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Levofloxacin

Distribution by Scientific Domains

Medical Sciences	85%
Chemistry	11%
Life Sciences	3%

Distribution within Medical Sciences

Gastroenterology & Hepatology	29%
Cardiovascular Disease	5%
13 Other Subdomains	61%

Selected Abstracts

Characterization of Histamine Release Induced by Fluoroquinolone Antibacterial Agents In-vivo and In-vitro

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2000
KAZUHIKO MORI
Characterization of histamine release induced by fluoroquinolone antibacterial agents, levofloxacin and ciprofloxacin, was investigated in-vivo and in-vitro. Intravenous injection of levofloxacin and ciprofloxacin at 1,10 mg kg,1 produced dose-related elevations in plasma histamine level in anaesthetized dogs. In contrast, levofloxacin was devoid of plasma histamine increment in anaesthetized rats at 100 mg kg,1, whereas ciprofloxacin at the same dose caused endogenous histamine release. Levofloxacin and ciprofloxacin induced non-cytotoxic secretion of histamine from all mast cells tested in a concentration-dependent manner, whereas rat skin and peritoneal mast cells were thirty- to one-hundred-times less sensitive to the effect of fluoroquinolones as compared with the canine skin mast cells. These results suggest that the functional heterogeneity of mast cells from different species in histamine releasing activity of fluoroquinolones may exist, and that mast cells from the dog appear to be particularly sensitive to the effect of the fluoroquinolones. [source]

Clinical trial: clarithromycin vs. levofloxacin in first-line triple and sequential regimens for Helicobacter pylori eradication

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2010
J. MOLINA-INFANTE
Aliment Pharmacol Ther,31, 1077,1084 Summary Background,Helicobacter pylori eradication rates with standard triple therapy have declined to unacceptable levels. Aim, To compare clarithromycin and levofloxacin in triple and sequential first-line regimens. Methods, A total of 460 patients were randomized into four 10-day therapeutic schemes (115 patients per group): (i) standard OCA, omeprazole, clarithromycin and amoxicillin; (ii) triple OLA, omeprazole, levofloxacin and amoxicillin; (iii) sequential OACM, omeprazole plus amoxicillin for 5 days, followed by omeprazole plus clarithromycin plus metronidazole for 5 days; and (iv) modified sequential OALM, using levofloxacin instead of clarithromycin. Eradication was confirmed by 13C-urea breath test. Adverse effects and compliance were assessed by a questionnaire. Results, Per protocol cure rates were: OCA (66%; 95% CI: 57,74%), OLA (82.6%; 75,89%), OACM (80.8%; 73,88%) and OALM (85.2%; 78,91%). Intention-to-treat cure rates were: OCA (64%; 55,73%), OLA (80.8%; 73,88%), OACM (76.5%; 69,85%) and OALM (82.5%; 75,89%). Eradication rates were lower with OCA than with all the other regimens (P < 0.05). No differences in compliance or adverse effects were demonstrated among treatments. Conclusions, Levofloxacin-based and sequential therapy are superior to standard triple scheme as first-line regimens in a setting with high clarithromycin resistance. However, all of these therapies still have a 20% failure rate. [source]

Levofloxacin Induced Polymorphic Ventricular Tachycardia with Normal QT Interval

PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 5 2001
BRENDON PALTOO
PALTOO, B., et al.: Levofloxacin Induced Polymorphic Ventricular Tachycardia with Normal QT Interval. Polymorphic ventricular tachycardia (PVT) is a form of ventricular tachycardia characterized by QRS complexes that seem to change direction during the tachycardia. If associated with a prolonged QT interval, it is called torsades de pointes. In the absence of a congenital long QT syndrome, torsades is seen with certain drugs such as antiarrythmic agents (Class IA, IC, III), psychotropic medications, antidepressants, antihistamines, and electrolyte disturbances. We report the first case of polymorphic ventricular tachycardia with normal QT interval associated with the oral use of levofloxacin in the absence of other etiologies known to cause these arrhythmias. [source]

Corneal penetration of simultaneously applied topical levofloxacin, norfloxacin and lomefloxacin in human eyes

ACTA OPHTHALMOLOGICA, Issue 2 2006
Masakazu Yamada
Abstract. Purpose:,This study was performed to assess the corneal penetration of three topically applied fluoroquinolones (levofloxacin, norfloxacin and lomefloxacin) in corneal buttons obtained from patients undergoing penetrating keratoplasty. Methods:,Fourteen patients received three drops each of 0.5% levofloxacin, 0.3% norfloxacin and 0.3% lomefloxacin (the standard clinically available preparations) over a 30-min interval beginning 90 mins before their scheduled keratoplasty. Corneal samples obtained from excised buttons at the time of surgery were stored at , 80 ° until analysis. The concentration of the administered fluoroquinolones was measured using high-performance liquid chromatography. Results:,The mean corneal concentration of levofloxacin (4.6 ± 3.5 µg/g, mean ± standard deviation) was significantly higher than that of lomefloxacin (2.7 ± 1.8 µg/g, p = 0.0018) and norfloxacin (1.3 ± 1.2 µg/g, p = 0.00012). Conclusion:,Levofloxacin achieves a higher mean corneal concentration than norfloxacin and lomefloxacin in the human cornea. [source]

Photophysical and Phototoxic Properties of the Antibacterial Fluoroquinolones Levofloxacin and Moxifloxacin

CHEMISTRY & BIODIVERSITY, Issue 5 2004
Giampietro Viola
Two antibacterial fluoroquinolones, levofloxacin and moxifloxacin, were investigated to evaluate their photophysical properties and to explore the mechanism of their phototoxicity. Photophysical experiments were carried out in aqueous solution by stationary and time-resolved fluorimetry, and by laser flash photolysis, to obtain information on the various decay pathways of the excited states of the drugs and on transient species formed upon irradiation. The results obtained show that levofloxacin is able to photosensitize red blood cell lysis in an oxygen-independent way and induce a high decrease in cell viability after UVA irradiation, although to a lesser degree than the racemic mixture ofloxacin. Moxifloxacin, which is an 8-MeO-substituted fluoroquinolone, is less phototoxic than the other compounds. Cellular phototoxicity was inhibited by the addition of superoxide dismutase, catalase, and free radical and hydroxyl radical scavengers (BHA, GSH, mannitol, and DMTU), indicating the involvement of superoxide anion and/or a radical mechanism in their cytotoxicity. A good correlation was observed between lipid peroxidation, protein photodamage, and cellular phototoxicity, indicating that test compounds exert their toxic effects mainly in the cellular membrane. Experiments carried out on pBR322 DNA show that these derivatives do not significantly photocleave DNA directly, but single-strand breaks were evidenced after treatment of photosensitized DNA by two base-excision-repair enzymes, and Endo III. [source]

Multiple fixed drug eruption due to drug combination

CONTACT DERMATITIS, Issue 6 2005
A. Yokoyama
We report the case of a multiple fixed drug eruption (FDE) after taking 1 g of PL® and 100 mg of levofloxacin (Cravit®) at the same time. Patch tests with PL® alone, levofloxacin alone and the combination of PL® and levofloxacin were all negative on the involved and uninvolved sites. Lymphocytic stimulation tests were also negative for PL® alone, levofloxacin alone and the combination of PL® and levofloxacin. Oral provocation tests with PL®alone or levofloxacin alone produced no reactivation. However, we could provoke multiple erythematous plaques on the involved areas by taking a 1/10th dose of the combination of PL® and levofloxacin at the same time. Drug eruption due to a drug combination appears to be very rare. This is the first case of multiple FDE caused by taking PL® -levofloxacin combination. [source]

Toxicity of fluoroquinolone antibiotics to aquatic organisms

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2005
April A. Robinson
Abstract Toxicity tests were performed with seven fluoroquinolone antibiotics, ciprofloxacin, lomefloxacin, ofloxacin, levofloxacin, clinafloxacin, enrofloxacin, and flumequine, on five aquatic organisms. Overall toxicity values ranged from 7.9 to 23,000 ,g/L. The cyanobacterium Microcystis aeruginosa was the most sensitive organism (5-d growth and reproduction, effective concentrations [EC50s] ranging from 7.9 to 1,960 ,g/L and a median of 49 ,g/L), followed by duckweed (Lemna minor, 7-d reproduction, EC50 values ranged from 53 to 2,470 ,g/L with a median of 106 ,g/L) and the green alga Pseudokirchneriella subcapitata (3-d growth and reproduction, EC50 values ranged from 1,100 to 22,700 ,g/L with a median 7,400 ,g/L). Results from tests with the crustacean Daphnia magna (48-h survival) and fathead minnow (Pimephales promelas, 7-d early life stage survival and growth) showed limited toxicity with no-observed-effect concentrations at or near 10 mg/L. Fish dry weights obtained in the ciprofloxacin, levofloxacin, and ofloxacin treatments (10 mg/L) were significantly higher than in control fish. The hazard of adverse effects occurring to the tested organisms in the environment was quantified by using hazard quotients. An estimated environmental concentration of 1 ,g/L was chosen based on measured environmental concentrations previously reported in surface water; at this level, only M. aeruginosa may be at risk in surface water. However, the selective toxicity of these compounds may have implications for aquatic community structure. [source]

Failure of Helicobacter pylori Treatment After Regimes Containing Clarithromycin: New Practical Therapeutic Options

HELICOBACTER, Issue 6 2008
Bruno Sanches
Abstract Failure of Helicobacter pylori treatment is a growing problem in daily practice. Aim:, To evaluate the efficacy of two new regimes as second-line options in a randomized and prospective study. Methods:, Patients in whom a first eradication regime containing clarithromycin had failed were included. After performing gastroscopy and a 13C-urea breath test (UBT), the patients were randomized to receive a combination of 20 mg of rabeprazole, 500 mg of levofloxacin, and 200 mg (two tablets) of furazolidone administered once daily for 10 days (RLF) or the combination of 20 mg of rabeprazole, 120 mg (two tablets) of bismuth subcitrate, 100 mg of doxycycline, and 200 mg of furazolidone, administered twice daily for 10 days (RBDF). Clinical examinations and new UBT were performed 60 days after therapy. Results:, Sixty patients were included (mean age, 46 years, 57% females). Two patients were excluded: one because of adverse effects and another as a result of protocol violation. Compliance was similar in both groups (90% took all medications correctly). Side-effects (96% mild) were observed in 87% of the patients and were comparable between groups, except diarrhea, which was more frequent in group RLF (p= .025). Intention-to-treat cure rates were 77% (95% confidence interval (CI): 62,93%) in the RLF group and 83% (95% CI: 68,97%) in the RBDF group (p= .750). Per-protocol cure rates were 80% (95% CI: 65,95%) in the RLF group and 82% (95% CI: 67,96%) in the RBDF group (p= 1.0). Conclusions:, Both once-daily triple (rabeprazole, levofloxacin, and furazolidone) and twice-daily quadruple therapy (rabeprazole, bismuth subcitrate, doxycycline, and furazolidone) for 10 days achieved encouraging results. Subsequent studies should be performed to evaluate antibiotic resistance, doses, dosing intervals, duration of treatment, and safety of these two regimes. [source]

Helicobacter pylori"Rescue" Therapy After Failure of Two Eradication Treatments

HELICOBACTER, Issue 5 2005
Javier P. Gisbert
ABSTRACT Nowadays, apart from having to know well first-line eradication regimens, we must also be prepared to face Helicobacter pylori treatment failures. Therefore, in designing a treatment strategy we should not focus on the results of primary therapy alone, but also on the final , overall , eradication rate. After failure of a combination of proton pump inhibitor (PPI), amoxicillin, and clarithromycin, the use of empirical quadruple therapy (PPI,bismuth,tetracycline,metronidazole), has been generally used as the optimal second-line therapy. Even after two consecutive failures, several studies have demonstrated that H. pylori eradication can finally be achieved in almost all patients if several "rescue" therapies are consecutively given. It seems that performing culture even after a second eradication failure may not be necessary, as it is possible to construct an overall strategy to maximize H. pylori eradication, based on the different possibilities of empirical treatment (when antibiotic susceptibilities are unknown). Thus, if one does not want to perform culture before the administration of the third treatment after failure of the first two, different empirical treatments exist, including regimens based on: 1, amoxicillin (amoxicillin,PPI at high doses); 2, amoxicillin plus tetracycline (PPI,bismuth,tetracycline,amoxicillin, or ranitidine,bismuth,citrate,tetracyline,amoxicillin); 3, rifabutin (rifabutin,amoxicillin,PPI); 4, levofloxacin (levofloxacin,amoxicillin,PPI); and 5, furazolidone (furazolidone,bismuth,tetracycline,PPI). [source]

Antibiotic prophylaxis in chemotherapy-induced neutropenia: time to reconsider

HEMATOLOGICAL ONCOLOGY, Issue 3 2006
Nangi Lo
Abstract The use of antibiotic prophylaxis in neutropenic patients remains controversial. The main arguments against prophylaxis are the lack of survival benefit and the risk of inducing antibiotic resistance. At present, clinical guidelines advise against routine use of antibiotic prophylaxis and current practice is to commence broad-spectrum antibiotics at the onset of fever in the neutropenic patient. However hospitalization, investigations and treatment all impact on resources as well as affecting patient quality of life, often resulting in chemotherapy delays and dose reductions. The benefits of prophylactic antibiotics have been emphasized by two major double-blind, placebo controlled trials with levofloxacin with very significant reductions in all infection-related events. Furthermore, the meta-analysis confirms a survival advantage and this is greatest with the use of fluoroquinolones. These benefits must be weighed against the problem of emerging antibiotic resistance. It has been shown that antibiotic prophylaxis does induce resistant organisms, but some studies have shown that the impact on clinical outcomes may not be as great as expected. Current evidence supports antibiotic prophylaxis with fluoroquinolones in acute leukaemia and high-dose chemotherapy patients, commencing at the same time as chemotherapy. Febrile episodes are much commoner with the first cycle in patients with solid tumours or lymphoma having moderately myelosuppressive chemotherapy, and these patients should be offered prophylaxis for at least the first cycle of chemotherapy. Further work is ongoing to facilitate the selection of patients with the greatest chance of benefit so that prophylaxis can be used efficiently. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Cutaneous sarcoid-like granulomas with alveolar hemorrhage and c-ANCA PR-3

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 9 2004
Natividade Rocha MD
A 28-year-old woman, employed as a leather factory worker, noted asymptomatic, well-delimited plaques on both knees, 6 years ago. The plaques were violaceous with a smooth surface. One appeared over a post-traumatic scar from childhood (Fig. 1). Two years later, she began to complain of symptoms suggestive of polyarthritis, first of the small joints of the hands (proximal interphalanges) and then of the larger joints (wrists, elbows, and knees). She was diagnosed with rheumatoid arthritis and began treatment with nonsteroidal anti-inflammatory drugs for 1 month without any change. Deflazacort, 12 mg/day, and hydroxychloroquine, 400 mg/day, were administered for 3 months, with improvement of her articular complaints, but not her skin lesions. Figure 1. Well-delimited, violaceous plaques with a smooth surface on the knees, one over an old post-traumatic scar One year later, she complained of dysphonia, which remitted spontaneously after some weeks. After one additional year, she noted papules, with similar characteristics to the plaques, on the elbows, and two well-delimited orange-to-brown plaques on the forehead (Fig. 2). Figure 2. Orange,brown plaques symmetrically placed on the forehead During the fifth year of the disease, she was referred for the first time to a dermatologist, who biopsied one of the knee lesions. The histologic result was compatible with "sarcoid granuloma." At that time, she presented with skin lesions as her only complaint. Sarcoidosis was suspected based on a chest X-ray, which revealed hilar lymphadenopathy and diffuse accentuation of the interstitium. In November 2000, she suddenly developed fever (40 °C), cough with hemoptysis, dysphonia, and subcutaneous nodules on the palmar surface of the fingers of both hands that were painless, well-delimited, 5 mm in diameter, and firm (Fig. 3). She reported a weight loss of 12 kg in the previous 3 months. Pulmonary condensation was found on auscultation, and she had palpable hepatomegaly. Peripheral lymphadenopathy was not present. Figure 3. Painless, well-delimited, firm subcutaneous nodules on the palmar surface of the fingers Laboratory investigations revealed normochromic, normocytic anemia (hemoglobin, 7.7 g/dL), iron deficit, a white blood cell count of 16,000/µL with neutrophilia, an erythrocyte sedimentation rate of 130 mm/h, elevation of liver enzymes, a slight increase in angiotensin-converting enzyme (ACE) level (72 U/L), hypergammaglobulinemia (IgG, 3350 mg/dL), antinuclear antibody (ANA) of 1 : 320, and a slight increase in CD4 and decrease in CD8 lymphocytes with normal cellular morphology in blood. Renal function, urine sediment, urine and serum calcium, complement (C4), dsDNA, antimitochondrial antibody, direct and indirect Coombs test, antineutrophil cytoplasmic antibody (ANCA), tuberculin skin tests, viral markers of hepatitis B, C, and human immunodeficiency virus (HIV), electrocardiogram (ECG), ophthalmic examinations, and culture for infectious agents in blood and sputum were all normal or negative. Computed tomography (CT) scan showed an infiltrate in the upper right pulmonary lobule with a central cavity and bilateral hilar lymphadenopathy (Fig. 4). Homogeneous hepatosplenomegaly was present. The bronchoalveolar lavage (BAL) showed a slight lymphocytic increase predominantly of CD8 cells and hemosiderosis. Stains for infectious agents, including acid-fast bacillus, fungi, Mycoplasma, and Legionella, were negative. Three biopsies from the forehead, elbows, and knees showed well-formed noncaseating epithelioid cell granulomas with giant cells of the Langhans type in the dermis, suggestive of sarcoidosis (Figs 5 and 6). A fourth biopsy from a finger nodule demonstrated inflammatory infiltration of the dermis and necrosis with cellular debris. Vasculitis was not seen (Fig. 7). Figure 4. Computed tomography scan showing an infiltrate in the upper right pulmonary lobule with a central cavity Figure 5. Beneath a flattened epidermis, several sarcoid granulomas composed of epithelioid histiocytes and several multinucleated giant cells of Langhans type can be seen (hematoxylin and eosin, ×10) Figure 6. Less well-formed sarcoid granulomas in a hyperkeratotic area, surrounded by a sparse rim of lymphocytes (hematoxylin and eosin, ×20) Figure 7. Foci of necrosis and fibrinoid degeneration with some neutrophil infiltration and nuclear dusting (hematoxylin and eosin, ×40) The patient was treated with a broad-spectrum empirical antimicrobial (levofloxacin, 500 mg daily intravenously) over 12 days, with prompt improvement in her symptoms and remission of the forehead and finger lesions. Nevertheless, on the first evaluation after hospitalization, the CT scan showed persistence of the pulmonary cavity (Fig. 8). A repeat ANCA determination was positive (cytoplasmic pattern, c-ANCA) at 1 : 640 by indirect immunofluorescence (IIF). Antiproteinase-3 antibody was demonstrated at 78 by enzyme-linked immunosorbent assay (ELISA). Figure 8. Computed tomography scan showing persistence of the pulmonary cavity She underwent an open lung biopsy which revealed intra-alveolar hemorrhage and scanty noncaseating epithelioid cell granulomas of the sarcoidosis type in the peripheral blood vessels without vasculitis. A diagnosis of Wegener's granulomatosis was made and she began prednisolone (1 mg/kg/day) and oral cyclophosphamide (2 mg/kg/day). One year later, she is asymptomatic, the skin lesions have completely remitted, c-ANCA is negative, and the CT scan shows partial regression of the pulmonary cavity. [source]

Treatment of men with urethritis negative for Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma parvum and Ureaplasma urealyticum

INTERNATIONAL JOURNAL OF UROLOGY, Issue 5 2007
Shin-Ichi Maeda
Objective: Some patients with symptomatic non-gonococcal urethritis (NGU) are negative for Chlamydia trachomatis, mycoplasmas and ureaplasmas. The optimal antimicrobial chemotherapy for such NGU has not fully been elucidated, though many studies of antimicrobial chemotherapies for C. trachomatis -positive NGU have been performed. We assessed the efficacy of antimicrobial agents that are active against C. trachomatis on non-mycoplasmal, non-ureaplasmal and non-chlamydial NGU (NMNUNCNGU). Methods: One hundred men whose first-pass urine samples were negative for C. trachomatis, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma parvum, and Ureaplasma urealyticum were treated with levofloxacin, gatifloxacin, minocycline, or clarithromycin for 7 days. Urethritis symptoms and the presence of polymorphonuclear leukocytes (PMNL) in urethral smears were assessed before and after treatment. Results: Eighty-eight (88.0%) of 100 men with NMNUNCNGU showed no signs of urethral inflammation after treatment, but two men complained of some symptoms of urethritis. Twelve (12.0%) of 100 men had significant numbers of PMNL in urethral smears, but five of these 12 men had no symptoms of urethritis. The efficacy for normalization of urethral smears was 90.7% for clarithromycin, 89.7% for levofloxacin, 87.5% for gatifloxacin, and 75.0% for minocycline. The 12 men who showed signs of urethral inflammation were retreated with levofloxacin, gatifloxacin, minocycline or clarithromycin for an additional 7 days. The 10 men who returned after the second treatment had negative urethral smears. Conclusion: Our present findings suggest that antimicrobial agents active against C. trachomatis are effective against NMNUNCNGU and that a 7-day treatment regimen with an appropriate antimicrobial agent may be sufficient to manage patients with NMNUNCNGU. [source]

Acute urethritis caused by Neisseria meningitidis

INTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2003
NORIYUKI KANEMITSU
Abstract A 48-year-old heterosexual Japanese man visited the outpatient clinic of Nagoya Urology Hospital, complaining of burning pain at voiding and pus discharge from the urethral orifice. These symptoms appeared the day following oral-genital contact (fellatio) with a commercial sex worker. On the basis of the presumptive clinical diagnosis of gonorrhea because of the microscopic detection of diplococci in the urethral discharge, he was treated with levofloxacin (300 mg per day) for 7 days. His symptoms responded quickly and urinalysis taken 7 days later was normal. Microbiological examinations isolated Neisseria meningitidis in the urethral discharge by culture with the use of enzymatic profiles. Further prevalence of sexually transmitted diseases (STD) through oral-genital contact would lead to an increase in meningococcal urethritis. [source]

Proarrhythmia as a Class Effect of Quinolones: Increased Dispersion of Repolarization and Triangulation of Action Potential Predict Torsades de Pointes

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2007
PETER MILBERG M.D.
Background: Numerous noncardiovascular drugs prolong repolarization and thereby increase the risk for patients to develop life-threatening tachyarrhythmias of the torsade de pointes (TdP) type. The development of TdP is an individual, patient-specific response to a repolarization-prolonging drug, depending on the repolarization reserve. The aim of the present study was to analyze the underlying mechanisms that discriminate hearts that will develop TdP from hearts that will not develop TdP. We therefore investigated the group of quinolone antibiotics that reduce repolarization reserve via IKr blockade in an intact heart model of proarrhythmia. Methods and Results: In 47 Langendorff-perfused, AV-blocked rabbit hearts, ciprofloxacin (n = 10), ofloxacin (n = 14), levofloxacin (n = 10), and moxifloxacin (n = 13) in concentrations from 100 ,M to 1,000 ,M were infused. Eight monophasic action potentials (MAPs) and an ECG were recorded simultaneously. After incremental pacing at cycle lengths from 900 ms to 300 ms to compare the action potential duration, potassium concentration was lowered to provoke TdP. All antibiotics led to a significant increase in QT interval and MAP duration, and exhibited reverse-use dependence. Eight simultaneously recorded MAPs demonstrated an increase in dispersion of repolarization in the presence of all antibiotics. MAP triangulation (ratio: MAP90/50) and fluctuation of consecutive action potentials were increased for all tested drugs at high concentrations. In the presence of low potassium concentration, all quinolones led to TdP: ciprofloxacin, 4 out of 10 (40%); ofloxacin, 3 out of 14 (21%); moxifloxacin, 9 out of 13 (69%); and levofloxacin, 2 out of 10 (20%). Hearts that developed TdP demonstrated a significant greater influence on dispersion of repolarization and on triangulation as compared with hearts without TdP. Conclusion: Quinolone antibiotics may be proarrhythmic due to a significant effect on myocardial repolarization. The individual response of a heart to develop TdP in this experimental model is characterized by a greater effect on dispersion of repolarization and on triangulation of action potential as compared with hearts that do not develop TdP. [source]

A general method for the fluorine-18 labelling of fluoroquinolone antibiotics

JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 8 2003
Oliver Langer
Abstract Fluoroquinolones are an important class of antibiotic agents with a broad spectrum of antibacterial activity. Labelling of fluoroquinolones with fluorine-18 is of interest for the performance of pharmacokinetic measurements and the visualization of bacterial infections in humans with positron emission tomography. A two-step radiosynthetic pathway to prepare fluorine-18-labelled ciprofloxacin (1-cyclopropyl-6-[18F]fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-quinoline-3-carboxylic acid) has previously been developed. In the present work this approach was applied to the preparation of the structurally related compounds [18F]norfloxacin (1-ethyl-6-[18F]fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-quinoline-3-carboxylic acid) and [18F]pefloxacin (1-ethyl-6-[18F]fluoro-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-quinoline-3-carboxylic acid). The first step of the radiosynthesis consisted of a 18F for 19F exchange reaction on a 7-chloro-substituted precursor molecule, followed by coupling reactions with the amines piperazine or 1-methylpiperazine. Starting from 51,58 GBq of [18F]fluoride 1.9,2.0 GBq of [18F]norfloxacin or [18F]pefloxacin, ready for intravenous injection, could be obtained in a synthesis time of 130 min (3.5,3.8% overall radiochemical yield). Moreover, the preparation of [18F]levofloxacin ((-)-(S)-9-[18F]fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylicacid) was attempted but failed to afford the desired product in practical amounts. Copyright © 2003 John Wiley & Sons, Ltd. [source]

Characterization of Histamine Release Induced by Fluoroquinolone Antibacterial Agents In-vivo and In-vitro

Analysis of interaction modes in calix[4]arene,levofloxacin complexes by quantum methods

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 3 2006
Alexandrine Lambert
Abstract Host,guest interactions between chiral calix[4]arenes and the antibiotic levofloxacin are analyzed on the basis of quantum mechanical calculations at the density functional (for model systems) and semi-empirical levels. The calix[4]arene macrocycle carries two (+)-isomenthyl groups attached to opposing phenyl groups at the lower rim and different substituents (R,=,H, CH3, tBu, CH2CHCH2, COCH3 and NO2) are considered at the upper rim. Nitro derivatives are expected to form ionized complexes whereas the other derivatives should form neutral complexes with a very low stability. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Clarithromycin or levofloxacin in the sequential therapy for H. pylori eradication?

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2010
A. Zullo
No abstract is available for this article. [source]

Clarithromycin or levofloxacin in the sequential therapy for H. pylori eradication? authors' reply

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2010
J. Molina-Infante
No abstract is available for this article. [source]

Clinical trial: clarithromycin vs. levofloxacin in first-line triple and sequential regimens for Helicobacter pylori eradication

Pharmacokinetics of levofloxacin in male camels (Camelus dromedarius)

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009
A. GOUDAH
First page of article [source]

Characterization of the pharmacokinetic disposition of levofloxacin in stallions after intravenous and intramuscular administration

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2008
A. GOUDAH
The target of the present study was to investigate the plasma disposition kinetics of levofloxacin in stallions (n = 6) following a single intravenous (i.v.) bolus or intramuscular (i.m.) injection at a dose rate of 4 mg/kg bwt, using a two-phase crossover design with 15 days as an interval period. Plasma samples were collected at appropriate times during a 48-h administration interval, and were analyzed using a microbiological assay method. The plasma levofloxacin disposition was best fitted to a two-compartment open model after i.v. dosing. The half-lives of distribution and elimination were 0.21 ± 0.13 and 2.58 ± 0.51 h, respectively. The volume of distribution at steady-state was 0.81 ± 0.26 L/kg, the total body clearance (Cltot) was 0.21 ± 0.18 L/h/kg, and the areas under the concentration,time curves (AUCs) were 18.79 ± 4.57 ,g.h/mL. Following i.m. administration, the mean t1/2el and AUC values were 2.94 ± 0.78 h and 17.21 ± 4.36 ,g.h/mL. The bioavailability was high (91.76% ± 12.68%), with a peak plasma mean concentration (Cmax) of 2.85 ± 0.89 ,g/mL attained at 1.56 ± 0.71 h (Tmax). The in vitro protein binding percentage was 27.84%. Calculation of efficacy predictors showed that levofloxacin might have a good therapeutic profile against Gram-negative and Gram-positive bacteria, with an MIC , 0.1 ,g/mL. [source]

Third-line rescue therapy with levofloxacin is more effective than rifabutin rescue regimen after two Helicobacter pylori treatment failures

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2006
J. P. GISBERT
Summary Background In patients with a first eradication failure, a second (rescue) therapy still fails in > 20% of cases. Aim To compare rifabutin and levofloxacin rescue regimens in patients with two consecutive Helicobacter pylori eradication failures. Methods Patients, in whom first treatment with omeprazole,clarithromycin,amoxicillin and a second trial with omeprazole,bismuth,tetracycline,metronidazole (or ranitidine bismuth citrate with these antibiotics) had failed, received 10 days of treatment with either rifabutin (150 mg b.d.) or levofloxacin (500 mg b.d.), plus amoxicillin (1 g b.d.) and omeprazole (20 mg b.d.). Cure rates were evaluated by the 13C-urea breath test. Results Twenty patients received rifabutin, and 20 levofloxacin. All the patients returned for follow-up. Compliance in the rifabutin group was 100%. Four patients in the levofloxacin group did not take the medication correctly (in two cases due to adverse effects: myalgia and rash). Side effects in the rifabutin and levofloxacin groups were reported in 60% and 50% of the cases, respectively. Five patients (25%) treated with rifabutin presented with leucopenia, and six (30%) treated with levofloxacin presented with myalgias. Per-protocol cure rates were 45% (95% confidence interval, 26,66%) in the rifabutin group, and 81% (57,93%) in the levofloxacin group (P < 0.05). Intention-to-treat cure rates were, 45% (26,66%) and 85% (64,95%), respectively (P < 0.01). Conclusions After two previous H. pylori eradication failures, a 10-day triple levofloxacin-based rescue regimen is more effective than the same regimen with rifabutin. [source]

Lansoprazole, levofloxacin and amoxicillin triple therapy vs. quadruple therapy as second-line treatment of resistant Helicobacter pylori infection

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2006
W. M. WONG
Summary Aim To test the efficacy of levofloxacin-based second-line therapy for resistant Helicobacter pylori infection. Methods One hundred and six patients who failed H. pylori eradication were randomized to receive (i) lansoprazole 30 mg, amoxicillin 1 g, levofloxacin 500 mg, all given twice daily for 7 days (LAL); or (ii) lansoprazole 30 mg twice daily, metronidazole 400 mg thrice daily, bismuth subcitrate 120 mg and tetracycline 500 mg four times daily for 7 days (quadruple). Post-treatment H. pylori status was determined by 13C-urea breath test. Results Intention-to-treat and per-protocol H. pylori eradication rates were 57/60% for the LAL group and 71/76% for the quadruple group respectively. Metronidazole, clarithromycin, amoxicillin and levofloxacin resistance were found in 76%, 71%, 0% and 18% of patients, respectively. Levofloxacin resistance led to treatment failure in the LAL group. For patients with dual resistance to metronidazole and clarithromycin, the eradication rates were 79% in the LAL group (levofloxacin-sensitive) and 65% in the quadruple group (P = 0.34). Conclusion Lansoprazole, amoxicillin plus levofloxacin second-line therapy is comparable with quadruple therapy in efficacy. Subjects, especially those with dual resistance to metronidazole and clarithromycin, may consider levofloxacin-based therapy for levofloxacin-sensitive strains. [source]

Helicobacter pylori first-line treatment and rescue options in patients allergic to penicillin

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2005
J. P. GISBERT
Summary Background :,Helicobacter pylori eradication is a challenge in patients allergic to penicillin, especially those who have failed a first-eradication trial. Aim :,To assess the efficacy and tolerability of H. pylori first-line treatment and rescue options in patients allergic to penicillin. Methods :,Prospective single centre study including 40 consecutive treatments administered to patients allergic to penicillin. Therapy regimens: First-line (12 patients) omeprazole, clarithromycin and metronidazole for 7 days; second-line (17 patients) ranitidine bismuth citrate, tetracycline and metronidazole for 7 days; third-line (nine patients) rifabutin, clarithromycin and omeprazole for 10 days; and fourth-line (two patients) levofloxacin, clarithromycin and omeprazole for 10 days. Outcome variable: a negative 13C-urea breath test 8 weeks after completion of treatment. Results :,Per-protocol/intention-to-treat eradication rates were: first-line (64/58%); second-line (ranitidine bismuth citrate; 53/47%); third-line (rifabutin; 17/11%) and fourth-line regimen (levofloxacin; 100/100%). Compliance with treatment was generally good, except with the rifabutin-based regimen, which presented adverse effects in 89% of the patients, including four cases of myelotoxicity. Conclusions :,H. pylori -infected patients who are allergic to penicillin may be treated with a first-line treatment combining a proton-pump inhibitor, clarithromycin and metronidazole. Rescue options may include a regimen with ranitidine bismuth citrate, tetracycline and metronidazole. A levofloxacin-based rescue regimen (with proton-pump inhibitor and clarithromycin) may also represent an alternative, even when two or more consecutive eradication treatments have previously failed. However, rifabutin + clarithromycin + proton-pump inhibitor regimen is ineffective and poorly tolerated. [source]

Rescue therapy with levofloxacin after multiple H. pylori treatment failures: Author's reply

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2005
L. G. V. Coelho
No abstract is available for this article. [source]

New once-daily, highly effective rescue triple therapy after multiple Helicobacter pylori treatment failures: a pilot study

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2005
L. G. V. Coelho
Summary Background:,Helicobacter pylori treatment failure is a growing problem in daily practice. Aim:, To determine the efficacy of the combination of rabeprazole, levofloxacin and furazolidone as a rescue therapy. Methods:, Duodenal ulcer patients previously submitted, without success, to at least two H. pylori treatment regimens were included. Gastroscopy (urease test, histological examination and culture) and 13C-urea breath test were performed. All patients received a combination of rabeprazole 20 mg, levofloxacin 500 mg and furazolidone 200 mg (two tablets) administered in a single dose in the morning for 10 days. Clinical examination and a new 13C-urea breath test were performed 90 days after therapy. Results:, Twelve patients (eight females and four males), mean age 43 (30,58) years were included. Two patients failed to complete the treatment because of nausea and vomiting. Ten patients completed the study and took all the medications as advised. Culture was obtained in six patients: 100 and 83% of the samples were sensitive to furazolidone and levofloxacin, respectively. Per-protocol and intention-to-treat eradication rates were 100 and 83% (P = 0.019). Conclusions:, the combination of rabeprazole, levofloxacin and furazolidone in a single daily dose for 10 days constitutes a highly-effective and low-cost alternative as a third-line therapy in patients infected with H. pylori. [source]

Nature versus nurture in two highly enantioselective esterases from Bacillus cereus and Thermoanaerobacter tengcongensis

MICROBIAL BIOTECHNOLOGY, Issue 1 2010
Stephan Grosse
Summary There is an increasing need for the use of biocatalysis to obtain enantiopure compounds as chiral building blocks for drug synthesis such as antibiotics. The principal findings of this study are: (i) the complete sequenced genomes of Bacillus cereus ATCC 14579 and Thermoanaerobacter tengcongensis MB4 contain a hitherto undescribed enantioselective and alkaliphilic esterase (BcEST and TtEST respectively) that is specific for the production of (R)-2-benzyloxy-propionic acid ethyl ester, a key intermediate in the synthesis of levofloxacin, a potent antibiotic; and (ii) directed evolution targeted for increased thermostability of BcEST produced two improved variants, but in either case the 3,5°C increase in the apparent melting temperature (Tm) of the mutants over the native BcEST that has a Tm of 50°C was outperformed by TtEST, a naturally occurring homologue with a Tm of 65°C. Protein modelling of BcEST mapped the S148C and K272R mutations at protein surface and the I88T and Q110L mutations at more buried locations. This work expands the repertoire of characterized members of the ,/,-fold hydrolase superfamily. Further, it shows that genome mining is an economical option for new biocatalyst discovery and we provide a rare example of a naturally occurring thermostable biocatalyst that outperforms experimentally evolved homologues that carry out the same hydrolysis. [source]

Bacteriology and antimicrobial susceptibility of gram-positive cocci isolated from pus specimens of orofacial odontogenic infections

MOLECULAR ORAL MICROBIOLOGY, Issue 2 2002
T. Kuriyama
We recently reported the ,-lactamase production and antimicrobial susceptibility of anaerobic gram-negative rods isolated from pus specimens of 93 orofacial odontogenic infections. In this report, we determine the bacteriology and antimicrobial susceptibility of bacteria other than anaerobic gram-negative rods, mainly gram-positive cocci, isolated from the same specimens. Streptococcus constellatus and Peptostreptococcus micros were frequent isolates from all types of infection examined. Peptostreptococcus prevotii, Corynebacterium species, and Eubacterium species were recovered only from dentoalveolar infections, while Gemella morbillorum was found more frequently in periodontitis than in the other infections. ,-Lactamase-positive strains were detected only in staphylococci. Ampicillin, ampicillin/sulbactam, cefazolin, cefotaxime, imipenem, erythromycin, clindamycin and levofloxacin showed high susceptibility rates (,77%) against viridans streptococci, Peptostreptococcus and Gemella. Minocycline showed a high MIC90 value against viridans streptococci (32 µg/ml), and metronidazole was effective against Peptostreptococcus and Gemella. These results provide useful information for the treatment of orofacial odontogenic infections. [source]