Emergence of phenotypic resistance to ciprofloxacin and levofloxacin in methicillin-resistant and methicillin-sensitive Staphylococcus aureus strains.
ABSTRACT The emergence of phenotypic resistance to ciprofloxacin and levofloxacin in methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MRSA) strains was studied. Twenty MRSA and 77 methicillin-sensitive S.aureus (MSSA) strains susceptible to both quinolones were investigated for resistance after single step or serial passages. No growth of 20 MRSA strains was observed at 4xMIC of levofloxacin after 48 h incubation, but 4 of 77 (5%) MSSA strains grew at the same concentration. At 4xMIC concentration of ciprofloxacin, 10 MSSA (13%) and five MRSA (25%) strains were grown. In the serial passages of MRSA strains, resistance to ciprofloxacin was 75 and 5% for levofloxacin by the third passage. In the seventh passage this resistance was 100 and 15%, respectively. In MSSA strains, resistance to ciprofloxacin was 75 and 19% to levofloxacin at the third passage and at the seventh passage, 100 and 61%, respectively. Emergence of ciprofloxacin resistance was more common and developed more rapidly than resistance to levofloxacin in both MRSA and MSSA strains.
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ABSTRACT: Newer fluoroquinolones such as levofloxacin, moxifloxacin, gatifloxacin and gemifloxacin have several attributes that make them excellent choices for the therapy of lower respiratory tract infections. In particular, they have excellent intrinsic activity against Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and the atypical respiratory pathogens. Fluoroquinolones may be used as monotherapy to treat high-risk patients with acute exacerbation of chronic bronchitis, and for patients with community-acquired pneumonia requiring hospitalisation, but not admission to intensive care. Overall, the newer fluoroquinolones often achieve clinical cure rates in > or =90% of these patients. However, rates may be lower in hospital-acquired pneumonia, and this infection should be treated on the basis of anticipated organisms and evaluation of risk factors for specific pathogens such as Pseudomonas aeruginosa. In this setting, an antipseudomonal fluoroquinolone may be used in combination with an antipseudomonalbeta-lactam. Concerns are now being raised about the widespread use, and possibly misuse, of fluoroquinolones and the emergence of resistance among S. pneumoniae, Enterobacteriaceae and P. aeruginosa. A number of pharmacokinetic parameters such as the peak concentration of the antibacterial after a dose (C(max)), and the 24-hour area under the concentration-time curve (AUC24) and their relationship to pharmacodynamic parameters such as the minimum inhibitory and the mutant prevention concentrations (MIC and MPC, respectively) have been proposed to predict the effect of fluoroquinolones on bacterial killing and the emergence of resistance. Higher C(max)/MIC or AUC24/MIC and C(max)/MPC or AUC24/MPC ratios, either as a result of dose administration or the susceptibility of the organism, may lead to a better clinical outcome and decrease the emergence of resistance, respectively. Pharmacokinetic profiles that are optimised to target low-level resistant minor subpopulations of bacteria that often exist in infections may help preserve fluoroquinolones as a class. To this end, optimising the AUC24/MPC or C(max)/MPC ratios is important, particularly against S. pneumoniae, in the setting of lower respiratory tract infections. Agents such as moxifloxacin and gemifloxacin with high ratios against this organism are preferred, and agents such as ciprofloxacin with low ratios should be avoided. For agents such as levofloxacin and gatifloxacin, with intermediate ratios against S. pneumoniae, it may be worthwhile considering alternative dose administration strategies, such as using higher dosages, to eradicate low-level resistant variants. This must, of course, be balanced against the potential of toxicity. Innovative approaches to the use of fluoroquinolones are worth testing in further in vitro experiments as well as in clinical trials.Drugs 02/2005; 65(7):949-91. · 4.13 Impact Factor
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ABSTRACT: 99mTc-Labeled antimicrobial peptide ubiquicidin, (99m)Tc-UBI (29-41) in a freeze-dried kit, was evaluated as a bacterial infection-seeking agent in Staphlococcus aureus- and Escherichia coli-induced infections. Thirty-three rabbits were classified in 3 groups. Biodistribution of (99m)Tc-UBI (29-41) was studied in 3 animals (group I). Uptake of peptide was determined by counting radioactivity in anatomically fitted regions drawn over the liver, kidneys, urinary bladder, and whole body and expressed as the percentage uptake per organ. Experimental thigh muscle infection was induced by injecting 2 x 10(8) colony-forming units of live S. aureus or E. coli bacteria into the right thigh muscle in 20 rabbits (group II). Turpentine oil and formalin-killed S. aureus were used for inducing sterile thigh muscle inflammation in 10 rabbits (group III). On scintigrams, anatomically adjusted regions of interest were drawn over infected/inflamed (target) and noninfected/noninflamed (nontarget) thigh, and accumulation of (99m)Tc-UBI (29-41) at sites of infection/inflammation was expressed as a target-to-nontarget (T/NT) ratio. A biodistribution study of (99m)Tc-UBI (29-41) revealed rapid removal of tracer from the circulation via the kidneys (10.6% +/- 2.1% at 5 min and 5.9% +/- 0.8% at 60 min) with accumulation of the major part in the urinary bladder within the first hour after injection (66.6% +/- 7.2%). A significantly higher (P < 0.05) accumulation of (99m)Tc-UBI (29-41) was seen at sites of S. aureus-infected animals (T/NT ratio, 2.2 +/- 0.5) compared with that of E. coli-infected animals (T/NT ratio, 1.7 +/- 0.4). The maximum tracer accumulation was observed at 60 min after injection followed by a gradual decline. No significant accumulation was noticed in thighs of rabbits injected with either turpentine oil or killed S. aureus with markedly lower T/NT ratios (P < 0.05) compared with that of S. aureus- and E. coli-infected thighs. A (99m)Tc-UBI (29-41) freeze-dried kit can be used for differentiating infections with S. aureus and E. coli with significantly higher scintigraphic intensity (P < 0.05) compared with that of sterile inflammatory sites. The optimum time for infection imaging is 60 min after injection. Relatively low (T/NT) ratios were observed in E. coli infections compared with those of the S. aureus group, which may be due to a low virulence of the former; however, other possible reasons may include low affinity of this peptide for E. coli microbial membranes.Journal of Nuclear Medicine 06/2004; 45(5):849-56. · 5.77 Impact Factor
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ABSTRACT: Methicillin-resistant Staphylococcus aureus (MRSA) otorrhea has become an increasing problem with regard to infection through the tympanic membrane perforation and postsurgical infection. In particular, dry ear, at the preoperative stage, is considered to be a crucial factor in surgery. We evaluated how to control MRSA otorrhea before and after ear surgery. Twenty-six patients having MRSA otorrhea were enrolled in the present study and randomly divided into 2 groups, namely, mupirocin ointment therapy for 16 patients and ofloxacin ear drops for 10 patients. Approximately 0.6 mg of mupirocin ointment was administered locally to the tympanic membrane and the promontory around and through the perforation with its adjacent external ear canal 1 to 4 times for 2 or 3 weeks at the clinic. On the other hand, ofloxacin ear drops were administered daily by the patients for 2 or 3 weeks at home. Complete elimination of MRSA from the ear was obtained in all patients of the mupirocin group. This showed a significant improvement (p < 0.001) as compared with the ofloxacin group (improvement + cure rate, 40%). Local application of mupirocin did not aggravate hearing acuity of any patients who were evaluated by pure-tone audiometry before and after treatment. The present findings first indicate that minimally essential application of mupirocin ointment is an extremely useful ototopical agent against MRSA otorrhea without ototoxicity.Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 09/2008; 29(5):676-8. · 1.44 Impact Factor