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The increase in the use of the fluoroquinolones, including for the treatment of lower respiratory tract infections, seems to be associated with a parallel increase in bacterial resistance. We studied the activity of penicillin and six fluoroquinolones against 101 viridans group streptococci isolated from blood (58 erythromycin-susceptible and 43 erythromycin-resistant). The percentage of strains not susceptible to penicillin was 35% and there were statistically significant differences in the percentages of penicillin resistance between erythromycin-susceptible and -resistant strains. The fluoroquinolones studied showed good activity against our viridans group streptococci independent of their susceptibility to erythromycin. The norfloxacin MIC(50) and MIC(90) were 8 and 16 mg/l, respectively. Ofloxacin and ciprofloxacin showed the same activity (MIC(50) 1 mg/l and MIC(90) 2 mg/l); levofloxacin was similar with MIC(50) and MIC(90) of 1 mg/l. The fluoroquinolones with enhanced activity were moxifloxacin and trovafloxacin (MIC(50) 0.12 mg/l and MIC(90) 0.25 mg/l). However, we found two strains resistant to trovafloxacin (MIC = 4 mg/l) that showed reduced susceptibility to all the fluoroquinolones tested, including moxifloxacin (MIC = 2 mg/l). Mutations in the topoisomerase genes parC and gyrA have been shown to occur in strains with reduced susceptibility; therefore, ongoing surveillance for the development of fluoroquinolone resistance in viridans streptococci is necessary.
The pyrrolocytosine RX-P873, a new broad-spectrum antibiotic in preclinical development, inhibits protein synthesis at the translation step. The aims of this work were to study RX-P873's ability to accumulate in eukaryotic cells, together with its activity against extracellular and intracellular forms of infection by Staphylococcus aureus and Pseudomonas aeruginosa, using a pharmacodynamic approach allowing the determination of maximal relative efficacies (Emax values) and bacteriostatic concentrations (Cs values) on the basis of Hill equations of the concentration-response curves. RX-P873's apparent concentration in human THP-1 monocytes was about 6-fold higher than the extracellular one. In broth, MICs ranged from 0.125 to 0.5 mg/liter (S. aureus) and 2 to 8 mg/liter (P. aeruginosa), with no significant shift in these values against strains resistant to currently used antibiotics being noted. In concentration-dependent experiments, the pharmacodynamic profile of RX-P873 was not influenced by the resistance phenotype of the strains. Emax values (expressed as the decrease in the number of CFU from that in the initial inoculum) against S. aureus and P. aeruginosa reached more than 4 log units and 5 log units in broth, respectively, and 0.7 log unit and 2.7 log units in infected THP-1 cells, respectively, after 24 h. Cs values remained close to the MIC in all cases, making RX-P873 more potent than antibiotics to which the strains were resistant (moxifloxacin, vancomycin, and daptomycin for S. aureus; ciprofloxacin and ceftazidime for P. aeruginosa). Kill curves in broth showed that RX-P873 was more rapidly bactericidal against P. aeruginosa than against S. aureus. Taken together, these data suggest that RX-P873 may constitute a useful alternative for infections involving intracellular bacteria, especially Gram-negative species.
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The pneumonia symptom severity score is a useful tool for advising patients regarding the time to symptomatic resolution of pneumonia.
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The full exposure-response surface identified linezolid-moxifloxacin zones of synergy, antagonism, and additivity. A regimen based on each of these zones was then used in the HFS model, with observed half-lives of 4.08 ± 0.66 for linezolid and 3.80 ± 1.34 hours for moxifloxacin. The kill rate constant was 0.060 ± 0.012 per day with the moxifloxacin-linezolid regimen in the additivity zone vs 0.083 ± 0.011 per day with standard therapy, translating to a bacterial burden half-life of 11.52 days vs 8.53 days, respectively.
A total of 340 MDR-TB patients were included in the study. Pre-XDR-TB was the most common form of drug-resistant TB observed overall in this Mumbai population at 56.8% compared to 29.4% for MDR-TB. The proportion of patients with MDR-TB was 39.4% in the period 2005-2007 and 27.8% in 2011-2013, while the proportion of those with XDR-TB and XXDR-TB was changed from 6.1% and 0% respectively to 10.6% and 5.6% during the same time period. During the same periods, the proportions of patients with ofloxacin, moxifloxacin and ethionamide resistance significantly increased from 57.6% to 75.3%, from 60.0% to 69.5% and from 24.2% to 52.5% respectively (p<0.05).
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There are multiple possible etiologies of TASS. However, as in our clusters, specific causes are often not identified. Thorough review of all steps in surgery, processing of equipment and preparation of injectable solutions and materials, and adoption of best practices can prevent additional cases of TASS. Prompt diagnosis and treatment of TASS are extremely important because this leads to a desirable outcome.
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This was a retrospective record review of all patients who received clozapine and antibiotics concurrently between June 30, 2010, and June 30, 2011.
The plasma and urinary pharmacokinetics of moxifloxacin were investigated after single doses of moxifloxacin 400mg administered orally either under fasting conditions or immediately after 250g of yoghurt that was to be consumed within 15 minutes. There was a 1-week interval between the study periods.
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The aim of this study was to determine the anti-inflammatory effects of besifloxacin, a novel fluoroquinolone under clinical evaluation for the treatment of ophthalmic infections, in human corneal epithelial cells (HCEpiC).
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12 male Caucasian volunteers (mean age 33.7 years) participated in the study.
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Tuberculosis (TB) is a common opportunistic infection after renal transplantation. The risk of TB in renal transplant recipients is reported to be 20 to 74 times higher than in the general population. Although extrapulmonary TB occurs frequently, isolated ankle joint TB is a rare form of extrapulmonary TB infection. It is often difficult to diagnose because of its atypical presentation; management is complex, especially with multidrug-resistant TB, the need for a prolonged course of therapy, and the risks of drug interactions and drug toxicity. We report herein a case of a 60-year-old female renal allograft recipient who developed multidrug-resistant ankle joint TB 11 months after her deceased donor renal transplantation. She presented to the emergency department with escalating pain and swelling of the left ankle, difficulty in ambulation, and a low-grade fever. An x-ray of the ankle revealed an effusion and soft tissue swelling. A synovial fluid culture was performed which tested positive for acid fast bacilli which grew a multidrug-resistant form of Mycobacterium tuberculosis. She was initially treated with isoniazid, rifampin, ethambutol, and pyrazinamide; then therapy was tailored secondary to the resistant nature of the organism. She received a combination of extensive debridement of the joint and institution of second-line anti-TB therapy with pyrazinamide, ethambutol, moxifloxacin, and ethionamide. To our knowledge, no other cases of multidrug-resistant TB have been reported in the literature after renal transplantation. This case shows both an atypical presentation of TB and the difficulties in managing a transplant patient with this disease.
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Coadministration of moxifloxacin with rifampicin and isoniazid resulted in an almost uniform decrease in moxifloxacin exposure (in 18 of 19 patients). The geometric means for the ratio of phase 1 area under the curve to phase 2 area under the curve and for the ratio of phase 1 peak plasma concentration to phase 2 peak plasma concentration were 0.69 (90% confidence interval, 0.65-0.74) and 0.68 (90% confidence interval, 0.64-0.73), respectively. The median time to reach peak plasma concentration for moxifloxacin was prolonged from 1 h to 2.5 h when combined with rifampicin and isoniazid (P=.003).
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Contacts of persons infected with multidrug-resistant tuberculosis (MDR TB) have few prophylaxis options. Of 50 contacts of HIV- and MDR TB-positive persons who were treated with moxifloxacin, 30 completed treatment and 3 discontinued treatment because of gastrointestinal symptoms. Moxifloxacin was generally well-tolerated; further research of its efficacy against MDR TB is needed.
To evaluate the efficacy and safety of moxifloxacin monotherapy for treatment of complicated intra-abdominal infections. PubMed, EMBASE, Science Direct, ClinicalTrials.gov and Cochrane Central Register of Controlled Trials were searched to retrieve randomised controlled trials (RCTs) compared moxifloxacin monotherapy with other antibiotics in the treatment of complicated intra-abdominal infections from January 1999 to July 2011. A meta-analysis of all included randomised controlled trials was performed. Four randomised controlled trials including a total of 2444 patients with complicated intra-abdominal infections were included for meta-analysis. The results of the meta-analysis indicated that the moxifloxacin was associated with similar clinical cure rate (four RCTs, 1934 patients, OR = 0.80, 95% CI: 0.61, 1.04, p = 0.09), bacteriological success rates (four RCTs, 1484 patients, OR = 0.79, 95% CI: 0.59, 1.05, p = 0.11) and mortality (four RCTs, 2227 patients, OR = 0.91, 95% CI: 0.45, 1.83, p = 0.79) compared with the control group. The overall incidence of adverse events of moxifloxacin was significantly higher than that in the control group (three RCTs, 1367 patients, OR = 1.33, 95% CI: 1.07, 1.63, p = 0.008), although the incidence of drug-related adverse events (three RCTs, 1601 patients, OR = 1.13, 95% CI: 0.69, 1.85, p = 0.63) and serious adverse events (three RCTs, 1815 patients, OR = 1.23, 95% CI: 0.59, 2.60, p = 0.58) were similar between the compared treatment groups. Moxifloxacin is an effective and relatively safe option for the treatment of patients with intra-abdominal infections. Moxifloxacin monotherapy has similar efficacy to combination therapy.
The activity of moxifloxacin was compared with ofloxacin and doxycycline against bacteria associated with periodontitis within a biofilm (single strain and mixed population) in vitro. MICs and minimal bactericidal concentrations (MBCs) of moxifloxacin, ofloxacin and doxycyline were determined against single strains and mixed populations in a planktonic state. Single-species biofilms of two Porphyromonas gingivalis and two Aggregatibacter actinomycetemcomitans strains and a multispecies biofilm consisting of 12 species were formed for 3 days. The minimal biofilm eradication concentrations (MBECs) were determined after exposing the biofilms to the antibacterials (0.002-512 µg ml(-1)) for 18 h, addition of nutrient broth for 3 days and subsequent subcultivation. Photographs were taken using confocal laser-scanning microscopy and scanning electron microscopy. The MICs and MBCs did not differ between ofloxacin and moxifloxacin against A. actinomycetemcomitans, whilst moxifloxacin was more active than the other tested antibacterials against anaerobes and the mixed population. The single-species biofilms were eradicated by moderate concentrations of the antibacterials, and the lowest MBECs were always found for moxifloxacin (2-8 µg ml(-1)). MBECs against the multispecies biofilms were 128, >512 and >512 µg ml(-1) for moxifloxacin, ofloxacin and doxycycline, respectively. In summary, moxifloxacin in a topical formulation may have potential as an adjunct to mechanical removal of the biofilms.
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The exclusion of ECGs with rapid HR changes influences the magnitude of drug-induced QT changes. The hysteresis phenomenon should not be neglected when dedicated QT studies are performed.
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This study identifies an increasing incidence of microsporidial keratitis in Singapore with a strong correlation with prior soil exposure. Diffuse endotheliitis and limbitis have not been described and resolves with topical steroid therapy. Topical fluoroquinolone monotherapy is a valid treatment option.
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This study showed that fampridine-SR at therapeutic and supratherapeutic doses was not associated with QT prolongation in healthy subjects.
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In order to characterize the diversity and frequency of gyrA and gyrB mutations and to describe the global distribution of these mutations, we conducted a systematic review, from May 1996 to April 2013, of all published studies evaluating Mycobacterium tuberculosis mutations associated with resistance to fluoroquinolones. The overall goal of the study was to determine the potential utility and reliability of these mutations as diagnostic markers to detect phenotypic fluoroquinolone resistance in Mycobacterium tuberculosis and to describe their geographic distribution.
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We demonstrate that tuberculosis lesions in C3HeB/FeJ are hypoxic. Activities of some key tuberculosis drug regimens in development are represented differently in C3HeB/FeJ versus BALB/c mice. Because C3HeB/FeJ display key features of human tuberculosis, this strain warrants evaluation as a more pathologically relevant model for preclinical studies.
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No author has a financial or proprietary interest in any material or method mentioned.
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The in vitro antimicrobial susceptibility of the anaerobic intestinal spirochete Brachyspira pilosicoli was investigated by an agar dilution method. Human (n = 123) and porcine (n = 16) isolates were susceptible to metronidazole, ceftriaxone, meropenem, tetracycline, moxifloxacin, and chloramphenicol; erythromycin and ciprofloxacin were not active. Resistance to amoxicillin and clindamycin varied. Amoxicillin susceptibility was restored by clavulanic acid.