Drug-induced QT prolongation is a major safety issue during drug development because it may lead to lethal ventricular arrhythmias. In this study, we evaluated the utility of multi-electrode arrays (MEA) with human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) to predict drug-induced QT prolongation and arrhythmia.
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We investigated the susceptibility to antibacterials, genotype of penicillin-binding protein (PBP) genes and macrolide resistant genes, and the serotypes against 377 strains of Streptococcus pneumoniae isolated from medical facilities in Gifu and Aichi prefectures between June 2008 and April 2009. These results were compared with those against 160 strains of S. pneumoniae isolated in 2004. Referring to CLSI (M100-S17), the overall incidence of penicillin-susceptible (PSSP), penicillin-intermediate (PISP) and penicillin-resistant (PRSP) S. pneumoniae was 143 (38%), 185 (49%) and 49 (13%) strains, respectively. PISP and PRSP were isolated higher in the material of nasal cavity and throat, and PRSP was isolated higher in the area of Chuno district. The number of gPSSP with 3 normal PBP genes, gPISP with 1 or 2 normal PBP genes and gPRSP with 3 abnormal genes was 23 (6.1%), 173 (46%) and 181 (48%) strains, respectively. The isolates with no macrolide-resistant gene, only mefA, only ermB, and both mefA and ermB were 28 (7.4%), 138 (37%), 166 (44%) and 45 (12%). The prevalent pneumococcal serotypes were type 19 (92 strains; 24%), following by type 23 (60 strains; 16%) and type 6 (56 strains; 15%). The 80% of pneumococcal serotypes of PRSP were serotype 19 and 6. The MIC90 of each antibacterial was as follows; 0.1 microg/mL for imipenem, panipenem and garenoxacin, 0.2 microg/mL for moxifloxacin, 0.39 microg/mL for meropenem and tosufloxacin, 0.78 microg/ mL for amoxicillin, clavulanic acid/amoxicillin, cefditoren and cefcapene, 1.56 microg/mL for benzylpenicillin, piperacillin, cefteram and levofloxacin, 3.13 microg/mL for cefotiam, flomoxef and pazufloxacin, 6.25 microg/mL for cefdinir, 12.5 microg/mL for norfloxacin and minocycline, > 100 microg/mL for clarithromycin, and these MIC90s were about the same as those in 2004.
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Episodes of acute rhinosinusitis are common among adults and are associated with a significant amount of morbidity. The symptoms of rhinosinusitis are nasal drainage, congestion, and sinus pressure. A bacterial sinus infection is more likely if these symptoms worsen after 5-7 days or do not improve after 10-14 days. The majority of bacterial episodes have been associated with Streptococcus pneumoniae and Haemophilus influenzae. In the current era of increasing resistance to beta -lactams and macrolides, treatment guidelines have been formulated worldwide to assist clinicians in the selection of antibacterials. According to one model, the following antibacterials are most likely to provide desired outcomes (90%-92% predicted clinical efficacy) for adults: respiratory fluoroquinolones (i.e., moxifloxacin, gatifloxacin, and levofloxacin), ceftriaxone, and high-dose amoxicillin-clavulanate (4 g of amoxicillin/day and 250 mg of clavulanate/day). Although the role of the fluoroquinolones in the treatment of this condition is evolving, fluoroquinolones are often recommended as second-line therapy or as first-line therapy for selected patients (e.g., those who received antibacterials in the previous 4-6 weeks or adults with moderate-to-severe disease).
Certain causes of uveitis are byphosphonates, topiramato and metipranolol eyedrops. Probable causes are rifabutin, sulfonamides, cidofovir, immunorecovery in patients following HAART therapy, topical corticosteroids, latanoprost, and intravitreous triamcinolone acetate. Possible causes of uveitis include bimatoprost, travoprost, brimonidine, other eyedrops and intraocular drugs, tubulointerstitial nephritis and uveitis (TINU) produced by nonsteroidal drugs, iopamidol, diethylcarbamazepine, interleukins 3 and 6, oral contraceptives, quinidine, vaccines and cobalt, ibuprofen and moxifloxacin.
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Moxifloxacin, a new respiratory quinolone, was compared with the macrolides azithromycin, clarithromycin and roxithromycin in a cohort study to assess clinical, safety and health-related outcomes of these antimicrobials in general practice settings. In total 332 patients with acute exacerbations of chronic bronchitis (AECB) each received one of the antimicrobial agents for a standard short course of therapy. Random allocation of therapeutic agents occurred by centre, not individuals, and the drugs were prescribed in an open manner. In addition to clinical evaluation by their physicians, all patients kept daily diaries to assess AECB symptoms over the study period, therapy received and quality of life. The overall clinical response rate was 96% and all four regimens were well tolerated. After 14 days there were no significant differences between the study groups, but analyses of patients' daily evaluations of certain AECB specific symptoms showed a faster response rate in the moxifloxacin group.
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Overall, moxifloxacin was the most effective of the four fluoroquinolones in reducing CFU/cornea in the rabbit model of gram-negative keratitis.
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Eradication of Helicobacter pylori remains a problematic treatment issue in clinical practice. The intention is to find a treatment that achieves a high rate of eradication at a low price and treatment options that are now used give us the opportunity to achieve this goal. Recently published results showing a low rate of resistance and better compliance with moxifloxacin-based treatment regimens indicate the need to investigate its efficacy in H. pylori eradication. This study is based on proving the efficacy of moxifloxacin in H. pylori eradication within the triple therapy.
Levofloxacin and moxifloxacin are characterized by a lower propensity to select in vitro for resistance in S. pneumoniae than ciprofloxacin and prulifloxacin, when tested at plasma and lung concentrations.
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Most of gram-positive isolates from urinary tract (100%), respiratory tract (89.7%), and bloodstream infections (BSIs; 65.5%) were obtained from leukemic patients. All gram-positive isolates from skin infections were isolated from solid-tumor patients. In both leukemic and solid-tumor patients, gram-positive bacteria causing nosocomial BSI were mainly Coagulase-negative staphylococcus (CNS) and S. aureus, whereas gram-positive bacteria causing nosocomial RTI were mainly alpha-hemolytic streptococci and CNS. Gram-positive bacteria were not isolated from GI tract infections. S. aureus, CNS, and alpha-hemolytic streptococci demonstrated methicillin resistance (81.5%, 92.3%, and 90% resistance, respectively). S. aureus and CNS were susceptible to linezolid (15.4% and 0% resistance, respectively), and vancomycin (15.5% and 11% resistance, respectively).
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Exogenous l-serine sensitized E. coli ATCC 25922 and clinically isolated fluoroquinolone-resistant E. coli to fluoroquinolones. This potentiation is independent of growth phase. Addition of serine increases the production of NADH. The underlying mechanism of this strategy is that the combination of serine with ofloxacin or moxifloxacin increases the NAD(+)/NADH ratio, disrupts the Fe-S clusters and increases the production of endogenous reactive oxygen species. Furthermore, we used a serine and ofloxacin or moxifloxacin combination in vitro to combat bacterial persister cells, compared with antibiotic treatment alone; combinational treatments of persister cells with antibiotics and l-serine resulted in a significantly greater decrease in cell viability.