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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To establish a model where the role of bacterial biofilms in chronic pneumonia with Pseudomonas aeruginosa could be investigated, hydrocortisone-treated guinea pigs were given P. aeruginosa, strain 2126 by inhalation which were used throughout this study, in planktonic form. In these animals, the bacteria were recovered only from the lungs more than 4 weeks after infection. The persistence in bacterial colonization in the lungs coincided with the formation of glanulomatous lesions that surrounded spherical grains consisting of outer shell and inner bacterial colonies. The outer shell of grain was stained with ruthenium red and was presumed to be polyanionic and therefore to be a biofilm-like material. In normal animals without hydrocortisone-treatment, the number of neutrophils recovered from bronchoalveolar lavage fluid increased significantly from 3 hours after infection and subsequently the inhaled bacteria were eliminated from the lungs by day 3 of infection. This early influx of neutrophils into the lungs tended to be suppressed by treatment with hydrocortisone. The formation of grains did not take place in the lungs of normal animals, indicating the significant role of grain-formation in the initiation and the prolongation of bacterial colonization in the lungs. P. aeruginosa, strain 2126, incubated in saline formed thick biofilms on the surface of teflon piece. Levofloxacin (LVFX), a quinolone antibacterial, exhibited killing activity against the bacteria in in vitro-forming biofilms at MIC. In contrast, gentamicin (GM), an aminoglycosid antibiotic, and ceftazidime (CAZ), a beta-lactams antibiotic, showed no such killing activity at MIC. Treatment of this model with oral LVFX achieved complete eradication of the bacteria, whereas subcutaneous injection of GM or CAZ was hardly effective. The pharmacokinetic study on these antibacterials revealed that the doses used in this study were sufficient to obtain the pulmonary levels of these drugs far above MIC even in GM and CAZ. These data indicate that the outer shell of grains, a characteristic finding in the pulmonary lesions of this model, may be one of the forms of pseudomonal biofilms and that this model represents the significant role of biofilm mode of growth of P. aeruginosa in persistence in pulmonary colonization.
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PMID:[Experimental pneumonia with Pseudomonas aeruginosa in immunosuppressed guinea pigs as a model for biofilm-associated infection]. 760 91

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

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

Interactions between biofilm cells of Pseudomonas aeruginosa and levofloxacin were studied. P. aeruginosa incubated for 6 days with Teflon sheets formed a biofilm on its surface. Against the biofilm bacteria, levofloxacin at an MIC determined by the standard method for the strain was highly bactericidal whereas gentamicin, ceftazidime, and ciprofloxacin showed no significant killing activity. Levofloxacin, ciprofloxacin, and gentamicin, but not ceftazidime, exhibited killing activity against nongrowing cells of the strain incubated in phosphate buffer. In addition, levofloxacin, ciprofloxacin, and ceftazidime, but not gentamicin, showed the ability to penetrate an agar containing alginate. These findings may explain the efficacy of levofloxacin and the ineffectiveness of gentamicin and ceftazidime against biofilm bacteria; however, the cause of the ineffectiveness of ciprofloxacin still remains to be determined. In experimental pneumonia in guinea pigs, in which the biofilm mode of growth of the strain was observed in the lung, only levofloxacin exhibited substantial therapeutic efficacy. These findings suggest the significant role of levofloxacin in therapy of biofilm bacterium-associated infectious diseases.
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PMID:In vitro and in vivo activities of levofloxacin against biofilm-producing Pseudomonas aeruginosa. 966 Sep 97

Levofloxacin, levo-isomer of the D,L-racemate ofloxacin, is a new fluoroquinolone antibiotic approved for use in the United States in December 1996. It has an extended spectrum of activity compared with older-generation fluoroquinolones (ciprofloxacin, ofloxacin), with improved activity against gram-positive bacteria and excellent activity against gram-negative bacteria and atypical organisms. Although its activity against anaerobic organisms is improved over that of earlier fluoroquinolones, levofloxacin should not be considered a first-line anaerobic agent. It is available in an injectable form, as well as an oral formulation with virtually 100% oral bioavailability. The plasma elimination half-life ranges from 6-8 hours in individuals with normal renal function. Approximately 80% of drug is eliminated unchanged in urine through glomerular filtration and tubular secretion. The pharmacokinetics are not appreciably affected by age, gender, or race when differences in renal function and body mass and composition are taken into account. Levofloxacin had impressive efficacy in clinical studies of community-acquired pneumonia, acute bacterial exacerbations of chronic bronchitis, acute sinusitis, skin and skin structure infections, and complicated urinary tract infections and pyelonephritis. It is well tolerated; its adverse event profile is similar to that of other fluoroquinolones, with gastrointestinal and central nervous system effects reported most commonly. Drug interactions are uncommon with levofloxacin; however, coadministration with antacids or with other agents containing divalent or trivalent cations reduces levofloxacin absorption. The agent should prove to be more effective than older fluoroquinolones, especially for infections caused by pneumococci highly resistant to penicillin.
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PMID:Levofloxacin, a second-generation fluoroquinolone. 975 6

A multinational, multicentre, open, randomised study in hospitalised patients with pneumonia compared levofloxacin 500 mg twice daily with ceftriaxone 4 g i.v. once daily. Levofloxacin patients started on i.v. treatment and switched to oral on d 3-5 of therapy if signs and symptoms had improved. The minimum treatment duration was 5 d, except for treatment failure, and the median 8 d. The primary efficacy analysis was based on the per-protocol assessment of the clinical cure rate determined 2-5 d after the end of treatment in the per-protocol (PP) population (levofloxacin 127, ceftriaxone 139). Of 625 patients enrolled and randomized, 6 received no treatment, giving an intention-to-treat (ITT) population of 619 (levofloxacin 314, ceftriaxone 305). At the clinical endpoint, 2-5 d after the end of treatment, the cure rates for levofloxacin and ceftriaxone were similar in both the ITT (76% and 75%, respectively) and PP (87% and 86%, respectively) populations. Both drugs were well tolerated. Twice-daily levofloxacin 500 mg, either i.v. or as sequential i.v./oral therapy, was as effective as i.v. once-daily ceftriaxone 4 g in the treatment of hospitalized patients with pneumonia and offers the advantage of sequential therapy.
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PMID:A comparative study of levofloxacin and ceftriaxone in the treatment of hospitalized patients with pneumonia. 981 22

This therapeutic review discusses the pharmacology, pharmacokinetics, in vitro activity, drug interactions, and adverse effects of levofloxacin, a fluoroquinolone antibiotic. Particular emphasis is placed on the clinical efficacy of levofloxacin and its place in therapy. Compared with ciprofloxacin and the earlier quinolone agents, levofloxacin has an improved pharmacokinetic profile that allows convenient once-daily dosing in either an oral or parenteral formulation. Levofloxacin has enhanced activity against gram-positive aerobic organisms, including penicillin-resistant pneumococci. In published comparative trials involving commonly used treatment regimens, levofloxacin had equivalent if not greater activity in the treatment of community-acquired pneumonia, acute bacterial exacerbations of chronic bronchitis, acute bacterial sinusitis, acute pyelonephritis, and complicated urinary tract infection. Levofloxacin is well tolerated and induces minimal adverse drug reactions. Based on the above attributes, it may be reasonable to include levofloxacin on the hospital formulary in place of older quinolones. More recently released quinolones such as trovafloxacin exhibit similar advantages; however, until direct comparative trials between levofloxacin and these newer agents are conducted, it is difficult to advocate one agent over another. Regardless of which quinolone is the primary agent on the formulary, it is imperative that this class of antimicrobial drugs be used with discretion to minimize the development of resistance.
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PMID:Levofloxacin: a therapeutic review. 991 2

The therapeutic efficacy of oral treatment with levofloxacin, ciprofloxacin, and ampicillin on an experimental pneumonia caused by the penicillin-intermediate Streptococcus pneumoniae for which the minimum inhibitory concentrations (MICs) of the quinolones are similar was assessed in immunocompetent CBA/J mice. Levofloxacin exhibited a dose-dependent therapeutic effect, and achieved complete eradication of S. pneumoniae from the lungs at 120 mg/kg/day, whereas ciprofloxacin and ampicillin were hardly effective at all. A pharmacokinetic study in infected mice revealed good oral absorption and lung tissue penetration of levofloxacin (peak lung concentration: 5.95 microg/g of lung), low oral absorption of ciprofloxacin in spite of a good penetration into lung tissue (1.10 microg/g of lung), and low lung tissue penetration of ampicillin despite rather good oral absorption (1.71 microg/g of lung). In an in vitro time-kill study that simulated the peak concentration of drugs in the lungs of infected animals, the killing activity of levofloxacin was found to be greater than that of ciprofloxacin and ampicillin. These data suggest that the therapeutic efficacy of levofloxacin in this model is attributable to both its potent bactericidal activity and excellent pharmacokinetic profile.
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PMID:Therapeutic effect of oral levofloxacin, ciprofloxacin, and ampicillin on experimental murine pneumonia caused by penicillin intermediate Streptococcus pneumoniae for which the minimum inhibitory concentrations of the quinolones are similar. 1022 40

In this study, the in-vitro activity of levofloxacin against Streptococcus pneumoniae was compared with the activities of a range of other antibiotics. In total, 320 penicillin-susceptible and 30 penicillin-intermediate clinical isolates of S. pneumoniae were collected in Germany between 1992 and 1994 from patients with bacteraemic pneumonia. MICs were determined using the agar dilution methodology recommended by the NCCLS and the results with levofloxacin compared with those with ofloxacin, D-ofloxacin, ciprofloxacin, amoxycillin, cefpodoxime, cefixime, cefuroxime, faropenem, erythromycin and tetracycline. Levofloxacin (MIC50 1 mg/L) was approximately twice as active against the isolates as ofloxacin (MIC50 2 mg/L). D-ofloxacin (MIC90 32 mg/L) showed no activity, while beta-lactam antibiotics showed elevated MIC90 values against penicillin-intermediate strains (amoxycillin, 1 mg/L; cefpodoxime, 2 mg/L; cefixime, 32 mg/L; cefuroxime, 8 mg/L) in comparison with the MIC90 obtained with penicillin-susceptible strains (amoxycillin, 0.015 mg/L; cefpodoxime, 0.03 mg/L; cefixime, 0.5 mg/L; cefuroxime, 0.03 mg/L). Faropenem showed good activity against pneumococcal isolates (penicillin-susceptible strains, MIC90 0.016 mg/L; penicillin-intermediate strains, MIC90 0.25 mg/L). Erythromycin (MIC90 8 mg/L) and tetracycline (MIC90 64 mg/L) were also less active against penicillin-intermediate pneumococcal isolates. In conclusion, levofloxacin and faropenem may be useful in the treatment of pneumococcal infections caused by organisms with decreased susceptibility to penicillin.
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PMID:A comparative study of the in-vitro activity of levofloxacin against Streptococcus pneumoniae. 1040 30


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