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Entamoeba histolytica infection is common in developing countries, and up to 100,000 individuals with severe disease die every year. Adequate therapy for amoebic colitis is necessary to reduce the severity of illness, prevent development of complicated disease and extraintestinal spread, and decrease transmission.
The frequence of mutations in the rifampicin resistant (RIF(r)) clones of microorganisms after adaption to ofloxacin and metronidazole was investigated to estimate the biological cost of H. pylori rifampicin (RIF) resistance. Mutations in rpoB gene responsible for RIF resistance of H. pylori were shown to have biological cost and be compensated by additional mutations in the microorganism genome. Comparison of the mutation frequency in the presence of metroniazole demonstrated that the acquired resistance to RIF resulted in changing of the adaptative capacity of the RIF(r) clones of H. pylori to metronidazole. Thus, a significant increase of the mutation frequency (> 700 times) in one of the RIF(r) clones and a broad spectrum of the mutations responsible for resistance to metronidazole vs. the H. pylori initial strain 26695 were observed. The findings could be evident of the fact that the adaptation to RIF changed the properties of the cell on one hand in such a way that its mutation capacity increased and that the target selection on the other hand revealed hypermutable cells, likely usual for the bacterial population.
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Gastric cancer and Helicobacter pylori infection remain a burden in many Asian countries. In the face of rising antibiotic resistance, the eradication rate of standard triple therapy is declining in many Asian countries. We reviewed the updated epidemiology of gastric cancer, prevalence of H. pylori infection, and antibiotic resistance in Asia. We also reviewed the strategies to improve the efficacy of H. pylori eradication therapies, including the use of high dose proton pump inhibitor, four drug therapies (including bismuth quadruple, concomitant, and sequential therapy), susceptibility guided therapy, extending the treatment duration to 14 days, and development of effective rescue therapy. Four drug therapies are usually more effective than triple therapy when given in the same duration, except in areas with concomitantly high metronidazole resistance and low clarithromycin resistance. The efficacies of different four drug regimens appeared to be similar. However, trials from different geographic areas showed contradictory results, indicating that the optimal therapy should be decided according to the local prevalence of antibiotic resistance. We proposed a prediction model to calculate the efficacy of different regimens according to the prevalence of antibiotic resistance. More large randomized trials which provide information on the antibiotic resistance are urgently needed to build a more accurate and reliable model. It is hoped that we will be able to decide the optimal regimens by routine surveillance of antibiotic resistance.
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To compare the efficacy of co-amoxiclav (amoxicillin + clavulanic acid) and the triple therapy of ampicillin + gentamycin + metronidazole as prophylactic antibiotic during Caesarean sections.
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Overall cure rates were poor for both dual therapies OA and OC (38% and 37%, respectively) and for triple therapies OMA, OMC, and OMD (57%, 55%, and 58%, respectively). The OMT combination was successful in 91% (95% confidence interval [CI], 80.4%-97%). Metronidazole resistance was present in 29.7% (95% CI, 24%-35%), amoxicillin resistance was present in 26% (95% CI, 21%-32%), clarithromycin resistance was present in 23.1% (95% CI, 18%-29%), tetracycline resistance was present in 14% (95% CI, 10%-20%), and doxycycline resistance was present in 33.3% (95% CI, 21%-47%). Antibiotic resistance markedly reduced the cure rates and accounted for most of the poor results with the triple therapies: 89% versus 23%; 77% versus 26%; 100% versus 60%; and 67% versus 23% for OMC, OMA, OMT, and OMD, respectively. OMT appeared to be the best because of the high success rate with metronidazole-resistant H. pylori (71%) and in low-level tetracycline resistance.
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The pathogen Campylobacter jejuni is considered a microaerophile yet has been shown to grow in vitro in atmospheres with partial oxygen tension of 21%. To achieve a better understanding of its microaerophily, the oxygen requirement and tolerance of four C. jejuni strains were investigated by measuring their growth under different conditions, by performing bioinformatic analyses and by determining their metronidazole resistance. At high cell densities, C. jejuni showed similar growth under microaerobic and fully aerobic oxygen tensions, but did not grow under oxygen-depleted conditions. At low cell densities, the bacteria grew only under microaerobic conditions. Eighteen genes were identified bioinformatically as potential contributors to the differences in oxygen tolerance between strains. Among them, cj0203, cj0264c, cj0415, cj0425, cj0628, cj0629 and cj0864 were considered the top potential contributors. The oxygen tolerance of the four C. jejuni strains was different, and this tolerance positively correlated with their resistance to metronidazole. This study provided evidence that C. jejuni was an obligate microaerophile. The data indicated that the strains had different oxygen tolerances; it suggested that they could result in phenotypic and physiological differences between strains grown under the same conditions. These differences could modulate the outcome of experiments, and may explain discrepancies in the results between strains.
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Compared to placebo, prescription of adjunctive systemic antibiotics failed to show clinically relevant benefit with regard to furcation class involvement.
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Amoebiasis, a worldwide explosive epidemic, caused by the gastrointestinal anaerobic protozoan parasite Entamoeba histolytica, infects the large intestine and, in advance stages, liver, kidney, brain and lung. Metronidazole (MNZ)-the first line medicament against amoebiasis-is potentially carcinogenic to humans and shows significant side-effects. Pyrazolo[3,4-d]pyrimidine compounds have been reported to demonstrate antiamoebic activity. In silico molecular docking simulations on nine pyrazolo[3,4-d]pyrimidine molecules without linkers (molecules 1-9) and nine pyrazolo[3,4-d]pyrimidine molecules with a trimethylene linker (molecules 10-18) along with the reference drug metronidazole (MNZ) were conducted using the modules of the programs Glide-SP, Glide-XP and Autodock with O-acetyl-L-serine sulfhydrylase (OASS) enzyme-a promising target for inhibiting the growth of Entamoeba histolytica. Docking simulations using Glide-SP demonstrate good agreement with reported biological activities of molecules 1-9 and indicate that molecules 2 and 4 may act as potential high affinity inhibitors. Trimethylene linker molecules show improved binding affinities among which molecules 15 and 16 supersede. MD simulations on the best docked poses of molecules 2, 4, 15, 16 and MNZ were carried out for 20 ns using DESMOND. It was observed that the docking complexes of molecules 4, 15 and MNZ remain stable in aqueous conditions and do not undergo noticeable fluctuations during the course of the dynamics. Relative binding free energy calculations of the ligands with the enzyme were executed on the best docked poses using the molecular mechanics generalized Born surface area (MM-GBSA) approach, which show good agreement with the reported biological activities.
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In our setting, the administration of a single dose of 160 mg of gentamicin in combination with 500 mg of metronidazole before emergency cesarean section for prevention of infection is clinically equivalent to existing conventional week-long postoperative therapy, but at approximately one-tenth of the cost.
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This study demonstrated that dequalinium chloride inhibits and kills clinical isolates of A. vaginae at concentrations similar to those of clindamycin and lower than those of metronidazole.