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Each of 433 adults traveling to Guadalajara, Mexico, from the United States during summer months was enrolled in one of four clinical trials of the protective effect of antimicrobial agents against travelers' diarrhea. Only one (2%) of 57 subjects taking trimethoprim-sulfamethoxazole (160 mg/800 mg daily) experienced diarrhea during a two-week study, whereas eight (14%) of 58 subjects taking trimethoprim alone (200 mg daily) and 10 (33%) of 30 taking placebo developed illness (P less than .05 and P less than .0001, respectively). Diarrhea occurred significantly less frequently among subjects receiving trimethoprim than among placebo recipients (P less than .05). None of 11 students given bicozamycin (500 mg four times daily) developed diarrhea during a three-week study, whereas 10 (53%) of 19 placebo recipients became ill (P = .003). Four (7%) of 54 subjects receiving norfloxacin (400 mg daily) experienced diarrhea during a two-week study; in contrast, 34 (60%) of 57 placebo recipients developed diarrhea (P less than .0001). The various antimicrobial agents prevented illness due to enterotoxigenic Escherichia coli and Shigella as well as that unassociated with a pathogen. The drugs were well tolerated. Current evidence suggests that trimethoprim-sulfamethoxazole is the optimal antimicrobial agent available for prophylaxis of travelers' diarrhea.
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Three novel complexes of norfloxacin (abbreviated as NFL), [M(NFL)2(H2O)2]Cl3.6H2O, (M = Fe, Co), and [Zn(NFL)2]Cl2.7H2O, have been prepared. The compounds were characterized by IR, UV-Vis, NMR spectra, molar conductivity, and elemental analyses. In all of the complexes, the ligand NFL was coordinated through two carboxyl oxygen atoms. Octahedral and tetrahegon geometries have been proposed for Fe(III)-, Co(II)-complexes and Zn(II)-complex, respectively. In vitro test of susceptibility of Fe(III)- and Zn(II)-complexes showed stronger activity than that of norfloxacin against G(-) E.Coli and Bacillus dysenteriae bacteria.
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A series of N-substituted-piperazinyl-quinolones were synthesized and evaluated for in vitro antibacterial activity. Compounds with a 2-(2,4-dichlorophenyl)-2-oxoethyl group attached to the piperazine ring (5a-c) had similar antibacterial activity to the reference drugs, ciprofloxacin, norfloxacin and enoxacin against both Gram-positive and Gram-negative bacteria. The oximes 6a-c and 6g-i were almost less active than corresponding ketones against the tested microorganisms, however the 2,4-difluorophenyl analogues (6g-i) were more active than 2,4-dichlorophenyl derivatives (6a-c). If the hydrogen of oxime is replaced with a benzyl group (6d-f & 6j-l), in-vitro antibacterial activity was decreased against both Gram-positive and Gram-negative bacteria. Generally ciprofloxacin derivatives were more active than norfloxacin and enoxacin derivatives.
After one year of use of pefloxacin in the intensive care unit, medicine unit and surgery unit and the following recent commercialization without prescription of norfloxacin, we studied for a period of two months (april and may 1986) the susceptibility to pipemidic acid, to pefloxacin and norfloxacin of 444 bacteria strains isolated obtained from clinical specimens. The antibiotic susceptibility is determined by disk diffusion test. We obtained the following results: susceptible methicillin Staphylococcus aureus (SMSA 63 strains): 85.7% PEFS, 11.1% PEFI, 79.4% NORS, 15.9% NORI, resistant methicillin Staphylococcus aureus (RMSA 36 strains): 33.3% PEFS, 2.9% PEFI, 41.6% NORS, 0% NORI; Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae (252 strains): 94% PIPS, 94.8% PEFS, 97.2% NORS; Enterobacter, Proteus indol (+), Providencia and Citrobacter (33 strains): 72.7% PIPS, 72.7% PEFS, 84.8% NORS; Pseudomonas aeruginosa (53 strains): 32% PEFS, 47.2% PEFI, 90.6% NORS, 5.6% NORI; Acinetobacter (7 strains): 57.2% PEFS, 42.8% PEFI, 42.8% NORS, 28.6% NORI. Norfloxacin in active in vitro against the majority of the P. aeruginosa isolated. We found an important methicillin and pefloxacin resistance among the Staphylococcus aureus isolated: 36 strains RMSA (36.4% out of Staphylococcus aureus) and 23 strains RMSA PEFR (63.8% out of RMSA). These later strains were isolated in eight different units mainly in visceral surgery unit and geriatric units but not in intensive care unit. After an epidemiologic study and the following recommendations to physicians and nurses: treatment by pefloxacin should be used only after bacteriological results and associated with an other antibiotic, the handwashing should be frequent and regular to prevent the spread of infection, four months later we isolated 26 strains of RMSA with 7 RMSA PEF (26.9%).2$
Norfloxacin is a quinolinecarboxylic acid compound. We examined the in vitro activity of this compound against gram-positive and -negative species, including anaerobic species. It inhibited 90% (MIC90) of strains of Escherichia coli at 0.05 microgram/ml, Klebsiella sp. at 0.4 microgram/ml, Salmonella and Shigella spp. at 0.1 microgram/ml, Citrobacter sp. at 0.4 microgram/ml, Enterobacter cloacae at 0.2 microgram/ml, Enterobacter aerogenes at 0.4 microgram/ml, and Enterobacter agglomerans at 0.2 microgram/ml. The MICs of Proteus mirabilis, Morganella sp., Proteus vulgaris, Proteus rettgeri, and Providencia sp. were 0.1, 0.2, 0.8, 0.3, and 1.6 micrograms/ml, respectively. The MIC90 of Serratia sp. was 1.6 micrograms/ml, and that of Acinetobacter sp. was 6.3 micrograms/ml. For Pseudomonas aeruginosa the MIC50, the MIC75, and the MIC90 were 0.8, 1.6, and 3.1 micrograms/ml, respectively. The MIC50 of Pseudomonas maltophilia was 3.1 micrograms/ml, and the MIC90 was 12.5 micrograms/ml. Yersinia, Arizona, and Aeromonas all were inhibited at concentrations below 1 microgram/ml, as was Campylobacter. The activity of the compound against gram-positive species was less impressive: the MIC90s of Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus faecalis were 1.6, 6.3, 3.1, and 12.5 micrograms/ml, respectively. All Listeria strains were inhibited by 3.1 micrograms/ml. The activity of norfloxacine was not affected by the type of medium, pH, or inoculum size. There was no major difference between MIC and minimum bactericidal concentration values. Norfloxacin inhibited bacteria in every species which was resistant to ampicillin, carbenicillin, cephalexin, gentamicin, and trimethoprim at concentrations lower than those of aminothiazolyl cephalosporins, moxalactam, and aminoglycosides.
This work aims to develop norfloxacin-solid lipid nanoparticles (NFX-SLN) as an oral delivery formulation. Hot homogenization and ultrasonic technique was employed to prepare NFX-SLN using stearic acid as lipid matrix and polyvinyl alcohol as surfactant. The physicochemical characteristics of SLN were investigated by optical microscope scanning electron microscopy and photon correlation spectroscopy. Antibacterial experiments of NFX-SLN were carried out by broth dilution technique. Pharmacokinetics was studied after oral administration in male Sprague-Dawley rats. The results showed that NFX-SLN was spherical and the SLN of the optimized formulation had diameters 301 ± 16.64 nm, polydispersity index 0.15 ± 0.04, zeta potential -30.8 ± 0.69 mv, loading capacity 8.58 ± 0.21% and encapsulation efficiency 92.35 ± 2.24% with good stability at 4 °C. The NFX-SLN had sustained release effect and sustained bactericidal activity. Cytotoxicity studies in cell culture demonstrated that the nanoparticles were not toxic. NFX-SLN resulted in significantly higher plasma drug concentration than native NFX. The SLN increased the relative bioavailability of NFX by 12 folds, prolonged the plasma drug level above the average minimum inhibition concentration from 14 to 168 h. These studies demonstrate that NFX-SLN could be a promising oral formulation for enhanced bioavailability and pharmacological activities.
The present work describes the development of a sensitive and highly selective innovative method for the simultaneous detection of six fluoroquinolone (FQ) antimicrobials (enrofloxacin, ciprofloxacin, norfloxacin, levofloxacin, danofloxacin, and sarafloxacin) in water samples. This detection is based on online solid phase extraction, coupled to liquid chromatography (LC), using for the first time tailor-made molecularly imprinted microspherical polymer particles prepared via precipitation polymerization. Various parameters affecting the extraction efficiency of the polymer have been optimized to reduce nonspecific interactions and to achieve selective uptake of the antibiotics from real samples. The method shows good recoveries ranging between 62% and 102% (V = 25 mL) for the different FQs tested and excellent interday and intraday precision with relative standard deviation (RSD) values between 2-5% and 2-6%, respectively. The detection limits were between 1-11 ng L(-1) (drinking water) and 1-12 ng L(-1) (fish farm water) when 25 mL samples were processed. The polymer showed selectivity for FQs containing a piperazine moiety whereas no retention was found for other antibiotics or nonrelated compounds. The method has been applied to the analysis of trace amounts of the FQs tested in drinking and fish farm water samples with excellent recoveries (>91%) and good precision (RSDs <5%).
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Cirrhotic patients at high risk of spontaneous bacterial peritonitis (SBP) were recruited and assigned N (400 mg daily) or T-S (160/800 mg daily). Patients were followed up for 12 months. The primary end-point was the incidence of infection. Secondary end-points included the incidence of SBP, bacteremia, extraperitoneal infection requiring antibiotic treatment, liver transplantation, death, side effects and rate of resistance to N or T-S.
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A novel method was developed for the determination of quinolone (QN) residues such as ofloxacin, norfloxacin, ciprofloxacin and lomefloxacin by high-performance liquid chromatography (HPLC) coupled with chemiluminescence (CL) detection. The procedure was based on the chemiluminescent enhancement by QNs of the Ce(SO(4))(2)-Ru(bpy)(3)(2+)-HNO(3) system. The separation was carried out with an isocratic elution using the mobile phase of 3:15:82 (v/v/v) acetonitrile-methanol-ammonium acetate buffer (containing 7.5 x 10(-4)M TBAB, 0.8% (v/v) TEA and 1.0 x 10(-4)M ammonium acetate, pH 3.65) at a flow rate of 1.0 ml/min. For the four QNs, the detection limits at a signal-to-noise of 3 ranged from 0.36 to 2.4 ng/ml. The relative standard deviations for the determination of QNs ranged from 1.6 to 4.5% within a day (n=11) and from 3.7 to 6.2% in three days (n=15), respectively. The method was successfully applied to the determination of QNs in prawn samples. The possible mechanism of the CL reaction was also discussed briefly.
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Patients with cirrhosis and tense ascites hospitalized from January to September 2000 in 5 hepatogastroenterology units prospectively underwent an exploratory paracentesis with cytobacteriological, biochemical and bedside inoculation into aerobic and anaerobic blood culture bottles. Patients studied were not receiving antibiotics except for norfloxacin and had no obvious sign of infection such as fever or hypothermia, chills, unusual abdominal tenderness, de novo or worsening hepatic encephalopathy, recent gastrointestinal bleeding, acute renal failure or marked arterial hypotension. Clinical and biological findings and ascitic fluid cytological and bacteriological results were evaluated at each exploratory paracentesis. The results are given in mean +/- standards deviations with range.
In this study, we evaluated the clinical efficacy of cefpodoxime proxetil (CPDX-PR) in otorhinolaryngological infections. The subjects were 205 patients (85 men and 120 women) with various otorhinolaryngological infections, aged from 16 to 81 years (mean 49.2 years): 113 patients had acute infections, 25 patients had chronic infections and 67 patients had acute exacerbation of chronic infections. 1. Clinical evaluation The overall efficacy rate was 75.6%. When classified by disease, the efficacy rate was 84.9%, 60.0%, 65.6% in acute infections, chronic infections and acute exacerbation of chronic infections, respectively. 2. Bacteriological evaluation Frequencies of isolation of different organisms were studied: 49 strains of Staphylococcus aureus, 27 strains of Staphylococcus sp. and 15 strains of Streptococcus sp. were found in the decreasing order of frequencies. Antibacterial activities against S. aureus, Staphylococcus sp. and several other organisms were compared among CPDX-PR, ampicillin, cefaclor, cefteram and norfloxacin: CPDX-PR showed the highest activity. 3. Side effect Mild urticaria was observed in only 1 patient. Abnormal laboratory test results were mild elevation of GOT and GPT in 3 of 43 patients. Based on the above results, we consider that CPDX-PR is useful for treatment of otorhinolaryngological infections.
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Compound 3a should be a potential lead antibacterial molecule with dual action modes.
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Bacterial isolates were identified and tested for antibiotic susceptibility using the Kirby-Bauer disc-diffusion technique.
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Cirrhosis is a major health problem, being the 5th cause of death in the U.K. and 12th in the U.S., but 4th in the 45 to 54 age group. Until recently cirrhosis was considered a single and terminal disease stage, with an inevitably poor prognosis. However, it is now clear that 1-year mortality can range from 1% in early cirrhosis to 57% in decompensated disease. As the only treatment for advanced cirrhosis is liver transplantation, what is urgently needed is strategies to prevent transition to decompensated stages. The evidence we present in this review clearly demonstrates that management of patients with cirrhosis should change from an expectant algorithm that treats complications as they occur, to preventing the advent of all complications while in the compensated phase. This requires maintaining patients in an asymptomatic phase and not significantly affecting their quality of life with minimal impairment due to the therapies themselves. This could be achieved with lifestyle changes and combinations of already licensed and low-cost drugs, similar to the paradigm of treating risk factors for cardiovascular disease. The drugs are propranolol, simvastatin, norfloxacin, and warfarin, which in combination would cost £128/patient annually-equivalent to U.S. $196/year. This treatment strategy requires randomized controlled trials to establish improvements in outcomes. In the 21st century, cirrhosis should be regarded as a potentially treatable disease with currently available and inexpensive therapies.
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A clinical audit was undertaken in the form of a cross-sectional study to evaluate the compliance on appropriate antibiotic prescription and strict adherence to Hospital Antibiotic Policy for therapeutic management of the patients infected with urinary Escherichia coli ESBL producers.
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Quinolone-based antibacterial chemoprophylaxis protected patients from aerobic gram-negative bacillary infections. Augmentation of the gram-positive activity reduced the incidence of gram-positive infections but did not influence the overall incidence of febrile neutropenic episodes.
Intensive care unit (ICU) in a general hospital.
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A method for the simultaneous analysis of antibiotics, antiviral and nasal decongestants in treated sewage effluent and surface water has been developed and validated. The method uses on-line solid phase extraction (SPE) of injected high-volume samples in conjunction with liquid chromatography-tandem mass spectrometry (LC-MS/MS). This method includes a range of antibiotics (Trimethoprim, Oxytetracycline, Ofloxacin, Norfloxacin, Ciprofloxacin, Azithromycin, Doxycycline, Sulfamethoxazole, Erythromycin and Clarithromycin), an antiviral (Oseltamivir) and nasal decongestants (Naphazoline, Oxymetazoline and Xylometazoline). The method's detection limits (MDLs) ranged from (0.2 ng L(-1)) to (3.1 ng L(-1)), based on a 1 mL extraction volume. Its intra-day precision was determined by performing nine runs with 200 ng L(-1) samples; the intra-day relative standard deviation (RSD) ranged from 1% to 19%. Inter-day precision was determined by analyzing samples in triplicate over the course of three days, yielding relative standard deviations ranging from <5% to <26%. The linearity (R(2)) for all compounds tested was >0.90. Spike relative recoveries ranged from 40% to 157% and 40% to 152% for STP effluent and surface water samples, respectively. Finally, the method was used to analyze real effluent and surface water.
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Fluoroquinolone resistance that arose in the test strain during ciprofloxacin therapy of experimental Staphylococcus aureus endocarditis was studied. In two isolates, resistance was due to a decreased sensitivity of the process of DNA synthesis to fluoroquinolones, suggesting the presence of an altered DNA gyrase. Another isolate had an enhanced energy-dependent mechanism, possibly an efflux system, by which cell-associated [3H]norfloxacin was reduced. When a 2.7-kb SphI-KpnI chromosomal fragment from this organism was cloned into pUC19, fluoroquinolone resistance was expressed in an Escherichia coli host, and such organisms acquired an energy-dependent ability to reduce cell-associated [3H]norfloxacin. Lack of homology between this DNA and other cloned gyrA genes indicated that its protein products are distinct from the gyrA protein. S. aureus has the capability of decreasing the quantity of cell-associated fluoroquinolone. An enhancement of this system by an as yet undefined mechanism and an alteration in DNA gyrase are two means by which this organism can develop resistance to fluoroquinolones.
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The anaphylactoid reaction in our patient was probably induced by ciprofloxacin as validated by the Naranjo probability scale. Although anaphylactoid/anaphylactic reactions are rare adverse effects of ciprofloxacin and other fluoroquinolones, clinicians should be aware of this potentially fatal event.
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The concomitant administration to broilers of ionophore coccidiostats and certain chemotherapeutic agents may cause deleterious interactions, with toxicosis and death as possible sequelae. In this study, co-administration of the ionophore monensin was not shown to alter blood levels of enrofloxacin or norfloxacin. In addition, exposure to lasalocid was not shown to change blood levels of enrofloxacin. However, norfloxacin + lasalocid co-administration induced aminopyrine N-demethylase (AD) activity by day 5 after the last administration of norfloxacin, and induced a rise of norfloxacin levels in the blood. This rise of blood norfloxacin levels after co-administration of norfloxacin + lasalocid implies that lower levels of norfloxacin could be administered in birds also receiving lasalocid.
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All 118 (100%) of the ascitic fluid samples demonstrated absolute neutrophil counts of <250/mm3 (mean = 6.5 +/- 22.5 pmn/mm3). Asymptomatic bacterascites was identified from three of the 118 (2.5%) fluid samples, but all of these subjects spontaneously recovered without treatment or sequelae. During follow-up, six episodes of symptomatic or hospital-associated peritoneal fluid infection were identified in study participants, emphasizing the importance of fluid studies in other clinical settings.