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Between November 1993 and October 1994, 85 patients, 15 years of age or less, with culture-proven enteric fever were randomly assigned to two groups. Group A (n = 41) received cefixime at a dosage of 10 mg/kg to 12 mg/kg per day in two divided doses. Group B (n = 44) received chloramphenicol at a dosage of 100 mg/kg daily in four divided doses. Both groups were treated for 2 weeks.
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Twenty clinical isolates of H. parainfluenzae with decreased susceptibility to aminopenicillins were examined and compared with a control group of 20 fully susceptible isolates. In this collection, the presence of amino acid substitutions in the transpeptidase domain of penicillin-binding protein 3 (PBP3), β-lactamase production and the surrounding genetic regions of blaTEM genes in selected isolates were analysed.
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The intent of this study was to determine the efficacy and tolerance of single dose oral cefixime use in the treatment of pregnant women with endocervical gonococcal carriage.
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The pharmacokinetics of FK027, a new oral cephalosporin, were investigated in rats and dogs and compared with those of cefaclor, cephalexin and amoxicillin. Upon oral administration to either rats or dogs, FK027 produced higher and more sustained serum levels than the reference drugs, hence a longer half-life. After both oral and intravenous administration, the half-life of FK027 in dogs was approximately three fold that in rats. Although the concentrations of FK027 in rat kidney, liver and spleen were lower than those of cephalexin and amoxicillin, they were sustained similarly to the serum levels. The 24-hour urinary and biliary recovery rates of FK027 in rats after oral dosing with 100 mg/kg were 34.1 and 21.9%, respectively. The urinary excretion of FK027 was significantly lower than that of the reference drugs, however, the biliary excretion was higher. In dogs, 23.4 and 0.2% of the given dose of 40 mg/kg of FK027 was excreted in the 24-hour urine and bile, respectively. Bioavailability of FK027 after oral dosing was 38% in rats and 47% in dogs, as calculated from intravenous data. Binding of FK027 to serum protein in all species was the highest of the test drugs: 63% for human, 93% for dog, 61% for rat serum.
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To determine the prevalence of Moraxella catarrhalis in sputum cultures from patients with lower respiratory tract infection and their antimicrobial sensitivity profiles.
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All listeriae were naturally sensitive or intermediate to tetracyclines, aminoglycosides, penicillins (except oxacillin), loracarbef, cefazoline, cefaclor, cefotiam, cefoperazone, carbapenems, macrolides, lincosamides, glycopeptides, dalfopristin/quinupristin, chloramphenicol and rifampicin (probably except L. grayi). Listeria spp. were naturally resistant or intermediate to most 'modern' cephalosporins (cefetamet, cefixime, ceftibuten, ceftazidime, cefdinir, cefpodoxime, cefotaxime, ceftriaxone, cefuroxime), aztreonam, pipemidic acid, dalfopristin quinupristin and sulfamethoxazole. Significant differences in natural susceptibility among the species were seen with the quinolones, trimethoprim, co-trimoxazole, rifampicin, fosfomycin and fusidic acid. It seems likely that L. grayi is naturally resistant to all antifolates; the species was least susceptible to rifampicin and most susceptible to quinolones, whereas L. ivanovii was naturally resistant to most quinolones. L. ivanovii was naturally sensitive to fosfomycin, whereas L. innocua and L. monocytogenes were naturally resistant. L. ivanovii was also the most susceptible species to fusidic acid.
A small GTP-binding protein, Rab8, is essential for apical localization of oligopeptide transporter PEPT1/SLC15A1 and sodium/glucose cotransporter SGLT1/SLC5A1 in small intestine; deficiency of rab8 gene results in mislocalization and reduced expression of these transporters. Here, we examined the role of PEPT1 and SGLT1 in vivo in gastrointestinal absorption of a beta-lactam antibiotic, cefixime, and alpha-methyl-d-glycopyranoside (alpha-MDG), respectively, using rab8 gene knockout [rab8(-/-)] mice as experimental animals deficient in those transporters. Plasma concentration of cefixime and alpha-MDG after oral administration in rab8(-/-) mice was much lower than that in wild-type mice, whereas such reduction in oral absorption was not observed for antipyrine, membrane permeation of which is not transporter-mediated. Uptake of cefixime from the apical side of isolated small intestine assessed by means of the everted sac method in wild-type mice was decreased in the presence of excess unlabeled glycylsarcosine, a PEPT1 substrate. In contrast, the uptake in rab8(-/-) mice was much lower than that in wild-type mice and comparable with that of an extracellular marker, mannitol, suggesting that the apical membrane permeability of cefixime was reduced in rab8(-/-) mice. Uptake of cefixime in wild-type mice was pH-dependent, being higher at lower pH, whereas that in rab8(-/-) mice remained at the background level at all pH values examined. These results suggest that PEPT1 and SGLT1 play an important role in gastrointestinal absorption of cefixime and alpha-MDG, respectively, in vivo in mice. The present findings also illustrate the pharmacokinetic influence of the sorting machinery protein Rab8.
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Low-energy X-ray irradiation was assessed as a means of eliminating Escherichia coli O157:H7 on lettuce. Round-cut iceberg lettuce samples (2.54-cm diameter) were dip or spot inoculated with a three-strain cocktail of E. coli O157:H7, stored for 24 h at 4 degrees C, and then irradiated at four dose levels up to 0.25 kGy using a prototype low-energy (70 kV) X-ray irradiator. E. coli O157:H7 survivors were quantified by plating on sorbitol MacConkey agar containing cefixime and tellurite. Dip inoculation yielded a D(10)-value of 0.040 +/- 0.001 kGy, which is 3.4 times lower than a previously reported value of 0.136 kGy using gamma radiation. The D(10)-value for E. coli O157:H7 on spot-inoculated samples was 0.078 +/- 0.008 kGy, which is about twice that of dip-inoculated samples. When 10 stacked leaves were irradiated from both sides, a dose of 0.2 kGy was achieved at the center of the stack with a surface dose of 1 kGy, corresponding to a approximately 5-log reduction of E. coli O157:H7 at the center of the stack. Based on these findings, low-energy X-ray irradiation appears to be a promising microbial inactivation strategy for leafy greens and potentially for other types of fresh produce.
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Urinary tract infection (UTI) is one of the most common bacterial infections in infancy, its prevalence being 5% in febrile infants (2 to 24 months of age). 10 to 20% of febrile UTIs may result in permanent renal damage (scar), whose long-term significance (hypertension or proteinuria) in previously normal kidneys remains unclear. A wide variety of antibiotic agents have been used, generally administered aggressively by intravenous route and for long periods (up to three weeks), to possibly prevent scar formation and/or sepsis complications. Recent studies suggest that children with febrile UTIs can be effectively treated with oral antibiotics such as cefixime or amoxycillin/clavulanic acid for 10 to 14 days.
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Three mosaic penA alleles were detected including two previously described alleles (XXXIV, XXXVIII) and one novel allele (LA-A). Of the 29 isolates with an alert value extended-spectrum cephalosporin MIC, all possessed the mosaic XXXIV penA allele and 18 were sequence type 1407, an internationally successful strain associated with multi-drug resistance. The modified RTPCR detected the mosaic XXXIV penA allele in urethral isolates and urine specimens and displayed no amplification of the other penA alleles detected in this study.
Urinary tract infections, among the leading causes of antibiotic prescriptions in adult women, are complicated by increasing antibiotic resistance. Current recommendations propose a 7 day treatment with fluoroquinolones or a 10-14 day course of third-generation cephalosporins (3GC). Our aim was to study the efficiency and tolerance of a short 7 day treatment with 3GC in uncomplicated acute pyelonephritis in women aged between 18 and 65 years.
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Crl:CD1(ICR) BR mice were fed chow containing Candida albicans or regular chow. Both groups were subsequently given either antibiotics or normal saline. Stool cultures were performed before, at the end of treatment and 1 week after treatment, to determine the effect on the stool yeast concentration. Candida-colonized mice treated with cefepime, cefixime or ceftibuten had higher (however not significantly) counts of the yeast in their stools than control Candida-fed mice treated with saline. A group of Candida-fed mice were treated with ceftriaxone, which is known to increase the yeast stool concentration significantly and served as positive control. Mice fed regular chow and treated with the study drugs or saline did not have any yeasts in their stools. Dissemination of Candida did not occur.
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Spectinomycin remains a useful reserve option for therapy of gonorrhea. The emergence of multidrug-resistant Neisseria gonorrhoeae strains with decreased susceptibility to cefixime and to ceftriaxone makes it the only medicine still effective for treatment of gonorrhea infection in analogous cases. However, adoption of spectinomycin as a routinely used drug of choice was soon followed by reports of spectinomycin resistance. The main molecular mechanism of spectinomycin resistance in N. gonorrhoeae was C1192T substitution in 16S rRNA genes. Here we reported a Thr-24→Pro mutation in ribosomal protein S5 (RPS5) found in spectinomycin resistant clinical N. gonorrhoeae strain, which carried no changes in 16S rRNA. In a series of experiments, the transfer of rpsE gene allele encoding the mutant RPS5 to the recipient N. gonorrhoeae strains was analyzed. The relatively high rate of transformation [ca. 10(-5) colony-forming units (CFUs)] indicates the possibility of spread of spectinonycin resistance within gonococcal population due to the horizontal gene transfer (HGT).
Variables related to compliance for families filling antibiotic prescriptions and children taking these products are important in the selection of antimicrobial therapy. Because final assessment is likely to vary considerably among health care personnel, decisions must be made on an individual basis.
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The prevalence of decreased susceptibility to both cefixime and ceftriaxone rose between 2007 and 2010 but was more noticeable for cefixime (an increase from 1·5% in 2007 to 17·1% in 2010), with a bimodal distribution of minimum inhibitory concentration recorded between 2009 and 2010. By multivariable analysis, isolates with decreased susceptibility to cefixime were associated with infection in men who have sex with men (odds ratio 5·47, 95% CI 3·99-7·48; p<0·0001) and year of isolation (in 2010, 13·08, 7·49-22·8; p<0·0001). Such isolates had a largely clonal population, with most belonging to genogroup G1407 and harbouring the penA mosaic gene. Data from 2011 showed a significant decline in prevalence of isolates with decreased cefixime susceptibility, falling from 17·1% in 2010 to 10·8% in 2011 (p<0·0001), concomitant with the change in prescribing practice in 2010 from cefixime to ceftriaxone plus azithromycin.
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For practical reasons, we would recommend use of either the Jarlier test or the commercial cephalosporin disks containing clavulanic acid to screen for ESBL producers. Cefoperazone, cefamandole, cefpodoxime and cefpirome showed good sensitivity across the methods tested.
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During 2013, N. gonorrhoeae isolates from 21 participating countries were examined. Antimicrobial susceptibility testing (Etest or agar dilution) was performed for cefixime, ceftriaxone, ciprofloxacin, azithromycin, spectinomycin and gentamicin. Statistical analyses were performed to identify significant changes in resistance between years and to investigate associations between patients with resistant gonococcal isolates and collected epidemiological variables.
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This longitudinal, observational study was conducted at Khan Research Laboratories Hospital, Islamabad, Pakistan, from May 2012 to December 2014. All patients presenting with typhoid fever with positive blood culture were included. Age, gender, salmonella serovar and sensitivity to 9 antimicrobial drugs were taken into account. The tested antimicrobial drugs were ampicillin, trimethoprim/sulphamethoxazole, chloramphenicol, nalidixic acid, ciprofloxacin, ofloxacin, levofloxacin, ceftriaxone and cefixime. SPSS 22 was used for analysis.
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Susceptibility testing was performed on 9172 isolates collected from 95 centers in North America, Europe, Australia, and Hong Kong by broth microdilution MIC determination, according to NCCLS methods, using amoxicillin/clavulanic acid and 16 comparator antimicrobial agents. Results were interpreted according to NCCLS breakpoints and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints based on oral dosing regimens.
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A cross sectional survey was carried out in Kathmandu valley. Five different brands from each eight molecules of drugs (Paracetamol tablet, Cloxacillin capsule, Amlodipine tablet, Metformin tablet, Losartan tablet, Cefixime tablet, Ofloxacin tablet, Carbamazepine tablet) were purposively selected. Registration compliance was verified from Department of Drug Administration (DDA) and laboratorial analysis was done in two different laboratories.
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Percentages of isolates susceptible to the antibiotics tested were as follows: ampicillin 59.5%, amoxicillin/clavulanate 99.2%, loracarbef 66.2%, cefprozil 70.2%, cefaclor 76.2%, cefuroxime 95%, ceftibuten 100%, cefpodoxime 100%, cefixime 100%, rifampin 99.8%, tetracycline 98.2%, chloramphenicol 99.2%, nalidixic acid 97.5%, ciprofloxacin 100%, trovafloxacin 100%, clarithromycin 74%, and azithromycin 100%.
De récentes études ont suscité des changements majeurs dans la prise en charge des infections urinaires chez les enfants. Le présent document de principes porte sur le diagnostic et la prise en charge des nourrissons et des enfants de plus de deux mois atteints d’une infection urinaire aiguë, sans affection sous-jacente connue des voies urinaires ou facteurs de risque de vessie neurogène. Il convient d’écarter la possibilité d’infection urinaire chez les enfants atteints d’une fièvre inexpliquée qui ne savent pas encore parler et chez les enfants plus âgés ayant des symptômes évocateurs de ce type d’infection (dysurie, urgences mictionnelles, hématurie, douleur abdominale, douleur lombaire ou nouvelle incontinence diurne). Chez les enfants qui sont propres, il faut faire un prélèvement d’urine à mi-jet pour analyse et culture. Chez les autres, le prélèvement par cathéter ou par ponction sus-pubienne est préconisé. L’infection urinaire est peu probable si l’analyse d’urine est complètement normale. La collecte d’urine dans un sac peut être utilisée pour analyse, mais pas pour culture. Une antibiothérapie de sept à dix jours est recommandée en cas d’infection urinaire fébrile. Si l’enfant n’est pas gravement malade et qu’il est susceptible de recevoir et de tolérer chaque dose, on peut lui donner un traitement initial d’antibiotiques par voie orale. Il faudrait soumettre les enfants de moins de deux ans à une échographie des reins et de la vessie après leur première infection urinaire fébrile, afin de déceler toute anomalie rénale d’importance. Lors d’une première infection urinaire, la cysto-urétrographie mictionnelle (CUGM) est inutile, à moins que l’échographie des reins et de la vessie ne donne des résultats évocateurs d’un reflux vésico-urétéral, de certaines anomalies rénales ou d’une uropathie obstructive.
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Bacterial pathogens were isolated in vaginal secretions of 84/90 (93%) girls. There were 6 girls receiving antibiotic treatment who had persistent discharge and repetitive isolations of Escherichia coli. Administration type was selected at random. Symptoms and signs were resolved in all girls, but we observed 1 recurrence (2.22%) in group 2 vs 6 recurrences (13.33%) in group 1 (P = .049). In group 1 we observed 3 cases (6.67%) of gastro-intestinal side effects vs no cases in group 2 (P = .079).
During August, 1994 to April, 1995, a total of 2278 clinical isolates of Haemophilus influenzae were obtained from 187 clinical laboratories in the United States (U.S.). The vast majority of these isolates (75%) were from respiratory sites, and the remaining organisms were from blood, ear, eye, and spinal fluid sources. The overall rate of beta-lactamase production and ampicillin resistance was 36%. The antimicrobial susceptibility of isolates was determined by reference broth microdilution testing against ten orally administered agents. MIC values were compared according to 12 geographical regions, inpatient or outpatient status, gender, and eight age groupings. Modest and occasionally significant differences were observed: 1) greater numbers of beta-lactamase-producing strains among outpatients, in males, in the mid-Atlantic region, and in children < or = 12 years of age; 2) lower prevalence of beta-lactamase-producing isolates in the Southeast and Pacific regions; 3) cefaclor, cefprozil, and loracarbef activity was lowest among the younger children (< or = six years); and 4) macrolide in vitro efficacy was lowest in patients > 50 years of age and in three eastern regions. Overall, more than 99% of the strains were susceptible to amoxicillin/clavulanic acid, cefixime, and cefpodoxime (e.g., widest potential clinical use). Susceptibilities using National Committee for Clinical Laboratory Standards (NCCLS) breakpoint criteria for the other agents were: 96.6% to cefuroxime, 86.5% to loracarbef, 84.0% to clarithromycin, 81.8% to cefaclor, and 80.7% to cefprozil. Non-beta-lactamase mechanisms of resistance to ampicillin were rare (0.2%) or episodic and were attributed to altered penicillin-binding proteins. Although there is an increased prevalence of beta-lactamase production among H. influenzae isolates compared to prior years, four beta-lactams remain highly active (> 95% susceptibility) against contemporary strains of H. influenzae. Other monitored compounds seem to have declined in spectrum and surveillance trials for resistance among H. influenzae isolates should continue in an effort to identify trends in the U.S.
The recent identification of a high-level-ceftriaxone-resistant (MIC = 2 to 4 μg/ml) isolate of Neisseria gonorrhoeae from Japan (H041) portends the loss of ceftriaxone as an effective treatment for gonococcal infections. This is of grave concern because ceftriaxone is the last remaining option for first-line empirical antimicrobial monotherapy. The penA gene from H041 (penA41) is a mosaic penA allele similar to mosaic alleles conferring intermediate-level cephalosporin resistance (Ceph(i)) worldwide but has 13 additional mutations compared to the mosaic penA gene from the previously studied Ceph(i) strain 35/02 (penA35). When transformed into the wild-type strain FA19, the penA41 allele confers 300- and 570-fold increases in the MICs for ceftriaxone and cefixime, respectively. In order to understand the mechanisms involved in high-level ceftriaxone resistance and to improve surveillance and epidemiology during the potential emergence of ceftriaxone resistance, we sought to identify the minimum number of amino acid alterations above those in penA35 that confer high-level resistance to ceftriaxone. Using restriction fragment exchange and site-directed mutagenesis, we identified three mutations, A311V, T316P, and T483S, that, when incorporated into the mosaic penA35 allele, confer essentially all of the increased resistance of penA41. A311V and T316P are close to the active-site nucleophile Ser310 that forms the acyl-enzyme complex, while Thr483 is predicted to interact with the carboxylate of the β-lactam antibiotic. These three mutations have thus far been described only for penA41, but dissemination of these mutations in other mosaic alleles would spell the end of ceftriaxone as an effective treatment for gonococcal infections.
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The objective of this review was to assess the effects of antibiotic regimens in the treatment of genital infection with gonorrhoea during pregnancy with respect to neonatal and maternal morbidity.