In vitro bactericidal activity and post-antibiotic effect of ABT-773 versus co-amoxiclav against anaerobes

Pendland, Susan L.; Neuhauser, Melinda M.; Prause, Jennifer L.

doi:10.1093/jac/dkf032

Cited by 5 publications

(2 citation statements)

References 7 publications

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“…Previous studies have suggested that compounds which exhibited <3 log 10 CFU/ml reduction from initial CFU count at 24 h indicated a bacteriostatic effect while compounds that displayed ≥3 log 10 CFU/ml reduction from initial CFU count at 24 h indicated a bactericidal action against the tested microbe/s [17, 18]. Results of this time-kill study corroborated with previous MBC/MIC ratio values [1] that suggested MFM501 has a bacteriostatic mechanism of action against MRSA and MSSA isolates.…”

Section: Discussionsupporting

confidence: 85%

In VitroEvaluations andIn VivoToxicity and Efficacy Studies of MFM501 against MRSA

Johari

Mohtar

Mohamad

et al. 2017

BioMed Research International

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Previously we have discovered a synthetically derived pyrrolidone alkaloid, MFM501, exhibiting good inhibitory activity against 53 MRSA and MSSA isolates with low cytotoxicity against three normal cell-lines with IC50 values at >625 µg/ml. Time-kill assay, scanning electron microscopy (SEM) analysis, in vivo oral acute toxicity test, and mice peritonitis model were carried out in this study. In the time-kill study, MFM501 showed a less than 3 log10 decrease in bacterial colony concentration value (CFU/ml) which represented a bacteriostatic action while displaying a time-dependent inhibitory mechanism. Following that, SEM analysis suggested that MFM501 may exert its inhibitory activity via cytoplasmic membrane disruption. Moreover, MFM501 showed no toxicity effect on treated mice at an estimated median acute lethal dose (LD50) value of more than 300 mg/kg and less than 2000 mg/kg. For the efficacy test, a mean effective dose (ED50) of 87.16 mg/kg was obtained via a single dose oral administration. Our data demonstrated that MFM501 has the potential to be developed further as a new, safe, and effective oral-delivered antibacterial agent against MRSA isolates.

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Section: Discussionsupporting

confidence: 85%

In VitroEvaluations andIn VivoToxicity and Efficacy Studies of MFM501 against MRSA

Johari

Mohtar

Mohamad

et al. 2017

BioMed Research International

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“…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, B. thetaiotaomicron, Peptostreptococcus magnus, and Clostridium perfringens) was observed at twice the MIC with levofloxacin (25). These in vitro investigations suggest that relatively low, prolonged concentrations of newer fluoroquinolones have the ability to eradicate susceptible anaerobic organisms.…”

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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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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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Macrolides and Ketolides

Xu¹,

Flavin²,

Eiznhamer³

2011

Antibiotic Discovery and Development

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In vitro bactericidal activity and post-antibiotic effect of ABT-773 versus co-amoxiclav against anaerobes

Abstract: In vitro bactericidal activity and post-antibiotic effect of ABT-773 versus co-amoxiclav against anaerobes

Cited by 5 publications

References 7 publications

In VitroEvaluations andIn VivoToxicity and Efficacy Studies of MFM501 against MRSA

In VitroEvaluations andIn VivoToxicity and Efficacy Studies of MFM501 against MRSA

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

Macrolides and Ketolides

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