Mohammad Mehdi Aslani

Antibiotic susceptibility profile of Helicobacter pylori isolated from the dyspepsia patients in Tehran, Iran

Background/Aim: Helicobacter pylori is an important pathogen for gastroduodenal diseases. Infection with H. pylori can be limited by regimens of multiple antimicrobial agents. However, antibiotic resistance is a leading cause of treatment failure. The aim of this study has been to determine the resistance patterns of H. pylori strains isolated from gastric biopsies of patients with dyspepsia by agar dilution method, in Tehran, Iran Patients and Methods: H. pylori isolates from patients with gastrointestinal diseases were evaluated for susceptibility testing by agar dilution method. Susceptibility testing was performed to commonly used antibiotics including clarithromycin, tetracycline, amoxicillin, metronidazole and ciprofloxacin. Results: Among 92 patients with dyspepsia, H. pylori strains were isolated from 42 patients. Seventeen (40.5%) of the isolates were resistant to metronidazole (MICs ≥ 8 μg/l), whereas one isolate (2.4%) was resistant to amoxicillin (MICs ≤ 0. 5 μg/ml) and ciprofloxacin (MICs ≤ 1μg/ml). The resistance rates to other antibiotics in H. pylori isolates are recorded as follows: clarithromycin 6 (14.3 %), tetracycline 2 (4.8%). In 5 of 42 resistant cases, combined resistance was found. Conclusions: These data suggest that metronidazole should be used among Iranian patients in first-line therapy with caution, and ciprofloxacin in association with amoxicillin and a proton pump inhibitor is more recommended.

Antimicrobial Susceptibility of Clostridium Difficile Clinical Isolates in Iran

Background Clostridium difficile infection (CDI) is major growing problem in hospitals and its high incidence has been reported in recent years. Objectives The aim of this study was to investigate the antimicrobial susceptibility patterns of C. difficile clinical isolates against antibiotics commonly used for treatment CDI in hospitalized patients. Material and Methods During a 12 month study, 75 C. difficile isolates were collected from 390 patients with CDI. All samples were treated with alcohol and yeast extract broth. The treated suspensions were cultured on a selective cycloserine cefoxitin fructose agar (CCFA) supplemented with 5% sheep blood and incubated in anaerobic conditions, at 37 °C for 5 days. Cdd-3, tcdA and tcdB genes were identified using PCR assay. Results The prevalence of A+B+ , A+ B- and A- B+ strains were 64(85.3%), 5(6.7%) and 6(8%) respectively. In vitro susceptibility of 75 clinical isolates of C. difficile to 5 antimicrobial agents, including metronidazole, vancomycin, clindamycin, erythromycin and cefotaxime were investigated by Clinical and Laboratory Standards Institute (CLSI) agar dilution method. Metronidazole and vancomycin had good activity against C. difficile isolates with MIC90s of 2 and 1 µg/ml, respectively. Seventy one (94.6%) of strains was inhibited by concentrations that did not exceed 2µg/ml for metronidazole. Resistant to metronidazole observed in 5.3% of isolates. Forty three (57.3%) of the isolates were resistant to erythromycin. Of 43 resistant strains to erythromycin, 9 (12%) isolates had high-level MIC of more than 64 µg/ml. All strains were resistant to cefotaxime. Sixty seven (89.3%) isolates were resistant to clindamycin (MIC90s > 256 µg/ml) and only 6.7% were sensitive to clindamycin. Multidrug-resistant (three or more antibiotics) was seen in 36(48%) isolates. Conclusions Metronidazole and vancomycin still seem to be most effective drugs for treatment CDI.

Towards a superior streptokinase for fibrinolytic therapy of vascular thrombosis.

Medical intervention with fibrinolytic drugs such as tissue plasminogen activator (tPA) and streptokinase (SK) is the principal treatment for life-treating thromboembolic disorders. Contrary to tPA, SK is a heterogenic and non-human (bacterial) protein produced by streptococci and its medical application may elicit sever immune and anaphylactic responses that restrict its utilization. Besides, human plasminogen (HPG) activation by SK is not blood-clot specific and associated with a risk of hemorrhage. Despite these limitations, comparative clinical trials on various thrombolytic agents suggested that SK is the most cost-effective fibrinolytic drug and almost as safe as its other counterparts such as tPA. Therefore, a number of studies were conducted to provide structurally modified SK with reduced immunogenicity, higher blood-clot specificity and half-lives. Although there are extensive overlaps in SK structural domains responsible for functionality, immunogenicity and stability that may limit its modifications, various strategies such as genetic manipulations (amino acid substitution /addition /deletion or domain fusions through production of chimeric SK proteins linked to HPG or hirudin) and chemical modification such as (homogenous/site-specific) PEGylation have been employed to develop a superior SK. In addition, data of the latest studies on SK screened from different streptococcal sources indicated the possibility of retrieving naturally occurring SKs with higher activities, less antigenicity and/or more fibrinspecificity. In the present review, after a survey on structure function relationships of SK domains and different strategies for SK improvement, recent advances and potential application of computer and matrix-based analyses for design and introduction of superior SKs will be presented.

Association of tcdA+/tcdB+ Clostridium difficile Genotype with Emergence of Multidrug-Resistant Strains Conferring Metronidazole Resistant Phenotype

Background: Reduced susceptibility of Clostridium difficile to antibiotics is problematic in clinical settings. There is new evidence indicating the cotransfer of toxin-encoding genes and conjugative transposons encoding resistance to antibiotics among different C. difficile strains. To analyze this association, in the current study, we evaluated the frequency of toxigenic C. difficile among the strains with different multidrug-resistant (MDR) profiles in Iran. Methods: Antimicrobial susceptibility patterns and minimal inhibitory concentrations (MIC) of the isolates were determined against metronidazole, imipenem, ceftazidime, amikacin, and ciprofloxacin by agar dilution method. The association of the resistance profiles and toxigenicity of the strains were studied by PCR targeting tcdA and tcdB genes. Results: Among 86 characterized strains, the highest and lowest resistance rates were related to ciprofloxacin (97%) and metronidazole (5%), respectively. The frequency of resistance to other antibiotics was as follow: imipenem (48%), ceftazidime (76%), and amikacin (76.5%). Among the resistant strains, double drug resistance and MDR phenotypes were detected in the frequencies of 10.4% and 66.2%, respectively. All of the metronidazole-resistant strains belonged to tcdA +/tcdB + genotype with triple or quintuple drug resistance phenotypes. MIC50 and MIC90 for this antibiotic was equally ≤ 8 μg/ml. Conclusion: These results proposed the association of tcdA +/tcdB + genotype of C. difficile and the emergence of resistance strains to broad-spectrum antibiotics and metronidazole.