Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023241 (Legionella)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activities of levofloxacin and ofloxacin against 22 clinical legionella isolates was determined by microbroth dilution susceptibility testing. Growth inhibition of two Legionella pneumophila strains grown in guinea pig alveolar macrophages by levofloxacin, ofloxacin, or erythromycin was also determined. The drug concentrations required to inhibit 90% of strains tested was 0.032 mg/L for levofloxacin or ofloxacin, and was 0.016 mg/L for ciprofloxacin. BYE alpha broth significantly inhibited the activities of all three drugs tested, as judged by the susceptibility of control Escherichia coli strains. Levofloxacin (0.25 mg/L) reduced bacterial counts of two L. pneumophila strains grown in guinea pig alveolar macrophages by 1 log10, but regrowth occurred over a 3 day period; levofloxacin (1 mg/L) reduced bacterial counts by 2-3 log10 cfu/mL. Levofloxacin was significantly more active than erythromycin, and as active as ofloxacin or ciprofloxacin in this assay. Pharmacokinetic and therapy studies of levofloxacin and ofloxacin were performed in guinea pigs with L. pneumophila pneumonia. For the pharmacokinetic study, levofloxacin was given (10 mg/kg) by the intraperitoneal route to infected guinea pigs; mean peak plasma and lung concentrations were 3.4 mg/L and 1.4 micrograms/g, respectively, at 0.5 h and 2.6 mg/L and 0.6 micrograms/g at 1 h. The terminal half-life phase of elimination from plasma and lung was c. 1 h. All 15 infected guinea pigs treated with levofloxacin (10 mg/kg/day given ip once daily) for 5 days survived for 9 days after antimicrobial therapy, as did all 14 guinea pigs treated with the same dose of ofloxacin. None of 13 animals treated with saline survived. Levofloxacin is effective against L. pneumophila in vitro and in a guinea pig model of legionnaire's disease. Levofloxacin should be evaluated as a treatment of human legionnaires' disease.
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PMID:In-vitro activity of levofloxacin against clinical isolates of Legionella spp, its pharmacokinetics in guinea pigs, and use in experimental Legionella pneumophila pneumonia. 864 52

Levofloxacin is a fluoroquinolone antibiotic and is the optical S-(-) isomer of the racemic drug substance ofloxacin. It has a broad spectrum of in vitro activity against Gram-positive and Gram-negative bacteria, as well as certain other pathogens such as Mycoplasma, Chlamydia, Legionella and Mycobacteria spp. Levofloxacin is significantly more active against bacterial pathogens than R-(+)-ofloxacin. Levofloxacin hemihydrate, the commercially formulated product, is 97.6% levofloxacin by weight. Levofloxacin pharmacokinetics are described by a linear 2-compartment open model with first-order elimination. Plasma concentrations in healthy volunteers reach a mean peak drug plasma concentration (Cmax) of approximately 2.8 and 5.2 mg/L within 1 to 2 hours after oral administration of levofloxacin 250 and 500mg tablets, respectively. The bioavailability of oral levofloxacin approaches 100% and is little affected by the administration with food. Oral absorption is very rapid and complete, with little difference in the serum concentration-time profiles following 500mg oral or intravenous (infused over 60 minutes) doses. Single oral doses of levofloxacin 50 to 1000mg produce a mean Cmax and area under the concentration-time curve (AUC) ranging from approximately 0.6 to 9.4 mg/L and 4.7 to 108 mg.h/L, respectively, both increasing linearly in a dose-proportional fashion. The pharmacokinetics of levofloxacin are similar during multiple-dose regimens to those following single doses. Levofloxacin is widely distributed throughout the body, with a mean volume of distribution of 1.1 L/kg, and penetrates well into most body tissues and fluids. Drug concentrations in tissues and fluids are generally greater than those observed in plasma, but penetration into the cerebrospinal fluid is relatively poor (concentrations approximately 16% of simultaneous plasma values). Levofloxacin is approximately 24 to 38% bound to serum plasma proteins (primarily albumin); serum protein binding is independent of serum drug concentrations. The plasma elimination half-life (t1/2 beta) ranges from 6 to 8 hours in individuals with normal renal function. Approximately 80% of levofloxacin is eliminated as unchanged drug in the urine through glomerular filtration and tubular secretion; minimal metabolism occurs with the formation of no metabolites possessing relevant pharmacological activity. Renal clearance and total body clearance are highly correlated with creatinine clearance (CLCR), and dosage adjustments are required in patients with significant renal dysfunction. Levofloxacin pharmacokinetics are not appreciably affected by age, gender or race when differences in renal function, and body mass and composition are taken into account. Important drug interactions exist with aluminium- and magnesium-containing antacids and ferrous sulfate, as with other fluoroquinolones, resulting in significantly decreased levofloxacin absorption when administered concurrently. These agents should be administered at least 2 hours before or after levofloxacin administration. Cimetidine and probenecid decrease levofloxacin renal clearance and increase t1/2 beta; the magnitudes of these interactions are not clinically significant. Levofloxacin appears to have only minor potential for significantly altering the pharmacokinetics of theophylline, warfarin, zidovudine, ranitidine, digoxin or cyclosporin; however, patients receiving these drugs concurrently should be monitored closely for signs of enhanced pharmacological effect or toxicity. Levofloxacin pharmacokinetics are not significantly altered by sucralfate when administration of these drugs is separated by at least 2 hours.
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PMID:The clinical pharmacokinetics of levofloxacin. 906 26

Status asthmaticus developed in a 72-year-old man who was being treated with oral prednisolone for severe persistent asthma. The dosage of prednisolone was increased, and amikacin was injected to treat pneumonia that had developed in the right lung. Progressive pulmonary infiltrates, respiratory compromise, and hypoxemia developed, and the patient eventually required mechanical ventilation. Antibiotic treatment was changed to imipenem/cilastatin, piperacillin, gentamicin, clarithromycin, erythromycin, and minocycline. Liver injury developed. More than one month after the patient was admitted, Legionella pneumonia was diagnosed. Levofloxacin (400 mg/day) was then given orally, in combination with injected imipenem/cilastatin. Liver function did not deteriorate, and the pneumonia resolved. Most diagnoses of Legionnaires' disease are made retrospectively by examination of serum. In this case, antibiotics active against Legionella pneumophila had been used before the diagnosis was established, which probably contributed to the patient's recovery. When aminoglycosides or beta-lactam antibiotics are ineffective, administration of agents effective against Legionnaires' disease should be considered.
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PMID:[Legionella pneumonia successfully treated despite late diagnosis]. 923 37

Five hundred ninety patients were enrolled in a prospective, multicenter, randomized trial comparing the efficacy and safety of 7 to 14 days of levofloxacin treatment with that of ceftriaxone and/or cefuroxime axetil in the management of community-acquired pneumonia in adults. Patients received either intravenous and/or oral levofloxacin (500 mg once daily) or the comparative agents, parenteral ceftriaxone (1 to 2 g once to twice daily) and/or oral cefuroxime axetil (500 mg twice daily). Erythromycin or doxycycline could be added to the comparator arm at the investigator's discretion. The decision to use an intravenous or oral antimicrobial agent for initial therapy was made by the investigator. Clinical and microbiological evaluations were completed at the baseline, during treatment, 5 to 7 days posttherapy, and 3 to 4 weeks posttherapy. Four hundred fifty-six patients (226 given levofloxacin and 230 administered ceftriaxone and/or cefuroxime axetil) were evaluable for clinical efficacy. Streptococcus pneumoniae and Haemophilus influenzae were isolated in 15 and 12%, respectively, of clinically evaluable patients. One hundred fifty atypical pathogens were identified: 101 were Chlamydia pneumoniae, 41 were Mycoplasma pneumoniae, and 8 were Legionella pneumophila. Clinical success at 5 to 7 days posttherapy was superior for the levofloxacin group (96%) compared with the ceftriaxone and/or cefuroxime axetil group (90%) (95% confidence interval [CI] of -10.7 to -1.3). Among patients with typical respiratory pathogens who were evaluable for microbiological efficacy, the overall bacteriologic eradication rates were superior for levofloxacin (98%) compared with the ceftriaxone and/or cefuroxime axetil group (85%) (95% CI of -21.6 to -4.8). Levofloxacin eradicated 100% of the most frequently reported respiratory pathogens (i.e., H. influenzae and S. pneumoniae) and provided a >98% clinical success rate in patients with atypical pathogens. Both levofloxacin and ceftriaxone-cefuroxime axetil eradicated 100% of the S. pneumoniae cells detected in blood culture. Drug-related adverse events were reported in 5.8% of patients receiving levofloxacin and in 8.5% of patients administered ceftriaxone and/or cefuroxime axetil. Gastrointestinal and central and peripheral nervous system adverse events were the most common events reported in each treatment group. In conclusion, these results demonstrate that treatment with levofloxacin is superior to ceftriaxone and/or cefuroxime axetil therapy in the management of community-acquired pneumonia in adults.
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PMID:A multicenter, randomized study comparing the efficacy and safety of intravenous and/or oral levofloxacin versus ceftriaxone and/or cefuroxime axetil in treatment of adults with community-acquired pneumonia. 930 95

The antibacterial activities of levofloxacin, erythromycin, and rifampin against intracellular Legionella pneumophila L-1033, serogroup 1, were studied. In an in vitro system utilizing adherent human monocytes, L. pneumophila L-1033, a phagocytosis time period of 1 h, and antibiotic (levofloxacin, erythromycin, and/or rifampin) at 1 to 10 times the MIC, the CFU/ml values for the monocyte lysate were determined during 0- to 4-day time periods. The decrease in CFU/ml with levofloxacin at pH 7.4 was rapid, occurring within 24 h, and was drug concentration dependent (P < 0.01). The decrease in CFU with rifampin was first observed at 48 h (P < 0.01), while only a minimal decrease in CFU/ml was observed with erythromycin. Combination of levofloxacin and rifampin and of levofloxacin and erythromycin at ten times their MICs significantly decreased the CFU/ml value (P < 0.01), to the value attained by levofloxacin alone, while combination of rifampin and erythromycin did not. Removal of levofloxacin after 24 h of incubation resulted in regrowth of L. pneumophila L-1033, while a continued slow decrease in CFU/ml was seen following rifampin removal; CFU/ml values were unaffected by the removal of erythromycin. At 4 days, and even in assays performed following antibiotic removal, the CFU/ml value continued to be lower in the levofloxacin and rifampin assays than in the assays with erythromycin. Levofloxacin had a significantly higher bactericidal activity against L. pneumophila L-1033 than erythromycin or rifampin. In these assays, the addition of erythromycin or rifampin did not affect the antibacterial activity of levofloxacin.
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PMID:Antibacterial effects of levofloxacin, erythromycin, and rifampin in a human monocyte system against Legionella pneumophila. 983 7

Levofloxacin is the first fluoroquinolone with enhanced activity against Streptococcus pneumoniae to be released in Canada. In vitro, it is active against more than 99% of isolates of S pneumoniae, even those resistant to penicillin. It is also active against respiratory pathogens such as Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella species. When given orally, bioavailability is greater than 99%, and the drug is highly concentrated in lung tissue and macrophages. Drug levels are compatible with once-daily dosing. In a large clinical trial, levofloxacin has shown clinical and microbiological superiority compared with ceftriaxone/cefuroxime. The characteristics of levofloxacin - high oral bioavailability, long duration of effect, activity against key respiratory pathogens and high tolerability - suggest that it will be a useful drug in the treatment of community acquired pneumonia.
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PMID:Levofloxacin in the treatment of community acquired pneumonia. 1020 32

Quinolones are broad-spectrum antibiotics active primarily against aerobic gram-negative organisms. All quinolones have activity against oral anaerobes, but only trovafloxacin provides coverage against Bacteroides fragilis, the primary anaerobe of the abdomen/pelvis. In addition, quinolones are very active against atypical pulmonary pathogens, e.g., Legionella, but trovafloxacin is the least active against Chlamydia. As with other antibiotics, the selection of quinolones depends not simply on the degree of microbiologic activity but also on safety profile and cost. Ciprofloxacin and trovafloxacin are associated with central nervous system side effects. Photosensitivity reactions may occur with sparfloxacin. Trovafloxacin is associated with more adverse reactions than any other quinolone, and its gastrointestinal side effects are most frequent among the quinolones. Resistance potential is highest with ciprofloxacin and lowest with levofloxacin. Sparfloxacin and grepafloxacin are available only as oral formulations. Among the parenteral quinolones, ciprofloxacin and trovafloxacin are the most expensive, levofloxacin, the least expensive. Levofloxacin is preferred for general use alone or in combination because it has virtually no side effects, induces no resistance, and is the least expensive and most versatile quinolone currently available.
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PMID:Quinolones: clinical use and formulary considerations. 1034 49

Levofloxacin possesses a wide antimicrobial spectrum which encompasses Gram positive (also including penicillin-resistant Streptococcus pneumoniae) and Gram negative, and atypical respiratory pathogens Chlamydia pneumoniae, Legionella pneumophila and Mycoplasma pneumoniae) as well. Comparative clinical studies (macrolides, beta-lactams, and other fluoroquinolones), have evidenced bacteriological and clinical efficacy in community-acquired pneumonia (CAP), acute exacerbation of chronic bronchitis, urinary tract infections, and skin and soft tissue infections. In clinical practice, levofloxacin in sequential therapy allowed to reduce length of stay, the efficacy being maintained unaltered. In severe pneumonia, or when a pseudomonas aetiology is suspected, an association therapy is suggested, although a reliable body of clinical evidence is still lacking. Recent in vitro studies showed a synergism between levofloxacin and imipenem against multiresistant Pseudomonas aeruginosa strains. A recent Italian clinical study evidenced the good efficacy and tolerability profile of prophylactic use of levofloxacin in neutropenic patients with cancer. Such a prophylaxis reduced number of febrile episodes, at a statistically significant level, and mortality (although at a not statistically significant level).
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PMID:[Experience accumulated in hospital setting with levofloxacin, in monotherapy and in association therapy]. 2042 35