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Higgins P.G.,University of Cologne | Stubbings W.,MerLion Pharmaceuticals | Wisplinghoff H.,University of Cologne | Seifert H.,University of Cologne
Antimicrobial Agents and Chemotherapy

This study compared the activity of finafloxacin, a novel fluoroquinolone which shows enhanced activity under acidic pH, and that of ciprofloxacin against Acinetobacter baumannii under standard conditions (pH 7.2) and at a pH of 5.8. Overall, finafloxacin demonstrated superior activity to ciprofloxacin under acidic conditions. Furthermore, finafloxacin showed comparable activity to ciprofloxacin at pH 7.2. Hence, finafloxacin could be a promising new antimicrobial agent for the treatment of A. baumannii infections at acidic body compartments. Copyright © 2010, American Society for Microbiology. All Rights Reserved. Source

Dalhoff A.,University of Kiel | Stubbings W.,MerLion Pharmaceuticals | Schubert S.,University of Kiel
Antimicrobial Agents and Chemotherapy

Kill kinetics and MICs of finafloxacin and ciprofloxacin against 34 strains with defined resistance mechanisms grown in cation-adjusted Mueller-Hinton broth (CAMHB) at pH values of 7.2 and 5.8 and in synthetic urine at pH 5.8 were determined. In general, finafloxacin gained activity at low pH values in CAMHB and remained almost unchanged in artificial urine. Ciprofloxacin MICs increased and bactericidal activity decreased strain dependently in acidic CAMHB and particularly in artificial urine. Copyright © 2011, American Society for Microbiology. All Rights Reserved. Source

Sharif S.,Washington University in St. Louis | Kim S.J.,Baylor University | Labischinski H.,MerLion Pharmaceuticals | Chen J.,Washington University in St. Louis | Schaefer J.,Washington University in St. Louis
Journal of Bacteriology

Peptidoglycan (PG) composition in intact cells of methicillin-resistant Staphylococcus aureus (MRSA) and its isogenic Fem mutants has been characterized by measuring the glycine content of PG bridge structures by solid-state nuclear magnetic resonance (NMR). The glycine content estimated from integrated intensities (rather than peak heights) in the cell walls of whole cells was increased by approximately 30% for the FemA mutant and was reduced by 25% for the FemB mutant relative to expected values for homogeneous structures. In contrast, the expected compositions were observed in isolated cell walls of the same mutants. For FemA mutant whole cells, the increase was due to the presence of triglycyl bridge PG units (confirmed directly by mass spectrometric analysis), which constituted 10% of the total PG. These species were coalesced in some sort of a lattice or aggregate with spatial proximity to other PG bridges. This result suggests that the triglycyl-bridged PG units form a PG-like structure that is not incorporated into the mature cell wall. © 2013, American Society for Microbiology. Source

Idelevich E.A.,University of Munster | Kriegeskorte A.,University of Munster | Stubbings W.,MerLion Pharmaceuticals | Stubbings W.,Basilea Pharmaceutica Ltd. | And 5 more authors.
Journal of Antimicrobial Chemotherapy

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. MIC50, MIC90 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. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. Source

Stubbings W.,MerLion Pharmaceuticals | Leow P.,MerLion Pharmaceuticals | Yong G.C.,MerLion Pharmaceuticals | Goh F.,MerLion Pharmaceuticals | And 4 more authors.
Antimicrobial Agents and Chemotherapy

Finafloxacin is a novel fluoroquinolone that exhibits enhanced antibacterial activity under acidic conditions. The aim of this study was to define the in vitro pH-activity relationship. Finafloxacin exhibited optimal antibacterial activity between pH 5.0 and 6.0 at which MICs were 4- to 8-fold lower than those determined at neutral pH. These observations were then confirmed against a larger collection of bacteria. These data suggest that finafloxacin could potentially offer a therapeutic advantage within acidic foci of infection. Copyright © 2011, American Society for Microbiology. All Rights Reserved. Source

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