio was less than 40 (26). In time-kill assays, maximal bactericidal activity against various anaerobes (B. fragilis, ...

Activity of moxifloxacin against Bacteroides fragilis and Escherichia coli in an in vitro pharmacokinetic/pharmacodynamic model employing pure and mixed cultures

“…Conversely, cidal moxifloxacin activity was found for respiratory pathogens (aerobes and anaerobes) even when sera were obtained 24 h after dosing. The results suggest that moxifloxacin may have clinical utility in the treatment of mixed aerobic/anaerobic respiratory tract infections (Stein et al, 2003b). In a recently published paper investigating serum bactericidal activity of moxifloxacin and gatifloxacin, Stein et al (2003a) reported little or no serum bactericidal activity of either drug if the MICs of gatifloxacin were >2 mg l À1 .…”

Fluoroquinolones and Anaerobes

“…The methoxyfluoroquinolones, gatifloxacin and moxifloxacin, have in vitro potency similar to that of trovafloxacin against a broad spectrum of anaerobic bacteria and appear to have the potential to treat mixed aerobic and anaerobic infections [12][13][14]. Moxifloxacin recently received approval from the US Food and Drug Administration for the treatment of complicated skin or skin-structure infections and complicated intra-abdominal infections.…”

Are Broad-Spectrum Fluoroquinolones More Likely To Cause Clostridium difficile -Associated Disease?

“…We used conditional logistic regression to estimate the odds ratio for the association between C. difficile-associated disease and previous treatment with the various fluoroquinolones, using levofloxacin exposure as the reference category. The two comparison groups were gatifloxacin and moxifloxacin (combined because the number of cases was smaller than expected and because of their similar antimicrobial activity) (17,29) and ciprofloxacin.…”