Comparative Activity of Moxifloxacin in Vitro Against Obligately Anaerobic Bacteria

Ackermann, Grit; Schaumann, Reiner; Pless, B.; Claros, Marina C.; Goldstein, Ellie J. C.; Rodloff, Arne C.

doi:10.1007/s100960050465

Cited by 68 publications

(32 citation statements)

References 8 publications

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“…Our findings are also supported by other pharmacodynamic models of bacterial killing with fluoroquinolones (16,26). The isolates utilized in our study were representative bacteria associated with respiratory tract infections and had MICs at or near the median MIC for these methoxyfluoroquinolones (1,3,6). All of these strains had MICs of Յ0.5 g/ml, which would result in AUC 24 /MIC ratios of Ն60 following a single 400-mg oral dose of gatifloxacin or moxifloxacin in healthy volunteers (29).…”

Section: Discussionsupporting

confidence: 82%

“…This agent provides prolonged bactericidal activity in serum against common anaerobic pathogens and clinical efficacy for mixed aerobic-anaerobic infections (10,30). The methoxyfluoroquinolones gatifloxacin and moxifloxacin also have broad-spectrum activity against anaerobic organisms, especially respiratory pathogens (1,6,15). The potency of these drugs is similar to that of trovafloxacin, and MICs are usually Յ2.0 g/ml against anaerobes such as Peptostreptococcus spp., Prevotella spp., and Fusobacterium spp.…”

Section: Discussionmentioning

confidence: 99%

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

Stein

Schooley

Tyrrell³

et al. 2003

Antimicrob Agents Chemother

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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, ...

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

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

Stein

Schooley

Tyrrell³

et al. 2003

Antimicrob Agents Chemother

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“…It has an antimicrobial activity against many Gram-positive and Gram-negative aerobic and anaerobic bacteria as well as atypical bacteria such as Chlamydia and Mycoplasma (Dalhoff et al, 1996;Bauernfeind, 1997;Goldstein et al, 1997;Edlund et al, 1998;Ackermann et al, 2000;Blondeau et al, 2000;Kleinkauf et al, 2001;Krasemann et al, 2001;Talan, 2001;Zhanel et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…Several in vitro studies have indicated that moxifloxacin has good in vitro activity against important anaerobic bacteria especially Bacteroides species (Edlund et al, 1998;Ackermann et al, 2000). However, compared to the activities of garenoxacin, clinafloxacin, sitafloxacin and trovafloxacin, moxifloxacin more recently was the least active agent against 589 Bacteroides fragilis group isolates (Snydman et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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

Schaumann

Goldstein

Forberg

et al. 2005

Journal of Medical Microbiology

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The objective of this study was to determine the pharmacodynamic (PD) activity of moxifloxacin against four selected Bacteroides fragilis strains (three strains with low MICs and one strain with a high MIC) and two Escherichia coli strains (one strain with a low MIC and one strain with a high MIC) in a pharmacokinetic (PK) in vitro model in pure cultures as well as in mixed cultures. PK/PD assays of moxifloxacin were carried out with an initial maximum concentration of 4 . 0 mg l À1 and a half-life of 13 h. The E. coli strain with the low MIC was rapidly killed in both pure and mixed cultures in the in vitro PK/PD model, while the E. coli strain with the high MIC was not killed. None of the B. fragilis strains were rapidly killed in pure or mixed cultures. The bacterial numbers of the B. fragilis strains with low MICs were reduced by about one to two logs after 12 h in pure cultures. The presence of an E. coli strain with a low or a high MIC in the mixed culture reduced this effect even further.

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“…There is a wealth of literature from the human clinical sector that supports the use of broad-spectrum fluoroquinolones under conditions where anaerobes are implicated (1,2,29,37,44). The utility of broad-spectrum fluoroquinolones against bacteria associated with dental infections has also been demonstrated by King et al (26) in a large pan-European study investigating the in vitro activities of a range of antianaerobic antimicrobials against gram-negative bacilli.…”

Section: Resultsmentioning

confidence: 99%

Activity of Pradofloxacin against Porphyromonas and Prevotella spp. Implicated in Periodontal Disease in Dogs: Susceptibility Test Data from a European Multicenter Study

Stephan

Greife

Pridmore

et al. 2008

Antimicrob Agents Chemother

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Collaborating veterinarians from five European countries collected subgingival bacterial samples from dogs exhibiting clinical periodontal disease. Sterile endodontic paper points were used for collection of the samples, which were transported to a central laboratory for susceptibility testing. Anaerobic bacteria were isolated and Porphyromonas and Prevotella isolates identified to the species level; susceptibility to pradofloxacin and metronidazole was determined using the CLSI agar dilution methodology. A total of 630 isolates, 310 of Porphyromonas spp. and 320 of Prevotella spp., were isolated. Pradofloxacin MIC data for all isolates were in the range of <0.016 to 1 g/ml, the overall MIC 50 was 0.062, and the overall MIC 90 was 0.25 g/ml. There were no differences in activity against Porphyromonas and Prevotella isolates or in the pradofloxacin susceptibility distributions from the different European countries. All isolates were within the wild-type distribution and were fully susceptible to pradofloxacin. Metronidazole was also highly active against these strains: 316 of 320 Prevotella strains (98.8%) and 309 of 310 Porphyromonas strains (99.7%) were susceptible (MICs of <8 g/ml). However, three Prevotella strains had intermediate metronidazole susceptibility (MICs of 16 g/ml), while one Prevotella and one Porphyromonas strain were metronidazole resistant (MICs of 128 and 256 g/ml, respectively). Pradofloxacin, a novel broad-spectrum fluoroquinolone, demonstrates a high degree of antianaerobic activity against strains isolated from clinical cases of periodontal disease and shows activity against metronidazole-resistant isolates. The broad-spectrum activity of pradofloxacin makes it a suitable candidate for the treatment of periodontal disease in dogs.

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Comparative Activity of Moxifloxacin in Vitro Against Obligately Anaerobic Bacteria

Cited by 68 publications

References 8 publications

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

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

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

Activity of Pradofloxacin against Porphyromonas and Prevotella spp. Implicated in Periodontal Disease in Dogs: Susceptibility Test Data from a European Multicenter Study

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