OBJECTIVES: Staphylococcal small colony variants (SCVs) are associated with chronic and relapsing infections and their intracellular location may shield them from host defences and antibiotics. Finafloxacin is a novel fluoroquinolone that exhibits optimal activity at slightly acidic conditions where the activity of other marketed fluoroquinolones decreases. Here, the in vitro activity of finafloxacin against clinical strain pairs consisting of an SCV and its clonally identical parental strain displaying the normal phenotype (NP) was compared with those of other fluoroquinolones at standard and low pH. METHODS: In vitro activities of finafloxacin, ciprofloxacin, levofloxacin and moxifloxacin were tested against 28 methicillin-susceptible Staphylococcus aureus (MSSA) and three methicillin-resistant S. aureus (MRSA) SCV-NP strain pairs. Additionally, two S. aureus mutants (ΔhemB and ΔthyA) displaying the SCV phenotype and their wild-type strains as well as four SCV-NP pairs of coagulase-negative staphylococcal (CoNS) strains were included. MIC(50,) MIC(90) and MIC ranges were calculated based on MIC determination by Etest(®) at pH 5.8 and pH 7.2. RESULTS: Under acidic conditions, finafloxacin demonstrated superior activity against MSSA, MRSA and CoNS regardless of the phenotype. At neutral conditions, the activity against MSSA was as follows: moxifloxacin > finafloxacin > levofloxacin > ciprofloxacin. In comparison with methicillin-susceptible NP isolates, ciprofloxacin was less active against their corresponding SCVs. For other fluoroquinolones, there was no marked difference in activity against SCVs compared with NPs. CONCLUSIONS: Particularly in acidic body compartments, finafloxacin appears to be a promising new antibiotic for the treatment of persistent staphylococcal infections, including those caused by SCVs.
OBJECTIVES: Staphylococcal small colony variants (SCVs) are associated with chronic and relapsing infections and their intracellular location may shield them from host defences and antibiotics. Finafloxacin is a novel fluoroquinolone that exhibits optimal activity at slightly acidic conditions where the activity of other marketed fluoroquinolones decreases. Here, the in vitro activity of finafloxacin against clinical strain pairs consisting of an SCV and its clonally identical parental strain displaying the normal phenotype (NP) was compared with those of other fluoroquinolones at standard and low pH. METHODS: In vitro activities of finafloxacin, ciprofloxacin, levofloxacin and moxifloxacin were tested against 28 methicillin-susceptible Staphylococcus aureus (MSSA) and three methicillin-resistant S. aureus (MRSA) SCV-NP strain pairs. Additionally, two S. aureus mutants (ΔhemB and ΔthyA) displaying the SCV phenotype and their wild-type strains as well as four SCV-NP pairs of coagulase-negative staphylococcal (CoNS) strains were included. MIC(50,) MIC(90) and MIC ranges were calculated based on MIC determination by Etest(®) at pH 5.8 and pH 7.2. RESULTS: Under acidic conditions, finafloxacin demonstrated superior activity against MSSA, MRSA and CoNS regardless of the phenotype. At neutral conditions, the activity against MSSA was as follows: moxifloxacin > finafloxacin > levofloxacin > ciprofloxacin. In comparison with methicillin-susceptible NP isolates, ciprofloxacin was less active against their corresponding SCVs. For other fluoroquinolones, there was no marked difference in activity against SCVs compared with NPs. CONCLUSIONS: Particularly in acidic body compartments, finafloxacin appears to be a promising new antibiotic for the treatment of persistent staphylococcal infections, including those caused by SCVs.
Authors: Justin R Lenhard; Christof von Eiff; Irene S Hong; Patricia N Holden; Michael D Bear; Amy Suen; Zackery P Bulman; Brian T Tsuji Journal: Antimicrob Agents Chemother Date: 2014-12-01 Impact factor: 5.191
Authors: Laetitia G Garcia; Sandrine Lemaire; Barbara C Kahl; Karsten Becker; Richard A Proctor; Paul M Tulkens; Françoise Van Bambeke Journal: Antimicrob Agents Chemother Date: 2012-09-17 Impact factor: 5.191
Authors: Andreas Vente; Christine Bentley; Mark Lückermann; Paul Tambyah; Axel Dalhoff Journal: Antimicrob Agents Chemother Date: 2018-03-27 Impact factor: 5.191
Authors: L G Garcia; S Lemaire; B C Kahl; K Becker; R A Proctor; O Denis; P M Tulkens; F Van Bambeke Journal: Antimicrob Agents Chemother Date: 2012-05-07 Impact factor: 5.191