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Microbiology Laboratories in 15 County Hospitals in the province of Barcelona.
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The effect of a single day treatment with 600 mg norfloxacin 600 mg ofloxacin or 1,920 mg trimethoprim-sulfamethoxazol was determined on 114 patients with acute cystitis. The overall clinical efficacy was excellent in 101 patients (89%), moderate in 9 patients (8%) and poor in 4 patients (3%). Recurrence was observed in 8 cases (8%) within 6 weeks after the treatment. The effectiveness rate and the recurrence rate were inferior in those caused by S. epidermidis compared with those caused by E. coli.
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One hundred eleven patients with advanced cirrhosis (at least 2 of the following: ascites, severe malnutrition, encephalopathy, or bilirubin >3 mg/dL) and gastrointestinal hemorrhage were randomly treated with oral norfloxacin (400 mg twice daily; n = 57) or intravenous ceftriaxone (1 g/day; n = 54) for 7 days. The end point of the trial was the prevention of bacterial infections within 10 days after inclusion.
Peritonitis in patients with ascites in the absence of secondary causes, such as peforation of a viscus, occurs primarily in patients with end-stage liver disease. Enteric organisms, mainly gram-negative bacilli, probably translocate to regional lymph nodes to produce bacteremia and seeding of ascitic fluid. Signs and symptoms of peritonitis are usually subtle. The ascitic fluid polymorphonuclear leukocyte count is the best determinant for early diagnosis and treatment of SBP. Third-generation cephalosporins such as cefotaxime are considered the drugs of choice for treatment, whereas quinolones such as norfloxacin are used to decrease recurrence.
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AM-833 showed potent activity against members of the family Enterobacteriaceae, Neisseria spp., and Haemophilus influenzae and good activity against staphylococci, Pseudomonas aeruginosa, and Branhamella catarrhalis. Against these bacteria, its activity was roughly comparable to that of norfloxacin and ofloxacin but was slightly less potent than that of ciprofloxacin. This compound also showed good activity against drug-resistant strains such as methicillin-resistant Staphylococcus aureus and gentamicin-resistant Pseudomonas aeruginosa. The protective effects of a single oral dose of AM-833 on systemic bacterial infections in mice were greater than those of norfloxacin. AM-833 was as effective as ofloxacin and ciprofloxacin against systemic infections with Escherichia coli and Pseudomonas aeruginosa, and it showed somewhat higher activity against staphylococcal infections than did the other quinolones. AM-833 exhibited good prophylactic activity against E. coli infections. AM-833 also proved effective against localized infections such acute pneumonia and ascending urinary tract infections in mice. The excellent therapeutic efficacy of AM-833 against these systemic and local infections may be a result of its good oral absorption and high levels in tissues.
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The fluoroquinolones have become attractive options as treatment for a broad range of infections caused by Gram-negative bacteria. However, the value of these antibiotics to patients with infections caused by Gram-positive pathogens remains controversial. Experience with quinolones as therapy for skin and skin structure infections, osteomyelitis and peritonitis in patients receiving continuous ambulatory peritoneal dialysis suggests that the concerns which have been expressed about the use of these agents against methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis and streptococci are justified; indeed, the frequent emergence of quinolone-resistant strains of MRSA and coagulase-negative staphylococci either during or following treatment is now well documented. The fluoroquinolones should be prescribed with caution to patients with community-acquired pneumonia or whenever severe infection of pneumococcal aetiology is proven or suspected. As prophylaxis for the granulocytopenic patient, quinolones such as norfloxacin and ciprofloxacin have been shown to be effective in reducing the incidence of morbidity attributable to Gram-negative bacteria, but they have not significantly affected the incidence of infection caused by Gram-positive bacteria. In the treatment of febrile episodes in the neutropenic patient, ciprofloxacin, the quinolone investigated most extensively in this clinical setting, produced high cure rates only when it was combined with an antibiotic which was predictably active against Gram-positive organisms. We review here the role of currently-available fluoroquinolones (norfloxacin, enoxacin, pefloxacin, ofloxacin and ciprofloxacin) as treatment for these and other infections.
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In vitro drug release showed a typical trend of swelling systems. Precorneal retention tests showed that TRH/NAT microspheres maintained fluorescence in tear fluid for 81.7 min, whereas TRH/GLT microspheres and water solution maintained fluorescence for 51.8 and 22.3 min, respectively. NOR released from microspheres permeated throughout RHC slower (J(s) = 23.08 microg/cm(2)h) than NOR from commercial eye drops (J(s) = 42.77 microg/cm(2)h) used as the control.
A laser flash photolysis investigation was carried out on the mechanism of electron photoejection in fluoroquinolone derivatives, bearing either electron donating or electron accepting substituents in position 8, laser excited at lambda(exc) = 355 nm in neutral aqueous solutions. The dependence of the hydrated electron absorption at 720 nm on the laser intensity and on the presence of N2O as electron scavenger evidenced that in enoxacin, norfloxacin, and lomefloxacin the photoionization is predominantly two-photon. With rufloxacin, besides the two-photon process, a one photon contribution with a quantum yield of 0.034 was measured.
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Fifty patients were randomized to receive either lansoprazole or omeprazole, with norfloxacin for 2 wk; the ulcer healing rates, H. pylori eradication rates, and recurrence rates were compared over a 6-month period.
We performed a 5-year retrospective study to evaluate the effect of long-term administration of norfloxacin on the epidemiology of severe hospital-acquired infections in patients with advanced cirrhosis. Sixty-seven episodes of spontaneous bacterial peritonitis and 60 episodes of bacteremia occurred in, respectively, 46 patients (group 1a) and 52 patients (group 1b) who did not receive norfloxacin, while 23 and 17 episodes occurred in 21 patients (group 2a) and 17 patients (group 2b) during or within 10 days after long-term administration of norfloxacin. Enterobacteriaceae were more prevalent in groups 1a and 1b than in the other two groups (P < .001 and P < .01, respectively); conversely, staphylococci were more prevalent in groups 2a and 2b (P < .001 and P < .05, respectively). The rate of staphylococcal resistance to methicillin was 53.6% in groups 1a and 1b and 77.3% in groups 2a and 2b. We conclude that long-term norfloxacin administration to cirrhotic patients reduces the risk of gram-negative infections but increases the risk of severe hospital-acquired staphylococcal infections and of high-level resistance to antibiotics.
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A simple and rapid ultrasound-assisted dispersive liquid-liquid microextraction (UA-DLLME) coupled with liquid chromatography-ultraviolet detection (LC-UV) was developed for the determination of four fluoroquinolones (ofloxacin, norfloxacin, enrofloxacin, and lomefloxacin) in pharmaceutical wastewater samples. Various parameters affecting the extraction efficiency including type and volume of extraction and dispersive solvents, sample pH, and extraction time were investigated. Good linear relationships were obtained for all analytes in a range of 0.01-2.0 μg/ml with LODs ranged from 0.14 to 0.81 μg/l. Average recoveries at three spiking levels were over the range of 82.7-110.9% with RSD less than 5.2% (n=3). Under the optimized conditions the enrichment factors for the four fluoroquinolones were ranged from 32 to 134 folds. The presented method was applied for the determination of four fluoroquinolones in pharmaceutical wastewater samples.
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In order to investigate the comparative activity of agents of the nalidixic acid series, cultures of nalidixic acid sensitive strains of E. coli were exposed to the drugs in an in-vitro model that simulates the hydrokinetic aspects of the treatment of bacterial cystitis. Intrinsic activity, as judged by the response to a single dose of drug and resistance as judged by response to a repeat dose, were investigated. All seven compounds tested in this way were able to inhibit bacterial growth for considerable periods of time even when the peak concentration achieved was as low as 10 mg/l. However, resistance emerged readily, particularly to nalidixic acid, pipemidic acid and piromidic acid. Norfloxacin was the most active of the seven compounds tested and was the only one to which resistance did not emerge at the concentrations tested. However, when two nalidixic acid resistant strains were tested in the bladder model, norfloxacin resistance was observed to emerge with one strain, but not with the other.
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The in vitro activities of 20 fluoroquinolones against Mycobacterium leprae were evaluated by using the BACTEC 460 system. M. leprae was incubated in BACTEC 12B medium at 33 degrees C under reduced oxygen for 2 to 3 weeks in the presence of fluoroquinolones at 0.31 to 5 micrograms/ml. Activity was determined by a reduction in 14CO2 evolution compared with that of drug-free controls. Of the commercially available agents, ofloxacin was most active, while enoxacin and norfloxacin were inactive. However, a number of newer fluoroquinolones (AT-4140, OPC-17100, OPC-17066, PD-117596, PD-124816, PD-127391, and WIN-57273), all containing a cyclopropyl group at R-1 and, with the exception of WIN-57273, either a halogen or methyl group at R-8, were more active than ofloxacin in vitro. Further in vivo evaluations of these agents should help determine their potential for use against leprosy.
Forty-one adult women with acute lower urinary tract infections (UTI) were randomly treated for three days with norfloxacin or trimethoprim/sulfamethoxazole (TMP/SMX). Infection was eradicated in 100% of norfloxacin-treated patients and in 95% of TMP/SMX-treated patients. UTI recurred in 29% of patients treated with norfloxacin and in 41% of those treated with TMP/SMX. Post-therapy vaginal administration of lactobacillus suppositories resulted in a recurrence rate of UTI of only 21%, while in patients given sterilized skim-milk suppositories the recurrence rate was 47%. This study indicates that lactobacillus vaginal suppositories are safe and may be effective in reducing the recurrence of UTI following antimicrobial therapy.
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CDMN both improves the isolation rate of C difficile from faecal specimens and reduces the growth of other organisms compared with CCFA.
The frequencies of isolation and susceptibilities to antimicrobial agents were investigated on 751 bacterial strains isolated from patients with urinary tract infections in 11 hospitals during the period of June 1991 to May 1992. Of the above total bacterial isolates, Gram-positive bacteria accounted for 28.6% and a majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for 71.4% and most of them were Escherichia coli. 1. Enterococcus faecalis Ampicillin (ABPC), imipenem (IPM) and vancomycin (VCM) showed the highest activities against E. faecalis isolated from patients with urinary tract infections. The MIC90s of them were 2 micrograms/ml. Piperacillin (PIPC) and chloramphenicol (CP) were also active with the MIC90s of 8 micrograms/ml. The others were not so active with the MIC90s of 32 micrograms/ml or above. 2. Staphylococcus aureus including MRSA Arbekacin (ABK) showed the highest activities against S. aureus isolated from patients with urinary tract infections. Its MIC90 was 0.5 microgram/ml. VCM was also active with its MIC90 of 1 microgram/ml. The others were not so active with the MIC90s of 32 micrograms/ml or above. 3. Citrobacter freundii Ciprofloxacin (CPFX) showed the highest activities against C. freundii isolated from patients with urinary tract infections. Its MIC90 was 0.5 microgram/ml. IPM, gentamicin (GM), ABK and norfloxacin (NFLX) were also active with the MIC90s of 1 microgram/ml. Penicillins and cephems were not so active. 4. Enterobacter cloacae IPM showed the highest activities against E. cloacae isolated from patients with urinary tract infections. Its MIC90 was 0.5 microgram/ml. CPFX was also active with the MIC90 of 2 micrograms/ml. Aminoglycosides were active comparatively. The MIC90s of them were 4 micrograms/ml. Penicillins and cephems generally showed lower activities. 5. Escherichia coli IPM and ciprofloxacin (CPFX) showed the highest activities against E. coli isolated from patients with urinary tract infections. The MIC90s of them were 0.125 micrograms/ml or below. Flomoxef (FMOX), cefmenoxime (CMX), cefuzonam (CZON), latamoxef (LMOX), norfloxacin (NFLX) and ofloxacin (OFLX) were also active with the MIC90s of 0.25 microgram/ml. Penicillins except mecillinam (MPC) were not so active showing the MIC90s of 32 micrograms/ml or above. 6. Klebsiella pneumoniae IPM showed the highest activities against K. pneumoniae isolated from patients with urinary tract infections. Its MIC90 was 0.25 microgram/ml. Gentamicin (GM) and arbekacin (ABK) were also active with the MIC90s of 0.5 microgram/ml, respectively. But minocycline (MINO) and penicillins were not so active showing the MIC90s of 32 micrograms/ml or above. 7. Proteus mirabilis Most of the agents were active against P. mirabilis.(ABSTRACT TRUNCATED AT 400 WORDS)
A high-performance liquid chromatographic method for the simultaneous determination of ofloxacin, norfloxacin and ciprofloxacin in human hair is described. A reversed-phase C18 column and a fluorescence detector with switching fluorescence wavelengths were used together with solid-phase extraction of the drugs from hair dissolved in 1 M sodium hydroxide. Reproducibility and linearity studies yielded coefficients of variation of 0.2-2.2, 1.4-3.1 and 1.5-3.4%, and correlation coefficients of 1.000, 0.999 and 0.999 within the concentration range 0.3-100 ng/ml for ofloxacin, norfloxacin and ciprofloxacin, respectively. For validation, hair samples were obtained from six subjects who had been taking one or two of the three fluoroquinolones. Assuming a hair growth-rate of 1 cm per month fluoroquinolones could be detected in the hair section(s) that had grown approximately between the dates of drug administration and hair sampling.
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The phototoxic fluoroquinolones ofloxacin, lomefloxacin, norfloxacin, ciprofloxacin and BAYy 3118 have ionizable groups with pKa values close to neutrality. Different ionic species of these fluoroquinolones, therefore, partition in various compartments and organelles of living cells according to their ionic equilibria. While all these fluoroquinolones accumulate in lysosomes, they more or less stain the rest of the cytoplasm of living HS 68 fibroblasts. As a result, photosensitized damage to other cytoplasmic sites than lysosomes can also be expected. Using microfluorometry and rhodamine 123 (Rh 123) as a specific fluorescent probe which is released from mitochondria by light absorption, we show that under ultraviolet A (UVA) irradiation norfloxacin and ciprofloxacin readily damage mitochondrial membranes. as evidenced by the UVA dose-dependent strongly accelerated release of Rh 123 from mitochondria in cells treated with norfloxacin and ciprofloxacin. Damages are already noticeable at UVA doses as low as 2 J/cm2. By contrast, no such photoinduced damage can be observed with ofloxacin, lomefloxacin and BAYy 3118, the latter being the most phototoxic derivative towards HS 68 fibroblasts. The initial photodamage induced by norfloxacin and ciprofloxacin can then propagate after the irradiation as shown by the strongly increased rate of release of Rh 123 from mitochondria of cells that have been incubated with these two fluoroquinolones and left in the dark after a pre-irradiation with 18 J/cm2 of UVA. Interestingly, the same pre-irradiation after cells have been treated with BAYy 3118 and lomefloxacin induces similar post-irradiation effects, although they have no apparent immediate photosensitizing action on mitochondria.
Enterohemorrhagic Escherichia coli (EHEC) O157:H7 infection causes severe clinical symptoms, due to its bacterial toxin, called Shiga-like toxin (SLT). However, little is known about the information to establish a safe and efficient prescription to treat for EHEC O157:H7 patients. Thus, we investigated the effect of SLT-II on intestinal function in rats by using the antibiotic norfloxacin (NFLX) as a model drug. The intestinal clearance (CLi) of NFLX, determined by loop method in the jejunum, was significantly decreased by SLT-II. In histopathological experiment, epithalaxia was observed in SLT-II-treated rats without structural changes of tight junction suggesting the deterioration of active transport systems by SLT-II. CLi of NFLX in normal rats was decreased by carnitine (CAR), suggesting the possible involvement of CAR-sensitive transporter in CLi of NFLX. Taken together, these results suggest that the EHEC O157:H7 infection might affect the intestinal disposition of NFLX due to the changing intestinal expression/function of drug transporters by SLT-II.
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Burkina Faso is one of the Subsaharan African nations. No national services for monitoring of antibiotic resistance are available, so the number of reports of resistance patterns among hospital pathogens are inconsistent. In order to evaluate antibiotic resistance, a total of 1998 valuable microrganisms were analysed during 2000 at the Medical Centre St. Camille of Ouagadougou, Burkina Faso's capital. They were isolated as follows: 1012 from urine-culture, 503 from tonsil swabs, 398 from pus, 53 from sputum and 32 from blood-cultures. Escherichia coli was the most isolated microrganism from urine (44%); Enterococcus faecalis from tonsil swabs (96.4%), Staphylococcus aureus from pus (17%) and K. pneumoniae (70%) from sputum. In general, resistance to the old antibiotics, such as aminopenicillins and cotrimoxazole was shown. The most active antibiotic was norfloxacin, a rarely used antibiotic in this country. In conclusion, our study shows that it is necessary to create antibiotic-resistance surveillance centers in the developing countries to adopt an accurate therapy to avoid exporting of antibiotic resistance to the developed countries linked to increased emigration.