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Although many combination therapies have been proposed, there is still interest in identifying simple, inexpensive, effective protocols that have high rates of success.
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The mitochondrial rRNA of the tapeworm species Echinococcus multilocularis carries an adenine at sequence position 2058 (numbering according to that for Escherichia coli) of the large-subunit rRNA (lsrRNA), while the nucleus-encoded rRNA, as determined in this study, is characterized by 2058G. This indicates a dichotomy in the drug susceptibilities of ribosomes: cytoplasmic ribosomes are predicted to be resistant to macrolide antibiotics, while mitochondrial ribosomes lack the most common chromosomal resistance determinant, lsrRNA 2058G. Upon incubation with the macrolide clarithromycin, the formation of vesicles from metacestode tissue was reduced in a dose-dependent manner. Electron microscopy revealed distinct morphological alterations both of the mitochondria and of the vesicle wall (e.g., loss of microtriches) in drug-treated vesicles. Adult worms lost their motility and displayed morphological changes (shortening and constriction of proglottids and the presence of vacuoles) upon incubation with clarithromycin. Our findings demonstrate that macrolides have distinct in vitro effects on E. multilocularis, endorsing the use of sequence-based in silico approaches for exploitation of available ribosomal drugs as anthelmintic agents.
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The aim of the present study was to examine the effect of Helicobacter pylori infection on gastric leptin expression to investigate the pathophysiological role of gastric leptin.
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Pulmonary edema is usually bilateral, but unilateral lobar pulmonary edema can also be encountered in clinical practice.
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The scope of present paper is the meta-analysis of eradication studies performed in Hungary between 1993-2002.
To compare the effectiveness of sequential therapy for Helicobacter pylori (H. pylori) infection with that of triple therapy of varying durations.
As standard triple therapies of achieve unsatisfactory eradication of Helicobacter pylori, several alternative regimens have been proposed.
Retrospective chart review, susceptibility testing, molecular fingerprinting, and DNA sequence analyses of resistant MAC isolates.
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On the intention-to-treat basis, eradication rates were 66% (46 out of 70) and 84% (58 out of 69) for the 5- and 7-day regimens, respectively (P < 0.05). Using per protocol analysis, eradication rates were 70% (46 out of 66) and 91% (58 out of 64) for the 5- and 7-day regimens, respectively (P < 0.01). Adverse events, which were observed in 14 patients from each group, caused discontinuation of treatment in only two patients, resulting in excellent compliance.
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After the first interim analysis, the study was stopped. M. avium complex infection developed in 19 of the 333 patients (6 percent) assigned to clarithromycin and in 53 of the 334 (16 percent) assigned to placebo (adjusted hazard ratio, 0.31; 95 percent confidence interval, 0.18 to 0.53; P<0.001). During the follow-up period of about 10 months, 32 percent of the patients in the clarithromycin group died and 41 percent of those in the placebo group died (hazard ratio, 0.75; P=0.026). In the clarithromycin group, isolates from 11 of the 19 patients with M. avium complex infection were resistant to clarithromycin. Prophylaxis with clarithromycin was associated with an increased incidence of taste perversion (11 percent in the clarithromycin group vs. 2 percent in the placebo group, P<0.001) and rectal disorders (8 percent vs. 3 percent, P = 0.007); however, the frequency of more severe adverse events was similar in the two groups (7 percent and 6 percent, respectively).
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Patterns of resistance were analysed in H. pylori isolates from 94 consecutive patients in whom H. pylori infection had persisted after two eradication attempts. Using the epsilometer test, susceptibility analysis was performed for amoxicillin, clarithromycin, metronidazole, tetracycline and levofloxacin. Patients were then treated with a culture-guided, third-line regimen: 89 patients with a 1-week quadruple regimen including omeprazole, bismuth, doxycycline and amoxicillin, and five patients with a 1-week triple regimen containing omeprazole, amoxicillin and levofloxacin or clarithromycin.
Over the last two decades, antimicrobial resistance in Streptococcus pneumoniae has been detected at an increasing rate. There have been several reports of increasing rate of macrolide resistance among the penicillin-resistant S. pneumoniae strains. The rapid evolution of such resistance necessitated new antimicrobials, such as streptogramins, oxazolidinones and ketolides, against beta-lactam and macrolide resistant pneumococci. This study was undertaken to determine the prevalence of macrolide resistance in pneumococci isolated in a Turkish University hospital and also to determine the activity of these newly developed agents against pneumococci. For that purpose a total of 264 pneumococci, isolated from clinical specimens, were tested for susceptibility against penicillin, erythromycin, clarithromycin, clindamycin, quinupristin/dalfopristin, linezolid and telithromycin by agar dilution method. Penicillin resistance and intermediate penicillin resistance was found in 7.6% and 40% of isolates respectively, while resistance rates of the tested isolates against erythromycin, clarithromycin and clindamycin were as 15.9%, 13.6% and 13.6%, respectively. Resistance to macrolides and clindamycin was higher among the penicillin-resistant isolates. No resistance was detected against quinupristin/dalfopristin, linezolid and telithromycin, except for four strains which had minimal inhibitory concentration (MIC) values of intermediately susceptible category to quinupristin/dalfopristin. These data indicate the presence of an important percentage of macrolide resistant pneumococci in our hospital. It can also be concluded that streptogramins, oxazolidinones and ketolides may be used as good alternatives especially in case of infections due to macrolide resistant pneumococci.
Bioequivalence between the Test and Reference formulation can be concluded.
Antrum-predominant gastritis is the most common pattern of gastritis seen in non-ulcer dyspepsia in Western populations. Heartburn and regurgitation improve after eradication therapy or placebo in patients with non-ulcer dyspepsia; the development of oesophagitis is uncommon.
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The occurrence of sixty pharmaceutically active compounds (PhACs), twenty metabolites and eight personal care products (PCPs) in the aquatic environment in Spain and their predicted environmental concentrations (PECs) were calculated and compared with measured environmental concentrations (MECs) obtained from relevant published research. The occurrence in the aquatic environment was calculated through a mass balance approach considering the following: the number of pharmaceutical prescriptions issued, the amount of pharmaceutical discharged without consumption, consumption, self-medication, pharmacokinetics, treatment in wastewater facilities and discharged to aquatic environment. The estimation of consumption of active compounds of pharmaceuticals was conducted by at least one of the following methodologies: number of commercial packages sold, data for the number of defined daily dose per 1000 inhabitants per day (DHD), and pattern of treatment. Comparison of these methodologies for some compounds showed similar estimated consumption ranges. The highest pharmaceutical occurrence in the aquatic environment was for acetaminophen glucuronide, Galaxolide®, Iso-E-super®, acetaminophen, valsartan, amoxicillin, 2-hydroxy-ibuprofen, iopromide, omeprazole, carbamazepine 10, 11-epoxide, iopamidol, salicylic β-d-O-glucuronide acid, Tonalide®, acetylsalicylic acid (ASA), clarithromycin and iohexol, with releases between 5 and 600 ty(-1). The relation of PEC/MEC was calculated for 58% of the compounds under study, and 64.7% of them had PEC/MEC ratios between 0.5 and 2. PEC values were mostly overestimated (57.4%). The predicted concentrations for pharmaceutical and personal care products (PPCPs) that had a high occurrence in the aquatic environment were very close to the measured concentrations. This research provides information that had not been calculated and analyzed previously, at least for Spain. Estimation of the PECs for pharmaceutical, personal care products and metabolites is a useful tool for identifying compounds that should be considered for environmental concern, and such estimations could be used to improve environmental risk assessment studies.
The DDI potential of five macrolide antibiotics was quantitatively predicted from in vitro studies using testosterone as the CYP3A substrate with HLM as the enzyme source.
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Pharmacokinetic interactions involving anti-infective drugs may be important in the intensive care unit (ICU). Although some interactions involve absorption or distribution, the most clinically relevant interactions during anti-infective treatment involve the elimination phase. Cytochrome P450 (CYP) 1A2, 2C9, 2C19, 2D6 and 3A4 are the major isoforms responsible for oxidative metabolism of drugs. Macrolides (especially troleandomycin and erythromycin versus CYP3A4), fluoroquinolones (especially enoxacin, ciprofloxacin and norfloxacin versus CYP1A2) and azole antifungals (especially fluconazole versus CYP2C9 and CYP2C19, and ketoconazole and itraconazole versus CYP3A4) are all inhibitors of CYP-mediated metabolism and may therefore be responsible for toxicity of other coadministered drugs by decreasing their clearance. On the other hand, rifampicin is a nonspecific inducer of CYP-mediated metabolism (especially of CYP2C9, CYP2C19 and CYP3A4) and may therefore cause therapeutic failure of other coadministered drugs by increasing their clearance. Drugs frequently used in the ICU that are at risk of clinically relevant pharrmacokinetic interactions with anti-infective agents include some benzodiazepines (especially midazolam and triazolam), immunosuppressive agents (cyclosporin, tacrolimus), antiasthmatic agents (theophylline), opioid analgesics (alfentanil), anticonvulsants (phenytoin, carbamazepine), calcium antagonists (verapamil, nifedipine, felodipine) and anticoagulants (warfarin). Some lipophilic anti-infective agents inhibit (clarithromycin, itraconazole) or induce (rifampicin) the transmembrane transporter P-glycoprotein, which promotes excretion from renal tubular and intestinal cells. This results in a decrease or increase, respectively, in the clearance of P-glycoprotein substrates at the renal level and an increase or decrease, respectively, of their oral bioavailability at the intestinal level. Hydrophilic anti-infective agents are often eliminated unchanged by renal glomerular filtration and tubular secretion, and are therefore involved in competition for excretion. Beta-lactams are known to compete with other drugs for renal tubular secretion mediated by the organic anion transport system, but this is frequently not of major concern, given their wide therapeutic index. However, there is a risk of nephrotoxicity and neurotoxicity with some cephalosporins and carbapenems. Therapeutic failure with these hydrophilic compounds may be due to haemodynamically active coadministered drugs, such as dopamine, dobutamine and furosemide, which increase their renal clearance by means of enhanced cardiac output and/or renal blood flow. Therefore, coadministration of some drugs should be avoided, or at least careful therapeutic drug monitoring should be performed when available. Monitoring may be especially helpful when there is some coexisting pathophysiological condition affecting drug disposition, for example malabsorption or marked instability of the systemic circulation or of renal or hepatic function.
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Widespread use of eradication therapy for Helicobacter pylori has increased the prevalence of clarithromycin-resistant strains. The purpose of the present paper was to measure the in vitro antibacterial activity of minocycline against H. pylori, and study the effectiveness of minocycline-based first- and second-line eradication therapies.
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Mycobacterium abscessus is ubiquitously found rapidly growing mycobacteria. Although it is an uncommon pathogen, it has been known to cause cutaneous infection following inoculation, minor trauma or surgery. This communication reports an immuno-competent patient developing multiple sinuses due to Mycobacterium abscessus in the post- operative period.
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The postantibiotic effect (PAE) of clarithromycin alone and in combination with ethambutol was determined for two clinical blood isolates of Mycobacterium avium complex. An average PAE, ranging from 5.5 to 18.0 h, was noted for each isolate at each clarithromycin concentration except when isolate B was exposed to clarithromycin at the MIC. The addition of ethambutol did not enhance the PAE observed with clarithromycin alone. The clinical implications of the PAE of clarithromycin for M. avium complex remain to be determined.
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Drug-related adverse event rates associated with oral moxifloxacin or the comparator therapy used in these studies did not significantly increase with advancing age. This pooled analysis suggests that oral moxifloxacin can be safely used in elderly patients with characteristics consistent with those enrolled into the clinical trials.