Heliopsis longipes extract and affinin were not toxic as a reduction in the number of His⁺ revertant bacteria colonies. Affinin (25 and 50 µg/plate) significantly reduced the frameshift mutations that were generated by 2-aminoanthracene (2AA) (40%) and reduced the oxidative DNA damage generated by norfloxacin (NOR) (37-50%). Affinin possessed antioxidant properties that were able to reduce 2AA- and NOR-induced mutations in S. typhimurium TA98 and TA102, respectively.
The susceptibility of 11 clinical isolates of Mycobacterium tuberculosis, 3 M. kansasii, 3 M. xenopi, 2 M. scrofulaceum, 2 M. marinum, 2 M. malmoense to fleroxacin, ciprofloxacin, norfloxacin, rifampicin, isoniazid, ethambutol, and streptomycin was determined by the standard proportion method (Middlebrook 7H10 agar). All M. tuberculosis, M. kansasii, M. xenopi, M. scrofulaceum, M. marinum, and M, malmoense isolates including those resistant to conventional antimycobacterials were inhibited by 0.5 mg/l of fleroxacin and ciprofloxacin, the lowest tested concentration. Fleroxacin and ciprofloxacin along with ofloxacin, pefloxacin, ansamycin, clofazimine and cycloserine were also tested against 14 isolates of the M. avium complex. Nine of 14 strains (64%) of the M. avium complex were found susceptible to 4 mg/l of fleroxacin and a similar percentage to the other quinolones. On the basis of its in-vitro potency and its favourable pharmacokinetic properties fleroxacin appears to be sufficiently active to warrant further experimental trials against difficult to treat mycobacteria.
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Liver injury due to idiosyncratic drug reactions can be difficult to diagnose and may lead to acute liver failure (ALF), which has a high mortality rate. N-acetylcysteine (NAC) is effective treatment for paracetamol toxicity, but its role in non-paracetamol drug-induced ALF is controversial. We report on the use of a validated bedside tool to establish causality for drug-induced liver injury (DILI) and describe the first case of resolution of norfloxacin-induced ALF after NAC therapy. NAC is easy to administer and generally has a good safety profile. We discuss the evidence to support the use of NAC in ALF secondary to DILI and possibilities for further clinical research in this field.
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To isolate environmental bacteria capable of transforming fluoroquinolones to inactive molecules.
The general lack of knowledge about the health effects of waterpipe smoking is among the reasons for its global spread. In this study, bacterial contamination of waterpipe hoses was investigated. Twenty hoses were collected from waterpipe cafés and screened for bacterial pathogens using standard culture and isolation techniques. Additionally, resistance of isolated bacteria to common antibiotics was determined by identifying the minimum inhibitory concentration (MIC) of each isolate. Forty eight bacterial isolates were detected. Isolates included both Gram-positive and Gram-negative pathogens from species that included Micrococcus (12), Corynebacterium (13) and Bacillus (9). In addition, some of the detected pathogens were found to be resistant to aztreonam (79%), cefixime (79%), norfloxacin, amoxicillin (47%), clarithromycin (46%) and enrofloxacin (38%). In conclusion, the hose of the waterpipe device is a good environment for the growth of bacterial pathogens, which can then be transmitted to users.
The in vitro and in vivo activity of ofloxacin (DL 8280, HOE 280) was compared with that of other antibacterial compounds. Ofloxacin was found to have a broad antibacterial spectrum which includes both gram-positive and gram-negative aerobic and anaerobic species. Its activity is generally higher than that of pipemidic acid and nalidixic acid. Against staphylococci and streptococci, ofloxacin proved to be more active than norfloxacin. In the case of Enterobacteriaceae and Pseudomonadaceae, ofloxacin and norfloxacin possess comparable activities. Ofloxacin was the most active compound against a number of aerobic isolates which are resistant to cefotaxime and ceftriaxone. Of the compounds compared, ofloxacin was the only one which exhibited reasonable activity against anaerobes. It inhibited all strains of Bacteroides fragilis at a concentration of 3.125 mg/l and the gram-positive anaerobes at 0.5 mg/l. In mice experimentally infected with various gram-positive and gram-negative bacteria, ofloxacin was more active than norfloxacin and pipemidic acid. With the gram-negative pathogens, orally administered ofloxacin was as active as gentamicin used parenterally. We conclude from our studies that ofloxacin could be a valuable therapeutic agent with a variety of indications.
Three clinical isolates of N gonorrhoeae susceptible to norfloxacin were exposed to increasing concentrations of norfloxacin. To identify mutations in the gyrA and parC genes of the gonococcal mutants, the quinolone resistance determining regions of the gyrA and parC genes were polymerase chain reaction (PCR) amplified and the PCR products were directly sequenced. Norfloxacin accumulation in the gonococcal cells was also measured.
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The interaction between pefloxacin, ciprofloxacin, norfloxacin, and ofloxacin and biofilms formed by Staphylococcus epidermidis (20 clinical isolates) was studied. In the presence of 1/2-MIC and 1/8-MIC of quinolones, the optical density of the biofilms was reduced to 22-24% and 65-74% of the controls, respectively. Treatment of preformed biofilms with quinolones in concentrations ranging from 12.5 microg/ml to 400 microg/mL caused reduction in the optical density of the adherent biofilms to 45-77% of the control. In an in vitro model of vascular catheter colonization, subinhibitory concentrations (12, 14 and 1/8 MIC) of fluoroquinolones reduced the number of adherent bacteria to 24-28%, 48-55% and 58-76% of the controls, respectively. The vascular catheter segments precolonized with Staphylococcus epidermidis for 24 h and exposed to the fluoroquinolones in 8-16 times MIC (100 microg/mL) for 2 h showed no growth of adherent cells. The activity of pefloxacin in reducing the bacterial adhesion and eradicating the preformed biofilms was demonstrated by scanning electron microscope. These data show that subinhibitory concentrations of ciprofloxacin, norfloxacin, pefloxacin, and ofloxacin inhibit the adhesion of Staphylococcus epidermidis to plastic surfaces and vascular catheters. Higher concentrations of fluoroquinolones were able to eradicate the preformed biofilms on vascular catheters.
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We analyzed and compared the distributions of 13 target pharmaceuticals in different water samples from the Hangzhou metropolitan area and Linan County, Southeast China.
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A highly effective analytical method for multi-residue determination of antibiotics in aquifer sediments was first established in this study. Microwave-assisted solvent extraction (MASE) and solid-phase extraction were used for sample pre-concentration and purification, ultra-high performance liquid chromatography coupled to hybrid quadrupole-high resolution Orbitrap mass spectrometry (UHPLC-Q-Orbitrap) was applied for detection. For high resolution mass spectrometry (HRMS), the target compounds were tentatively identified by retention time and accurate mass which was measured with precursor ions in Target-SIM scan, and then confirmed by the monitoring of daughter ion fragments which were generated in dd-MS(2) scan. The results provided good mass accuracy with mass deviations below 2ppm (except norfloxacin with -2.3ppm) for quantitative analysis of the compounds by HRMS. Reasonable recoveries of all analytes were obtained more than 60% (except doxytetracycline) in fortification samples at concentrations higher than 10μgkg(-1). Relative standard deviations of repeatability and inter-day precision were below 21% and 11%. Limits of detection (LOD) ranged from 0.1 to 3.8μgkg(-1), whereas limits of quantification (LOQ) were established between 0.3-9.0μgkg(-1). The method was applied to analyze real aquifer sediment samples in different aquifer depth of 4.0, 7.5, 13.0 and 18.0m. Chlorotetracycline and ofloxacin were observed at relative high concentrations of 53 and 19μgkg(-1) respectively in 18.0m deepness. The exposure to low doses of these compounds in subsurface environment increases concerns on long-term ecological security of underground system.
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Emergency of multi-drug resistance in Pseudomonas aeruginosa isolates after exposure to gentamicin was investigated with reference to their LPS-compositions. Three strains each of P. aeruginosa, different in LPS-compositions (long- and short-LPS strains, and LPS-deficient strain) were once or repeatedly incubated overnight at 35 degrees C in Mueller-Hinton broth including different concentrations of gentamicin, a poly-cationic antibiotic. LPS-compositions of the bacteria which survived and were grown after exposure to gentamicin were analyzed and the susceptibility to some of anti-pseudomonal drugs was determined. Of the test 9 strains after single exposure, No. 4 (long-LPS) and No. 41 (short-LPS) formed the LPS-deficient mutants. The resistance to ceftazidime and gentamicin was found in No. 4 strain, but not in No. 41 strain. Drug resistance in different patterns was also found in Nos. 43, 29, 45 and 52 strains without any change in their LPS-compositions. Contrary to these results, the susceptibility to norflxacin increased in Nos. 21 and 45 strains without any change in their LPS-compositions. After repeated exposures to gentamicin, the LPS-compositions of Nos. 4 and 14 (short-LPS) were altered and formed the LPS-deficient and the Intermediate-LPS (between short and long compositions) mutants, respectively. The LPS-alteration in both strains were accompanied by the development of resistance to ceftazidime and gentamicin, respectively. The drug resistance in different patterns were also found in Nos. 43, 156, 29, 41, 21, 45 and 52 strains, without any change in the LPS-compositions, whereas the increase in susceptibility to norfloxacin was simultaneously found in No. 45 strain. The ionic-binding of [3H]-gentamicin to the cell surfaces of two LPS-deficient mutants of P. aeruginosa decreased markedly, in comparison with that of the respective parents, and these results might lead to the drug resistance in the LPS-deficient mutants. However, the gentamicin-induced resistance of some strains of P. aeruginosa (but no change in the LPS-compositions) to the test drugs including gentamicin indicates a possibility that negative charges on the bacterial surface were decreased by the drug exposure. The drug resistance and LPS-compositions in the gentamicin-induced mutants of P. aeruginosa were stable during or after the 15th in vitro serial transfers.
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This cross-sectional study was conducted in a teaching hospital outside the city of Ujjain in India. Seven antibiotics--amoxicillin, ceftriaxone, amikacin, ofloxacin, ciprofloxacin, norfloxacin and levofloxacin--were selected. Prescribed quantities were obtained from hospital records. The samples of the hospital associated water were analysed for the above mentioned antibiotics using well developed and validated liquid chromatography/tandem mass spectrometry technique after selectively isolating the analytes from the matrix using solid phase extraction. Escherichia coli isolates from these waters were tested for antibiotic susceptibility, by standard Kirby Bauer disc diffusion method using Clinical and Laboratory Standard Institute breakpoints.
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Phenotypically, 43 out of 95 isolates showed multidrug resistance. Among the 17 antibiotics tested, resistance was observed as follows: sulphonamides (45.2%), nalidixic acid (44.25%), tetracycline (42%), ampicillin (36.8%), erythromycin (34.7%), carbenicillin (31.5%), chrolamphenical (28.4%), gentamicin (27.3%), kanamycin (24.2%), spectinomycin (21%), sulfamethoxazole-trimethoprim (16.8%), streptomycin (12.6%), cephalothion (8.4%), ofloxacin (5.2%), ciprofloxacin (4.2%), and norfloxacin (4.2%). Fifty-two isolates were susceptible to the antimicrobial agents tested. A total of 3.1% of the isolates had the integron gene pattern combination of dfrA2-aadA2 (2100 bp), dfrA12 (2100 bp); 4.2% had dfrA12-aadA2-sulI (2100 bp); 2.1% had dfrA12-aadA2 (2100 bp); and 1% had dfrA2-aadA2-sulI (2100 bp), oxa1-aadA2 (1500 bp), dfrA12-aadA2-sulI, and blaPSE (2100 bp).
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This study investigated the species distribution and antimicrobial resistance among 99 enterococci isolated from hospitalized patients in 12 hospitals in Cuba from October 2000 to September 2001. Species identification was performed by WIDER Automatic System (Francisco Soria Melguizo, Madrid, Spain), and the susceptibility testing was performed by disk diffusion, agar dilution, and E-test methods. Enterococcus faecalis was the most prevalent (85%) species, followed by E. faecium (10%), E. gallinarum (2%), E. casseliflavus (2%), and E. durans-hirae (1%). A higher percentage of resistance to ampicillin (50%), fosfomycin (40%), ciprofloxacin (30%), norfloxacin (20%), and tetracycline (90%) was detected in E. faecium isolates, whereas E. faecalis strains showed higher rates of resistance to erythromycin (52.4%), chloramphenicol (34.5%), rifampicin (62.5%), moxifloxacin (3%), and nitrofurantoin (2.4%). Resistance to glycopeptide was detected in E. faecalis (1.2%) and E. faecium (10%). Thirty-one E. faecalis (37%) and 3 E. faecium (30%) showed a high-level resistance to gentamicin. The results of this work will be very helpful to guide empirical antimicrobial therapy and the implementation of infection control measures in Cuban hospitals.
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The fluoroquinolone compounds, such as ciprofloxacin, norfloxacin, and ofloxacin, have broad spectrum bactericidal activity and have proved to be effective in both the treatment and prevention of certain infections in patients with cancer. The triazole drug fluconazole is useful in the treatment of oral, esophageal, and disseminated candidiasis and cryptococcal meningitis. Early studies suggest that a new acyclic nucleoside, ganciclovir, has some effect in the treatment of cytomegalovirus infections, but its precise use in patients with cancer has not been fully established.
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Methicillin-resistant Staphylococcus aureus bacteria are one of the key etiological factors of hospital-acquired and community-acquired infections. MRSA strains have an ability of causing a broad spectrum infections: from a relatively mild skin infections to severe life-threatening systemic infections. They are characterized by multi-drug resistance, virulence of a number of factors, may clonally spread within the hospitals and between hospitals.
To report a case of fulminant hepatic failure associated with the use of gatifloxacin.
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A hospital based cross sectional study was conducted from May to November, 2013. Simple random sampling technique was used. Demographic variables were collected using a structured questionnaire. Clinical data were collected by physicians. Two vaginal swab specimens were collected from each participant. Wet mount and Gram staining were carried out to identify motile T.vaginalis, budding yeast and clue cells. All vaginal specimens were cultured for aerobic bacterial isolates using standard microbiology methods. Antimicrobial susceptibility was performed using disc diffusion technique as per the standard by Kirby-Bauer method. The results were analyzed using descriptive, chi-square and fisher's exact test as appropriate.
Though O157 can cause a life-threatening diseases, the therapeutic protocol using antibiotics for the infection is still controversial. Main reasons for hesitating the uses of antibiotics for the infection is their possibility to enhance the release of verotoxins (VT). We have recently established the mouse model of O157 infection using germfree mice. Using this animal model of O157 infection, we examined therapeutic efficacy of antibiotics. Fosfomycin (FOM) and norfloxacin (NFLX) were selected for in vivo examination, because of their lower MIC under anaerobic condition (MIC:FOM = 0.78; NFLX = 0.10 microgram/ml) than those of the other antibiotics including kanamycin, doxycycline, minocycline, choramphenicol, cefaclor and ampicilin. When germfree BALB/c mice were orally infected with 1 x 10(5)CFU of O157 (clinically-isolated strain, TI001) at day 0, all mice died at 8 to 9 d after the infection. Oral treatment of the mice with FOM (500 mg/kg/d, twice a day) or NFLX (50 mg/kg/d, twice a day) everyday for 5 days starting at 3 hr after the infection significantly improved the survival rate from 0% to 83.3%, and 100%, respectively. VT could not be detected in the feces of the mice in either groups, suggesting that neither of these antibiotics enhanced the release of VT. Interestingly, when FOM treatment was started at 3, 6, 12 or 24 hr after the infection, the survival rate was 100%, 100%, 0% and 0%, respectively. Thus, in conclusion, FOM and NFLX are both useful as the therapeutic agents for O157 infection. However, the treatment should be started in the early phase after the infection.
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Norfloxacin is more effective and less costly than the alternative, TMP-SMX. Norfloxacin treatment will save $195.85 per patient, resulting in an aggregate saving of more than $40 million annually. Patients are expected to enjoy a better quality of life with an incremental 0.0601 QALD per patient, if they are treated with norfloxacin. These results are robust across a wide range of probabilities and costs.
In our study a levofloxacin resistance rate of 0.7% was found among invasive isolates. Although resistance level is low, surveillance is necessary, especially to prevent cases of in vivo resistance development as reported.
The efficacy and safety of 7-10-day courses of lomefloxacin (single daily dose of 400 mg) or norfloxacin (twice-daily doses of 400 mg) for the treatment of uncomplicated urinary tract infections were compared in two large, multicenter, randomized trials. This article presents the combined results of these trials, which were conducted in a total of 27 centers throughout the United States. A total of 727 adults, mostly women, with symptoms of acute urinary tract infection were enrolled; 370 patients were randomized to lomefloxacin treatment, and 357 received norfloxacin. The bacteriologic cure rate at 5-9 days post-therapy was 98.2% in the lomefloxacin group and 96.3% in the norfloxacin group (p = nonsignificant). The clinical success rate of 99.1% in the lomefloxacin group was significantly higher than the success rate of 93.5% in the norfloxacin group (p = 0.002). Adverse events were reported by 157 lomefloxacin-treated patients and 129 patients receiving norfloxacin. Adverse events attributable to drug treatment occurred in 41 patients (11.1%) in the lomefloxacin group and 27 (7.6%) in the norfloxacin group. Eight lomefloxacin (2.2%) and three norfloxacin patients (0.8%) were withdrawn from treatment because of adverse events probably attributable to the drug. The incidence of dizziness, tremor, and photosensitivity rash was higher in the lomefloxacin group than in the norfloxacin group, while the incidence of nausea was higher in the norfloxacin group. The results of these trials demonstrate that once-daily administration of 400 mg lomefloxacin is as safe and effective clinically as, and superior bacteriologically to, twice-daily administration of 400 mg norfloxacin in the treatment of acute uncomplicated urinary tract infections in adult patients.
A sensitive, selective, and efficient method was developed for simultaneous determination of 11 fluoroquinolones (FQs), ciprofloxacin, danofloxacin, difloxacin, enrofloxacin, flumequine, marbofloxacin, norfloxacin, ofloxacin, oxolinic acid, pipemidic acid, and sarafloxacin, in eggs by molecularly imprinted polymer (MIP) and column liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). Samples were diluted with 50 mM sodium dihydrogen phosphate at pH 7.4, followed by purification with a commercial MIP (SupelMIP SPE-Fluoroquinolones). Recoveries for the 11 quinolones were in the range of 90-106% with intra- and interday relative standard deviation ranging from 1 to 6% and from 3 to 8%, respectively. Limits of detection (LODs) were 0.12-0.85 ng/g, and limits of quantification (LOQs) were 0.36 and 2.59 ng/g, whereas the decision limit (CC(α)) and detection capability (CC(β)) ranged from 0.46 to 3.35 ng/g and from 0.59 to 4.12 ng/g, respectively. The calculated relevant validation parameters are in an acceptable range and in compliance with the requirements of Commission Decision 2002/657/EC. Moreover, a comparison to two other sample treatments [solid-phase extraction (SPE) and solvent extraction] has been carried out. The method was applied to lying hens, Japanese quail, and black-headed gull eggs, in which FQs were not found. The method was also applied to study the depletion of sarafloxacin in eggs.