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The DPO-PCR is an interesting tool to detect H. pylori on gastric biopsies and to study its susceptibility to clarithromycin in laboratories that cannot perform real-time PCR assays.
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There is a pool of streptococci carrying genes associated with macrolide resistance in the normal respiratory flora of generally healthy adults. Differences between the patients treated with clarithromycin and those treated with azithromycin were difficult to assess because of the large number of patients in each group with macrolide-resistant streptococci before treatment. Although there were some differences these were not statistically significant.
Mycobacterium abscessus and Mycobacterium massiliense lung infections have different clarithromycin susceptibilities, making proper identification important; however, standard multi-gene sequencing in clinical laboratories is laborious and time consuming. We developed a pyrosequencing-based method for rapid identification of strains belonging to the M. abscessus group by targeting erm(41). We examined 55 isolates from new pulmonary M. abscessus infections and identified 28 M. abscessus, 25 M. massiliense, and 2 Mycobacterium bolletii isolates. Multi-gene sequencing of 16S rRNA, hsp65, rpoB, and the 16S-23S ITS region was concordant with the results of erm(41) pyrosequencing; thus, the M. abscessus group can be identified by single-nucleotide polymorphisms in erm(41). The method also enables rapid identification of polymorphic, inducible clarithromycin-resistant sequevars (T28 or C28). Pyrosequencing of erm(41) is a rapid, reliable, high-throughput alternative method for identifying and characterizing M. abscessus species. Further testing of a diverse collection of isolates is necessary to demonstrate the discriminatory power of erm(41) sequencing to differentiating species with this highly divergent group.
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Clarithromycin increased the mean C(max) of ketamine by 3.6-fold (p<0.001) and the mean AUC(0-infinity) of ketamine by 2.6-fold (p=0.001). The relative amount of the CYP3A dependent metabolite norketamine was decreased by 54% by clarithromycin (p=0.004). Self-rated drug effect of S-ketamine was enhanced by clarithromycin (p<0.05) but other behavioral effects or cold pain scores were not affected.
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The aims of this study were to determine the prevalence of H. pylori seropositivity in patients with psoriasis, to evaluate the relationship between PASI (Psoriasis Area and Severity Index) scores and H. pylori infection, and to assess the impact of H. pylori infection on the response to treatment. A total of 300 patients with psoriasis and 150 non-psoriatic healthy controls were enrolled in the study. Patient PASI scores were recorded and H. pylori stool antigen tests performed in both patients and controls. Fifty patients with H. pylori infections were randomly assigned to one of two groups, one of which received acitretin with H. pylori treatment and the other acitretin alone. Statistical analyses were performed using chi-square and logistic regression tests. PASI scores were significantly higher in patients with H. pylori infections. Treatment aimed at eradicating H. pylori infection enhanced the effectiveness of acitretin therapy and shortened response times. Our results suggest that H. pylori infection plays a role in the severity of psoriasis, and that eradicating such infections enhances the effectiveness of psoriasis treatment.
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A multi-center surveillance study was conducted in Thailand during 1999-2000 to determine antimicrobial susceptibilities among the respiratory pathogens Streptococcus pneumoniae (n = 206), Haemophilus influenzae (n = 305), and Moraxella catarrhalis (n = 39). Of the S. pneumoniae isolates collected, 33.5% were penicillin-susceptible, 27.2% intermediate and 39.3% resistant. Expectedly, resistance rates to beta-lactams were higher among penicillin-resistant (ceftriaxone, 14.8%; amoxicillin-clavulanate, 42.0%; cefuroxime, 100%) than penicillin-susceptible (ceftriaxone, 0%; amoxicillin-clavulanate, 0%; cefuroxime, 0%) isolates. Likewise, azithromycin and clarithromycin resistances were 4.3% and 5.8% among penicillin-susceptible isolates, and 77.8% and 95.1% among penicillin-resistant isolates. All S. pneumoniae remained susceptible to vancomycin and 99.5% were susceptible to levofloxacin. Multidrug resistance (resistance to >3 antimicrobial classes) was present in 25.2% of pneumococcal isolates (n = 52), with resistance to azithromycin, penicillin and trimethoprim-sulfamethoxazole the most common phenotype (40/52 isolates; 77.0%). Among the isolates of H. influenzae, the prevalence of beta-lactamase production was 45.2%. All isolates of H. influenzae were susceptible to amoxicillin-clavulanate, azithromycin, ceftriaxone, cefuroxime and levofloxacin while 49.5% were resistant to trimethoprim-sulfamethoxazole. All 39 isolates of M. catarrhalis produced beta-lactamase. Azithromycin (MIC90, < or = 0.03 microg/ml) and levofloxacin (MIC90, 0.03 microg/ml) were the most active agents tested against M. catarrhalis. The results of this study may serve as a baseline for future studies to monitor antimicrobial susceptibilities among respiratory pathogens in Thailand.
A randomized controlled trial was conducted in 160 patients comparing nizatidine 150 mg with 300 mg b.d. (standard vs. double dose), in combination with clarithromycin (500 mg) and amoxycillin (1000 mg) b.d. for 14 days, in Australia and Taiwan. Compliance was based on a clinical assessment and pill count. H. pylori status was determined by histology (antrum and corpus) and CLO-test.
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The spectre of an influenza pandemic is being widely mooted. Most of the strategies explored to date for controlling or treating the condition have centred on controlling the spread of the infection, the use of vaccines or anti-viral agents. There has been relatively little discussion about treating the lung and systemic inflammatory reactions that occur during influenza infection. In this review a range of therapeutic agents are proposed to treat the inflammatory reactions, principally in the lung as well as the systemic cytokine-mediated immuno-inflammatory reactions that may be a major cause of the morbidity and mortality associated with influenza infections. Among these are pentoxifylline, the statins, the macrolide antibiotics (e.g. azithromycin, clarithromycin, erythromycin), resveratrol (a component of wine and fruits with inhibitory effects on influenza virus replication) and nutraceuticals (including those that contain flavonoids, the marine oils eicosapentanoic and docosanoic acids or the green-lipped mussel extract, Liprinol which may by virtue of the inhibitory effects on the production or actions of pro-inflammatory cytokines, be useful for their anti-inflammatory actions. The efficacy, mode of actions and side effects of non-steroidal anti-inflammatory drugs (NSAIDs) are considered. There are a number of issues relating to their use in treating the inflammatory reactions in the respiratory tract. Among these are the development of gastro-intestinal ulcers and bleeding and hepato-renal reactions in patients that may because of severe systemic inflammation be prone to the development of these adverse reactions. There are also theoretical issues concerning the impact of COX-1 mediating reduction in prostaglandin and increased cytokine production that might have some negative consequences for respiratory inflammation.In conclusion, further consideration should be given to exploring the actions of these anti-inflammatory agents to control the respiratory inflammatory in influenza infections which can have serious consequences for the outcome of the infection.
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The objective of this study is to examine the effectiveness of oral antibiotics in the prevention of infection development in traumatic wounds.
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Our new PCR-based assay for 23S rRNA mutations of H. pylori is a useful method for detecting clarithromycin-resistant strains of H. pylori easily.
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Macrolides, such as clarithromycin and azithromycin, possess antimicrobial, immunomodulatory, and potential antiviral properties. They represent a potential therapeutic option for asthma, a chronic inflammatory disorder characterised by airway hyper-responsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing. Results from clinical trials, however, have been contentious. The findings could be confounded by many factors, including the heterogeneity of asthma, treatment duration, dose, and differing outcome measures. Recent evidence suggests improved effectiveness of macrolides in patients with sub-optimally controlled severe neutrophilic asthma and in asthma exacerbations. We examine the evidence from clinical trials and discuss macrolide properties and their relevance to the pathophysiology of asthma. At present, the use of macrolides in chronic asthma or acute exacerbations is not justified. Further work, including proteomic, genomic, and microbiome studies, will advance our knowledge of asthma phenotypes, and help to identify a macrolide-responsive subgroup. Future clinical trials should target this subgroup and place emphasis on clinically relevant outcomes such as asthma exacerbations.
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In 1982-1984 we conducted a six-month clinical trial in 50 previously untreated lepromatous leprosy patients randomly assigned to directly observed monotherapy with one of two thioamides, ethionamide or prothionamide, each given six times a week at doses of either 250 mg or 500 mg. The findings of this study have only recently been analyzed, and the potential for the use of these thioamides in leprosy patients placed in perspective. However, because of the small number of patients included in this study, the results must be interpreted with some caution. Clinical improvement was noted in 74% of the patients treated with ethionamide and in 83% of those treated with prothionamide. Therapy was well tolerated and drug-related hepatotoxicity did not require discontinuation of therapy. The 500-mg dose of both ethionamide and prothionamide resulted in loss in Mycobacterium leprae viability more rapidly than did the 250-mg dose, and prothionamide at both dose levels was superior to the equivalent dose of ethionamide. Overall killing of M. leprae in this study was found to be similar to that obtained previously with dapsone and clofazimine, but less than was obtained with rifampin, minocycline, clarithromycin, pefloxacin, and ofloxacin.
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This study aims to evaluate Helicobacter pylori with clarithromycin resistant genotypes in Manisa region, Turkey. Two hundred patients, who received diagnosis of Helicobacter pylori infection histopathologically, were included. The sex, age and endoscopy indications of the patients were recorded. Polymerase chain reaction method was applied to determine the clarithromycin resistance rate and resistance genotypes at the histologic sections prepared from gastric biopsies that had been embedded in paraffin after fixation by formalin. Helicobacter pylori resistance to clarithromycin was found in 19/200 (9.5%) patients. 10/19 (52.6%) of these clarithromycin-resistant patients had A2143G mutation and 9/19 (47.4%) had A2142G mutation. A2142C mutation on 23S rRNA gene was not detected for any of the patients. Clarithromycin can be used as a first step treatment in the eradication of Helicobacter pylori for the children in our region; if the treatment fails for some patients, clarithromycin resistance, especially A2143G and A2142G mutations should be considered.
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The in vitro activity of Bay 12-8039, a new oral 8-methoxyquinolone, was compared to the activities of 11 other oral antimicrobial agents (ciprofloxacin, levofloxacin, ofloxacin, sparfloxacin, azithromycin, clarithromycin, amoxicillin clavulanate, penicillin, cefuroxime, cefpodoxime, and doxycycline) against 250 aerobic and 140 anaerobic bacteria recently isolated from animal and human bite wound infections. Bay 12-8039 was active against all aerobic isolates, both gram-positive and gram-negative isolates, at < or = 1.0 microg/ml (MICs at which 90% of isolates are inhibited [MIC90s < or = 0.25 microg/ml) and was active against most anaerobes at < or = 0.5 microg/ml; the exceptions were Fusobacterium nucleatum and other Fusobacterium species (MIC90s, > or = 4.0 microg/ml) and one strain of Prevotella loeschii (MICs, 2.0 microg/ml). In comparison, the other quinolones tested had similar in vitro activities against the aerobic strains but were less active against the anaerobes, including peptostreptococci, Porphyromonas species, and Prevotella species. The fusobacteria were relatively resistant to all the antimicrobial agents tested except penicillin G (one penicillinase-producing strain of F. nucleatum was found) and amoxicillin clavulanate.
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The in vitro kinetic constants of CYP3A inactivation (K (I) and k (inact)) were estimated by varying the time of pre-incubation and the concentration of troleandomycin, erythromycin, clarithromycin, roxithromycin or azithromycin. CYP3A activity was determined from the measurement of testosterone 6beta-hydroxylation with human liver microsomes (HLM) and recombinant CYP3A4 as the enzyme sources. The mechanism-based pharmacokinetic model was fitted with inactivation data to predict the increase in oral area under the plasma concentration-time curve (AUC) for midazolam.
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Rabeprazole- and omeprazole-based triple therapy regimens are therapeutically equivalent in the eradication of H. pylori and well tolerated. The statistical interaction observed between the proton pump inhibitor and supplementary antibiotic may be due to chance.
Thirty-three percent of the cultures were contaminated with other bacteria. Seven children had at least one sputum culture positive for one mycobacterium. Five children had only one positive AFB culture. Their clinical status and lung function remained stable during follow-up. Two teenagers with severe lung disease had several positive AFB smears and cultures for Mycobacterium chelonae and Mycobacterium abscessus. The isolation of M. chelonae and M. abscessus was associated with a clinical and functional decline. Clarithromycin treatment resulted in temporary improvement with the disappearance of the mycobacteria after 6 months of treatment. This prospective study shows an incidence of 2.3% for positive cultures. The prevalence was 6.6% for mycobacterial colonization but only 1.9% for mycobacterial lung disease in our pediatric population.
Respiratory pathogens are becoming increasingly resistant to antimicrobials. A new group of drugs, called respiratory quinolones have been synthesized to overcome this problem.
Chlamydia (C.) trachomatis is the most common bacterial cause of sexually transmitted disease in the world. A well documented feature of chlamydial infection is its high rate of recurrence among sexually active populations. However, it is difficult to distinguish whether the high rate of recurrent disease is due to reinfection or to persistent infection with the same organism. Of particular concern in this era of increasing antibiotic resistance is whether persistent infection is the consequence of increasing resistance to standard antimicrobial therapy. Azithromycin and doxycycline are considered by the Centers for Disease Control and Prevention (CDC) as first line drugs for the treatment of chlamydial infections; erythromycin, ofloxacin and levofloxacin are recommended as alternative-regimen. Although C. trachomatis has been historically sensitive to these antibiotics, in vitro resistance is being increasingly reported. However, although in vitro antimicrobial resistance has been described, the clinical significance of these findings is unknown. C. pneumoniae is associated with community-acquired pneumonias, acute exacerbations of chronic bronchitis, otitis media, sinusitis and reactive airway disease. Persistent nasopharyngeal infection with C. pneumoniae has been documented in adults following acute respiratory infection. Chronic infection with C. pneumoniae has also been implicated in the pathogenesis of atherosclerosis, although this is still very controversial. Azithromycin, clarithromycin and quinolones are frequently used for the treatment of C. pneumoniae respiratory infections. Microbiologic failure has been described in C. pneumoniae infections, even after prolonged courses of azithromycin, erythromycin and doxycycline.
Erythromycin, which was introduced over 50 years ago, was the first macrolide to be used clinically. "New" macrolides, for the treatment of patients with various infectious diseases, were not clinically introduced until 40 years later. The pharmacokinetic and adverse events profile of erythromycin initially limited its use to an alternative agent for patients with allergy to beta-lactam agents. However, the emergence of atypical and/or new pathogens and the ongoing escalation of acquired antimicrobial resistance has impacted on the empirical and organism directed therapy of infectious diseases. Azithromycin and clarithromycin were developed by enhancing the basic macrolide structure. Some of the basic features associated with these new agents include a pharmacokinetic profiles that allow once or twice daily dosing with a much lower incidence of side effects and a substantially broader spectrum of activity which includes some Gram-negative bacilli, atypical pathogens and new, unconventional or uncommon pathogens. Clinical trial data has supported the use of "new" macrolides in a wide range of clinical indications, however, some specific indications are currently restricted to treatment with either azithromycin or clarithromycin. Macrolide resistance is a class effect and depending on the mechanism will confer either low or high level resistance. While resistance is problematic, it does not always result in clinical failure. The macrolides are a valuable class of antimicrobial agent and play an important role in the management of infectious diseases.