Antimicrobial Susceptibility StudiesCharacterization of variables that may influence ozenoxacin in susceptibility testing, including MIC and MBC values☆,☆☆
Introduction
Ozenoxacin, a novel non-fluorinated quinolone antibacterial agent (Fig. 1), is currently in late stage phase III trials for the topical treatment of impetigo. It has shown an excellent in vitro activity against relevant Gram-positive cocci, such as Staphylococcus aureus and Streptococcus pyogenes, causing skin and soft tissue infections (SSTI), including clinical isolates with resistance to levofloxacin or with mutations in gyrA and/or parC genes, which confer resistance to fluoroquinolones (Morrissey et al., 2012, López et al., 2013). A similar potency to retapamulin has also been demonstrated, and it is more potent than other commonly prescribed topical agents such as fusidic acid or mupirocin. Moreover, it is more potent than levofloxacin (Morrissey et al., 2012). Ozenoxacin could represent a first-in-class treatment option for a variety of infectious skin conditions, including those due to S. pyogenes and S. aureus, the most frequent pathological causes of impetigo (Drucker, 2012).
In this study, we compared the in vitro bacteriostatic and bactericidal activity of ozenoxacin with the activities of ciprofloxacin and levofloxacin and determined the effects of different testing parameters on their MICs and MBCs. Testing parameters were selected according to M23-A3 document guidelines (CLSI, 2003) that consider the study of procedural variations known to impact antimicrobial susceptibility testing of other structurally established antimicrobial agents. The activity of quinolones has been shown to be influenced by cation supplementation and mainly by pH, including pH changes that occur during CO2 incubation (Bolmstrom and Karlsson, 2002, Smith et al., 1988). We focused our study on the effect of these 2 parameters. Additionally, the effect of inoculum size, inoculum preparation, incubation time, human serum, and incubation with CO2 were also investigated.
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Bacterial strains
Sixteen ATCC quality control (QC) strains and 40 non-duplicated clinical isolates from blood or SSTI collected at Ramón y Cajal University Hospital during 2010 were tested. ATCC strains included S. aureus ATCC 29213, S. aureus ATCC 33591, S. aureus ATCC 700789, Staphylococcus epidermidis ATCC 12228, Staphylococcus haemolyticus ATCC 29970, Enterococcus faecalis ATCC 29212, E. faecalis ATCC 51299, S. pyogenes ATCC 19615, Escherichia coli ATCC 25922, E. coli ATCC 35218, Klebsiella pneumoniae ATCC
Results and discussion
The ozenoxacin, ciprofloxacin, and levofloxacin MIC range, MIC50, and MIC90 values obtained by the broth microdilution method for the 40 clinical isolates under standard CLSI test conditions are summarized in Table 1. We mainly focused on the main pathogens associated with skin infection, but a representative low number of some species such as P. aeruginosa or Enterococcus spp. has also been included. Despite this limitation, we observed differences not only in the ozenoxacin activity among
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Funding: The study was performed with a research grant from Ferrer International S.A. (Barcelona, Spain) and partially supported by the Ministerio de Sanidad, Instituto de Salud Carlos III, Spanish Network for Research in Infectious Diseases (REIPI RD12/0015).
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Conflict of interest: Fernando Garcia-Alonso and Domingo Gargallo-Viola are employed by Ferrer Laboratories. Other authors declare no conflicts of interest.