The study compared a series of 6 focused case-control studies. Cases consisted of patients with laboratory-confirmed CDI admitted from July-October 2009. Controls were selected from patients without CDI hospitalized during the same period. Five groups of controls were matched to cases (2:1 ratio) using group-specific matching criteria, including admission date, age, type of admission, length of stay (LOS) to discharge, and/or LOS to CDI diagnosis. The final control group was selected from patients who received antibiotics during hospitalization. Data, including demographics and antibiotic usage, were compared between case and control groups.
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This study compares the in vitro activity of novel fluoroquinolones against clinical Legionella pneumophila isolates. We determined both the MICs and intracellular efficacy of moxifloxacin, trovafloxacin, clinafloxacin and levofloxacin in the Mono Mac 6 infection model. Six legionella strains were tested and all proved highly susceptible to the fluoroquinolones. Clinafloxacin and trovafloxacin were found to have the lowest MICs (0.004 mg/L) followed by levofloxacin and moxifloxacin (0.015-0.03 mg/L). In the Mono Mac 6 infection model, inhibition of L. pneumophila was achieved at concentrations four times below the respective in vitro MICs. Concentrations as low as 0.015 mg/L of moxifloxacin and levofloxacin, 0.004 mg/L of trovafloxacin and 0.002 mg/L of clinafloxacin markedly decreased viable intracellular bacterial counts. These data strongly support further clinical evaluation of new fluoroquinolones for empirical treatment of lower respiratory tract infection including atypical pneumonia caused by L. pneumophila.
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To review clinical information on fluoroquinolone antimicrobials to distinguish between these agents and help define their place in clinical practice.
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English-language documents were reviewed for pharmacology, pharmacokinetics, efficacy, and safety, with priority on clinical trials.
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To compare the in vitro antimicrobial susceptibilities of Gram-positive cocci isolated from the ocular infections to the second and fourth generation fluoroquinolones at a tertiary eye care centre in south India.
In five patients, a uveitis-like episode followed oral moxifloxacin therapy, afterwards they experienced photophobia. At slitlamp investigation, the patients showed almost complete iris transillumination, not restricted to one sector, and persistent mydriasis of the pupil, with no reaction to light and no near reflex. Follow-up of 3 years in one of the patients showed no change of symptoms. Only in one patient, with a history of anterior uveitis, an anterior chamber tap was positive for herpes simplex genome. Only after the use of moxifloxacin did she experience continuous photophobia.
Drug-induced prolongation of the QT interval on the electrocardiogram (ECG) infrequently results in Torsades de pointes, a potentially fatal arrhythmia. Therefore, thorough QT analysis of new drugs is a regulatory requirement. The objective of this phase 1 study was to assess the effects of oral tedizolid phosphate on the QT interval corrected with Fridericia's formula (QTcF) in healthy adult subjects. A single therapeutic dose (200 mg) and a supratherapeutic dose (1200 mg) of tedizolid phosphate were administered to characterise QTc changes following typical systemic exposure and with markedly higher exposures, respectively. This was a four-way crossover study with 48 subjects randomly assigned to receive therapeutic and supratherapeutic doses of tedizolid phosphate, moxifloxacin (positive control for QT interval prolongation) and placebo (negative control). A continuous 12-lead ECG was recorded from 1 h before drug administration to 23 h after administration. Adverse events, which were generally mild, occurred most frequently with moxifloxacin or with a supratherapeutic dose of tedizolid phosphate; however, all treatments were well tolerated. This study demonstrated that therapeutic or supratherapeutic doses of the antibacterial tedizolid had no clinically significant effect on QT interval in healthy adults [ClinicalTrials.gov registration no.: NCT01461460].
Chronic obstructive pulmonary disease is a disease state characterized by the presence of airflow obstruction due to chronic bronchitis and/or emphysema. The airflow obstruction is generally progressive. In the past asthma was often confused with chronic obstructive pulmonary disease but as the cellular inflammatory mechanisms are quite different to chronic bronchitis and emphysema it is prudent to separate this condition of airway hyper-responsiveness. Exacerbation of chronic obstructive pulmonary disease is a considerable burden on health service resources in terms of morbidity and mortality. Approximately one half of exacerbations can be attributed to bacterial pathogens, the major pathogens being Haemophilus influenzae, Streptococcus pnemoniae and Moraxella catarrhalis. Resistance to common first-line treatment antibiotics such as the beta-lactams can be variable. Newer fluoroquinolones such as grepafloxacin, levofloxacin, sparfloxacin, clinafloxacin, moxifloxacin, gatifloxacin and gemifloxacin are characterized by improved activity against Gram positive bacteria as well as their Gram negative properties. However, more randomized controlled trials need to be accomplished before the true role of quinolones in exacerbation of chronic obstructive pulmonary disease is clearly ascertained.
The pharmacokinetics of moxifloxacin in critically ill patients with acute renal failure undergoing CVVHDF was comparable to healthy subjects and patients without renal impairment. We recommend 400 mg of intravenous moxifloxacin once per day in anuric patients during CVVHDF.
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We investigated the aqueous humor concentration of topically applied gatifloxacin (GFLX) 0.3% and moxifloxacin (MFLX) 0.5% in a rabbit model of surgical and nonsurgical eyes. Topical administration in eyes was performed eight times, at 15-min intervals. Surgical eyes had undergone cataract surgery with the implantation of an intraocular lens (IOL). Aqueous humor was sampled at 5, 30, and 120 min after drug administration. Drug concentrations were determined by high-performance liquid chromatography (HPLC). The GFLX concentrations in surgical eyes at 5, 30, and 120 min post-administration were 12.1, 14.0, and 6.1 microg/ml, and those in nonsurgical eyes were 11.3, 11.5, and 7.1 microg/ml; there were no differences between surgical and nonsurgical eyes. The concentrations of MFLX in surgical eyes were 46.2, 42.7, and 31.1 microg/ml. The concentration of MFLX was higher than that of GFLX at 5 and 120 min post-administration (P < 0.05). A multiple-drop schedule produced much higher aqueous concentrations. There was no difference in drug penetration in eyes that had undergone cataract surgery compared with nonsurgical eyes.
Our study indicated that, in a successful experiment, the action potential duration (APD) can be stably maintained for several hours without intervention. Dofetilide, DL-sotalol, cisapride, risperidone and moxifloxacin increased endo- and epicardial APD(90), QT interval and T(P-E) (peak-to-end time of the T wave) in a reverse use-dependent manner within clinically relevant concentration ranges. Phase 2 early afterdepolarizations (EADs) were observed at 1.6, 2.3, 16.7, 37.5 and 7.9 fold, respectively, their corresponding unbound therapeutic concentrations. In contrast, fluoxetine at up to 3 microM (approximately 35 fold unbound therapeutic mean plasma concentration after 60 mg/day, p.o. for 5 weeks) had only a mild prolonging effect on APD(90) and QT with essentially no effect on T(P-E).
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Evaluate dalcetrapib's potential to prolong QT intervals in healthy subjects.
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We determined the antibiotic concentration that prevents the selection of resistant mutants following inoculation with a high mycobacteria inoculum on Middlebrook 7H11 plates with serial dilutions of the antibiotics in 224 M. tuberculosis isolates.
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After several decades without any notable progress, there are encouraging results in research and development of anti-TB drugs, the result of a large number of projects now in competition. Along with developing new drugs to treat tuberculosis (TMC207, SQ109, LL3858) are being reassessed others to optimize their effectiveness in order to shorten and simplify therapy (rifampin and rifapentine) and three other drugs, currently used for other indications, were forwarded towards TB (gatifloxacin and moxifloxacin, linezolid). Time to approval as a antiTB drug is 10-15 years, consisting of phases of preclinical and clinical research. Substitution of moxifloxacin for isoniazid during intensive phase treatment of pulmonary tuberculosis resulted in a small but statistically nonsignificant increase in 8th- week culture negativity. TMC207, a diarylquinoline with a unique way to address Mycobacterial ATP synthetase, shows high activity in vitro against Mycobacterial strains sensitive or resistant to all drugs in the first and second line, including fluoroquinolones, demonstrating exceptional qualities in vivo against several species of mycobacteria, in various animal models. TMC207 was added to a basic standard regimen in a study of MDR-TB patients. After two months and satisfactory tolerability, sputum conversion rate in culture was 48% (versus 9% in the placebo group). Two nitroimidazole (PA-824 and OPC-67683) are currently in clinical development. PA-824 demonstrated good safety and tolerability in adult patients with pulmonary TB in South Africa, when given once daily for 7 days. Associating isoniazid, would prevent the selection of mutants resistant to Isoniazid. Linezolid 600 mg is currently being tested in a Phase II for treatment of XDR-TB in the Republic of Korea. PNU-100480, analogous to the previous one, has the potential to significantly shorten the treatment in cases where there is sensitivity and in those with resistance to drugs. 300 mg dose is under investigation in a phase II pilot study in MDR-TB in South Africa. With this interest and commitment, it appears that there is a chance of having a new drug available soon.
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The pharmacokinetic characteristics of levofloxacin, moxifloxacin, and gatifloxacin include excellent oral bioavailability (90-99%), extensive penetration into tissues and body fluids, and an elimination half-life (6-12 hrs) that allows for once-daily dosing in patients with normal renal function. Levofloxacin and gatifloxacin primarily are excreted unchanged in the urine, whereas moxifloxacin undergoes hepatic metabolism. The pharmacodynamic values that correlate with successful clinical and microbiologic outcomes, as well as prevent emergence of bacterial resistance, are ratios of maximum or peak unbound drug concentration (Cmax) to minimum inhibitory concentration (MIC), and 24-hour unbound area under the concentration curve (AUC(0-24hr)) to MIC. For gram-negative infections, a Cmax:MIC greater than or equal to 10 and AUC(0-24hr):MIC greater than or equal to 125 are associated with increased probability of a successful outcome. For infections caused by Streptococcus pneumoniae, an AUC(0-24hr):MIC of 30 or more is suggested for favorable clinical outcomes. Pharmacokinetic and pharmacodynamic values influence rational therapeutic decisions in the selection and dosages of these drugs.
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To examine current practice patterns in the management of bacterial keratitis among U.S. ophthalmologists and differences in the management and opinions between cornea specialists and non-cornea specialists.
One hundred thirty-four (11.3%) of 1191 patients received a diagnosis of hepatotoxicity and needed to stop anti-TB treatment. The risk factor was abnormal baseline transaminase levels. Twenty-two of the 134 patients received the control medication, 40 received levofloxacin, and 45 received moxifloxacin; the remaining patients were excluded from the study. There were no significant prestudy differences between groups. Time to liver function normalization was almost the same for all groups (mean +/- standard deviation, 29.1+/-21.4, 25.5+/-17.6, and 29.7+/-14.3 days, respectively).
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BAK substantially lowered the MIC and MPC of gatifloxacin and moxifloxacin against Gram-positive staphylococci compared to gatifloxacin alone, moxifloxacin alone, and/or levofloxacin. These findings suggest that the presence of BAK in the ophthalmic formulation of gatifloxacin (Zymar) may serve to enhance the potency of gatifloxacin and decrease its propensity to select for fluoroquinolone-resistant S. aureus strains.
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Streptococcus pneumoniae is one of the most common pathogens to cause mucosal and invasive infection in humans. Resistance to fluoroquinolones (FQ) is associated with clinical failure when treating pneumococcal diseases and increase of mortality.
Fluoroquinolone-containing therapy is effective in eradicating Helicobacter pylori. However, the resistance rate of H. pylori to fluoroquinolones in Taiwan has not yet been reported. In this study, we aimed to investigate the susceptibility to antibiotics commonly used in eradication schedules and fluoroquinolones in H. pylori.
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These results support clinical investigation of the effectiveness of besifloxacin in treating Pseudomonas keratitis.
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Three different strains of B fragilis with different degrees of resistanceto moxifloxacin (minimum inhibitory concentrations [MICs]: 4, 8, and 16 pg/mL) were added to the challenge inoculum in 3 separate experiments. Groups of 20 animals were used in each experiment. Group 1 served as saline-treated controls; group 2 received moxifloxacin 15 mg QD; group 3 received gatifloxacin 25 mg QD; group 4 received piperacillin-tazobactam 93 mg (-83 mg of piperacillin) QD; and group 5 received a combination of clindamycin 15 mg TID plus gentamicin 2 mg TID. All treatments were given intramuscularly. For all antimicrobials, dose was based on peak and trough serum drug concentrations determined by prior testing, with animal doses adjusted based on the ratio of body surface area to body weight, and comparing these doses and levels with studies in humans.
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The ethambutol/rifampicin combination with clarithromycin or moxifloxacin had significant bactericidal activity against M. xenopi. The nude mouse, being highly susceptible to M. xenopi, can be utilized for in vivo chemotherapy studies for this infection.
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The concentrations of moxifloxacin achieved after a single 400 mg dose were measured in serum, epithelial lining fluid (ELF), alveolar macrophages (AM) and bronchial mucosa (BM). Concentrations were determined using a microbiological assay. Nineteen patients undergoing fibre-optic bronchoscopy were studied. Mean serum, ELF, AM and BM concentrations at 2.2, 12 and 24 h were as follows: 2.2 h: 3.2 mg/L, 20.7 mg/L, 56.7 mg/L, 5.4 mg/kg; 12 h: 1.1 mg/L, 5.9 mg/L, 54.1 mg/L, 2.0 mg/kg; 24 h: 0.5 mg/L, 3.6 mg/L, 35.9 mg/L, 1.1 mg/kg, respectively. These concentrations exceed the MIC(90)s for common respiratory pathogens such as Streptococcus pneumoniae (0.25 mg/L), Haemophilus influenzae (0.03 mg/L), Moraxella catarrhalis (0.12 mg/L), Chlamydia pneumoniae (0.12 mg/L) and Mycoplasma pneumoniae (0. 12 mg/L) and indicate that moxifloxacin should be effective in the treatment of community-acquired, lower respiratory tract infections.
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88.9-92.5% of the streptococci were sensitive to beta-lactam agents tested with a minimum inhibitory concentration (MIC)(90s) ranging from 0.094 to 0.19 mg/l. The resistance to erythromycin and clindamycin was 40.8% (MIC(90HR) = 256 mg/l) and 21% (MIC(90HR) = 256 mg/l), respectively. The MIC(90) to moxifloxacin was 0.125 mg/l.
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Costs of treating a CAP episode amounted to 144E with moxifloxacin/co-amoxiclav; 222E with co-amoxiclav/clarithromycin; 211E with cefuroxime/moxifloxacin; and 193E with clarithromycin/moxifloxacin. The rate of first-line failure was 5%, 16%, 19% and 18% for these four treatment strategies, respectively. The rate of second-line treatment amounted to 4%, 13%, 16% and 15%, respectively. The hospitalisation rate was 1%, 4%, 4% and 4%, respectively. The death rate was 0.01%, 0.04%, 0.03% and 0.03%, respectively. Sensitivity analyses supported the dominance of moxifloxacin/co-amoxiclav in nearly all scenarios.
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Concomitant ingestion with sucralfate and/or oral Al3+-containing antacids significantly reduces the bioavailability of moxifloxacin. This is compatible with reduced solubilisation as a consequence of a chelation reaction with polyvalent cations, a common finding for quinolones. Therefore, staggered administration of moxifloxacin and Al3+-containing or related cationic interactants should be considered to avoid a loss of therapeutic efficacy due to subtherapeutic plasma concentrations of the quinolone.
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A total of 61 patients were enrolled [cefazolin and tobramycin (n = 20), gatifloxacin (n = 21), and moxifloxacin (n = 20)]. Overall, 57 patients (93%) healed on treatment. On comparison of the mean time taken to heal, no statistically significant difference was found among all the 3 treatment groups (P = 0.98). Positive bacterial culture was obtained in only 38 patients (62%). There was no significant difference in the bacterial isolates in each treatment group. There were 4 (7%) treatment failures (perforation or nonhealing ulcer): 1 (5%) each in moxifloxacin and gatifloxacin group and 2 (10%) in fortified antibiotics group. All regimens were well tolerated.