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The 2-year follow-up results for a randomized placebo-controlled study of 47 patients with multidrug-resistant pulmonary tuberculosis treated with either the new diarylquinoline TMC207, recently renamed bedaquiline, or placebo, added to the first 8 weeks of a background regimen, are presented. Bedaquiline significantly reduced the time to culture conversion over 24 weeks (hazard ratio, 2.253; 95% confidence interval, 1.08 to 4.71; P = 0.031). With the exception of nausea reported in 26% of patients receiving bedaquiline and none receiving placebo, adverse events occurred at similar frequencies in both groups of patients: bilateral hearing impairment, extremity pain, acne, and noncardiac chest pain occurred in 13 and 21%, 17 and 13%, 9 and 17%, and 4 and 17% of patients, respectively, receiving bedaquiline or placebo. Excluding resistance to ethambutol and ethionamide, only one patient receiving bedaquiline acquired resistance to companion drugs, but five patients receiving placebo (4.8% versus 21.7%; P = 0.18) acquired resistance to companion drugs, and resistance to ofloxacin was acquired in four patients receiving placebo and none receiving bedaquiline (0% versus 22%; 0 = 0.066). In all, 23 patients (49%), including 13 receiving placebo (54%) and 10 receiving bedaquiline (44%), discontinued the study prior to its completion, 12 during the first 24 weeks of treatment. Eight subjects were withdrawn for noncompliance or default, and seven withdrew consent, citing the rigorous program of investigations for safety and pharmacokinetic monitoring. Bedaquiline may contribute to the management of multidrug-resistant tuberculosis by effecting more rapid sputum culture negativity and by preventing acquired resistance to companion drugs.
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A 53-year-old white woman was involved in two motor vehicle accidents on the same day after experiencing syncopal episodes. Cardiac and neurologic evaluations were negative; the syncopal episodes were attributed to QT prolongation associated with the concomitant use of cisapride and agents known to inhibit its metabolism.
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To study the effectiveness and tolerance of the combination of omeprazole, clarithromycin and amoxycillin taken for a week on the eradication of Helicobacter pylori (HP) in patients with peptic ulcer and symptomatic chronic gastritis.
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Eradication of Helicobacter pylori has become a therapeutic option in the treatment of patients with peptic ulcer disease. The aim of this study was to evaluate the current management strategies of Israeli gastroenterologists in the diagnosis and treatment of H. pylori-related peptic ulcer disease, 14 years after the discovery of H. pylori.
Pharmaceutical and personal care products, biocides and iodinated contrast media (ICM) are persistent compounds, which appear in ng to μg L(-1) in secondary effluents of sewage treatment plants (STPs). In this work, biogenic metals manganese oxides (BioMnOx) and bio-palladium (Bio-Pd) were applied in lab-scale membrane bioreactors (MBR) as oxidative and reductive technologies, respectively, to remove micropollutants from STP-effluent. From the 29 substances detected in the STP-effluent, 14 were eliminated in the BioMnOx-MBR: ibuprofen (>95%), naproxen (>95%), diuron (>94%), codeine (>93%), N-acetyl-sulfamethoxazole (92%), chlorophene (>89%), diclofenac (86%), mecoprop (81%), triclosan (>78%), clarithromycin, (75%), iohexol (72%), iopromide (68%), iomeprol (63%) and sulfamethoxazole (52%). The putative removal mechanisms were the chemical oxidation by BioMnOx and/or the biological removal by Pseudomonas putida and associated bacteria in the enriched biofilm. Yet, the removal rates (highest value: 2.6 μg diclofenac L(-1) d(-1)) need to improve by a factor 10 in order to be competitive with ozonation. ICM, persistent towards oxidative techniques, were successfully dehalogenated with a novel reductive technique using Bio-Pd as a nanosized catalyst in an MBR. Iomeprol, iopromide and iohexol were removed for >97% and the more recalcitrant diatrizoate for 90%. The conditions favorable for microbial H(2)-production enabling the charging of the Pd catalyst, were shown to be important for the removal of ICM. Overall, the results indicate that Mn oxide and Pd coupled to microbial catalysis offer novel potential for advanced water treatment.
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To determine the efficacy and safety of 1-week triple therapy with omeprazole, amoxicillin and clarithromycin for eradicating H. pylori infection in patients with active duodenal ulcer living in Asian and African regions.
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Eradication was achieved in 87.3% of patients (n = 93; 95% CI = 82-93%). In the multivariate analysis the variables which influenced H. pylori eradication were: time of evolution of ulcer disease (p = 0.002) and active chronic gastritis in the antrum (p = 0.04) (chi 2 model = 15.8; p = 0.001). Ulcer healing was demonstrated in 89.5% of patients (84-95%), and healing rate was higher when eradication was achieved (94%; 90-98%) than in H. pylori-positive patients (59%; 36-78%) (p < 0.001). In the multivariate analysis the variables which influenced ulcer healing were: age (p = 0.02) and H. pylori eradication (p = 0.001) (chi 2 model = 21.2; p = 0.0001). An improvement of histologic gastritis was observed when eradication was achieved (p < 0.001). Compliance of therapy was complete in all patients but one and no relevant adverse effects were reported.
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Helicobacter pylori infection is found in at least 80% of people in developing countries. This randomized controlled trial was performed to evaluate the efficacy of 4 different H. pylori eradication regimens in Iranian patients.
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Treatment-naive H pylori-positive individuals were randomly assigned to a 10-day regimen (oral twice-daily doses) with rabeprazole (20 mg): standard triple therapy (proton pump inhibitor, added clarithromycin [500 mg] and amoxicillin [1 g] [PPI-CA]); sequential therapy (ST) added amoxicillin (1 g) on days 1 to 5, and metronidazole (500 mg) and clarithromycin (500 mg) on days 6 to 10. Participants with clarithromycin-resistant H pylori were randomly assigned to ST or quadruple therapy. Treatment effectiveness was estimated as per cent (95% CI) with a negative urea breath test at least 10 weeks after treatment.
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The aim of the study was to evaluate the prevalence of resistance to amoxicillin, metronidazole, and clarithromycin before treatment of Helicobacter pylori infection in children and to assess the evolution of resistance with time. The study was carried out between 1994 and 1999 with 150 H. pylori-positive children through gastric culture (antimicrobial susceptibility) and histology. All cultured H. pylori strains were sensitive to amoxicillin, 64 (43%) were resistant to metronidazole, 32 (21%) were resistant to clarithromycin, and 14 (9%) were resistant to both metronidazole and clarithromycin. The overall prevalence of resistance to metronidazole and clarithromycin did not change significantly with time. The study highlights the generalized high-level and stable metronidazole and clarithromycin resistance of H. pylori strains from children.
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During a median follow-up period of 3 years, 10 patients who received H pylori eradication and 17 controls developed metachronous carcinoma; this difference was not significant (P = .15). The incidence of metachronous carcinoma between the 2 groups did not differ significantly at 1, 2, 3, and 4 years after administration of the therapy. There were no significant differences in the development of metachronous carcinoma among patients who were positive (n = 16) or negative (n = 11) for H pylori infection (P = .32).
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Isolation of Mycobacterium xenopi from the respiratory tract may indicate pneumonia, often clinically indistinguishable from tuberculosis. Resistance to the classic antituberculous drugs renders the treatment of these infections problematic. We report on a case of cavernous pneumonia caused by M. xenopi in a 36-year-old male with natural killer cell deficiency but without severe immunodeficiency. He was successfully treated with a novel triple-drug combination comprising clarithromycin, sparfloxacin, and rifabutin. An impressive subsequent regression of pathological pulmonary changes was observed, and mycobacteria could no longer be detected. The therapeutic potential of clarithromycin and sparfloxacin in the treatment of M. xenopi infections is discussed.
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P. aeruginosa PAO-1 was grown for 24 h on agar containing sub-MIC antibiotics, and then mice were challenged intranasally with 10(7) cfu of bacteria.
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Traditional antibiotics such as amoxicillin, tetracycline and erythromycin remain the drugs of first choice for most bacterial respiratory infections. However, the usefulness of these agents varies, depending on local bacterial resistance patterns and patient factors. In the United States, amoxicillin and penicillin resistance currently occurs in 20 to 30 percent of Streptococcus pneumoniae strains, 30 to 40 percent of Haemophilus influenzae strains and 70 to 90 percent of Moraxella catarrhalis strains. For infections with these pathogens, selective use of the newer extended-spectrum oral antibiotics may be indicated. Cefuroxime axetil (a second-generation cephalosporin), cefpodoxime (a third-generation cephalosporin), amoxicillin-clavulanate (a beta-lactamase inhibitor combination agent) and clarithromycin or azithromycin (extended-spectrum macrolides) are all relatively effective against organisms that are commonly resistant to penicillin and amoxicillin.
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The study included 200 R. equi isolates, including 160 isolates from horses and 40 isolates from other animal sources, from the USA and Europe. MIC testing of 32 antimicrobial agents or combinations thereof followed a recently published protocol. A novel PCR protocol for the joint amplification of the three rpoB regions in which rifampicin resistance-mediating mutations have been reported was applied to isolates with elevated rifampicin MICs. The amplicons were sequenced and screened for mutations.
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The study was done in a group of 244 pregnant women, aged from 17 to 43, hospitalized and treated for various reasons in the Department of Pathology of Pregnancy at Medical University in Lódź. The biocenosis of the uterine cervix and the results of microbiological bacterial culture have been analyzed and the sensitivity of bacterial flora on the applied antibiotics has been assessed.
Evidence of a NTM in a pulmonary sample is not synonymous with infection. The diagnosis depends on the association of clinical, radiological and microbiological factors. If a NTM is isolated from a respiratory sample, the probability of infection depends on the species. The main NTMs responsible for pulmonary infection in France are Mycobacterium avium intracellulare, Mycobacterium xenopi, Mycobacterium kansasi and Mycobacterium abscessus. Their management is difficult and poorly understood. Treatment is well established for M. avium intracellulare and M. kansasii, with combinations of clarithromycin-rifampicin-ethambutol and isoniazid-rifampicin-ethambutol respectively. For M. xenopi, the optimal treatment is not known and a combination of clarithromycin-rifampicin-ethambutol, with moxifloxacin as an alternative, is currently recommended. In general, treatment is prolonged and often associated with problems of tolerance.
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In this report a case of Mycobacterium chelonae keratitis in a patient without any previously described risk factors is described. The only risk factor found was a rheumatoid arthritis related Sjogren''s syndrome.
A newborn colonized with Chlamydia trachomatis will often show symptoms of conjunctivitis and/or pneumonia. We report a case of interstitial pneumonia caused by C. trachomatis in a 2-month-old boy admitted with RSV. We point to the importance of C. trachomatis in the differential diagnostics of an infant with respiratory symptoms even in the presence of additional infectious agents.
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The in vitro and in vivo antibacterial activities of clarithromycin (CAM), a new oral macrolide antibiotic, were compared with those of erythromycin (EM), josamycin (JM) and rokitamycin (RKM). The antibacterial spectrum and in vitro activities of CAM were similar to those of EM. Therapeutic efficacies of CAM against various experimental infections in mice--including systemic infections caused by gram-positive bacteria such as Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae, and subcutaneous abscess due to S. aureus, and bacterial pneumonia caused by S. pneumoniae--were superior to those of EM, JM and RKM. CAM exhibited higher serum levels than EM in mice after a single oral dose of 50 mg/kg.
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We report three Japanese children with Mycobacterium avium infection of the skin who also developed lichen scrofulosorum, a previously undescribed association. They were healthy except for the presence of several noduloulcerative lesions associated with multiple asymptomatic papules on the trunk and extremities. Histology of the ulcerative lesions showed features of mixed-cell granuloma, whereas the papular lesions showed features consistent with lichen scrofulosorum. M. avium was identified by polymerase chain reaction-aided DNA-DNA hybridization analysis in specimens obtained from the noduloulcerative lesions. Both the noduloulcerative and the papular lesions responded well to combination chemotherapy consisting of antituberculous agents and antibiotics.
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Recognizing adverse drug reactions (ADRs) is becoming more important in clinical practice.
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H. pylori eradication therapy and 7-week rebamipide monotherapy were not superior to PPI monotherapy, but this combination therapy for smaller sized ulcers was an optimal therapeutic option for healing. Serious adverse events were not observed in either group.
The eradication rate with PPI-based standard triple therapy for Helicobacter pylori infection has fallen considerably. One recent innovation is sequential therapy with PPI and three antibiotics, but the complexity of this regimen may reduce its usability. Concomitant administration of nonbismuth quadruple drugs (concomitant therapy) is also an effective treatment strategy. To investigate which regimen is a reasonable choice for Korean population, we performed two pilot studies with sequential and concomitant therapies.
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It has been reported that approximately 10% of patients infected with Helicobacter pylori have both clarithromycin-susceptible and clathromycin-resistant strains. However, there have been no reports indicating whether only one gastric biopsy is sufficient to detect clarithromycin-resistant strains.
Sixty-six patients (93%) completed the trial and five patients were lost to follow-up. H. pylori infection was cured in 61 out of the 66 patients who completed the trial (per-protocol analysis: 92.4%, 95% CI: 83.2-97.5%; intention-to-treat analysis: 85.9%, 95% CI: 75.7-93.0%). At final endoscopy, 65 out of 66 patients had healed ulcer (98.5%). Mild adverse events occurred in six patients (9.1%).
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Due to the low amoxicillin and clarithromycin resistance observed in this study, therapies using these antimicrobials remain appropriated first-line H. pylori therapy.
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Fifty-three Mycoplasma pneumoniae strains were isolated from pediatric patients in Shanghai, China, from October 2005 to February 2008. Of 53 clinical isolates, 44 (83%) were resistant to erythromycin (MICs of >128 microg/ml for all 44 strains), azithromycin, and clarithromycin. All macrolide-resistant M. pneumoniae strains harbored an A-to-G transition mutation at position 2063 in 23S rRNA genes. Forty-five (85%) clinical isolates were classified into the P1 gene restriction fragment length polymorphism type I, and six (11%) were type II.