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.

Institut Clínic d'Infeccions i Immunologia, IDIBAPS, Departament de Microbiologia, Facultat de Medicina, Hospital Clínic, Barcelona, Spain.
Clinical Microbiology and Infection (Impact Factor: 5.2). 12/2002; 8(12):781-90. DOI: 10.1046/j.1469-0691.2002.00400.x
Source: PubMed

ABSTRACT To study the activity of five different fluoroquinolones against 22 epidemiologically related and unrelated strains of Staphylococcus aureus (13 methicillin-resistant (MRSA) strains and nine methicillin-susceptible (MSSA) strains) in which the mechanisms of quinolone resistance are also investigated.
The MICs of the different fluoroquinolones were determined by the microdilution method, in the presence and absence of reserpine. The quinolone resistance-determining regions of the gyrA, gyrB, grlA and grlB genes were amplified and sequenced to establish the presence of mutations. The molecular epidemiology of the 22 strains was performed by low-frequency restriction analysis of chromosomal DNA with SmaI.
MSSA strains showed lower homology than MRSA strains, in which only two clones were seen. Trovafloxacin showed the best activity against these clinical isolates of S. aureus, since strains carrying one amino acid change in both GyrA and GrlA subunits remained susceptible to this antimicrobial agent. Furthermore, trovafloxacin did not seem to be a substrate for NorA.
Trovafloxacin was the most active quinolone tested against S. aureus strains, followed by levofloxacin and sparfloxacin, whereas ciprofloxacin and norfloxacin were the least active quinolones, in both the presence and absence of reserpine. Epidemiologically related S. aureus strains presented different mechanisms of quinolone resistance, suggesting a divergent evolution of the same clone. Finally, 16 S. aureus strains with a ciprofloxacin plus reserpine MIC > or = 1 mg/L already showed a mutation in the grlA gene. This MIC may be useful as a marker of mutation in this gene, contraindicating the use of this quinolone, since a second mutation may develop during treatment.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In vitro activity of ozenoxacin, a novel nonfluorinated topical (L. D. Saravolatz and J. Leggett, Clin. Infect. Dis. 37:1210–1215, 2003) quinolone, was compared with the activities of other quinolones against well-characterized quinolone-susceptible and quinolone-resistant Gram-positive bacteria. Ozenoxacin was 3-fold to 321-fold more active than other quinolones. Ozenoxacin could represent a first-in-class nonfluorinated quinolone for the topical treatment of a broad range of dermatological infections.
    Antimicrobial Agents and Chemotherapy 12/2013; 57(12). DOI:10.1128/AAC.01509-13 · 4.45 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Fluoroquinolones are an important class of wide-spectrum antibacterial agents. The first quinolone described was nalidixic acid, which showed a narrow spectrum of activity. The evolution of quinolones to more potent molecules was based on changes at positions 1, 6, 7 and 8 of the chemical structure of nalidixic acid. Quinolones inhibit DNA gyrase and topoisomerase IV activities, two enzymes essential for bacteria viability. The acquisition of quinolone resistance is frequently related to (i) chromosomal mutations such as those in the genes encoding the A and B subunits of the protein targets (gyrA, gyrB, parC and parE), or mutations causing reduced drug accumulation, either by a decreased uptake or by an increased efflux, and (ii) quinolone resistance genes associated with plasmids have been also described, i.e. the qnr gene that encodes a pentapeptide, which blocks the action of quinolones on the DNA gyrase and topoisomerase IV; the aac(6')-Ib-cr gene that encodes an acetylase that modifies the amino group of the piperazin ring of the fluoroquinolones and efflux pump encoded by the qepA gene that decreases intracellular drug levels. These plasmid-mediated mechanisms of resistance confer low levels of resistance but provide a favourable background in which selection of additional chromosomally encoded quinolone resistance mechanisms can occur.
    Microbial Biotechnology 01/2009; 2(1):40-61. DOI:10.1111/j.1751-7915.2008.00063.x · 3.21 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Nadifloxacin has good activity against Propionibacterium acnes as well as against both meticillin-susceptible and -resistant Staphylococcus aureus (MSSA and MRSA, respectively) and Staphylococcus epidermidis. The aim of this study was to evaluate the activity of this fluoroquinolone against the abovementioned microorganisms, comparing isolates collected in 2007 in Germany, a country where nadifloxacin has been used for the last 2 years, with isolates collected from 2006-2007 in Spain where nadifloxacin has not been used. A collection of P. acnes from Hungary (strains collected during 2005-2006) and a collection of P. acnes from different countries in Europe (collected during 2002) were also included. The activity of nadifloxacin was compared with ciprofloxacin, erythromycin and clindamycin. Susceptibility testing of P. acnes was performed by agar dilution, whereas the susceptibility of the different staphylococci was determined by microdilution. Although the isolates were collected from three different countries (Spain, Hungary and Germany) where the use of quinolones can produce a different effect, no significant differences in the percentages of resistance to nadifloxacin were observed in P. acnes, MSSA, MRSA and S. epidermidis. Therefore, topical antibiotics such as nadifloxacin do not have an additional effect on resistance. Moreover, nadifloxacin presented much better activity than the comparator drugs used in this study against the studied microorganisms.
    International journal of antimicrobial agents 03/2009; 33(3):272-5. DOI:10.1016/j.ijantimicag.2008.08.024 · 3.03 Impact Factor


Available from
Sep 1, 2014