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Many countries are having problem of substandard and counterfeit drugs which results in life threatening issues, financial loss of consumers and loss in trust on health system. This study is concerned with the assessment of drugs quality available in the Nepalese market.
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We demonstrate a WGS-based MIC prediction approach that allows reliable MIC prediction for five gonorrhoea antimicrobials. Our approach should allow reasonably precise prediction of MICs for a range of bacterial species.
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In contrast to West-European countries, in our region, resistance to azithromycin has increased up to 30 % in the last 5 years, so the recommendation of the European Guideline -500 mg of ceftriaxone combined with 2 g of azithromycin as first choice therapy against N. gonorrhoeae- should be seriously considered in case of Hungary.
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Resistance to antibiotics is a major public-health concern and antibiotic use is being ever more recognized as the main discriminatory pressure driving this resistance. The aim was to assess the outpatient usage of antibiotics in teaching hospitals in various parts of capital city of Iran, Tehran and its association with resistance. 600 outpatient antibiotic prescriptions between December 2011 and May 2012 were reviewed in our teaching hospitals. All prescriptions were scrutinized in order to evaluate the antibiotic prescribing. The medical doctors from all grades were asked to note the chief complaints and the most possible diagnosis on each prescription. Clinical data, patient demographic and ultimately the total quantities of antibiotics were recorded. Our data was then compared against the major antibiotic guidelines and similar studies in other countries. The most common prescribed antibiotics are Penicillins (Penicillin, Co-Amoxiclav and Amoxicillin) (40 %), Cephalosporins (Cefixime, Cephalexin and Ceftriaxone) (24.5 %) and Macrolides (particularly Azithromycin) (15.3 %). In total, 18.2 % of cases were combinational antibacterial therapies (≥ 2). The most common diagnosis was upper respiratory tract infections as common cold (29.2 %) and sore throat (11.8 %). Directions (instructions for use) of 58 % of selected antibiotics were acceptable. Parenteral administration remains the common route of administration with 22 % of all reviewed prescriptions. Based on Cochrane reviews the antibiotic prescribing was unjustified in 42.7 % of the cases. The prescribing habit, correct diagnosis and the use of antibiotics need instant consideration. These data can provide useful information for assessing public-health policy that aims to reduce the antibiotic use and resistance levels.
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Shigellosis is still an important health problem in developing and underdeveloped countries as it is resistance to commonly used antibiotics including ampicillin, trimethoprim-sulfamethoxazole, chloramphenicol and tetracycline. Between May 1996 and October 1996, in a prospective randomized double-blind trial, cefixime was compared with ampicillin-sulbactam, both given orally for a period of 5 days, for the treatment of 80 children with acute bloody diarrhea. Forty patients were treated with a single-dose (8 mg/kg per day) of cefixime and the other 40 patients were given three doses of 100 mg/kg per day of ampicillin-sulbactam. After identification of Shigella organisms in stool specimens, nine patients in the cefixime receiving group and six patients in the ampicillin-sulbactam receiving group were excluded from the study. Differences in average age, sex and weight between the cefixime and ampicillin-sulbactam group were statistically meaningless (P > 0.05). Fever and bloody diarrhea were universal features. The efficacy of cefixime was found to be better than ampicillin-sulbactam. Patients given cefixime had a shorter duration of fever (P < 0.01), shorter duration to disappearance of blood in the stool (P < 0.01), reduced time with diarrhea (P < 0.01) and reduced hospitalization time during the 5 study days (P < 0.01) than patients given ampicillin-sulbactam. No adverse effects were observed in the two study groups. This controlled trial showed good efficacy with cefixime compared to ampicillin-sulbactam in the treatment of shigellosis. Single-dose daily oral therapy with cefixime also showed good tolerability. Cefixime should be considered as an alternative drug of choice for shigellosis in children.
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Bacterial isolates of S. pneumoniae and H. influenzae were obtained by tympanocentesis and subsequent culture of middle ear effusion from children with acute otitis media enrolled in a multicenter trial. Susceptibility to test agents was assessed by disk diffusion and broth dilution techniques with criteria established by the National Committee for Clinical Laboratory Standards.
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Enteric fever is systemic illness caused by Salmonella Typhi and Salmonella Paratyphi A, B and C. It is believed to be a readily treatable illness by many clinicians in the developing world where it is endemic; however, with the emergence of drug resistance to fluoroquinolones, treatment is becoming increasingly difficult. While drugs such as cefixime, previously believed to be effective, have been proven otherwise, new agents such as gatifloxacin and azithromycin have proven to be promising. Re-emergence of chloramphenicol sensitive strains in previously resistant areas points towards the concept of antibiotic recycling, preserving the use of older antibiotics. Antibiotic recycling has been used successfully in hospital settings. However, its usefulness in community settings, where the main burden of enteric fever resides, is challenging to manage due to logistics and a lack of infrastructure. Nalidixic acid resistance used to be a marker for clinical response to flouroquinolones; however, recent studies highlight the importance of decreased ciprofloxacin susceptibility as a better marker. Enteric fever, as a public health problem, has been tackled by protection of food and water supplies in the industrialised countries of the world. Nonetheless, that goal seems too far-fetched in the developing world where there are hundreds of villages, towns and cities without adequate infrastructures. Perhaps the key to solving this problem is combining point-of-use-purification of water (by chlorination) with the treatment of illness in the community. Treatment of chronic carriers is also necessary in order to halt the cycles of transmission.
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Pseudomonas aeruginosa is one of the common pathogenic causes of serious infections in burn patients throughout the world. Type III secretion toxins are thought to promote the dissemination of P. aeruginosa from the site of infection, the bacterial evasion of the host immune response and inhibition of DNA synthesis leading to host cell death. A total of 96 isolates of P. aeruginosa were collected from wound infections of burn patients, from April to July 2010. Antimicrobial susceptibility of the isolates were determined by disk agar diffusion method. Polymerase chain reaction (PCR)-based method was used for targeting the genes encoding the type III secretion toxins. The quantitative determination of biofilm-forming capacity was determined by a colorimetric microtiter plate assay. All the isolates were resistant to cefixime and ceftriaxone. More than 90% of the isolates were resistant to amikacin, carbenicillin, cefepime, cefotaxime, cefpodoxime, gatifloxacin, gentamicin, piperacillin/tazobactam, ticarcillin and tobramycin. All the isolates carried the exoT gene, 95% carried exoY, 64.5% carried exoU and 29% carried the exoS gene. Most of the isolates (58%) carried both exoY and exoU genes while 24% showed the concomitant presence of exoS and exoY and 1% carried both exoS and exoU. Coexistence of exoS, exoY and exoU was seen in 4% of the isolates. Biofilm formation was seen in more than 96% of the isolates among which 47% were strong biofilm producers, 26% were moderate and 22.9% were weak biofilm formers. In conclusion, the findings of this study show that the genes, particularly the exoU gene, encoding the type III secretion toxins, are commonly disseminated among the P. aeruginosa strains isolated from burn patients.
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In an open, controlled, randomized multicenter study, 160 children suffering from pharyngitis and/or tonsillitis were treated with either 8 mg cefixime/kg body weight once daily for 5 days or 20,000 I.U. penicillin V/kg body weight t.i.d. for 10 days. One hundred fifty-one children were evaluable for clinical efficacy. In the cefixime group, 65 (86.7%) children were cured, seven (9.3%) were significantly improved, one (1.3%) relapsed and in two (2.7%) therapy failed. Of the patients treated with penicillin V, 69 (90.8%) were cured, five (6.6%) improved, one (1.3%) relapsed and in one (1.3%) therapy failed. Elimination of initial pathogens occurred in 57 (82.6%) patients treated with cefixime and in 60 (88.2%) treated with penicillin V. At 3 to 4 weeks after the end of treatment, six relapses were seen in the cefixime group and eight in the penicillin V group. Mild-to-moderate adverse events that were possible related to the medication were seen in four children treated with cefixime and in five treated with penicillin V.
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Urinary tract infections are quite frequent in children. Urinary tract obstruction combined with recurrent urinary tract infections increase the risk for renal impairment. Therefore prophylaxis of reinfection is an important nephroprotective procedure. The aim of this open, controlled, randomised pilot study was to compare the efficacy and tolerance of a low dose prophylaxis with Cefixime versus Nitrofurantoin. 60 girls aged 1 to 11 years with at least 2 urinary tract infections within the preceding year were included in the study. The minimum duration of therapy was 6 months and was extended to 12 months for most of the children. The number of recurrent infections was the main criteria for efficacy evaluation, whereas adverse events were analysed to evaluate tolerance. Statistical significant differences between the two treatment groups, regarding recurrence rates could not be demonstrated. Tolerance was comparable in both groups. The influence on gut flora of cefixime given as a low dose regimen over a long period of time corresponds with already published results and was not correlated with a higher number of gastrointestinal side effects.
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Salmonella strains and Escherichia coli O157:H7 were detected in 17 and 5 small ruminants in Virginia, respectively, of 287 tested. Background microflora interfered with the fecal analysis. The combination of Salmonella enzyme immunoassay (EIA) detection and xylose-lysine-deoxycholate agar isolation was satisfactory. Modifying enrichment to a 1:100 dilution enabled effective E. coli O157:H7 detection by EIA and isolation by sorbitol-MacConkey agar with cefixime-tellurite.
Widespread resistance of Neisseria gonorrhoeae to penicillin, tetracycline, and fluoroquinolones has challenged effective treatment and control; recent international case reports of cefixime, ceftriaxone, and azithromycin resistance suggest that the remaining treatment options are now additionally threatened. To explore trends in antimicrobial susceptibility of N. gonorrhoeae, we reviewed provincial laboratory data from British Columbia, 2006 to 2011.
In order to evaluate antimicrobial activity of cefetamet (CEMT), minimum inhibitory concentrations (MICs) of CEMT and control drugs were determined against Gram-negative rods mainly from complicated urinary tract infections examined in our laboratory from April to September of 1994. The results are summarized as follows; 1. The obtained strains were Citrobacter diversus 20, Citrobacter freundii 30, Enterobacter aerogenes 20, Enterobacter cloacae 30, Serratia marcescens 30, Proteus mirabilis 30, Proteus vulgaris 20 and Morganella morganii 30 strains, a total of 210 strains. 2. Excluding some resistant strains, the MIC-distribution showed showed that CEMT had strong antimicrobial activities against those strains from the MIC-distribution of this investigation. Compared to reports on CEMT in 1989, the MIC80 of CEMT in this investigation against clinical isolates were similar. The MIC50's of CEMT against E. aerogenes, S. marcescens, P. mirabilis, P. vulgaris and M. morganii in the previous examination were equal to or similar to the current results, but the MIC50's against C. freundii and E. cloacae were lower than the value of this report. The detection frequency of highly resistant strains of C. freundii and E. cloacae to cefteram and cefixime were similar to that of CEMT-resistant strains. Multiple drug resistant strains, among these bacterial species seemed to be increasing. 3. Compared to oral antibacterial agents of oxime cephems that were used in the past, CEMT showed higher peak values of urinary excretion concentration and higher blood levels were sustained for a longer period of time. CEMT-PI will be effective against urinary tract infections.
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Concerns regarding the appearance of gonococci associated with treatment failure with oral cephalosporins are increasing. The origins, causes and patterns of spread of these clinically resistant gonococci are reminiscent of the earlier experiences with quinolone-resistant gonococci. Preventive measures require simultaneous implementation of disease-control principles, coupled with those for antimicrobial resistance.
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In healthy volunteers, the simultaneous administration of nifedipine and cefixime has been shown to increase the oral absorption of the antibiotic. To investigate the pharmacological basis of this interaction, we used an in situ intestinal perfusion technique in the rat. pH 5.5 yielded optimum cefixime absorption, which was greater in segments from the duodenojejunum than in those from the jejunoileum. Cefixime absorption was similar when perfused at 0.5 and 1.0 mg/ml, suggesting transport saturation at the lower concentration. Cefixime arterial and portal blood concentrations after an intestinal perfusion of 0.5 mg/ml cefixime were significantly increased by a previous 15-min intestinal perfusion of 0.05 mg/ml nifedipine. Nifedipine did not significantly alter intestinal blood flow. At the end of the cefixime perfusion, intestinal blood flow was higher in the nifedipine group than in the control group (0.44 +/- 0.12 vs. 0.26 +/- 0.09 ml.min-1.g of intestine wt-1, respectively), although the difference did not reach statistical significance. The absorption kinetics of salicylic acid, which is strictly absorbed by passive diffusion, were unaffected by nifedipine. After 15 and 50 min of recirculation, residual salicylate levels fell from 85.1 +/- 5.6% to 57.1 +/- 2.8% with nifedipine compared with 87.4 +/- 1.4% to 52.8 +/- 1.6% without nifedipine. Thus, the improvement in cefixime absorption by nifedipine was not secondary to increased local blood flows or to induced passive diffusion mechanisms. Nifedipine did not affect intestinal motility. The action of nifedipine appears to indirect, involving a neural regulation, because any increase in cefixime absorption was prevented by tetrodotoxin and hexamethonium administration.
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Gonorrhoea remains an important health problem worldwide. The latest European guidelines have recommended the introduction of dual antimicrobial therapy due to the increase in its resistance to antimicrobial agents.
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The isolates comprised 42 different molecular types as defined by NG-MAST. The susceptibility of the clinical isolates to ertapenem was similar to that of cefixime, with a Pearson's correlation coefficient of R = 0.89. The MIC90 and MIC50 values of ertapenem were 0.25 and 0.12 mg/L, respectively, while those of cefixime were 0.12 and 0.06 mg/L, respectively. However, these isolates were more susceptible to ceftriaxone than ertapenem, with a Pearson's correlation coefficient of R = 0.65 and ceftriaxone MIC90 and MIC50 values of 0.03 and 0.016 mg/L, respectively. The isolates that were least susceptible to ertapenem were all non-producers of penicillinase. However, one isolate that was highly resistant to cefixime and ceftriaxone was more susceptible to ertapenem than either cefixime or ceftriaxone.
Microbial changes including the shedding of Clostridium difficile, fecal beta-lactamase activity, and gastrointestinal symptoms were assessed in 51 healthy volunteers given 200 mg of cefixime twice daily for 8 days. The number of organisms of the family Enterobacteriaceae (means +/- standard deviations) dropped from 6.9 +/- 1.1 to 3.9 +/- 1.8 log CFU/g of feces (P < 0.01), whereas counts of enterococci rose from 7.0 +/- 1.5 to 9.0 +/- 1.0 log CFU/g of feces (P < 0.01). Both counts returned to their initial levels 50 days after the cessation of treatment. Cefixime did not significantly modify the frequency of fecal excretion of Pseudomonas aeruginosa, Staphylococcus spp., yeasts, or members of the Enterobacteriaceae resistant to ceftazidime or ampicillin. The proportion of subjects shedding C. difficile rose from 6% before treatment to 57% (P < 0.01) at the end of treatment but returned to 8% 50 days thereafter. No case of pseudomembranous colitis was observed. Stool changes occurred in 13 volunteers during treatment (25%) and in 2 others more than 10 days after the end of treatment (4%). These changes were not significantly associated with the shedding of toxigenic strains of C. difficile or with the presence of toxin A in feces. By contrast, during treatment, stool changes occurred in 8 of the 18 volunteers (44%) who had antibiotic activity in their feces but in only 5 of the 33 (15%) for whom no such activity was found (P < 0.05). The absence of antibiotic activity in the feces was itself linked with the presence of beta-lactamase activity in the feces. Since we had found earlier that fecal beta-lactamase activity afforded protection against alteration in stool consistency during treatments with oral cephalosporins, the present study confirmed our previous preliminary results in this respect.
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The retrospective study was conducted at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised medical records from December 2011 to November 2013 which were reviewed to identify persons with laboratory-confirmed Shigella infections. Demographic information, clinical history, seasonal variation, microbiological details, treatment given, and outcomes in term of symptoms resolution and mortality at two weeks were noted.
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The frequencies of isolation and susceptibilities to antimicrobial agents were investigated on 680 bacterial strains isolated from patients with urinary tract infections (UTIs) in 10 hospitals during the period of June 1996 to May 1997. Of the above bacterial isolates, Gram-positive bacteria accounted for 30.4% and a majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for 69.6% and most of them were Escherichia coli. Susceptabilities of several isolated bacteria to antimicrobial agents were as followed; 1. Enterococcus faecalis Ampicillin (ABPC) showed the highest activity against E. faecalis isolated from patients with UTIs. Its MIC90 was 1 microgram/ml. Imipenem (IPM) and vancomycin (VCM) were also active with the MIC90S of 2 micrograms/ml. The others had low activities with the MIC90S of 16 micrograms/ml or above. 2. Staphylococcus aureus including MRSA Arbekacin (ABK) and VCM showed the highest activities against both S. aureus and MRSA isolated from patients with UTIs. The MIC90S of them were 1 or 2 micrograms/ml. The others except minocycline (MINO) had low activities with the MIC90S of 32 micrograms/ml or above. 3. Staphylococcus epidermidis ABK and VCM showed the strongest activities against S. epidermis isolated from patients with UTIs. The MICs for all strains were equal to or lower than 2 micrograms/ml. Cefazolin (CEZ), cefotiam (CTM) and cefozopran (CZOP) were also active with the MIC90S of 4 micrograms/ml. Compared with antimicrobial activities of cephems is 1995, the MIC90S of them had changed into a better state. They ranged from 4 micrograms/ml 16 micrograms/ml in 1996. 4. Streptococcus agalactiae All drugs except MINO were active against S. agalactiae. ABPC, CZOP, IPM, and clarithromycin (CAM) showed the highest activities. The MICs for all strains were equal to or lower than 0.125 micromilligrams. Tosufloxacin (TFLX) and VCM were also active with the MIC90S of 0.5 micromilligrams. 5. Citrobacter freundii Gentamicin (GM) showed the highest activity against C. freundii isolated from patients with UTIs. Its MIC90 was 0.5 micrograms/ml. IPM and amikacin (AMK) were also active with the MIC90S of 1 microgram/ml and 2 micrograms/ml, respectively. Cefpirome (CPR) and CZOP were also active with the MIC90S of 8 micrograms/ml. The MIC90S of the others were 16 micrograms/ml or above. 6. Enterobacter cloacae IPM showed the highest activity against E. cloacae. The MICs for all strains were equal to or lower than 0.5 microgram/ml. The MIC90S of ciprofloxacin (CPFX) and TFLX were 1 microgram/ml, the MIC90 of AMK was 2 micrograms/ml, the MIC90S of CZOP, GM and ofloxacin (OFLX) were 4 micrograms/ml. The MIC50S of cephems except CEZ, cefmetazole (CMZ) and cefaclor (CCL) had changed into a better state in 1996, compared with those in 1995. 7. Escherichia coli All drugs except penicillins and MINO were active against E. coli. Particularly CPR, CZOP and IPM showed the highest activities against E. coli. The MIC90S of them were 0.125 microgram/ml or below. Among E. coli strains, those with low susceptibilities to cephems except CEZ, cefoperazone (CPZ), latamoxef (LMOX) and CCL have increased in 1996, compared with those in 1995. 8. Klebsiella pneumoniae K. pneumoniae was susceptible to all drugs except penicillins, with the MIC90S of 2 micrograms/ml or below. CPR had the strongest activity, the MICs for all strains were equal to or lower than 0.25 microgram/ml. Flomoxef (FMOX), cefixime (CFIX), CZOP and carumonam (CRMN) were also active with the MIC90S of 0.125 microgram/ml or below. 9. Pseudomonas aeruginosa All drugs except quinolones were not so active against P. aeruginosa with the MIC90S were 32 micrograms/ml or above. Quinolones were more active in 1996 than 1995. The MIC90S of them were between 4 micrograms/ml and 8 micrograms/ml, and the MIC50S of them were between 1 microgram/ml and 2 micrograms/ml. 10. Serratia marcescens GM showed the highest activity against S. marcescens. Its MIC90 was 1 micro