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2019 | 68 | 1 |

Tytuł artykułu

In vitro and in vivo activity of zabofloxacin and other fluoroquinolones against MRSA isolates from a University Hospital in Egypt

Warianty tytułu

Języki publikacji

EN

Abstrakty

EN
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 vivoefficacy 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.

Słowa kluczowe

Wydawca

-

Rocznik

Tom

68

Numer

1

Opis fizyczny

p.59-69,fig.,ref.

Twórcy

autor
  • Department of Microbiology and Immunology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
autor
  • Department of Microbiology and Immunology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
autor
  • Department of Microbiology and Immunology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
  • Department of Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt

Bibliografia

  • Abdel-Maksoud M, El-Shokry M, Ismail G, Hafez S, El-Kholy A, Attia E, Talaat M. Methicillin-Resistant Staphylococcus aureusrecovered from healthcare- and community-associated infections in Egypt. Int J Bacteriol. 2016;2016:1–5. doi:10.1155/2016/5751785 Medline
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  • CLSI. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically: approved standard-Ninth Edition M07-A9. 2012. Wayne (USA): Clinical and Laboratory Standards Institute.
  • CLSI. Performance standards for antimicrobial susceptibility testing. CLSI approved standard M100-S23. 2013. Wayne (USA): Clinical and Laboratory Standards Institute.
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  • Park HS, Jung SJ, Kwak JH, Choi DR, Choi EC. DNA gyrase and topoisomerase IV are dual targets of zabofloxacin in Streptococcus pneumoniae. Int J Antimicrob Agents. 2010;36(1):97–98.doi:10.1016/j.ijantimicag.2010.02.022 Medline
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  • Sierra JM, Marco F, Ruiz J, Jiménez de Anta MT, Vila J. Correlation between the activity of different fluoroquinolones and the presence of mechanisms of quinolone resistance in epidemiologically related and unrelated strains of methicillin-susceptible and -resistant Staphylococcus aureus. Clin Microbiol Infect. 2002;8(12):781–790. doi:10.1046/j.1469-0691.2002.00400.x Medline
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Typ dokumentu

Bibliografia

Identyfikatory

Identyfikator YADDA

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