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Polymorphonuclear leukocytes (PMNL) concentrate, transport, and release certain antimicrobial agents as they move in a chemotactic gradient. Antipyretic agents are frequently used in febrile patients receiving antimicrobial agents. Thus, the influence of ibuprofen, acetaminophen, and acetylsalicylic acid on uptake, transport, and release of azithromycin and moxifloxacin was studied. Uptake of the antimicrobial agents by human PMNL and the effect of the antipyretics were quantitated by bioassay of released antimicrobial agent. Transport and release were determined in chemotactic plates overlaid with sentinel bacteria that could detect transported and released antimicrobial agent. None of the antipyretics altered PMNL directed or non-directed movement. Uptake of azithromycin was significantly inhibited by acetylsalicylic acid but not by the other antipyretics. All of the antipyretic agents studied at therapeutic levels inhibited transport and release of both azithromycin and moxifloxacin. Administration of any of these antipyretic agents with antimicrobial agents that are transported and released by PMNL could compromise the efficacy of therapy.
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To observe the effects of moxifloxacin at various concentrations on the expression of Caspase-3, the alteration of mitochondria membrane potential (ΔΨm) and the apoptosis of airway smooth muscle cells (ASMCs), and to explore the possible mechanisms.
To compare the equivalence of moxifloxacin 0.5% with a combination of fortified cefazolin sodium 5% and tobramycin sulfate 1.3% eye drops in the treatment of moderate bacterial corneal ulcers.
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The 19 S. maltophilia ABM cases included 11 men and 8 women, aged 28-70 years. Of these 19 cases, 89.5% (17/19) had underlying neurosurgical (NS) conditions as the preceding event. Before the development of S. maltophilia ABM, 52.6% (10/19) of them had long stays in hospital and 63.2% (12/19) had undergone antibiotic treatment. Among the implicated S. maltophilia cases, three strains were found to have a resistance to sulfamethoxazole-trimethoprim (SMZ-TMP). Two of our five cases had resistant strains to levofloxacin. Among the antibiotics chosen for treatment, SMZ-TMP was the most common followed by quinolone (ciprofloxacin, levofloxacin, moxifloxacin). The therapeutic results showed 2 cases expired while the other 17 cases survived.
The aim of the present investigation was to prepare a colloidal ophthalmic formulation to improve the residence time of moxifloxacin. Moxifloxacin-loaded poly(dl-lactide-co-glycolide) (PLGA) nanosuspensions were prepared by using the solvent evaporation technique. The nanosuspensions were characterised physically by using different techniques like particle size, zeta potential, FTIR, DSC, and XRD analysis. In vitro and ex vivo studies of nanosuspensions were carried out using a modified USP dissolution apparatus and all-glass Franz diffusion cells, respectively. The antibacterial activities of the nanosuspension and marketed formulations were performed against S. aureus and P. aeroginosa. The moxifloxacin-loaded PLGA nanosuspensions showed uniform particle size, ranging between 164-490 nm with negative zeta potential for all batches. The percentage entrapment efficiency of the drug-loaded nano-suspension was found to be between 84.09 to 92.05%. In vitro drug release studies suggest that all of the formulations showed extended drug release profiles and follow Korsemeyer-Peppas release kinetics. In vitro corneal permeability was found to be comparable with that of the marketed formulation across isolated goat cornea, indicating the suitability of the nanosuspension formulation in the ophthalmic delivery of moxifloxacin. The optimised nano-suspension was found to be more active against S. aureus and P. aeruginosa compared to the marketed eye drops.
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To evaluate the activity of macrolides and fluoroquinolones against Legionella pneumophila by intracellular susceptibility testing.
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In this study, it was aimed to investigate in vitro activity of moxifloxacin and rifampicin on biofilm formation by clinical MRSA isolates.
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Of 336 patients enrolled, 277 (82%) were eligible for the efficacy analysis, 186 (67%) were male, 175 (63%) were enrolled at African sites, 206 (74%) had cavitation on chest radiograph, and 60 (22%) had HIV infection. Two-month cultures were negative in 71% of patients (99 of 139) treated with moxifloxacin versus 71% (98 of 138) treated with ethambutol (p = 0.97). Patients receiving moxifloxacin, however, more often had negative cultures after 4 wk of treatment. Patients treated with moxifloxacin more often reported nausea (22 vs. 9%, p = 0.002), but similar proportions completed study treatment (88 vs. 89%). Dosing frequency had little effect on 2-mo culture status or tolerability of therapy.
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The increase in multiple antimicrobial-resistant bacteria seriously threatens global public health. Novel effective strategies are urgently needed. l-Serine was reported as the most effective amino acid inhibitor against bacterial growth and can sensitize Escherichia coli cells to gentamicin. It is currently unknown whether l-serine affects other type of antibiotics such as β-lactams and fluoroquinolones.
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Listeria monocytogenes and Staphylococcus aureus invade and multiply in THP-1 monocytes. Fluoroquinolones accumulate in these cells, but are less active against intracellular than extracellular forms of L. monocytogenes and S. aureus. We examined whether differentiation of THP-1 monocytes into adherent, macrophage-like cells increases fluoroquinolone uptake and activity.
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This paper presents data relating to Haemophilus influenzae and Moraxella catarrhalis from PROTEKT (1999-2000), a surveillance study that examined the susceptibility of respiratory pathogens to current and new antibacterials. Beta-lactamase production is the principal mechanism of resistance to ampicillin and other beta-lactam antibacterials in H. influenzae and M. catarrhalis. The PROTEKT study showed that globally, the prevalence of beta-lactamase production in H. influenzae varied considerably: of 2948 isolates, 489 (16.6%) were beta-lactamase-positive [range: 1.8% (Italy) to 65% (South Korea)]. Beta-lactamase-negative, ampicillin-resistant (BLNAR) strains of H. influenzae were uncommon (<0.1%) but their very detection highlights the need for continued vigilance. Overall, few isolates of H. influenzae showed resistance to either macrolides or telithromycin. The emergence of clarithromycin-resistant strains is worrying, however, as such isolates may also show resistance to other macrolides. There was a geographical correlation between beta-lactamase production and the prevalence of resistance to chloramphenicol and tetracycline among the H. influenzae isolates. Of 1131 M. catarrhalis isolates, 92% were beta-lactamase-positive. Most isolates, however, were fully susceptible to nearly all the antibacterials tested, except ampicillin. The most active were ciprofloxacin and levofloxacin (both having MIC(90) values of 0.03 mg/L), moxifloxacin (MIC(90) 0.06 mg/L), azithromycin (MIC(90) < or = 0.06 mg/L) and telithromycin (MIC(90) 0.12 mg/L). Overall, there were no concerns in terms of resistance to fluoroquinolones for both H. influenzae and M. catarrhalis. In summary, the PROTEKT surveillance study confirmed the problem of widespread prevalence of beta-lactamase-producing strains of H. influenzae and M. catarrhalis, although these pathogens generally remain susceptible to macrolides, fluoroquinolones and the new ketolide telithromycin.
There was no QT prolongation effect of clinical concern by tocilizumab at both the therapeutic (10 mg/kg) and the supratherapeutic (20 mg/kg) dose in healthy subjects.
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A baseline evaluation was conducted on 30 healthy volunteers for conjunctival hyperemia, conjunctival vascularity, pupil size, and anterior chamber (AC) cell and flare. Pupils were measured under scotopic conditions with a Colvard pupillometer. Conjunctival hyperemia and vascularity, and AC reaction were measured on a Likert-like scale of 0-3. Subjects then received drops in both eyes from masked bottles of gatifloxacin ophthalmic solution 0.3% with BAK (in one eye determined randomly) and moxifloxacin ophthalmic solution 0.5% without BAK (in the contralateral eye) in a double-masked fashion. Subjects graded pain and ocular irritation in each eye on a scale of 1-10 after 5 min with their eyes closed. The examination was then repeated.
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Streptococcus pneumoniae infections constitute a public health problem. In our country there is scarce information regarding isolates from bacteraemic episodes in adult population. The antibiotic susceptibility, serotypes and clonal relationship of 56 isolates of S. pneumoniae from adult patients with bacteraemic infections in Concepcion-Talcahuano, Bio-Bio Region, Chile, were studied. Resistance to tetracycline (21.4%), trimethoprim/ sulfamethoxazole (18%), erythromycin (18%), chloramphenicol (7%) and 1 penicillin resistant isolate from a meningeal focus (2%) was found. Also, all the isolates were susceptible to cefotaxime, levofloxacin, moxifloxacin and vancomycin. A wide variety of capsular serotypes was demonstrated, with predominance of serotypes 1, 5, 23F, 7F and 3. The macrorestriction analysis by pulse field electrophoresis revealed 31 electrophoretic patterns and 12 clonal groups, discarding a predominant clone. According to the results, at least, 80% of the S. pneumoniae serotypes isolated from bacteraemic adult patients are included in the available commercial vaccine.
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Infections with rapidly growing mycobacteria are rare and most often seen in immunocompromised patients. We herein present the case of a 69-year-old man with a T-cell lymphoma treated by chemotherapy and mogamulizumab with a 6-month history of febrile episodes and subcutaneous nodules in both arms and arthritis of metacarpophalangeal joints. Blood cultures and DNA sequencing results demonstrated the growth of Mycobacterium chelonae. The patient was successfully treated with clarithromycin, moxifloxacin, and tobramycin, but died shortly after due to lymphoma progression.
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GSK1322322 is a peptide deformylase inhibitor active against Staphylococcus aureus strains resistant to currently marketed antibiotics. Our aim was to assess the activity of GSK1322322 against intracellular S. aureus using an in vitro pharmacodynamic model and, in parallel, to examine its cellular pharmacokinetics and intracellular disposition. For intracellular activity analysis, we used an established model of human THP-1 monocytes and tested one fully susceptible S. aureus strain (ATCC 25923) and 8 clinical strains with resistance to oxacillin, vancomycin, daptomycin, macrolides, clindamycin, linezolid, or moxifloxacin. Uptake, accumulation, release, and subcellular distribution (cell fractionation) of [(14)C]GSK1322322 were examined in uninfected murine J774 macrophages and uninfected and infected THP-1 monocytes. GSK1322322 demonstrated a uniform activity against the intracellular forms of all S. aureus strains tested, disregarding their resistance phenotypes, with a maximal relative efficacy (E max) of a 0.5 to 1 log10 CFU decrease compared to the original inoculum within 24 h and a static concentration (C s) close to its MIC in broth. Influx and efflux were very fast (<5 min to equilibrium), and accumulation was about 4-fold, with no or a minimal effect of the broad-spectrum eukaryotic efflux transporter inhibitors gemfibrozil and verapamil. GSK1322322 was recovered in the cell-soluble fraction and was dissociated from the main subcellular organelles and from bacteria (in infected cells). The results of this study show that GSK1322322, as a typical novel deformylase inhibitor, may act against intracellular forms of S. aureus. They also suggest that GSK1322322 has the ability to freely diffuse into and out of eukaryotic cells as well as within subcellular compartments.
The fluoroketolide solithromycin is 2-fold more potent in vitro than telithromycin against pneumococci (including macrolide-resistant strains) and Haemophilus influenzae and very active on pathogens causing atypical pneumonia. In contrast, it is a 30-fold less potent inhibitor of nicotinic receptors incriminated in telithromycin toxicity. In Phase II/III trials, oral solithromycin once-daily (800 mg on day 1; 400 mg on days 2-5) proved effective and safe when compared to respiratory fluoroquinolones for the treatment of community-acquired bacterial pneumonia (CABP). A Phase III intravenous trial vs. moxifloxacin has been recently completed for the same indication. Solithromycin may restore interest in ketolides as a first-line therapy for CAPB. Solithromycin safety should nevertheless be confirmed in larger populations allowing for detection of rare adverse events.
Mycoplasma hominis is a rare cause of infection after neurosurgical procedures. The Mycoplasma genus contains the smallest bacteria discovered to date. Mycoplasma are atypical bacteria that lack a cell wall, a feature that complicates both diagnosis and treatment. The Gram stain and some types of culture media fail to identify these organisms, and typical broad-spectrum antibiotic regimens are ineffective because they act on cell wall metabolism. Mycoplasma hominis commonly colonizes the genitourinary tract in a nonvirulent manner, but it has caused postoperative, postpartum, and posttraumatic infections in various organ systems. The authors present the case of a 17-year-old male with a postoperative intramedullary spinal cord abscess due to M. hominis and report the results of a literature review of M. hominis infections after neurosurgical procedures. Attention is given to time to diagnosis, risk factors for infection, ineffective antibiotic regimens, and final effective antibiotic regimens to provide pertinent information for the practicing neurosurgeon to diagnose and treat this rare occurrence.
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Tafenoquine is being developed for relapse prevention in Plasmodium vivax malaria. This Phase I, single-blind, randomized, placebo- and active-controlled parallel group study investigated whether tafenoquine at supratherapeutic and therapeutic concentrations prolonged cardiac repolarization in healthy volunteers. Subjects aged 18-65 years were randomized to one of five treatment groups (n = 52 per group) to receive placebo, tafenoquine 300, 600, or 1200 mg, or moxifloxacin 400 mg (positive control). Lack of effect was demonstrated if the upper 90% CI of the change from baseline in QTcF following supratherapeutic tafenoquine 1200 mg versus placebo (ΔΔQTcF) was <10 milliseconds for all pre-defined time points. The maximum ΔΔQTcF with tafenoquine 1200 mg (n = 50) was 6.39 milliseconds (90% CI 2.85, 9.94) at 72 hours post-final dose; that is, lack of effect for prolongation of cardiac depolarization was demonstrated. Tafenoquine 300 mg (n = 48) or 600 mg (n = 52) had no effect on ΔΔQTcF. Pharmacokinetic/pharmacodynamic modeling of the tafenoquine-QTcF concentration-effect relationship demonstrated a shallow slope (0.5 ms/μg mL(-1) ) over a wide concentration range. For moxifloxacin (n = 51), maximum ΔΔQTcF was 8.52 milliseconds (90% CI 5.00, 12.04), demonstrating assay sensitivity. In this thorough QT/QTc study, tafenoquine did not have a clinically meaningful effect on cardiac repolarization.
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Use density ratios (UDR) for fluoroquinolones: ciprofloxacin, gatifloxacin, levofloxacin, and moxifloxacin, and for three other antibiotic classes (carbapenems: ertapenem, doripenem, imipenem, and meropenem; other antipseudomonal beta-lactams: cefepime, ceftazidime, and piperacillin/tazobactam; and aminoglycosides: gentamicin and tobramycin) were derived from drug purchase data for up to 9 years, ending in 2008. Susceptibility data were obtained from hospital antibiograms in corresponding years. A mixed model repeated measures ANOVA (Analysis of Variance) explored associations between 9-year repeated imipenem susceptibility and fluoroquinolone UDR in each year while controlling for other drug classes, teaching status, and number of beds.
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Previously we reported a 2-month clinical trial of moxifloxacin therapy in eight patients with MB leprosy (7 LL and 1 BL), finding both rapid killing of M. leprae and clinical improvement, without serious side effects or toxicities. Here we report the outcomes in two patients treated with moxifloxacin.
Adult zebrafish model of M. marinum-induced tuberculosis has not been fully exploited as a drug screening tool. In the present report, a protocol is suggested that is simple, reproducible and resource-efficient for screening of anti-tuberculosis agents. This protocol is an attempt to refine the published protocols and use this model as a surrogate model of human TB for the purpose of drug screening.
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Current North American guidelines advocate the use of respiratory fluoroquinolones for the empirical management of community-acquired pneumonia (CAP). While community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as a pathogen frequently encountered in skin and skin structure infections, it has also now been recognised as a causative pathogen in CAP. Since fluoroquinolones may be used empirically to treat unsuspected CA-MRSA pneumonia, the objective of this study was to evaluate the antibacterial properties of levofloxacin and moxifloxacin using human simulated drug exposures in epithelial lining fluid (ELF).
A pharmacy database of a large, urban, academic teaching hospital was used to retrospectively calculate changes in drug-ordering frequencies before and after study drugs were added to an ED automated medication management system. Study drugs had been recently added to our ED automated medication management system but were still available from the hospital central pharmacy and were not the subject of changes in hospital prescribing protocols.
A chromatographic method was implemented and validated for the simultaneous determination of antimicrobials proposed for the treatment of mycetoma: three fluoroquinolones: ciprofloxacin, moxifloxacin and sparfloxacin; two oxazolidinones: DA-7157 (DA2; torezolid) and its prodrug DA-7218 (DA1). Separation of analytes was achieved on an Atlantis dC18 column (150 × 4.6 mm i.d., 5 µm particle size) with a mobile phase composed of acetonitrile and trifluoroacetic acid 0.1% (v/v) using a gradient program. Total running time was 30 min. Quantification of sparfloxacin was carried out using a DAD at 278 nm; the oxazolidinones DA1 and DA2 and the quinolones ciprofloxacin and moxifloxacin were analyzed by fluorescence with an excitation wavelength of 292 nm and an emission wavelength of 525 nm. Intraday precision was in the range of 3.2 and 14.1%. Linearity range was from 0.3 to 10 µg/mL for sparfloxacin using DAD detector, and from 0.2 to 10 µg/mL for ciprofloxacin, 0.3 to 10 µg/mL for DA2, 0.4 to 10 µg/mL for DA1 and 0.04 to 10 µg/mL for moxifloxacin with fluorescence detector. Acetonitrile was used to precipitate proteins from plasma. Recoveries at low, medium and high concentration were between 80 and 120%. Limits of quantification were between 0.04 and 0.4 µg/mL in plasma. The method can be applied for individual or simultaneous determination of the antimicrobials in plasma.
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Frequent COPD exacerbations have a large impact on morbidity, mortality and health-care expenditures. By 2020, the World Health Organization expects COPD and COPD exacerbations to be the third leading cause of death world-wide. Furthermore, In 2005 it was estimated that COPD exacerbations cost the U.S. health-care system 38 billion dollars. Studies attempting to determine factors related to COPD readmissions are still very limited. Moreover, few have used a organized machine-learning, sensitivity analysis approach, such as a Random Forest (RF) statistical model, to analyze this problem. This study utilized the RF machine learning algorithm to determine factors that predict risk for multiple COPD exacerbations in a single year. This was a retrospective study with a data set of 106 patients. These patients were divided randomly into training (80%) and validating (20%) data-sets, 100 times, using approximately sixty variables intially, which in prior studies had been found to be associated with patient readmission for COPD exacerbation. In an interactive manner, an RF model was created using the training set and validated on the testing dataset. Mean area-under-curve (AUC) statistics, sensitivity, specificity, and negative/positive predictive values (NPV, PPV) were calculated for the 100 runs. THE FOLLOWING VARIABLES WERE FOUND TO BE IMPORTANT PREDICTORS OF PATIENTS HAVING AT LEAST TWO COPD EXACERBATIONS WITHIN ONE YEAR: employment, body mass index, number of previous surgeries, administration of azithromycin/ceftriaxone/moxifloxacin, and admission albumin level. The mean AUC was 0.72, sensitivity of 0.75, specificity of 0.56, PPV of 0.7 and NPV of 0.63. Histograms were used to confirm consistent accuracy. The RF design has consistently demonstrated encouraging results. We expect to validate our results on new patient groups and improve accuracy by increasing our training dataset. We hope that identifying patients at risk for frequent readmissions will improve patient outcome and save valuable hospital resources.
This article reviews the characteristics of the main fluoroquinolones used in dentistry (ciprofloxacin, levofloxacin and moxifloxacin), including pharmacokinetic/ pharmacodynamic parameters, susceptibility profiles of oral bacteria and clinical trials on their efficacy in dental practice. It seems that some of these antibiotics might represent a safe alternative in patients with allergy, intolerance, or lack of response to beta-lactams.
To study the clearance of a single dose of intravitreally injected moxifloxacin in rabbits.
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The prevalence of resistance to a range of antimicrobials was determined for isolates of Streptococcus pneumoniae examined in the PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) surveillance study (1999-2000) using NCCLS testing methods and interpretative criteria. Of 3362 pneumococcal isolates collected from 69 centres in 25 countries, 22.1% overall were resistant to penicillin G, with the highest rates of resistance found among isolates from Asia (53.4%), France (46.2%) and Spain (42.1%). Erythromycin A resistance occurred in 31.1% of isolates overall with the highest rates found in Asia (79.6%), France (57.6%), Hungary (55.6%) and Italy (42.9%). Marked geographical differences in the prevalence of both penicillin G (the Netherlands 0%; South Korea 71.5%) and erythromycin A (Sweden 4.7%; South Korea 87.6%) resistance were observed. Asia was characterized by the highest prevalence of resistance, overall, with only eight of 19 antimicrobials (co-amoxiclav, linezolid, vancomycin, teicoplanin, quinupristin/dalfopristin, levofloxacin, moxifloxacin and telithromycin) retaining high activity against isolates of S. pneumoniae from this region. Notable rates of resistance to clarithromycin, azithromycin, co-trimoxazole and tetracycline were observed in the majority of countries submitting isolates of S. pneumoniae to the PROTEKT surveillance study. Fluoroquinolone resistance was low (1%), overall, although 14.3% of 70 isolates from Hong Kong were resistant to levofloxacin and moxifloxacin, all but one of these isolates belonging to a single clone of the 23F serotype. Although, at present, apparently limited to pockets of clonal spread, continued vigilance with regard to the evolution of fluoroquinolone resistance is indicated. Telithromycin (MIC(90) 0.12 mg/L; 99.9% of isolates susceptible) and lin- ezolid (MIC(90) 2 mg/L; 100% of isolates susceptible) were the two most active oral agents tested, both compounds retaining activity against isolates of fluoroquinolone-resistant S. pneumoniae. The results of the PROTEKT surveillance study 1999-2000 emphasize the widespread evolution of resistance to a variety of antimicrobials amongst isolates of S. pneumoniae and demonstrate the potential of telithromycin as a therapeutic option for the treatment of community-acquired respiratory tract infections caused by this organism.