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Thiopurine methyltransferase (TPMT) enzymes play a crucial role in azathioprine metabolism. Mutations in the enzyme initiate generation of excess thioguanine, which causes suppression of various cell lineages. The objectives of this study were to investigate the prevalence of TPMT mutation in Bangladeshi patients with systemic lupus erythematosus (SLE) requiring azathioprine therapy and its relation to the development of myelosuppression. 250 patients with SLE were enrolled, then monitored for myelosuppression adverse events for 4 months. TPMT*3C (rs1142345), TPMT*3B (rs1800460), and TPMT*2 (rs1800462) polymorphisms were analyzed using polymerase chain reaction–restriction fragment length polymorphism. The risk of myelosuppression (i.e., leukopenia, thrombocytopenia, and anemia) was estimated as the odds ratio (OR) with 95% confidence intervals (CIs) and p values. Of the 250 patients, 17 (6.8%) were heterozygous for the TPMT*3 mutation and 233 (93.2%) were homozygous for the wild type; no patients carried a homozygous mutation. Grade III/IV leukopenia, thrombocytopenia, and anemia occurred in 12.0%, 12.0%, and 27.9% of wild-type TPMT patients respectively; corresponding rates in heterozygous TPMT*3C patients were 70.6%, 64.7%, and 5.9%. Patients with Grade III/IV azathioprine-induced leukopenia were significantly more likely to have the heterozygous TPMT*3C genotype than the wild-type variant (OR 17.6; 95% CI 5.8–53.6; p

Background/Purpose Nearly all published studies of recurrent Clostridium difficile infections (CDI) report recurrent CDI within 8 weeks after the primary infection. This study explored the molecular characteristics of C. difficile isolates from the first recurrent CDI more than 8 weeks after the primary infection. Methods Consecutive hospitalized patients with a recurrent CDI more than 8 weeks after a primary infection were enrolled prospectively from January 2008 to February 2011. All C. difficile isolates of the primary and recurrent infections were collected and subjected to polymerase chain reaction ribotyping and antimicrobial susceptibility testing. Results There were 62 cases of CDI in this study, which included 32 cases (51.6%) of recurrence due to the same ribotype of C. difficile , 26 (41.9%) cases due to a different ribotype, and four (6.5%) cases with 2–4 recurrences due to the same or different strains. One hundred and forty C. difficile isolates were obtained, which included 62 primary CDI isolates and 78 recurrent isolates. Ribotype 020 was the most common C. difficile strain in primary and recurrent infections. Ribotype 001 accounted for 15.4% (10/78) of recurrent infections and 3.2% (2/62) of primary infections ( p = 0.0447). The minimum inhibitory concentration at 90% (MIC 90 ) values of linezolid, moxifloxacin, and clindamycin against type 001 strains were much higher, compared to the three other common ribotypes. Conclusion Recurrent CDI more than 8 weeks after a primary infection can be caused by the same or different C. difficile ribotype at similar percentages. Ribotype 001 C. difficile strains, which have a lower susceptibility to antimicrobials, were isolated more frequently in patients with a recurrent CDI.

The objective of this study was to examine the restorative effects of methanol extract of Commelina benghalensis leaves in antidiarrheal activity in Swiss albino mice model and anthelmintic activity in Tubifex tubifex. Antidiarrheal activity study in Swiss albino mice were divided into four groups. Group I was treated as the control group and received 10 ml/kg of 2% Tween-80 orally; Group II served as a positive control and took standard drug (loperamide) in 5 mg/kg orally; Groups III and IV were the test groups which received the methanol extract of C. benghalensis orally at 200 and 400 mg/kg, respectively. Dependent upon the model comprehensive weight of dry feces, aggregate weight of wet defecation, length of intestinal travel and intestinal weight were gathered. At long last, information were investigated using restricted analysis of variance (ANOVA) took after by Dunnett test. Anthelmintic action on aquarium worm T. tubifex by utilizing three focuses of 10, 5, and 2.5 mg/ml of C. benghalensis movement was assessed by in vitro system. The property of the extract on defecation, intestinal transit and intestinal fluid accumulation (antienteropooling) were assessed in castor oil induced diarrhea. Leaves extract of C. benghalensis at 200 and 400 mg/kg exhibited significant (p

Sixty-eight hospital-admitted patients with a first episode of Clostridium difficile infection (CDI) were included and followed up during 1 year. Faeces samples were collected at 1, 2, 6 and 12 months after inclusion and analyzed for the presence of C. difficile toxin B, genes for toxin A, toxin B, binary toxin and TcdC deletion by PCR. All strains were also PCR-ribotyped and the MICs of the isolates were determined against eight antimicrobial agents. In 68 patients initially included, antibiotics, clinical signs and co-morbidities were analyzed and 56 were evaluable for recurrences. The mean number of different antibiotics given during 3 months prior to inclusion was 2.6 (range 0-6). Six patients had not received any antibiotics and three of them had diagnosed inflammatory bowel disease. Thirty-two patients (57%) had either a microbiological or clinical recurrence, 16 of whom had clinical recurrences that were confirmed microbiologically (13, 23%) or unconfirmed by culture (3, 5%). Twenty-nine patients were positive in at least one of the follow-up tests, 16 had the same ribotype in follow-up tests, i.e. relapse, and 13 a different ribotype, i.e., reinfection. Most common ribotypes were 078/126, 020, 023, 026, 014/077, 001 and 005. No strain of ribotype 027 was found. Strains ribotype 078/126 and 023 were positive for binary toxin and were the strains most prone to cause recurrence. All strains were sensitive to vancomycin and metronidazole. Patients with recurrences were significantly older (p = 0.02) and all patients had a high burden of comorbidities, which could explain the high fatality rate, 26 (38%) patients died during the 1-year follow-up.

The present study was undertaken to evaluate safety and efficacy of methotrexate in Rheumatoid arthritis patients. This study was carried out on ARA criteria fulfilling 35 diagnosed Rheumatoid arthritis patients of either gender, aged 20-60 years, presented in Medicine department of Rajshahi Medical College Hospital, Rajshahi from July 2007 to June 2008. Patients with normal liver function tests and HBsAg and anti-HCV negative cases were given oral methotrexate (10-15 mg/wk) for 6 weeks. Baseline prothrombin time was 12.97±0.34 seconds. After 6 weeks of methotrexate therapy prothrombin time was found 13.47±0.46 seconds. During methotrexate therapy change of prothrombin time was not significant (p>0.05).KYAMC Journal Vol. 6, No.-1, Jul 2015, Page 550-552

The aim of this study was to assess the impact of ciprofloxacin, clindamycin, and placebo administration on culturable Gram-negative isolates and the antibiotic resistance genes they harbor. Saliva and fecal samples were collected from healthy human volunteers before and at intervals, up to 1 year after antibiotic administration. Samples were plated on selective and nonselective media to monitor changes in different colony types or bacterial species. Following ciprofloxacin administration, there was a decrease of Escherichia coli in feces and after clindamycin administration a decrease of Bacteroides in feces and Leptotrichia in saliva, which all returned to pretreatment levels within 1 to 4 months. Ciprofloxacin administration also resulted in an increase in ciprofloxacin-resistant Veillonella in saliva, which persisted for 12 months. Additionally, 949 aerobic and anaerobic isolates purified from ciprofloxacin- and clindamycin-containing plates were screened for the presence of resistance genes. Resistance gene carriage was widespread in isolates from all three treatment groups, and no association was observed between genes and antibiotic administration. Although the anaerobic component of the microbiota was not a major reservoir of aerobe-associated antimicrobial resistance (AMR) genes, we detected the sulfonamide resistance gene sul2 in anaerobic isolates. The longitudinal nature of the study allowed identification of distinct Escherichia coli clones harboring multiple resistance genes, including one carrying an extended-spectrum β-lactamase bla CTX-M group 9 gene, which persisted in the gut for up to 4 months. This study provided insight into the effects of antibiotic administration on healthy microbiota and the diversity of resistance genes harbored therein.

The purpose of the study was to assess the effect of ciprofloxacin (500 mg twice daily for 10 days) or clindamycin (150 mg 4 times daily for 10 days) on the fecal microbiota of healthy humans for a period of 1 year as compared to placebo. Two different methods, culture and microbiome analysis, were used. Fecal samples were collected for analyses at 6 time-points. The interval needed for the normal microbiota to be normalized after ciprofloxacin or clindamycin treatment differed for various bacterial species. It took 1-12 months to normalize the human microbiota after antibiotic administration, with the most pronounced effect on day 11. Exposure to ciprofloxacin or clindamycin had a strong effect on the diversity of the microbiome, and changes in microbial composition were observed until the 12th month, with the most pronounced microbial shift at month 1. No Clostridium difficile colonization or C. difficile infections were reported. Based on the pyrosequencing results, it appears that clindamycin has more impact than ciprofloxacin on the intestinal microbiota. © 2015 The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

The present study was engineered to find out the anti-arthritic and thrombolytic activity of methanolic extract of Protium serratum by using in vitro method. Methanolic extract of P. serratum was assessed with the inhibition of protein denaturation model which was used to evaluate anti-arthritic potential and this extract assessed with human blood to evaluate thrombolytic effect. The extract showed remarkable anti-arthritic activity which was evaluated by the percentages of inhibition of protein denaturation in different concentration of plant extract compared to diclofenac sodium, a reference drug. The maximum percentage inhibition of protein denaturation was observed as 83.94% at 1000 μg/ml. It has significant thrombolytic effect compared to streptokinase. During assay for thrombolytic activity, the methanolic extract of P. serratum revealed 59.653 ± 8.626% lysis of clot, while standard streptokinase (SK) and water used as positive and negative controls, demonstrated 72.835 ± 5.702 and 2.725 ± 0.983% lysis of clot, respectively. These findings demonstrate that the leaves extract of P. serratum have excellent anti-arthritic and thrombolytic effect. Key words: Protium serratum, anti-arthric, thrombolytic, % lysis of clot, protein denaturation.

An in vitro thrombolytic model was used to check the clot lysis effect of two herbal extracts viz., Desmodium paniculatum (L.) and Sarchochlamys pulcherrima (Roxb.) by using Streptokinase as positive control and water as negative control. D. paniculatum and S. pulcherrima showed 31.92 ± 8.09% and 36.12 ± 6.81% clot lysis, respectively. From our study we found that D. paniculatum and S. pulcherrima showed significant % of clot lysis effect with reference to Streptokinase (72.54 ± 6.03%). and water (3.48 ± 0.84%). DOI: http://dx.doi.org/10.3329/bpj.v17i1.22318 Bangladesh Pharmaceutical Journal 17 (1): 67-69, 2014

This study included 34 healthy volunteers (16 male and 18 female) aged 19-37 years, of whom 17 received doxycycline 40 mg capsules orally once daily (o.d.) and 17 received placebo 40 mg capsules orally o.d. for 16 weeks. Plasma, saliva and faecal samples were collected before drug administration and at 4, 8, 16 and 20 weeks. Plasma samples were assayed for doxycycline concentrations, and saliva and faecal samples were investigated for doxycycline concentrations and microbiological analyses. Plasma concentrations of doxycycline in the doxycycline group were as follows: baseline visit (2 h), 0.20-0.61 mg/L; 4-week visit, 0.30-1.04 mg/L; 8-week visit, 0.43-1.49 mg/L; 16-week visit, 0.32-1.12 mg/L; and 20-week visit 0 mg/L. No doxycycline was detected in plasma in the placebo group. No doxycycline concentrations in the saliva samples were found in the doxycycline or placebo groups at the five visits. Faecal concentrations of doxycycline in the doxycycline group were as follows: baseline visit, 0 mg/kg; 4-week visit, 0-3.71 mg/kg; 8-week visit, 0-1.85 mg/kg; 16-week visit, 0-4.10 mg/kg; and 20-week visit, 0 mg/kg. No doxycycline faecal concentrations were detected in the placebo group. Minor effects on the aerobic and anaerobic oropharyngeal microflora were observed both in the doxycycline and placebo groups. There were minor changes in the number of enterococci and Escherichia coli in the doxycycline and placebo groups. The anaerobic intestinal microflora in the doxycycline and placebo groups was not changed, and no Clostridium difficile strains were isolated.

One hundred thirty-three Clostridium difficile strains were collected from 71 patients and analyzed for the presence of C. difficile toxin B by the cell cytotoxicity neutralization assay, genes for toxin A, toxin B, binary toxin and TcdC deletion by PCR. All strains were also PCR-ribotyped and analyzed for sporulation frequency. The MICs of the isolates were determined against cadazolid and seven other antimicrobial agents by the agar dilution method. All isolates were positive for toxin B by the cell cytotoxicity neutralization assay. One hundred fourteen isolates were positive for toxin A and B and 16 isolates were positive for toxin A, toxin B and binary toxin by PCR. Three isolates were negative for toxin A but positive for toxin B. Thirty-three different ribotypes were identified. No strain of ribotype 027 was found. No differences in sporulation were noticed between the primary and recurrent isolates. All 133 isolates were sensitive to cadazolid (0.064–0.5 mg/l), fidaxomicin (0.008–0.125 mg/l), metronidazole (0.125–2 mg/l), vancomycin (0.125–1 mg/l) and tigecycline (0.032–0.25 mg/l). Three isolates were resistant to linezolid (8 mg/l), 15 isolates were resistant to moxifloxacin (8–32 mg/l) and 103 isolates were resistant to clindamycin (8–256 mg/l). No association between toxins A, B and binary toxin, ribotypes or the sporulation and the sensitivity to cadazolid could be found. Cadazolid has a potent in vitro activity against C. difficile.

Solithromycin is a novel fluoroketolide with high activity against bacteria associated with community-acquired respiratory tract infections as well as gonorrhea. However, data on the activity of solithromycin against anaerobic bacteria from the normal intestinal microbiota are scarce. In this study, 1024 Gram-positive and Gram-negative anaerobic isolates from the normal intestinal microbiota were analyzed for in-vitro susceptibility against solithromycin and compared to azithromycin, amoxicillin/clavulanic acid, ceftriaxone, metronidazole and levofloxacin by determining the minimum inhibitory concentration (MIC). Solithromycin was active against Bifidobacteria (MIC50, 0.008 mg/L) and Lactobacilli (MIC50, 0.008 mg/L). The MIC50 for Clostridia, Bacteroides, Prevotella and Veillonella were 0.5, 0.5, 0.125 and 0.016 mg/L, respectively. Gram-positive anaerobes were more susceptible to solithromycin as compared to the other antimicrobials tested. The activity of solithromycin against Gram-negative anaerobes was equal or higher as compared to other tested agents.

The study aimed to determine the effects of a single-dose antibiotic prophylaxis on normal oral microflora. A single dose of 2 g amoxicillin was given to 29 healthy volunteers. Saliva was collected before antibiotic administration (day 1), and again on days 2, 5, 10, 17 and 24 and subjected to culturing and antibiotic sensitivity analysis. Twenty-one per cent (6/29) of the individuals carried penicillin-V- and amoxicillin-resistant viridans streptococci before antibiotic administration. After a single dose of amoxicillin there was a significant reduction in Streptococcus salivarius on days 2 and 5, a significant reduction in other viridans streptococci on day 2 and the proportion of viridans streptococci with reduced susceptibility to amoxicillin was significantly increased on days 2 and 5. A single dose of amoxicillin can cause an ecological disturbance and induce selection of resistant strains in the oral microflora.

Telavancin is a new lipoglycopeptide antibiotic for the treatment of Gram-positive infections. It has a dual mechanism of action by inhibiting bacterial cell wall synthesis and disrupting the bacterial plasma membrane. The purpose of the present study was to investigate the effect of administration of telavancin on the human intestinal microflora. Thirteen healthy subjects (six males and seven females; age range 18-40 years) received 10mg/kg body weight telavancin by intravenous infusion over a 60-min period once every 24h for 7 days. Plasma and urine were collected on Days 5, 6 and 7 for pharmacokinetic analysis of telavancin. Faecal samples were collected on Days -1 (pre-dose), 2, 5, 7, 9, 14 and 21. Faecal specimens were cultured on non-selective and selective media. Different colony types were counted, isolated in pure culture and identified to genus level. No measurable concentrations of telavancin were found in faeces. No significant effects on the number of Enterobacteriaceae, enterococci, Candida albicans, bifidobacteria, lactobacilli, clostridia and Bacteroides spp. were observed during the study period. No Clostridium difficile strains or toxins were found. No new colonising aerobic and anaerobic Gram-positive bacteria with telavancin minimum inhibitory concentrations of ≥ 2 mg/L were found. Based on the microbiological data, telavancin has no significant ecological impact on the human intestinal microflora.

Ciprofloxacin is a well-known fluoroquinolone, active in vitro against most Gram-negative and Gram-positive bacteria. The purpose of the present study was to evaluate the ecological effects of an orally administered extended-release formulation of ciprofloxacin in comparison with an immediate-release formulation of ciprofloxacin on the normal human intestinal microflora. Thirty-six healthy female subjects were included in the study. the extended-release formulation of ciprofloxacin was given as 500 mg once daily and the immediate-release formulation as 250 mg twice daily. The treatment period was 3 days. the microbiological investigation was blinded with respect to treatment. Mean fecal concentration in the volunteers receiving the extended-release formulation ciprofloxacin was 453 mg/kg and in the immediate-release formulation ciprofloxacin volunteers, the mean fecal concentration was 392 mg/kg. The numbers of Escherichia coli were significantly suppressed while the enterococci decreased moderately in both treatment groups. No toxigenic Clostridium difficile strains were found. No major differences were observed between the two studied formulations on the normal human intestinal microflora.

Aim To elucidate the origin of Enterococcus faecalis isolated from secondary root canal infections and the possibility for a foodborne transmission by comparing them to strains recovered from food, blood and stool regarding putative virulence factors and antibiotic susceptibility profiles, where strains from common origin were hypothesized to harbour similar characteristics. Methodology A total of 108 E. faecalis strains recovered in the county of Stockholm, Sweden, were screened using PCR for putative virulence factors esp, cylA, gelE/gelatinase-negative phenotype (ef1841/fsrC), efaA, ace and asa1. The minimum inhibitory concentration (MIC) for ampicillin, piperacillin–tazobactam, imipenem, gentamicin, vancomycin, ciprofloxacin and linezolid was determined using the agar dilution method. Results Next to strains from blood, the food isolates presented the highest average number of virulence determinants and were frequently enriched with asa1 coding for aggregation substance. None of the endodontic strains carried cylA, and the gelatinase-negative phenotype caused by a deletion dominated the group. Altogether, the most prevalent genes were gelE, efaA and ace, and a combination of them was equally present in approximately 80% of the strains from food, stool and root canals in comparison with 43.3% of the blood isolates. High-level resistance to ciprofloxacin and gentamicin was observed in 30% of the blood isolates, whereas the isolates from other origins, with single exceptions, were susceptible to all tested antibiotics. Conclusions Evidence for a foodborne transmission, explaining the high reported prevalence of E. faecalis in root filled teeth, could not be determined based on the similarities in virulence factor patterns and antibiotic susceptibility. The only linkage between isolates from food and root canals consisted of a shared common combination of the genes gelE, efaA and ace. The high occurrence of putative virulence traits in food isolates questions the safety of E. faecalis in food products.

Ceftazidime/avibactam is a new combination of the antibiotic ceftazidime with the novel, non-β-lactam β-lactamase inhibitor avibactam. The purpose of the present study was to investigate the effect of ceftazidime/avibactam on the human intestinal microbiota following intravenous (i.v.) administration. Twelve healthy volunteers received ceftazidime/avibactam by i.v. infusion (2000mg ceftazidime and 500mg avibactam) given over 2h every 8h on Days 1-6 (inclusive) and a single dose on Day 7. Faecal samples were collected on Day-1 (pre-dose), during administration on Days 2, 5 and 7 and post-dose on Days 9, 14 and 21. Samples were cultured on non-selective and selective media. The number of Escherichia coli and other enterobacteria decreased significantly during administration of ceftazidime/avibactam, whereas the number of enterococci increased. Lactobacilli, bifidobacteria, clostridia and Bacteroides decreased significantly during ceftazidime/avibactam administration. The effects on lactobacilli, bifidobacteria and Bacteroides were similar in the 12 volunteers, whilst clostridia showed different ecological patterns among the volunteers. Toxigenic Clostridium difficile strains were detected in five volunteers during the study. In four of the volunteers, loose stools were reported as adverse events. Plasma samples were collected on Days -1, 2, 5 and 7. Ceftazidime and avibactam concentrations in plasma (ceftazidime 0-224.2mg/L of plasma and avibactam 0-70.5mg/L of plasma) and faeces (ceftazidime 0-468.2mg/kg of faeces and avibactam 0-146.0mg/kg of faeces) were found by bioassay. New colonising resistant clostridia were found in five volunteers and lactobacilli were found in three volunteers.

Thirty healthy subjects (15 males and 15 females) were randomly assigned in three groups and clindamycin (150 mg qid) or ciprofloxacin (500 mg bid) or placebo was given for a 10-day period. Skin, nasal, saliva, faeces samples were collected at day – 1, day 11, 1 month, 2 months, 4 months and 12 months post administration for microbiological analysis. Ciprofloxacin or clindamycin had no impact on the anaerobic skin microbiota and the proportions of antibiotic resistant anaerobic bacteria were similar as in the placebo group. Ciprofloxacin had impact on the Propionibacterium acnes in the nasal microbiota that normalized after 1 month, however, ciprofloxacin-resistant P. acnes strains increased at month 2 and month 12. Clindamycin had no impact on the nasal microbiota. In the oropharyngeal microbiota, a higher proportion of ciprofloxacin resistant Veillonella was found, it lasting up to 12 months post dosing. In the clindamycin group, clindamycin-resistant Prevotella spp. were found in increased proportions compared to placebo at various time points except month 4 in the saliva samples. The relative proportion of ciprofloxacin-resistant Bifidobacteria increased in the faecal samples on day 11, 1 month, 4 months and 12 months post dosing compared to placebo. The proportion of clindamycin-resistant Bacteroides spp. increased at 1, 2, 4 and 12 months post dosing compared to placebo in the faecal samples. No Clostridium difficile was recovered from any of the samples from any of the volunteers at any visit. The concentrations of ciprofloxacin or clindamycin in the faeces were higher than the MICs for most of the organisms present in the normal microbiota. No obvious correlation between the groups in resistant patterns for anaerobic bacteria was observed. In conclusion, based on the microbiological data of the microbiota as well as the results of the bioassays for ciprofloxacin and clindamycin concentrations in the faecal samples, oral administration of ciprofloxacin and clindamycin has an impact on the anaerobic microbiota and may have a long-term effect on the development and persistence of antibiotic-resistant anaerobes in the normal microbiota.

One hundred fourteen Clostridium difficile strains were collected from 67 patients and analyzed for the presence of C. difficile toxin B by the cell cytotoxoicity neutralization assay, genes for toxin A, toxin B, binary toxin and Tcd C deletion by PCR. All strains were also PCR-ribotyped. The MICs of the isolates were determined against MCB3681 and nine other antimicrobial agents by the agar dilution method. All isolates were positive for toxin B as well as for toxin A and B genes. In addition, 13 isolates were positive for the binary toxin genes. Thirty-two different ribotypes were identified. No strain of ribotype 027 was found. All 114 isolates were sensitive to MCB3681 (0.008–0.5 mg/l), cadazolid (0.064–0.5 mg/l), fidaxomicin (0.008–0.125 mg/l), metronidazole (0.125–2 mg/l), vancomycin (0.125–1 mg/l) and tigecycline (0.032–0.25 mg/l). Three isolates were resistant to linezolid (8 mg/l), 12 isolates were resistant to moxifloxacin (8–32 mg/l), 87 isolates were resistant to clindamycin (8–256 mg/l) and 107 isolates were resistant to ciprofloxacin (8–256 mg/l). No association between toxins A, B and binary toxin, ribotypes and the sensitivity to MCB3681 could be found. MCB3681 has a potent in vitro activity against C. difficile .

Antibiotic-resistant bacteria have emerged due to the selective pressure of antimicrobial use in humans and animals. Water plays an important role in dissemination of these organisms among humans, animals and the environment. We studied the antibiotic resistance patterns among 493 Escherichia col/isolates from different aquatic environmental sources collected from October 2008 to May 2009 in Leon, Nicaragua. High levels of antibiotic resistance were found in E. coli isolates in hospital sewage water and in eight of 87 well-water samples. Among the resistant isolates from the hospital sewage, ampicillin, chloramphenicol, ciprofloxacin, nalidixic acid, trimethoprim-sulphamethoxazole was the most common multi-resistance profile. Among the resistant isolates from the wells, 19% were resistant to ampicillin, ceftazidime, ceftriaxone, cefotaxime, chloramphenicol, ciprofloxacin, gentamicin, nalidixic acid and trimethoprim-sulphameth-oxazole. E. coli producing ESBL and harbouring bla CTX-M genes were detected in one of the hospital sewage samples and in 26% of the resistant isolates from the well-water samples. The bla CTX-M-9 group was more prevalent in E. coli isolates from the hospital sewage samples and the bla CTX-M-1 group was more prevalent in the well-water samples.

The present study was undertaken to evaluate methotrexate induced early hepatotoxicity in rheumatoid arthritis patients. This study was carried out on ARA criteria fulfilling 35 diagnosed rheumatoid arthritis patients of either gender, aged 20-60 years, presented in Medicine Department of Rajshahi Medical College Hospital, Rajshahi from July 2007 to June 2008. Patients with normal liver function tests and HBsAg and anti-HCV negative cases were given oral Methotrexate (10-25mg/week) for 3 months. Baseline level of SGPT, serum bilirubin and prothrombin time was 10.07±0.32u/l, 0.59±0.03mg/dl and 12.97±0.34 seconds respectively. After 3 months of methotrexate therapy, level of SGPT, serum bilirubin and prothrombin time was found to be 12.60±1.16 u/l, 0.70±0.06mg/dl and 13.87±0.45 seconds respectively. During methotrexate therapy SGPT level changed significantly (p