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A beta-lactamase prevalence of 23% was found among 1,730 Haemophilus influenzae isolates. Ampicillin susceptibility was 70%, and 12% of beta-lactamase-negative strains presented diminished susceptibility to ampicillin (BLNAR phenotype). Susceptibility of 90% was found for cefaclor and clarithromycin, whereas it was nearly 100% for cefotaxime, cefixime, azithromycin, and cefuroxime. Ciprofloxacin-resistant (0.1%) and beta-lactamase-positive amoxicillin/clavulanate-resistant (BLPACR) phenotypes (0.1%) are anecdotal so far.
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A 26-year-old woman presented with a high-grade fever and chills of 2 days' duration. She complained of associated joint pain, especially in the wrists and knees. One day before admission, tender skin lesions began to develop on the fingers, and subsequently spread to the more proximal extremities. The patient recalled having a sore throat and a nonproductive cough before the onset of the fever and eruption. The past medical history was significant for Gardnerella vaginitis and several urinary tract infections. The patient was taking oral contraceptive pills; her most recent menstruation was 3 weeks before admission. She reported having sexual intercourse with her boyfriend 2 weeks before admission. The patient's temperature was 40 degrees C. Dermatologic examination revealed a 6-mm, hemorrhagic pustule on an ill-defined pink base, overlying the volar aspect of the left second proximal interphalangeal joint (Fig. 1a). Scattered on the upper and lower extremities were occasional round, ill-defined pink macules with central pinpoint vesiculation (Fig. 1b). A skin biopsy of the digit revealed a dense neutrophilic infiltrate with leukocytoclasis and marked fibrin deposition in the superficial and deep dermal vessels (Fig. 2a). Gram stains demonstrated the presence of Gram-negative diplococci (Fig. 2b). Laboratory findings included leukocytosis (leukocyte count of 20 x 109/L, with 81% neutrophils). Analysis of an endocervical specimen by polymerase chain reaction was positive for Neisseria gonorrhoeae and negative for Chlamydia trachomatis. Throat and blood cultures grew N. gonorrhoeae. Specimen cultures obtained by skin biopsy yielded no growth. Results of serologic analysis for human immunodeficiency virus, hepatitis, syphilis, and pregnancy were negative. Beginning on admission, intravenous ceftriaxone, 2 g, was administered every 24 h for 6 days, followed by oral cefixime, 400 mg twice daily for 4 days. Oral azithromycin, 1 g, was administered to treat possible coinfection with C. trachomatis. By treatment day 4, the patient was afebrile, with the resolution of leukocytosis and symptomatic improvement of arthralgias.
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Intestinal absorption of the orally active cephalosporin, cefdinir, was investigated using brush-border membrane vesicles prepared from rabbit small intestine. The initial uptake of cefdinir was pH-dependent, with increased uptake at acidic pH, and was not influenced by either sodium gradient or membrane potential difference. Cefdinir uptake was saturable with an apparent Michaelis constant of 8.1 mM. Initial uptake of cefdinir was inhibited by dipeptides (glycyl-L-proline and glycylsarcosine), beta-lactam antibiotics (cephradine, cefixime and penicillin V), and monocarboxylic acids (acetic acid and L-lactic acid), whereas the uptake of cephradine and cefixime was not inhibited by monocarboxylic acids. Cefdinir significantly inhibited the initial uptake of cephradine, cefixime and [3H]acetic acid. From these results, it was suggested that cefdinir was transported across brush-border membranes by both dipeptide and monocarboxylic acid carriers.
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The prevalence of in-vitro susceptibilities to antibiotics were (hospital, state health service clinic, health center-primary-care): imipenem (100%-100%-100%; p=NS), amikacin (100%-100%-99.7%; p=NS), fosfomicyn (98.6%-98.4%-99.6%; p=NS), cefepime (96%-96.9%-98.3%; p=NS), piperacillin-tazobactam (96%-95.3%-96.6%; p=NS), aztreonam (93.5%-94.7%-97.7%; p<0.001), ceftazidime (93.5%-94.3%-97.8%; p<0.001), cefotaxime (93.1%-95%-97.7%; p<0.001), cefixime (92.7%-94.6%-96.7%; p<0.05), nitrofurantoin (92%-94.7%-94.7%; p=NS), cefuroxime (88.4%-93.1%-95%; p<0.001), amoxicillin-clavulanic (87.7%-88.7%-93.8%; p<0.001), tobramicyn (87%-93.7%-93.8%; p<0.001), gentamcin (85.9%-92.8%-93%; p<0.001), cefazolin (84.4%-88.7%-91.6%; p<0.01), ciprofloxacin (63.8%-71.4%-78.4%; p<0.001), norfloxacin (63%-70.8%-78.2%; p<0.001), cotrimoxazole (65.2%-68.6%-74.9%; p<0.01) and ampicillin (35.5%-42.5%-47.8%; p<0.01). (*NS= No significant differences).
This double-blind randomized study compared 3-day regimens of cefixime (400 mg once daily) and ofloxacin (200 mg twice a day) in the treatment of urinary tract infections in women. The respective clinical cure rates for the two groups of women were 89 and 92% after 7 days and 81 and 84% after 4 weeks. The respective microbiological cure rates (free of bacteriuria) for the two groups of women were 83 and 86% after 7 days and 77 and 80% after 28 days. A 3-day cefixime regimen seems to be as efficient as a 3-day ofloxacin regimen in the treatment of uncomplicated cystitis in women.
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The bacterial strains isolated from 490 patients diagnosed as having urinary tract infections (UTIs) in 14 institutions in Japan were collected between August 2004 and July 2005. The susceptibilities of them to many kinds of antimicrobial agents were measured. Of them, 577 strains were estimated as causative bacteria and used for the measurement. The strains consisted of 156 gram-positive bacterial strains (27.0%) and 421 gram-negative bacterial strains (73.0%). Against Staphylococcus aureus, arbekacin (ABK), vancomycin (VCM) showed the strongest activity and prevented the growth of all strains with 2 microg/mL. Against Enterococcus faecalis, ampicillin (ABPC) and VCM showed a strong antibacterial activity. The antibacterial activity of cephems to Escherichia coli was generally good, and especially cefozopran (CZOP) and cefpirome (CPR) showed the strongest activity (MIC90: < or = 125 microg/mL). Quinolone resistant E. coli [MIC of ciprofloxacin (CPFX): > or = 4 microg/mL] was detected at frequency of 18.8%, which was higher than that in the last year. Against Klebsiella pneumoniae, CZOP, meropenem (MEPM), and carumonam (CRMN) showed the strongest activity and prevented the growth of all strains with 0.125 microg/mL or less. The antibacterial activity of the other cephems was relatively good, and decrease in their activity observed in the last year study was not recognized. Against Serratia marcescens, imipenem (IPM) and gentamicin (GM) had the strongest antibacterial activity. Against Proteus mirabilis, CRMN showed the strongest activity and prevented the growth of all strains with 0.125 microg/mL or less. MEPM prevented the growth of all strains with 0.25 microg/mL. Next, cefmenoxime (CMX), ceftazidime (CAZ), CZOP, cefixime (CFIX), cefpodoxime (CPDX), and cefditoren (CDTR) showed a strong activity. The antibacterial activity of the drugs to Pseudomonas aeruginosa was generally low, and MIC90 of all the drugs was ranged from 32 to > 128 microg/mL except IPM and MEPM having 16 microg/mL. The antibacterial activities of CZOP and CAZ were considered to be relatively good on MIC50 comparison (MIC50: 2 microg/mL).
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Because of the widespread existence of Neisseria gonorrhoeae resistant to penicillin or tetracycline, ceftriaxone is now recommended for the treatment of gonorrhea. There is, however, a need for effective antibiotics that can be administered orally as an alternative to ceftriaxone, which requires intramuscular administration. Cefixime is an orally absorbed cephalosporin that is active against resistant gonococci and has pharmacokinetic activity suitable for single-dose administration.
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Between 1 January and 31 March 1991, 20 laboratories in England and Scotland sent a total of 413 consecutive clinical isolates of Moraxella catarrhalis to The London Hospital Medical College (LHMC). After confirmation of identity, the susceptibility of all isolates to 11 antimicrobial agents was determined. Of the 375 (90.8%) isolates which were found at LHMC to be beta-lactamase-positive, 174 produced zones of inhibition around 2 micrograms ampicillin disc which were greater than or equal to 20 mm in diameter and 252 were inhibited by less than or equal to 0.5 mg/L of ampicillin. However, 71 of these 375 had been reported to be ampicillin-susceptible by peripheral centres. While beta-lactamase had not been detected in 35 of these 71 isolates, the other 36 had been reported to be ampicillin-susceptible and beta-lactamase-positive. All 38 beta-lactamase-negative isolates produced zones greater than or equal to 30 mm in diameter and were inhibited by less than or equal to 0.06 mg/L of ampicillin. No M. catarrhalis isolate was found to be resistant to co-amoxiclav, tetracycline, chloramphenicol or cefaclor. Two strains showed intermediate susceptibility to erythromycin (MIC 1 mg/L) and 27 required greater than or equal to 32 mg/L of sulphamethoxazole for inhibition. Resistance to trimethoprim was uniform (MICs 2-128 mg/L). Two isolates showed intermediate susceptibility to cefixime (MIC 2 mg/L) but none was resistant to the new oral cephalosporin cefetamet or to the oral carbacephem loracarbef.(ABSTRACT TRUNCATED AT 250 WORDS)
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To establish whether antibiotic resistance in Neisseria gonorrhoeae is uniform within a given sequence type as determined by N gonorrhoeae multi-antigen sequence typing (NG-MAST).
Our results demonstrate that mixed populations of E. coli O157 with distinguishable PFGE profiles that are simultaneously present in bovine faeces can be isolated with IMS/CT-SMAC technique.
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The in vitro activities of fosfomycin and seven other antibiotics commonly used for oral treatment of urinary tract infections (UTIs) were evaluated for 499 Escherichia coli isolated from urine samples during a nationwide laboratory-based surveillance study in 2010. Overall, the highest resistance rates were found for amoxicillin (42.9%), followed by amoxicillin/clavulanic acid (32.7%), trimethoprim/sulfamethoxazole (SXT) (30.9%), ciprofloxacin (19.8%), cefuroxime (10.0%), cefpodoxime (8.6%) and cefixime (8.2%). One-half of the isolates (n=252; 50.5%) were fully susceptible to the eight drugs, whilst only 6 strains (1.2%) were resistant to fosfomycin. Combined resistance to amoxicillin, cefuroxime, ciprofloxacin and SXT was detected in 29 isolates (5.8%). Moreover, 40 isolates (8.0%) produced an extended-spectrum β-lactamase (ESBL), including CTX-M-type ESBLs detected in 39/40 isolates (97.5%) and a TEM-52 ESBL in 1 strain (2.5%). The predominant CTX-M-type ESBL was CTX-M-15 (27/39; 69.2%). Of the 27 CTX-M-15 producers, 19 (70.4%) belonged to the clonal lineage E. coli O25b-ST131. All but one ESBL-producing strains were fosfomycin-susceptible. In view of the emergence of multidrug resistance to standard oral antibiotics, these data support that oral fosfomycin (trometamol salt) may represent a valuable option in the treatment of uncomplicated UTIs.
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This is one of the first attempts to check the rationality of fixed dose antibiotic combination of cefixime and azithromycin in India market. Though results of this study cannot be generalized considering the limitations of low sample size and in vitro model, our data provides stepping stone for further validation of cefixime and azithromycin fixed dose combinations (FDCs) in clinical setting by conducting randomized controlled trials. We think that judicious and rational use of FDCs may help to reduce the risk of selection of further drug resistance along with better clinical outcome.
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The disposition of cefixime, a potent, third generation, orally active cephalosporin, was characterized in the pregnant and lactating rat. After a single iv dose of 17.8 mg/kg 14C-cefixime to day 18 pregnant rats, the half-life for elimination of radioactivity from both maternal serum and placentas was 6.9 hr. Elimination from fetal plasma and tissues was somewhat longer, 12.5 and 13.7 hr, respectively. However, comparison of areas under the curve indicated that exposure of the fetuses to cefixime was far less than that of placentas. Whole body autoradiography showed the greatest radioactivity in maternal liver, kidney, and intestines. In the lactating rat, steady state plasma concentrations of 14C-cefixime were achieved by continuous ip infusion of 2.54 mg/kg/day via Alza osmotic Mini-pumps from days 10 to 14 postpartum. Plasma concentrations of radioactivity in the dams were, on the average, 70 times greater than in their nursing pups throughout the study. After 102 hr of drug infusion, total radioactivity in the body of the pups, including the stomach and intestinal contents, was 1% of the 14C-cefixime estimated to be in the mother's body at steady state. Overall, these data indicate that exposure of the developing rat fetus and nursing pup to cefixime after maternal drug administration is quantitatively small.
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Resistance of Neisseria gonorrhoeae to expanded-spectrum cephalosporins such as ceftriaxone and cefixime has increased markedly in the past decade. The primary cephalosporin resistance determinant is a mutated penA gene, which encodes the essential peptidoglycan transpeptidase, penicillin-binding protein 2 (PBP2). Decreased susceptibility and resistance can be conferred by mosaic penA alleles containing upward of 60 amino acid changes relative to wild-type PBP2, or by nonmosaic alleles with relatively few mutations, the most important of which occurs at Ala501 located near the active site of PBP2. Recently, fully cefixime- and ceftriaxone-resistant clinical isolates that harbored a mosaic penA allele with an A501P mutation were identified. To examine the potential of mutations at Ala501 to increase resistance to expanded-spectrum cephalosporins, we randomized codon 501 in a mosaic penA allele and transformed N. gonorrhoeae to increased cefixime resistance. Interestingly, only five substitutions of Ala501 (A501V, A501T, A501P, A501R, and A501S) that increased resistance and preserved essential transpeptidase function were isolated. To understand their structural implications, these mutations were introduced into the nonmosaic PBP2-6140CT, which contains four C-terminal mutations present in PBP2 from the penicillin-resistant strain FA6140. The crystal structure of PBP2-6140CT-A501T was determined and revealed ordering of a loop near the active site and a new hydrogen bond involving Thr501 that connects the loop and the SxxK conserved active site motif. The structure suggests that increased rigidity in the active site region is a mechanism for cephalosporin resistance mediated by Ala501 mutations in PBP2.
Randomised trials of one regimen of antibiotic versus another in pregnant women with culture confirmed genital gonococcal infection.
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Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major public health concern worldwide. In Vietnam, knowledge regarding N. gonorrhoeae prevalence and AMR is limited, and data concerning genetic characteristics of N. gonorrhoeae is totally lacking. Herein, we investigated the phenotypic AMR (previous, current and possible future treatment options), genetic resistance determinants for extended-spectrum cephalosporins (ESCs), and genotypic distribution of N. gonorrhoeae isolated in 2011 in Hanoi, Vietnam.
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The central nervous system (CNS) is frequently involved in patients with Whipple's disease and is the most common site of disease relapse. Antibiotics such as trimethoprim-sulfamethoxazole (TMP-SMX) that have reliable CNS penetration, are therefore recommended as first-line therapy. We report a patient with Whipple's disease who was treated with TMP-SMX and presented 14 months after initiation of therapy with visual decline and severe headaches. The patient was also treated concurrently with low-dose weekly methotrexate for severe psoriasis. Evaluation by magnetic resonance imaging revealed bilateral posterior white matter abnormalities that pathologically were consistent with Whipple's disease. He was ultimately treated with cefixime, an orally administered third-generation cephalosporin. Visual function improved on this regimen and follow-up magnetic resonance imaging showed regression of the lesions. This case represents the first report of both CNS relapse during therapy with TMP-SMX and successful treatment with cefixime. We also speculate that methotrexate, which impairs cell-mediated immunity, may have contributed to the relapse.
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The diagnosis and management of urinary tract infections (UTIs) in young children are clinically challenging. This report was developed to inform the revised, evidence-based, clinical guideline regarding the diagnosis and management of initial UTIs in febrile infants and young children, 2 to 24 months of age, from the American Academy of Pediatrics Subcommittee on Urinary Tract Infection.
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This study demonstrated that CFX has comparable clinical efficacy and a better adverse events profile than A/C when used to treat AOM of childhood.
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The method for predicting the fraction absorbed (Fa) of the PEPT1 substrates was established based on the in vitro uptake into Caco-2 cells. Uptake of a drug into Caco-2 cells was measured, and the carrier-mediated initial uptake clearance (DeltaCL uptake) was calculated as the difference between the uptake clearance in the absence of glycyl-sarcosine (Gly-Sar) and that in the presence of 30 mM Gly-Sar. The DeltaCL uptake of each drug was then divided by that of cephradine to obtain DeltaCL*uptake, which was a normalized parameter to correct for inter-day and/or inter-cell variability. Then, cephradine (CED), cefixime (CFIX), and cefotiam (CTM) were selected as marker compounds having excellent, medium and poor absorption, respectively. The DeltaCL*uptake and Fa values for CED, CFIX and CTM were fitted to the equation derived from the complete radial mixing (CRM) model, and the scaling factor (A') was obtained. Using the A' value, Fa was predicted from the DeltaCL*uptake value of each drug. Good correlation was observed between the predicted and reported Fa values, which demonstrated that Fa of PEPT1 substrates can be predicted based on the in vitro uptake in Caco-2 cells.
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A range of sensitivities exhibited by Escherichia coli O157 to cefixime and potassium tellurite are demonstrated. The sensitivity was shown by growth on cefixime tellurite sorbitol MacConkey agar and by the effect on the metabolic activity in glucuronate trimethylamine-oxide conductance broth. These antimicrobials are regularly used in the isolation of this pathogen from food and clinical specimens, and such sensitivity may lead to the reporting of false negative samples.
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Electroreduction and adsorption of cefixime was studied in phosphate buffer by cyclic voltammetry (CV), differential pulse cathodic adsorptive stripping voltammetry (DPCAdSV), and square-wave cathodic adsorptive stripping voltammetry (SWCAdSV) at hanging mercury drop electrode (HMDE). These fully validated sensitive and reproducible cathodic adsorptive stripping voltammetric procedures were applied for the trace determination of the bulk drug in pharmaceutical formulations and in human urine. The optimal experimental parameters were as follows: accumulation potential=-0.1 V (vs. Ag/AgCl, 3M KCl), accumulation time=50s, frequency=140 Hz, pulse amplitude=0.07 V, and scan increment=10 mV in phosphate buffer (pH 2.6). The first peak current showed a linear dependence with the drug concentration over the range of 50 ng ml(-1) to 25.6 μg ml(-1). The achieved limit of detection and limit of quantitation were 3.99 and 13.3 ng ml(-1) by SWCAdSV and 7.98 and 26.6 ng ml(-1) by DPCAdSV, respectively. The procedure was applied to assay the drug in tablets. Applicability was also tested in urine samples. Peak current was linear with the drug concentration in the range of 1 to 60 μg ml(-1) of the urine, and minimum detectability was found to be 12.6 ng ml(-1) by SWCAdSV and 58.4 ng ml(-1) by DPCAdSV.