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FK482 is an oral aminothiazolyl hydroxyimino cephalosporin with a C-3 vinyl group. Its activity was compared with those of cephalexin, cefuroxime, cefixime, and amoxicillin-clavulanate. FK482 inhibited 90% of Staphylococcus aureus isolates at 1 micrograms/ml and 90% of Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus pneumoniae isolates at less than or equal to 0.012 micrograms/ml, superior to cephalexin and cefuroxime and similar to cefixime. It did not inhibit oxacillin-resistant S. aureus. FK482 inhibited 90% of Enterococcus faecalis isolates at 8 micrograms/ml. Although 90% of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Salmonella species, and Shigella species isolates were inhibited by less than or equal to 2 micrograms/ml, FK482 was less active than cefixime against Citrobacter, Enterobacter, Morganella, Serratia, and Providencia species, with MICs for many isolates of greater than 8 micrograms/ml. FK482 inhibited Haemophilus influenzae and Neisseria gonorrhoeae at concentrations comparable to that of cefixime and superior to those of cephalexin and cfaclor. Bacteroides and Pseudomonas species were resistant. FK482 was not hydrolyzed by the TEM-1 and TEM-2 beta-lactamases but was hydrolyzed by TEM-3 and the Proteus vulgaris enzyme. It had a high affinity for chromosomal beta-lactamases.
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Children with sickle cell disease are at increased risk for bacterial sepsis and, when febrile, are usually hospitalized for intravenous antibiotic therapy pending results of blood cultures. In this study, we prospectively identified a group of febrile patients with sickle cell disease who were at low risk for sepsis and treated them with outpatient therapy.
Therapy to eradicate pharyngeally carried group A streptococci (GAS) has increasingly been used in the management of institutional outbreaks and is now recommended for household contacts of patients with streptococcal toxic shock syndrome. In this randomized, controlled trial, contacts of patients with GAS infections were screened for pharyngeal GAS colonization. Those whose cultures were positive were randomized to receive either cefixime (8 mg/[kg.d]; maximum 400 mg) or rifampin (20 mg/kg; maximum, 600 mg) once a day for 4 days. Two to five days following completion of therapy, repeated cultures were negative for 13 (38%) of 34 rifampin recipients and 71 (77%; 95% CI, 69%-85%) of 97 cefixime recipients. At 10-14 days after treatment, only 53% of cefixime recipients remained culture-negative. Rates of successful clearance improved with increasing age (P < .01); among 17 adults who received cefixime, the success rate was 94%. Four days of therapy with rifampin is not effective for eradication of pharyngeally carried GAS. Four days of therapy with cefixime may be effective for adults, but further studies are needed.
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The primary outcome measure was fever clearance time. The secondary outcome measure was overall treatment failure (acute treatment failure and relapse).
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Effective treatment of gonorrhoea is fundamental to public health control; however, the ability of Neisseria gonorrhoeae to successively develop resistance to different treatments has hampered control efforts. The extended-spectrum cephalosporins--cefixime and ceftriaxone--have been recommended in the UK for treatment of gonorrhoea since 2005. We looked at surveillance data from England and Wales to ascertain the current usefulness of these drugs and to inform changes to national treatment guidelines.
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The pharmacokinetics of cefixime, a third-generation broad-spectrum cephalosporin, were determined following administration of a 8 mg/kg single oral dose of cefixime suspension to six children with urinary tract infections, ages from 6 to 13 years and weights from 17 to 60 kg. Blood samples for determination of plasma cefixime concentrations were obtained for up to 12 hr and complete urine collections were obtained for urinary excretion of unchanged parent drug for up to 24 hr after administration. Plasma and urine concentrations of cefixime were determined using a reversed phase HPLC assay and pertinent pharmacokinetic parameters were estimated by model-independent standard methods. Mean peak plasma concentration was 4.04 micrograms/ml and was reached after 3.2 hr. The mean area under the plasma concentration-time curve was 33.07 micrograms.hr/ml and the mean elimination half-life was 3.91 hr. The mean apparent total clearance was 4.74 ml/min./kg and about 15% of the dose administered was recovered unchanged in urine. In conclusion, the estimated pharmacokinetic values of cefixime were comparable to those observed in healthy adult subjects based on equivalent mg/ kg doses. Plasma and urine concentrations of the drug were well above the reported minimal plasma and urinary concentrations for most common urinary tract pathogens for up to 12 and 24 hr after administration, respectively.
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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.
In vitro antibacterial activity of telithromycin (TEL) against the isolates of Neisseria gonorrhoeae (212 isolates) derived from urine or genital secretion in 2002 (April to December) was examined in comparison with those of macrolides (erythromycin [EM], clarithromycin [CAM]), penicillins (penicillin G [PCG]), cephems (cefodizime [CDZM], cefixime [CFIX]), quinolones (levofloxacin [LVFX]), tetracyclines (minocycline [MINO]), and aminoglycosides (spectinomycin [SPCM]). The MIC of TEL was ranged from < or = 0.039 to 0.25 microg/mL and the MIC50 and MIC90 of TEL were respectively 0.125 and 0.25 microg/mL, which were the lowest values compared with those of other oral antibacterial agents measured. When compared TEL with other agents in the order of the MIC50 and MIC90, TEL was more superior to EM and CAM (both eight times), MINO (four times and twice), and LVFX (16 and 64 times). The MIC90 of TEL was superior in twice though the MIC50 was the same in comparison with CFIX. The CDZM resistant strain did not exist and SPCM also inhibit growth with 32 microg/mL or less that was the breakpoint MIC excluding one stock though the PCG sensitive strain was only 1.4% in the injection drug. However, clinical breakpoint MIC is not established, but the efficacy of TEL is prospective because of its high antibacterial activity to inhibit growth of all stocks for gonococcus with 0.25 microg/mL. It is expected that TEL can become an oral antibiotic recommended for treatment of gonococcus if dosage and administration are considered.
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Ninety-four clinical isolates of Moraxella catarrhalis were examined for susceptibility to 21 antimicrobial drugs; 67 isolates (= 71.3%) produced beta-lactamase(s). In terms of antibiotic resistance, the number of isolates resistant to penicillin G, ampicillin, and cotrimoxazole were 56, 32, and 1, respectively. The number of isolates with intermediate susceptibility to penicillin G, ampicillin, ciprofloxacin, ofloxacin, cotrimoxazole, and fosfomycin were 11, 34, 1, 2, 2, and 47, respectively. All 94 isolates proved susceptible to ampicillin + 10 micrograms/ml of sulbactam, amoxicillin + 4 micrograms/ml of clavulanic acid, cefuroxime, cefotaxime, cefepime, cefepime, cefixime, imipenem, meropenem, chloramphenicol, doxycycline, tetracycline, fusidic acid, erythromycin, clarithromycin, and rifampin, as based on currently valid NCCLS criteria, where applicable. There were no very major or major discrepancies between agar dilution and agar disk diffusion test results. There were only a few minor discrepancies between test results, specifically: penicillin G (category IV = 4, category VI = 1); ampicillin (category IV = 4, category V = 1, category VI = 7), amoxicillin + clavulanic acid (category III = 11), cotrimoxazole (category IV = 1, category V = 1, category VI = 1), ciprofloxacin (category V = 1), and ofloxacin (category VI = 2). The sole exception was fosfomycin, with a total of 25 minor discrepancies encountered (category III = 14, category V = 9, category VI = 2). Wilkins-Chalgren agar compared favorably with Mueller-Hinton agar following examination with 11 selected antimicrobial drugs against 31 representative isolates of M. catarrhalis.
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We evaluated Neisseria gonorrhoeae Etest minimum inhibitory concentrations (MICs) relative to agar dilution MICs for 664 urethral isolates for ceftriaxone (CRO) and azithromycin (AZM), 351 isolates for cefpodoxime (CPD) and 315 isolates for cefixime (CFM). Etest accurately determined CPD, CFM and AZM MICs, but resulted in higher CRO MICs.
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Third-generation cephalosporins in oral formulations have become an increasingly important first-line choice against common bacterial infections. Cefixime is one such agent, which possesses excellent efficacy against a broad spectrum of pathogens, including Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis. Clinical success rates are similar to cefaclor, clarithromycin, and other cephalosporins. Importantly, cefixime also possesses excellent activity against beta-lactamase-producing strains. The pharmacodynamic features of the drug include a half-life of 3-4 h and a Cmax of 4.4 microg/ml, well above the MIC90 for susceptible pathogens, permitting once-daily dosing. In this brief overview, the bacteriological and clinical efficacy of cefixime is discussed, as well as its indications.
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The sensitivity data of 4,323 positive isolates of S. Typhi and S. Paratyphi A isolated during the three-year period were reviewed. The majority of isolates were S. Typhi (59.6%).Over three years, the incidence of multidrug-resistant (MDR) S.Typhi remained high, ranging from 64.8%-66.0%, while MDR S. Paratyphi A decreased from 4.2% to 0.6%. Fluoroquinolone resistance increased for S. Typhi from 84.7% to 91.7%. Cefixime- and ceftriaxone-resistant S. Typhi were isolated in two children.
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We report a case of progressive, cephalosporin-susceptible, Neisseria gonorrhoeae conjunctivitis despite successful treatment of male urethritis syndrome. We hypothesize that conjunctival infection progressed due to insufficient penetration of cefixime and azithromycin and point out that extragenital infection and male urethritis may not be cured simultaneously in settings where the syndromic approach is used.
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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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beta-Lactamase production in Canadian isolates of Haemophilus influenzae has remained relatively constant (25-35%) over the last decade despite increasing cefaclor resistance (MIC >/= 32 mg/L). TEM (294/324, 90.7%) and ROB-1 (30/324, 9.3%) prevalence rates among 324 isolates of H. influenzae obtained from across Canada in 1997-1998 were similar (P > 0.05) to previously published reports. However, 66. 7% (26/39) of cefaclor-resistant isolates were ROB-1-positive (P < 0. 001) and the remaining four ROB-1-positive isolates were cefaclor-intermediate (MIC 16 mg/L). Susceptibilities to loracarbef (P < 0.001) and cefprozil were also reduced in the presence of ROB-1 while the activities of cefuroxime, cefotaxime, cefixime and imipenem were similar in both TEM- and ROB-1-positive solates.
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Knowledge regarding characteristics and transmission of Neisseria gonorrhoeae, Chlamydia trachomatis and Mycoplasma genitalium and antibiotic resistance in N gonorrhoeae in Guinea-Bissau, West Africa, is entirely lacking.
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beta-Lactams have been considered ineffective against organisms growing inside mammalian cells because of their poor penetration into cells. However, cefixime has been shown to be clinically effective against typhoid fever. The probable mechanism of therapeutic effectiveness of cefixime against typhoid fever was investigated using Salmonella enterica serovar Typhimurium instead of S. enterica serovar Typhi both in a cellular and in a mouse infection model. Cefixime was able to inhibit the growth of serovar Typhimurium inhabiting monocyte-derived THP-1 cells. Elongation of serovar Typhimurium in THP-1 cells was observed microscopically. Apparent morphological changes of serovar Typhimurium in THP-1 cells were also observed by electron microscopy. The concentration of cefixime inside THP-1 cells was almost half (46 to 48%) of the concentration outside the cells when serovar Typhimurium coexisted in the solution. The length of time after oral dosing (8 mg/kg) that cefixime was present-calculated from levels in serum-at a concentration above the MIC at which 90% of the serovar Typhi organisms inside human cells were inhibited was presumed to be more than 12 h. Cefixime also showed excellent activity in the mouse systemic and oral infection models based on infections caused by serovar Typhimurium. It is concluded that a fair amount of cefixime can enter mammalian cells and inhibit the growth of bacteria inside cells when the bacteria are sensitive enough to cefixime, as are serovars Typhimurium and Typhi.
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Cattle are an important reservoir for the foodborne pathogens Salmonella and Escherichia coli O157:H7; they frequently harbor these microorganisms in their digestive tracts and shed them in their feces. Thus, there is potential for contamination of cattle hides and, subsequently, carcasses. Interventions aimed at reducing or eliminating pathogen shedding preharvest will also reduce the likelihood of beef product contamination by these pathogens. Therefore, this study used an in vitro model to evaluate Bdellovibrio bacteriovorus, a gram-negative microorganism that preys upon other gram-negative microorganisms, as a preharvest intervention to control Salmonella and E. coli O157:H7. Rumen fluid and feces were inoculated with pansusceptible or antimicrobial-resistant strains of one pathogen. Control samples were treated with HEPES buffer, whereas experimental samples were exposed to HEPES buffer plus B. bacteriovorus. Salmonella and E. coli O157:H7 populations were quantified at 0, 24, 48, and 72 h. The most-probable-number (MPN) technique, followed by streaking onto xylose lysine Tergitol 4 agar, was used to determine Salmonella populations, whereas spread plating onto sorbitol MacConkey agar supplemented with cefixime and tellurite was employed to enumerate E. coli O157:H7. B. bacteriovorus reduced pansusceptible Salmonella in cattle feces by 2.02 Log MPN/g (P = 0.0005) and antimicrobial-resistant Salmonella by 3.79 (P < 0.0001) and 2.24 (P = 0.0013) Log MPN/g after 24 and 48 h, respectively, in comparison to control samples. Significant reductions were not observed for E. coli O157:H7 in rumen or feces. These data suggest that further investigation into B. bacteriovorus efficacy as a preharvest intervention to control Salmonella in cattle is warranted.
In November 2007, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2007, Issue 4), MEDLINE, EMBASE, LILACS, mRCT, conference proceedings, and reference lists.
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We established the cefixime content after exposing on different conditions of temperature and environment. The obtained results demonstrated that cefixime is stable at environmental temperature and degrades fast and strong in aggressive environments.
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General practitioners often have to manage urinary tract infections (UTI) with probabilistic treatments, although bacterial resistances are increasing. Therefore, the French Society of Infectious Diseases published new guidelines in 2014. The aim of this study was to investigate the bacterial epidemiology of UTI in the general population in primary care and analyse risk factors for Escherichia coli resistance to antibiotics. A cross-sectional study was conducted in 12 ambulatory laboratories. Patients over 18 years of age coming for urinalysis were included. Risk factors for UTI were collected using a questionnaire and the laboratory records. Bacteria meeting criteria for UTI were analysed. A positive urinalysis was found in 1119 patients, corresponding to 1125 bacterial isolates. The bacterial species were: E. coli (73 %), Enterococcus spp. (7 %), Klebsiella spp. (6 %), Proteus spp. (4 %), Staphylococcus spp. (3 %) and Pseudomonas spp. (2 %). Regardless of the bacteria, the most common resistance was that to co-trimoxazole: 27 % (95 % confidence interval [CI] = [0.24; 0.30]), followed by ofloxacin resistance: 16 % [0.14; 0.18]. Escherichia coli resistances to co-trimoxazole, ofloxacin, cefixime, nitrofurantoin and fosfomycin were, respectively, 25.5 % [0.23; 0.28], 17 % [0.14; 0.20], 5.6 % [0.04; 0.07], 2.2 % [0.01; 0.03] and 1.2 % [0.005; 0.02]. Independent risk factors for E. coli resistance to ofloxacin were age over 85 years (odds ratio [OR] = 3.08; [1.61; 5.87]) and a history of UTI in the last 6 months (OR = 2.34; [1.54; 3.52]). Our findings support the guidelines recommending fluoroquinolone sparing. The scarcity of E. coli resistance to fosfomycin justifies its use as a first-line treatment in acute cystitis. These results should be reassessed in a few years to identify changes in the bacterial epidemiology of UTI.