The widespread of
infections caused by methicillin-resistant Staphylococcus aureus (MRSA), has necessitated the search for
alternative therapies; introduction of new agents being a suggestion. This study compares the in vitro and in vivo activities of
zabofloxacin, a novel
fluoroquinolone, with
moxifloxacin,
levofloxacin and
ciprofloxacin against clinical isolates of MRSA from patients hospitalized in the Alexandria Main University hospital; a tertiary hospital in Alexandria, Egypt, where
zabofloxacin has not been yet introduced. The strains tested showed the highest percentage of susceptibility to
zabofloxacin (61.2%) among the tested
fluoroquinolones with the most effective MIC50 and MIC90 (0.25 and 2 µg/ml, respectively). Time-kill curve analysis revealed a rapid bactericidal activity of
zabofloxacin after 6 h of incubation with a
quinolone-resistant isolate and complete killing when tested against a
quinolone-sensitive isolate with inhibition of regrowth in both cases. PCR amplification and sequencing of QRDRs in selected strains revealed the following amino acid substitutions: Ser-84→Leu in GyrA, Ser-80→Phe in GrlA and Pro-451→Ser in GrlB. The in vivo studies demonstrated that
zabofloxacin possessed the most potent protective effect against systemic
infection in mice (ED50: 29.05 mg/kg) with lowest count in the dissected lungs (3.66 log10 CFU/ml). The histopathological examination of lung specimens of mice treated with
zabofloxacin displayed least congestion,
inflammation, oedema and
necrosis with clear alveolar spaces and normal vessels. In conclusion,
zabofloxacin was proved to possess high in vitro and in vivo efficacy encompassing its comparators and could be considered as a possible candidate for the treatment of
infections caused by MRSA. To our knowledge, this is the first study evaluating the in vitro and in vivo activity of
zabofloxacin against Egyptian MRSA clinical isolates.
The widespread of
infections caused by methicillin-resistant Staphylococcus aureus (MRSA), has necessitated the search for
alternative therapies; introduction of new agents being a suggestion. This study compares the in vitro and in vivo activities of
zabofloxacin, a novel
fluoroquinolone, with
moxifloxacin,
levofloxacin and
ciprofloxacin against clinical isolates of MRSA from patients hospitalized in the Alexandria Main University hospital; a tertiary hospital in Alexandria, Egypt, where
zabofloxacin has not been yet introduced. The strains tested showed the highest percentage of susceptibility to
zabofloxacin (61.2%) among the tested
fluoroquinolones with the most effective MIC50 and MIC90 (0.25 and 2 µg/ml, respectively). Time-kill curve analysis revealed a rapid bactericidal activity of
zabofloxacin after 6 h of incubation with a
quinolone-resistant isolate and complete killing when tested against a
quinolone-sensitive isolate with inhibition of regrowth in both cases. PCR amplification and sequencing of QRDRs in selected strains revealed the following amino acid substitutions: Ser-84→Leu in GyrA, Ser-80→Phe in GrlA and Pro-451→Ser in GrlB. The in vivo studies demonstrated that
zabofloxacin possessed the most potent protective effect against systemic
infection in mice (ED50: 29.05 mg/kg) with lowest count in the dissected lungs (3.66 log10 CFU/ml). The histopathological examination of lung specimens of mice treated with
zabofloxacin displayed least congestion,
inflammation, oedema and
necrosis with clear alveolar spaces and normal vessels. In conclusion,
zabofloxacin was proved to possess high in vitro and in vivo efficacy encompassing its comparators and could be considered as a possible candidate for the treatment of
infections caused by MRSA. To our knowledge, this is the first study evaluating the in vitro and in vivo activity of
zabofloxacin against Egyptian MRSA clinical isolates.