Mutations in the quinolone resistance determining region in Staphylococcus epidermidis recovered from conjunctiva and their association with susceptibility to various fluoroquinolones

Division for Vision Research, National Institute of Sensory Organs, National Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo 152-8902, Japan.
The British journal of ophthalmology (Impact Factor: 2.81). 07/2008; 92(6):848-51. DOI: 10.1136/bjo.2007.129858
Source: PubMed

ABSTRACT Staphylococcus epidermidis is one of the prominent pathogens in ocular infection. The prevalence of mutations in the quinolone resistance determining region (QRDR) area in S epidermidis isolated from the ocular surface and its association with fluoroquinolone resistance has not been fully elucidated.
Mutations in the QRDR of gyrA, gyrB, parC, and parE genes of 138 isolates of S epidermidis recovered from the human conjunctival flora were analysed. The minimal inhibitory concentrations (MICs) of four fluoroquinolones (levofloxacin, gatifloxacin, moxifloxacin and tosufloxacin) against these isolates were also determined using agar dilution methods.
The MIC(90) values of levofloxacin, gatifloxacin, moxifloxacin and tosufloxacin were 3.13, 1.56, 0.78 and 3.13 microg/ml, respectively. The MIC values of all fluoroquinolones showed a bimodal distribution (susceptible strain and less susceptible strain). Mutations with amino acid substitution in the QRDR were present in 70 (50.7%) isolates. 19 different combinations of mutations were detected: 3 isolates (2.2%) had four mutations, 8 (5.8%) had three mutations, 43 (31.2%) had double mutations and 16 (11.6%) had single mutations. Isolates with mutations in the QRDR of both gyrA and parC (n = 53) were less susceptible to fluoroquinolones.
The present findings show that approximately half the S epidermidis isolates from the normal human conjunctiva have mutation(s) in the QRDR. The presence of mutations in both gyrA and parC is strongly associated with reduced susceptibility to fluoroquinolones.

Download full-text


Available from: Masakazu Yamada, Jul 29, 2015
  • Journal of Clinical Epidemiology 01/1997; 50. DOI:10.1016/S0895-4356(97)87223-X · 5.48 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Levofloxacin 0.5% ophthalmic solution (Cravit, Quixin, Oftaquix) has well established efficacy and tolerability in the treatment of external ocular infections. Levofloxacin 0.5% ophthalmic solution was generally more effective than ofloxacin 0.3% ophthalmic solution in the treatment of external ocular infections, and noninferiority was seen between levofloxacin 0.5% ophthalmic solution and both moxifloxacin 0.5% and tosufloxacin 0.3% ophthalmic solutions in the treatment of bacterial conjunctivitis. Although levofloxacin 0.5% ophthalmic solution administered in the hour prior to surgery did not reduce the incidence of endophthalmitis in patients undergoing intraocular surgery, additional data are needed to examine an optimal preoperative regimen of this antibacterial; preoperative levofloxacin 0.5% ophthalmic solution plus an iodine eyewash reduced positive culture rates in patients undergoing intraocular surgery. Levofloxacin 0.5% ophthalmic solution was well tolerated in the treatment of external ocular infections. Thus, levofloxacin 0.5% ophthalmic solution remains an important option in the treatment of bacterial conjunctivitis and other external ocular infections, as well as for perioperative use.
    Drugs 02/2009; 69(9):1267-86. · 4.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Studies were conducted to evaluate the ocular penetration and systemic exposure to besifloxacin, a fluoroquinolone antibiotic, following topical ocular administration to animals and humans. Besifloxacin ophthalmic suspension (0.6%) was administered as a topical ocular instillation to pigmented rabbits, cynomolgus monkeys, and human subjects. At predetermined intervals after dosing, samples of ocular tissues and plasma were collected and analyzed for besifloxacin levels using HPLC/MS/MS methods. Besifloxacin demonstrated good ocular penetration in rabbits and monkeys, with rapid absorption and sustained concentrations observed in anterior ocular tissues through 24 h after a single administration. Maximum besifloxacin concentrations in conjunctiva, cornea, and aqueous humor of monkeys were 6.43 microg/g, 2.10 microg/g, and 0.796 microg/mL, respectively, after a single topical dose, and concentrations declined in these tissues with an apparent half-life of 5-14 h. Following a single topical ocular administration to humans, the maximum besifloxacin concentration in tears was 610 microg/g with concentrations decreasing to approximately 1.6 microg/g at 24 h. The resulting pharmacokinetic parameters for besifloxacin in human tears were evaluated relative to the MIC(90) values (microg/mL) for besifloxacin against Streptococcus pneumoniae (0.125), Staphylococcus aureus (0.25), Staphylococcus epidermidis (0.5), and Haemophilus influenzae (0.06). Following a single topical administration, the C(max)/MIC(90) ratios for besifloxacin in human tears were > or =1,220, and the AUC((0-24))/MIC(90) ratios were > or =2,500 for these relevant ocular pathogens. Following repeated 3-times daily (TID) topical ocular administration to human subjects with clinically diagnosed bacterial conjunctivitis, maximum besifloxacin concentrations in plasma were less than 0.5 ng/mL, on average. Taken together, the results of the current investigation provide a PK/PD-based rationale that supports the use of besifloxacin for the safe and effective treatment of ocular infections.
    Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 06/2009; 25(4):335-44. DOI:10.1089/jop.2008.0116 · 1.42 Impact Factor
Show more