Male Sprague Dawley rats (n = 38) were infused each compound separately or in different combination ratios. Infusion was maintained until the onset of maximal seizures. Cerebrospinal fluid and plasma samples were collected for high performance liquid chromatography drug determination. The nature and intensity of the pharmacodynamics interaction between drugs was quantified with an isobolographic approach.
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To evaluate AP prescription tendencies for gastrointestinal bleeding, and primary and secondary prophylaxis of spontaneous bacterial peritonitis (SBP).
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Adsorption on carbon nanotubes (CNTs) may affect the environmental behavior of organic contaminants including antibiotics. In this study, sorption of norfloxacin (NOR) onto graphitized multiwall CNTs (G-CNTs), carboxylated multiwall CNTs (C-CNTs), hydroxylated multiwall CNTs (H-CNTs), and activated carbon (AC) was investigated. All sorption isotherms were highly nonlinear and were fitted well by Freundlich and Polanyi-Manes models. AC showed the highest NOR sorption capacity because of its highest surface area. H-CNTs had much higher NOR sorption than C-CNTs, and the pi-pi electron donor-acceptor (EDA) interactions could explain the distinction between the two types of CNTs. Comparison of sorption coefficients at different pHs indicates that hydrophobic and electrostatic interaction also played major roles in sorption of NOR on CNTs. Furthermore, high sorption capacity and hysteresis of NOR on CNTs were demonstrated in this study, which needs to be considered for predicting environmental risks of CNTs and NOR. The results from thermodynamic analysis show that sorption of NOR on AC and CNTs was thermodynamically favorable and generally endothermic. Sorption site energy analysis illustrates a distribution of sorption energy, consistent with nonlinear isotherms, which indicates the heterogeneous sites on CNTs for NOR adsorption.
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Nitroxolin or 5-nitro-8-hydroxyquinoline, used in the treatment of acute or recurrent uncomplicated urinary tract infection (UTI), has been investigated to demonstrate inhibitory effect on bacterial adherence to epithelial cells or solid surfaces. Nitroxolin in vitro and in urine inhibits bacterial adherence of E. coli 38 (MS/MS) on HeLa cells and epithelial cells from human bladder mucosa. In the same conditions, norfloxacin has no effect. Nitroxolin (MIC/8) decreases with a statistically significant difference (p less than 0.001) the bacterial attachment to a urinary catheter surface made in siliconated latex. These results justify the performance of a clinical trial in the prophylaxis of recurrent UTI and the outcome of a bacteriuria associated with indwelling or intermittent bladder catheter.
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A series of novel 2-methyl-3-substituted quinazolin-4-(3H)-ones have been synthesized by treating (2-methyl-4-oxo-3H-quinazolin-3-yl)dithiocarbamic acid methyl ester with different amines, the starting material dithiocarbamate was synthesized from anthranilic acid. The compounds synthesized were investigated for analgesic, anti-inflammatory and antibacterial activities. All the test compounds exhibited significant activity, the compounds VA2, VA3 and VA4 shown more potent analgesic activity, and the compounds VA3 and VA4 shown more potent anti-inflammatory activity than the reference compound diclofinac sodium.
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The in vitro interactions between bismuth subcitrate and a variety of antimicrobial agents against 12 Campylobacter pyloridis (C. pylori) isolates were studied by the agar dilution checkerboard technique. The combination of bismuth subcitrate with the older quinolone, oxolinic acid, produced synergistic activity against all strains. This observation, however, could not be extended to the (aryl) fluoroquinolones, norfloxacin, ofloxacin, and difloxacin, since synergy was rare or absent when bismuth subcitrate was combined with these antibiotics. Among the other antimicrobial agents tested, rifampin and the beta-lactams frequently showed showed MICs for C. pyloridis similar to those of bismuth subcitrate.
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The authors studied the effect of milk on the bioavailability of norfloxacin in six healthy male volunteers in a randomized crossover trial. After an overnight fast, 200 mg of norfloxacin was given with 200 mL of water or milk. Area under the curve (AUC) of norfloxacin with milk was significantly (P < 0.01) smaller than that with water. The mean peak serum concentration was decreased to 60% after oral administration of norfloxacin with milk (P < 0.01). The apparent volume of distribution at central compartment (Vc/f) value of norfloxacin was significantly (P < 0.05) increased with milk. Milk exhibits a clinically significant effect on norfloxacin absorption.
In 2002, population- and treatment center-based surveillance was used to study the disease burden of shigellosis in rural Hebei Province in the People's Republic of China. A total of 10,105 children with diarrhea or dysentery were enrolled. Infants were treated most frequently for diarrhea (1,388/1,000/year) followed by children < or = 5 years old (618/1,000/year). Shigellosis was treated most often in children 3-4 years old (32/1,000/year) and people > 60 years of age (7/1,000/year). Fifty-six percent (184 of 331) Shigella isolates were detected in patients who had non-bloody diarrhea. Shigella flexneri was identified in 93% of 306 isolates. The most common S. flexneri serotypes were 1a (34%), X (33%), and 2a (28%). More than 90% of the Shigella isolates were resistant to cotrimoxazole and nalidixic acid, but remained susceptible to ciprofloxacin, norfloxacin, and gentamicin. Widespread resistance to antibiotics adds urgency to the development and use of vaccines to control shigellosis.
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The postantibiotic effect (PAE) of fluoroquinolones against Staphylococcus aureus was determined in Mueller-Hinton broth and normal human serum. At both 4X and 10X the MIC, serum significantly increased the duration of the PAE in all strains tested (P less than 0.05). Reducing the pH of the serum from 7.9 to 7.2 had no effect on the PAE. Heat treating the serum (56 degrees C, 30 min) reduced the PAE of ciprofloxacin at 10X the MIC approximately 25% (P less than 0.05). The PAE of cloxacillin was reduced approximately 80% in serum, and PAE experiments with gentamicin and cephalexin produced findings similar to those obtained with the fluoroquinolones. Serum increased the MICs of ciprofloxacin and norfloxacin less than twofold and increased the MIC of pefloxacin approximately fourfold. We conclude that normal human serum considerably increases the PAE of fluoroquinolones against S. aureus.
Korean regulatory actions regarding fluoroquinolones had an effect of reducing use in pediatric population.
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We designed a prospective study to evaluate the incidence of Escherichia coli in stools at admission in patients with cirrhosis that had previously received norfloxacin as primary or secondary prophylaxis of spontaneous bacterial peritonitis (SBP) (group I, n = 28) vs those who did not (group II, n = 55).
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Urinary tract infections are commonly encountered in clinical practice and are usually readily treatable. Although many antimicrobial agents that have been available for some time remain effective in the eradication of bacteriuria, the recent introduction of the fluoroquinolone norfloxacin represents an important addition to the therapeutic armamentarium. The efficacy of single-dose therapy with antimicrobial agents such as trimethoprim-sulfamethoxazole or amoxicillin has been shown to be similar to that with conventional (7- to 10-day) treatment in women with uncomplicated lower urinary tract infections. The long-term administration of agents such as trimethoprim-sulfamethoxazole or nitrofurantoin in low doses is usually effective for suppression or prophylaxis of recurrent bacteriuria.
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The clinical efficacy of norfloxacin (NFLX) was evaluated on 40 patients. They had subjective symptoms suggestive of prostate inflammations and more than five white blood cells (WBC)/hpf in their prostatic secretions (EPS) or VB3. Of these, gram negative rods were isolated from the EPS in 3 patients and gram positive cocci were obtained in 26 patients. The overall clinical efficacy was determined at the second week. The effectiveness rate of the subjective symptoms was 82.5%. The effectiveness rate of the WBC in the EPS was 47.4%. The effectiveness rate of the bacteria in the EPS was 64.3%. The overall clinical effectiveness rate was 77.8%. A subjective side effect was observed only in one patient who had skin eruption like urticaria. Mild liver dysfunction of blood chemistry analysis was shown only in two patients but they had had long standing chronic hepatitis. We conclude that NFLX is an effective drug for the patients with chronic prostatitis.
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This study provides information on the efficacy of ocular antibacterials commonly used against bacterial pathogens of keratitis. It is hoped that this information will help decision-making in empiric initial treatment of bacterial keratitis.
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The high prevalence of ASB in pregnant women warrant the need to screen all pregnant women and treat those infected with appropriate antimicrobial regimens in order to reduce its complications.
The new chemotherapeutic agent NFLX was orally administered 600 mg a day for 5 consecutive days in 44 cases having complicated urinary tract infection, and its clinical efficacy was evaluated. They consisted of 8 marked effective cases, 19 moderately effective cases and 17 ineffective cases, and its overall clinical efficacy was 61%. The bacteria disappeared in 10 cases, and decreased in 9 cases. Thirteen cases showed bacterial alternation, and 12 cases remained unchanged. By type of disease group, the efficacy was slightly inferior in the indwelling catheter group compared with that of the nonindwellt group.
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The choice of an antimicrobial agent is primarily dependent on its antimicrobial activity and the pharmacokinetics in the host. The gyrase inhibitors differ in their antimicrobial spectrum as well as in their pharmacokinetics. In this review we compare key pharmacokinetic parameters of the most important 4-quinolones. Clearly, there are differences in their absorption, their sensitivity of the absorption process to food or di-or trivalent cations. On a weight basis enoxacin tends to have higher plasma levels then e.g. ciprofloxacin or norfloxacin and also tissue penetration of enoxacin as determined in the Body Fluid Model is superior to ciprofloxacin or norfloxacin. The elimination of enoxacin is mostly by the kidney (approximately 50-60% of dose) another 12-15% are metabolized in the liver. Renal failure therefore requires dose adjustments. The inhibitory effect of enoxacin on other compounds' metabolism has to be considered.
A hospital based study was carried out in the Department of Microbiology, Tribhuvan University Teaching Hospital, Institute of Medicine with the aim to initiate the isolation and identification of Aeromonas spp. from the stool samples of gastroenteritic patients and to determine the prevalence of Aeromonas spp. in other clinical samples and water. Altogether 293 samples were investigated that include 172 stool samples, 60 pus/wound swabs, 20 body fluids and 41 water samples. The samples were collected and processed by standard microbiological techniques in order to isolate Aeromonas. Ampicillin blood agar (20 microg/ml) was used as selective medium for the isolation of Aeromonas. The specimen prevalence rate of Aeromonas spp. in stool was found to be 5.2% and the A. hydrophila (55.5%) was the predominant species followed by A. caviae (33.3%) and A. sobria (11.1%) in the stool samples. Likewise, 3.3% of pus sample showed positive growth of A. hydrophila. Aeromonas was not detected in any of the body fluids. Aeromonas spp. were isolated from 58.5% of water samples obtained from different hospitals. The commonest species was A. hydrophila (62.5%) followed by A. caviae (20.8%) and A. sobria (16.7%). In vitro susceptibility testing showed that the aminoglycosides and fluroquinolones were the effective antibiotics against Aeromonas. It was found that 88.9% of Aeromonas spp. isolated from stool samples were sensitive to gentamicin, 77.8% to ciprofloxacin, norfloxacin, tetracycline and ceftriaxone and 66.6% to nalidixic acid whereas cent percent Aeromonas spp. from water samples were sensitive to gentamicin, ciprofloxacin, norfloxacin, tetracycline and ceftriaxone and 75.0% to nalidixic acid. The enteric Aeromonas isolates were more resistant to antimicrobial agents than the water isolates.
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The study analyzed the prevalence of ESBL -type enzymes among 256 Klebsiella pneumoniae strains isolated from various clinical materials collected from patients hospitalized between 1997 and 2000. ESBLs were detected by double-disk synergy test (DDST). The prevalence of strains resistant to selected aminoglycosides (gentamicin, amikacin, netilmicin) and quinolones (ciprofloxacin, norfloxacin, nalidixic acid) in the particular years was analyzed. Drug sensitivity was determined by disk-diffusion method according to the recommendations of the National Reference Center for Microbial Drug Sensitivity.
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The prevalence of PMACBL-producing E. coli was relatively low in the Auckland community, but has increased in recent years. Typing revealed that the majority of the PMACBL-producing E. coli in the Auckland region were genetically unrelated meaning that a point source or direct person to person transmission are not drivers of local community spread currently. The isolates were more resistant to non-beta-lactam antimicrobials than other non-AmpC, non-ESBL-producing E. coli, leaving few treatment options. The majority of the PMACBL-producing E. coli isolates seemed to be acquired in the community and were most frequently isolated from women with UTI. A large proportion of patients with community-acquired UTI had not been hospitalised nor had any antimicrobial treatment in the previous 6 months.
Drug interactions related to inhibition of hepatic drug metabolism have been identified for some fluoroquinolone antibiotics. This study was designed to investigate whether the fluoroquinolone norfloxacin at the usual clinical dosage interacts with the anticoagulant agent warfarin. Ten healthy male subjects were administered a single oral dose of 30 mg warfarin sodium alone or during multiple-dose treatment with norfloxacin, 400 mg bid, in a randomized, crossover fashion. Plasma warfarin concentrations and prothrombin times were measured for 6 days after each of the two warfarin doses. The pharmacokinetic parameters of warfarin were comparable in the absence and presence of norfloxacin, including no significant differences in warfarin's elimination half-life, apparent total clearance, apparent volume of distribution, or peak plasma concentration. Norfloxacin also had no significant effect on the anticoagulant effect of warfarin, as assessed by the area under the prothrombin time versus time curve and the maximum response for prothrombin time. The lack of pharmacokinetic or pharmacodynamic interaction observed in this study suggests that a clinically important interaction of norfloxacin and warfarin is unlikely to occur in patients requiring both drugs.
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Fluoroquinolones have been the preferred antibiotics for treating CBP. Because of their low rate of drug resistance, fluoroquinolones are suitable therapeutic agents for E. faecalis strains causing CBP in Korea. Even though tetracycline, erythromycin, and trimethoprim/sulfamethoxazole have been prescribed as an empirical antimicrobial therapy for chronic prostatitis, we cannot recommend these drugs for treatment of E. faecalis isolates because of the high rates of drug resistance.
Despite the fact that patients with diabetes more often received longer and more potent initial treatment than patients without diabetes, pre- and postmenopausal women with diabetes more often had recurrences of their UTIs.
Enteric pathogens were isolated in 51% of the evaluable patients: Campylobacter species in 29%, Salmonella species in 16%, Shigella species in 3.5%, and other pathogens in 2.6%.
The complexation of iron(III) with norfloxacin in acidic solution at 25 degrees C, at an ionic strength of about 0.3 M and a pH of 3.0 has been studied. The water-soluble complex formed, which exhibits an absorption maximum at 377 nm, was used for the spectrophotometric determination of trace amounts of iron(III). The molar absorptivity was 9.05 x 10(3) I mol-1 cm-1 and the Sandell sensitivity 6.2 ng cm-2 of iron(III) per 0.001 A. The formation constant (Kf) was determined spectrophotometrically and was found to be 4.0 x 10(8) at 25 degrees C. The calibration graph was rectilinear over the range 0.25-12.0 p.p.m. of iron(III) and the regression line equation was A = 0.163c - 0.00042 with a correlation coefficient of 0.9998 (n = 9). Common cations, except cerium (IV), did not interfere with the determination. The results obtained for the determination of iron(III) using the described procedure and the thiocyanate method were compared statistically by means of the Student t-test and no significant difference was found.
Nineteen eyes of 17 patients having microbiologically proven Bacillus keratitis were reviewed. The mean age of the patients was 32.64 years (range, 3-70). The duration of symptoms ranged from 1 day to 3 months, with 11 eyes seen within a week of onset of symptoms. Trauma (five eyes), lagophthalmos (two eyes), topical corticosteroid therapy (one eye), bullous keratopathy (two eyes), previous corneal scars (two eyes), and diabetes (one eye) were identified as predisposing factors. Severe corneal features, disproportionate to the duration of symptoms, were present in most of the eyes. Gram stain of corneal scrapings showed variably stained bacilli in eight (42.1%) cases. Polymicrobial infection was present in six eyes (two fungal, four bacterial). Of the 16 isolates tested for in vitro antibiotic susceptibility, 100% were sensitive to gentamicin, 15 (93.75%) were sensitive to ciprofloxacin and norfloxacin, 14 (87.5%) were sensitive to chloramphenicol, and 10 (62.5%) were sensitive to cefazolin. Whereas 12 (63.1%) eyes required only medical therapy, adjunctive procedures were required in seven (36.8%) eyes. The ulcers healed (mean time to healing, 37.4+/-28.6 days) in 16 eyes (lost to follow-up, three). Visual acuity had improved after treatment in 10 (71.4%) of 14 eyes in whom vision could be recorded.
To make sure the reliability of phototoxic tests in vitro by comparing the phototoxic potential of 4 fluoroquinolones (FQ).
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During the last decade in Sweden H. pylori eradication has been frequently prescribed, but the incidence of eradication has slowly declined. Most eradications followed the recommended regimen, including those occurring after a previous eradication.
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In this work we have studied the molecular pathways responsible for DSBs repair in the quinolone susceptibility: the stalled replication fork reversal (recombination-dependent) (RFR), the SOS response induction, the translesional DNA synthesis (TLS) and the nucleotide excision repair mechanisms (NER). For this reason, at the European University in Madrid, we analysed the minimal inhibitory concentration (MIC) to three different quinolones in Escherichia coli mutant strains coming from different type culture collections.
In a randomized, double blind, placebo-controlled, multicentre trial, 447 travellers to Africa, Asia or Latin America started three days treatment with norfloxacin 400 mg bd or placebo within 24 h after the onset of travellers' diarrhoea. One hundred and four subjects developed diarrhoea and of those 94 (46 in the norfloxacin group and 48 in the placebo group) could be analysed for efficacy. By the last treatment day, 34 patients in the norfloxacin and 18 in the placebo group were cured (P = 0.0001), four and three improved and five and 19, respectively, were failures. Recurrences were seen in three patients on norfloxacin and eight on placebo. The mean time to cure was 3.2 days in the norfloxacin group and 4.4 days in the placebo group (P less than 0.005). The number of loose stools was significantly lower in the norfloxacin group. Nine adverse events were reported; seven in the placebo and two in the norfloxacin group. Pre- and post-travel faecal samples were studied in 19 patients treated with norfloxacin, 21 treated with placebo and 21 untreated subjects without diarrhoea. In treated subjects, increased frequencies of Escherichia coli resistant to ampicillin, co-trimoxazole, doxycycline and chloramphenicol were found in both groups, though more frequently in the placebo one. No subject had norfloxacin resistant Esch. coli pre- and post-travel.
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Quinolone-resistant Escherichia coli was isolated from blood cultures in 43% of the patients (n = 15) presenting with fever between 24 and 48 h postbiopsy. The urine culture was positive in 13% and no patient had symptoms suggestive of a urinary tract infection (UTI). In patients presenting after 48 h (n = 42), quinolone-resistant E. coli was never isolated from blood; E. coli was cultured from urine in 45% of the patients and in 48% it was associated with UTI symptoms.
The drugs examined were ofloxacin (OFLX), lomefloxacin (LFLX), and norfloxacin (NFLX). The amount of drug uptake in the cultured cells that were exposed to the drugs was measured by high-performance liquid chromatography (HPLC).
Randomized, double-blind, placebo-controlled, crossover study.
We retrospectively studied 146 cirrhosis patients diagnosed with a first episode of SBP from 2005 to 2006. Of these, 89 patients survived; the survivors were divided into two groups based on recurrence and non-recurrence of SBP, and clinical parameters, survival time and cause of death were analysed.
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Multiple-dose kinetics of pefloxacin was determined in 12 normal male subjects given 400 mg pefloxacin by iv 1 h-infusion every 12 h for 16 doses. Twelve other subjects (6 men and 6 women) were given 400 mg pefloxacin by mouth every 12 h for 18 doses. Plasma and urine concentrations of pefloxacin and its main metabolites (N-desmethyl pefloxacin or norfloxacin and pefloxacin N-oxide) were measured by high performance liquid chromatography. The bioavailability of pefloxacin was complete and plasma concentrations after iv or oral administration were similar. Pefloxacin was rapidly absorbed from the gastrointestinal tract and reached maximum plasma concentrations about 1 h after dosing. Pefloxacin elimination (T 1/2 beta) increased from 11.00 +/- 2.64 h after the first iv dose to 13.93 +/- 3.58 h after the last iv dose (P less than 0.01). Apparent total body clearance decreased from 148.5 +/- 47.6 to 106.9 +/- 39.2 ml/min (P less than 0.01) because of decreased non-renal clearance (apparent volume of distribution did not significantly change over the repeated pefloxacin administration). Similar results were obtained after repeated oral dosing. Renal clearance of pefloxacin was low (7.47 +/- 2.28 ml/min) indicating that non-renal clearance represents the major route of elimination of this quinolone. Urinary excretion of pefloxacin and N-desmethyl and N-oxide metabolites was approximately 31% of the pefloxacin dose and beta-elimination half-lives of these metabolites were very close to that of pefloxacin (13.34 +/- 2.72 h and 11.95 +/- 2.64 h respectively). Due to a possible saturable process in the metabolic pathway, some accumulation occurred during repeated iv or oral treatment (accumulation ratio = 1.37 +/- 0.20). These results show that concentrations of pefloxacin in excess of the minimum inhibitory concentrations for many important pathogens can be rapidly achieved in plasma and urine with the 400 mg bid regimen with both iv and oral routes.
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The adverse reactions and therapeutic effects of fluoroquinolones were studied retrospectively in patients with typhoid fever and paratyphoid fever.
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This randomised, double-blind, multicenter study compared the safety and efficacy of lomefloxacin and norfloxacin in adult female outpatients with uncomplicated urinary tract infections. Patients were randomly assigned to one of 3 treatment groups: 400 mg lomefloxacin once daily for 3 days (L3), 400 mg lomefloxacin once daily for 7 days (L7), or 400 mg norfloxacin twice daily for 7 days (N7). A total of 703 patients (age 17-75 years) were enrolled at 21 investigative sites in southern Sweden. Clinical and microbiological evaluations were conducted at the start, 5-9 days and 3-4 weeks post therapy. Patients with quantitative urine cultures of > or = 10(4) CFU/ml of a susceptible pathogen were considered evaluable for efficacy. Escherichia coli and Staphylococcus saprophyticus were the most commonly isolated pathogens. In both L3 and L7 groups, 196 patients and in the N7 group 195 patients met the criteria for efficacy evaluation. At the 5-9 day post-treatment evaluation, 88% of the pathogens were eradicated in the L3 group, 93% in the L7 group and 93% in the N7 group. At the 3-4 week post-treatment evaluation, 81%, 82%, and 85% of urine cultures remained negative in the L3, L7, and N7 groups, respectively. No statistically significant differences between the 3 treatment groups were noted with the exception of eradication of S. saprophyticus, for which the 7 day courses were more effective at 4-9 days post treatment. No persistent pathogen developed resistance to the study drugs. All 3 treatment regimens were equally well tolerated, except for photosensitivity reactions, which were more frequently reported in patients in the lomefloxacin groups.
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La présente étude visait à déterminer si on décelait du Clostridium difficile dans les produits de viande hachée et de porc haché non cuits vendus au détail à Winnipeg, au Manitoba. Au moyen d’un protocole de traitement par l’alcool et d’inoculation de cultures sur la C difficile Moxalactam Norfloxacin (CDMN), les chercheurs ont trouvé du C difficile toxicogénique dans 6,3 % des 48 échantillons de viande. Les isolats de C difficile appartenaient à divers pulsotypes, tous déjà isolés dans les selles de patients manitobains atteints d’une maladie à C difficile. Puisque la cuisson de la viande n’éradique pas les spores C difficile, ce phénomène soulève de l’inquiétude au sujet de la transmissibilité potentielle de cet organisme par voie alimentaire.