Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · Dec 2011
Randomized Controlled Trial Multicenter Study Comparative StudyRandomized, double-blind, phase II, multicenter study evaluating the safety/tolerability and efficacy of JNJ-Q2, a novel fluoroquinolone, compared with linezolid for treatment of acute bacterial skin and skin structure infection.
JNJ-Q2 is a fluoroquinolone with broad coverage including methicillin-resistant Staphylococcus aureus (MRSA). A double-blind, multicenter, phase II noninferiority study treated 161 patients for 7 to 14 days, testing the efficacy of JNJ-Q2 (250 mg, twice a day [BID]) versus linezolid (600 mg, BID) in patients with acute bacterial skin and skin structure infections (ABSSSI). The prespecified criterion for noninferiority was 15%. ⋯ Nausea and vomiting were the most common adverse events. Of the patients, 86% (104/121) had S. aureus isolated from the infection site; 63% of these were MRSA. The results suggest JNJ-Q2 shows promise as an effective treatment for ABSSSI, demonstrating (i) efficacy for early clinical response (i.e., lack of spread of lesions and absence of fever at 48 to 72 h), and (ii) cure rates for ABSSSI pathogens (especially MRSA) consistent with the historical literature.
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Antimicrob. Agents Chemother. · Dec 2011
Multicenter StudyProspective multicenter study of the epidemiology, molecular identification, and antifungal susceptibility of Candida parapsilosis, Candida orthopsilosis, and Candida metapsilosis isolated from patients with candidemia.
A 13-month prospective multicenter study including 44 hospitals was carried out to evaluate the epidemiology of Candida parapsilosis complex candidemia in Spain. Susceptibility to amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole, posaconazole, anidulafungin, caspofungin, and micafungin was tested by the microdilution colorimetric method. A total of 364 C. parapsilosis complex isolates were identified by molecular methods: C. parapsilosis (90.7%), Candida orthopsilosis (8.2%), and Candida metapsilosis (1.1%). ⋯ Applying the new species-specific fluconazole and echinocandin breakpoints, the rates of resistance to fluconazole for C. parapsilosis and C. orthopsilosis increased to 4.8% and 0.3%, respectively; conversely, for C. parapsilosis they shifted from 1.9 to 0.6% (anidulafungin) and from 2.5 to 0.6% (micafungin). Our study confirms the different prevalence of C. parapsilosis complex candidemia among age groups: neither C. orthopsilosis nor C. metapsilosis was isolated from neonates; interestingly, C. metapsilosis was isolated only from adults and the elderly. The disparity in antifungal susceptibility among species could be important for therapy.
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Antimicrob. Agents Chemother. · Dec 2011
ReviewCurrent prospects for the fluoroquinolones as first-line tuberculosis therapy.
While fluoroquinolones (FQs) have been successful in helping cure multidrug-resistant tuberculosis (MDR TB), studies in mice have suggested that if used as first-line agents they might reduce the duration of therapy required to cure drug-sensitive TB. The results of phase II trials with FQs as first-line agents have been mixed, but in at least three studies where moxifloxacin substituted for ethambutol, there was an increase in the early percentage of sputa that converted to negative for bacilli. ⋯ The principal risk for resistance may be when FQs are used to treat nonspecific respiratory symptoms that are in fact TB, so curtailing this use of FQs could reduce the development of resistance and also the delays in TB diagnosis and treatment that have been documented when an FQ is given in this setting. While the future of FQs as first-line therapy will likely depend upon the results of the ongoing phase III trials, if they are to be effectively employed in high-TB-burden regions their use for community-acquired pneumonias should be restricted, the prevalence of FQ-resistant TB should be monitored, and the cost of the treatment should be comparable to that of current standard drug regimens.
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Antimicrob. Agents Chemother. · Dec 2011
Sterilizing activity of novel TMC207- and PA-824-containing regimens in a murine model of tuberculosis.
To truly transform the landscape of tuberculosis treatment, novel regimens containing at least 2 new drugs are needed to simplify the treatment of both drug-susceptible and drug-resistant forms of tuberculosis. As part of an ongoing effort to evaluate novel drug combinations for treatment-shortening potential in a murine model, we performed two long-term, relapse-based experiments. In the first experiment, TMC207 plus pyrazinamide, alone or in combination with any third drug, proved superior to the first-line regimen including rifampin, pyrazinamide, and isoniazid. ⋯ In the second experiment evaluating 3-drug combinations composed of TMC207, pyrazinamide, PA-824, moxifloxacin, and rifapentine, TMC207 plus pyrazinamide plus either rifapentine or moxifloxacin was the most effective, curing 100% and 67% of the mice treated, respectively, in 2 months of treatment. Four months of the first-line regimen did not cure any mice, whereas the combination of TMC207, PA-824, and moxifloxacin cured 50% of the mice treated. The results reveal new building blocks for novel regimens with the potential to shorten the duration of treatment for both drug-susceptible and drug-resistant tuberculosis, including the combination of TMC207, pyrazinamide, PA-824, and a potent fluoroquinolone.