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Cefdinir, a so-called third-generation oral cephalosporin was tested in vitro against over 700 pathogens from patients with bacteremia. Cefdinir was very active against the Enterobacteriaceae with a 50% minimum inhibitory concentration (MIC50) value range of less than or equal to 0.03-8 micrograms/ml. The enteric species having the highest MIC90S (greater than or equal to 16 micrograms/ml) were Citrobacter freundii, and the enterobacters, Morganella morganii, Proteus vulgaris, and Serratia marcescens. Cefdinir was generally two- to fourfold less active than cefixime, but markedly more potent with a wider spectrum compared with older oral cephalosporins, cefaclor or cefuroxime. In contrast to cefixime, cefdinir inhibited Staphylococcus aureus (MIC90, 1 micrograms/ml) and other staphylococci. Pneumococci, beta-hemolytic streptococci, Haemophilus influenzae, Moraxella catarrhalis, and pathogenic Neisseria spp. (MIC90S, 0.12-0.5 micrograms/ml) were cefdinir susceptible, but Pseudomonas aeruginosa, oxacillin-resistant staphylococci and Bacteroides fragilis gr. strains were resistant. Cefdinir was generally bactericidal with a minimal inoculum effect at 10(6) colony-forming units per spot. Cefdinir beta-lactamase hydrolysis by some recently described extended broad spectrum beta-lactamases was suspected. Cefdinir exhibited a wide, balanced spectrum for an oral cephalosporin indicating possible clinical use against susceptible pathogens in respiratory tract, urinary tract, genital and cutaneous infections.
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We studied the action of nifedipine on the bioavailability of cefixime, a molecule absorbed via the gut wall dipeptide carrier system in the rat, and on the bioavailability of D-xylose, which is absorbed via a pH (and Na(+)-)-dependent transporter. Each compound was administered alone or in combination with 20 mg of nifedipine to eight healthy male volunteers. Nifedipine significantly increased the absorption rate of cefixime (20.7 +/- 4.3 versus 16 +/- 3.5 mg/h in the absence of nifedipine). The absolute bioavailability of cefixime alone was 31% +/- 6% compared with 53% +/- 1% (P < 0.01) in the presence of nifedipine. The observed peak concentrations in serum were significantly different (2.5 +/- 0.3 mg/liter without nifedipine and 3.7 +/- 1.1 mg/liter with nifedipine; P < 0.02). In contrast, nifedipine induced no significant differences in the pharmacokinetic profile of xylose following oral administration. We conclude that (i) cefixime is absorbed in humans by an apparently active process which can be enhanced by a calcium channel blocker, in this case, nifedipine; and (ii) nifedipine does not modify the activity of the pentose transporter.
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22/44 (55%) cephalosporins were third-generation, which accounted for more than 50% of total expenditure. The top five cephalosporins (sorted by their defined daily doses) were cefodizime sodium, cefoperazone/sulbactam sodium, cefaclor, cefixime and cefmenoxime hydrochloride, which were used 182.93, 110.63, 109.09, 101.47 and 100.05 defined daily dose per 10,000 days, respectively. Third-generation cephalosporins were responsible for 747/1337 ADEs (55.87%). In particular, 208 episodes (15.56%) were associated with ceftriaxone. The most frequently reported damages were involved in the skin and its appendages (967, 68.92%). 603 (45.10%) were identified as definite in causality evaluation. Cefaclor was found to be safer than other cephalosporins, whereas ceftriaxone was found to be less safe.
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Enteric fever is a major cause of concern in developing countries across the globe. The primary choice of antibiotics remains fluoroquinolones, followed by cephalosporins. Resistance to third-generation cephalosporins is rarely reported in Salmonella enterica serovar Typhi. This study reports the whole genome sequence of an S. Typhi isolate resistant to cefixime [minimum inhibitory concentration (MIC)=512μg/mL] by microbroth dilution. Interestingly, the isolate was negative for the cephalosporin resistance gene blaCTX-M by PCR, which is a known mechanism for higher cephalosporin resistance. The isolate was further subjected to next-generation sequencing that identified blaTEM-1B and blaDHA-1 genes in association with qnrB4 and sul1. blaTEM is a known gene coding for β-lactam resistance. In certain cases, overexpression of blaTEM was reported to result in cephalosporin resistance. This suggests that the high cefixime MIC would have been contributed by overexpression of blaTEM-1B. The blaTEM-1B gene was found to be associated with a promoter Px with -35 and -10 regions as TTAATA and TAAAGT, respectively. The promoter regions were unique, but the -10 region was similar to that found in Pa/Pb (previously reported promoter for blaTEM) with a single nucleotide change. In addition, an IncN plasmid was identified, which is usually reported in association with the most prevalent extended-spectrum β-lactamase (ESBL), metallo- and non-metallo-carbapenemase, and plasmid-mediated quinolone resistance (PMQR) genes. Plasmids such as IncN might possibly confer resistance and enhance spread. It is imperative to continuously monitor the drug resistance profile and evolving genetic elements.
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These data demonstrate the continued evolution of and geographical variation in bacterial resistance and highlight the need for appropriate prescribing of antimicrobials in CARTI, using agents with adequate activity, based on local susceptibility profiles and PK/PD parameters.
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Randomized, four-period, crossover study.
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After an allergological work-up, over 90% of the children evaluated were finally confirmed as tolerant to BLs. Most reactions were of the non-immediate type, and DPT was an essential tool for diagnosis.
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A number of oral third-generation cephalosporins (cefixime, cefetamet pivoxil, ceftibuten and cefpodoxime proxetil) have been widely trialled and are becoming available. In addition, cefdinir may also be marketed. Compared with first- and second-generation agents, the oral third-generation cephalosporins have an improved antibacterial spectrum and reduced minimum inhibitory concentrations against common Gram-negative pathogens. In contrast, with the exception of cefdinir, they are less active against Staphylococcus aureus. They have favourable pharmacokinetic profiles and are generally administered in once- or twice-daily regimens. They are well tolerated, but cefixime has been associated with a particularly high rate of diarrhoea. Possible clinical indications for the use of oral third-generation cephalosporins include upper and lower respiratory, genitourinary and soft-tissue infections and follow-on treatment of severe infections requiring hospitalisation. At present, these drugs offer no particular clinical advantages over standard therapy in most circumstances. However, they may be considered where there is hypersensitivity to penicillins, a high incidence of resistance to first-line therapy in the community, or failure of standard therapy. Further studies are needed to define the efficacy of oral third-generation agents in the prevention of rheumatic fever and as follow-on therapy for severe infections. The oral third-generation cephalosporins are generally more expensive than standard agents, but detailed studies that include extended costs (e.g. treatment of adverse effects, treatment of clinical failure, return visits to physicians) have yet to be reported.
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Gonococcal isolates were collected from 113 patients attending the GUM clinic at Newham General Hospital over a one year period. Isolates (104) were tested for susceptibility to various antibiotics. Plasmid profiles were obtained for penicillinase producing gonococci (PPNG) and isolates exhibiting high-level tetracycline resistance (TRNG). Epidemiological information was collected from clinic attenders by routine note-taking.
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We used a cost-effectiveness decision- analysis model to compare the two methods: the standard, ceftriaxone 125 mg given by IM injection; and an alternative, cefixime 400 mg given orally. The effect of the costs associated with the risk of accidental needlestick during IM administration was also evaluated. Key baseline assumptions (with ranges, when tested) were from the literature or costs to our hospital. These included ceftriaxone, $8.60 per dose; cefixime, $4.67 per dose; ceftriaxone efficacy, 98% (range, 94.9% to 100%); cefixime efficacy, 97% (94.1% to 100%); and a 15% probability of pelvic inflammatory disease (PID) related to failed treatment. We included costs for PID necessitating hospitalization, disseminated gonococcal infection, infertility, and ectopic pregnancy. Assumptions related to accidental needlestick included the rate of needlesticks with the disposable syringe, 6.9 per 100,000 injections (range, 0 to 69); cost of accidental needlestick to hospital; risk of HIV seroconversion after needlestick exposure to HIV-infected blood, .36% (range, 0% to .86%); rate of HIV infection in 15- to 19-year-olds attending sexually transmitted diseases clinics, .4% (range, 0 to 5); and lifetime treatment costs for a person with HIV.
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Using data from postmarketing surveillance studies of six antibiotics and six antidepressants, conducted using the observational cohort technique of PEM, the number of reports of vaginal candidiasis was determined in women aged > or =16 years, in each of the first 7 weeks following a prescription for one of these drugs. The relative risks for vaginal candidiasis following the use of these antibiotics and for each of the individual antibiotics compared with antidepressants were calculated for each week and for the overall 7-week period. Women treated with antidepressants were the most suitable comparator group from the PEM database, as they were of a similar age range and the studies were conducted at a similar time period to those of the antibiotics. Also, there was no pharmacological plausibility for vaginal candidiasis being associated with antidepressants.
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Infections caused by Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBLs) are a growing clinical problem. However, there is wide variation in the level of resistance to third generation beta-lactams conferred by these enzymes.
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A new chemiluminescence reaction, the luminol-Cu(2+) reaction, was investigated for the determination of thirteen (13) cephalosporin antibiotics, namely cefalexin, cefadroxil, cefradine, cefazolin sodium, cefaclor, cefuroxime axetil, cefotaxime sodium, cefoperazone sodium, ceftriaxone sodium, ceftazidime, cefetamet pivoxil hydrochloride, cefixime, and cefpodoxime. It was found that, without adding any special oxidant, strong chemiluminescent (CL) signal could be produced from the reaction of the alkaline luminol with the above-mentioned antibiotics in the presence of Cu(2+). The experimental conditions for the reaction were carefully optimized with flow-injection mode. The detection limits are 0.3 ng/mL cefalexin, 3 ng/mL cefadroxil, 0.3 ng/mL cefradine, 0.02 μg/mL cefazolin sodium, 0.8 ng/mL cefaclor, 0.02 μg/mL cefuroxime axetil, 5 ng/mL cefotaxime sodium, 0.02 μg/mL cefoperazone sodium, 0.8 ng/mL ceftriaxone sodium, 1 ng/mL ceftazidime, 0.08 ng/mL cefetamet pivoxil hydrochloride, 0.8 ng/mL cefixime, and 2 ng/mL cefpodoxime. The proposed method was validated by direct application to commercial formulations and spiked milk samples containing cefradine. A possible reaction mechanism is also discussed.
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In this 31-site multicenter trial, 565 adult patients with urinary tract infections were randomly assigned to receive either a 10-day course of cefixime 400 mg once daily (n = 279) or amoxicillin 250 mg three times daily (n = 286). Although all patients were included in the safety analysis, only 93 (33 percent) cefixime-treated and 99 (35 percent) amoxicillin-treated patients were fully evaluable for the efficacy analysis. One week after therapy, the evaluable patients treated with cefixime demonstrated a 90 percent clinical cure rate and a 92 percent eradication rate of the baseline pathogen. This compared with an 83 percent clinical cure rate and an 84 percent bacterial eradication rate in the amoxicillin-treated group. The most frequently isolated pathogen was Escherichia coli (80 percent) followed by Proteus mirabilis (10 percent). One hundred thirty-seven (49 percent) of the 279 cefixime-treated and 126 (44 percent) of the 286 amoxicillin-treated patients reported at least one adverse experience during the study. Adverse reactions associated with cefixime were similar to those reported for other beta-lactam antibiotics. The most frequent adverse experiences reported by cefixime-treated patients were diarrhea (15 percent) and stool changes (12 percent). Headaches (11 percent) and diarrhea (9 percent) were the most frequently reported adverse reactions by the amoxicillin-treated patients. Eleven cefixime-treated patients (3.9 percent) and 10 amoxicillin-treated patients (3.5 percent) discontinued therapy because of adverse experiences. Results of this study demonstrate that a once-daily regimen of cefixime is as safe and effective as a three-times-daily regimen of amoxicillin in the treatment of acute urinary tract infections. Although the incidence of bowel changes was somewhat higher in the cefixime treatment group, these events usually resolved when therapy was discontinued.
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In our STI laboratory, all gonococcal isolates are subjected to antimicrobial susceptibility testing by disc diffusion method as per CLSI guidelines. β-Lactamase production is determined by chromogenic cephalosporin test. Minimum Inhibitory Concentration (MIC) for ceftriaxone is determined by E-test.
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Cefixime was found to be superior to ciprofloxacin in terms of efficacy in the treatment of community-acquired pneumonia in adults in Nigeria. However, both antibiotics were well-tolerated by all the patients as there were no reports or documentation of adverse events.
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Immunoglobulin A (IgA) nephropathy, the most common cause of glomerulonephritis worldwide, is usually idiopathic in origin and renal limited. Secondary IgA nephropathy has been associated with systemic disease, including such gastrointestinal tract disturbances as celiac sprue and inflammatory bowel disease. We describe gross hematuria and reversible acute renal failure from IgA nephropathy in a patient with cephalosporin-induced Clostridium difficile colitis. In addition to mesangial IgA and C3 deposition, renal histological examination showed glomerular bleeding, intratubular red blood cell casts, and acute tubular necrosis. To the best of our knowledge, this is the first report of an association between IgA nephropathy and C difficile colitis.
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Typhoid fever is the persistent cause of morbidity worldwide. Salmonella enterica serovar's carriers among food handlers have the potential to disseminate this infection on large scale in the community. The purpose of this study was to determine the prevalence of typhoidal S. enterica serovars among food handlers of Karachi.
To determine the occurrence of Escherichia coli O157: H7 in hides and faeces of slaughtered ruminants in Nigeria.
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A simple, precise, accurate, and sensitive RP-HPLC method for simultaneous determination of cefixime trihydrate and dicloxacillin sodium in combined tablet dosage form was developed and validated. Chromatographic separation of the two drugs was performed on a Purospher BDS C18 column (25 cm x 4.6 mm id, 5 microm particle size). The mobile phase methanol-0.01 M phosphate buffer (75 + 25, v/v), adjusted to pH 3 with glacial acetic acid, was delivered at a flow rate of 1.0 mL/min. Detection was performed at 227 nm. Separation was completed within 10 min. Calibration curves were linear with R2 between 0.99 to 1.0 over a concentration range of 2-10 microg/mL for cefixime trihydrate and 5-25 micromL for dicloxacillin sodium. The RSD for intraday and interday precision was < 2.0%.