gemifloxacin and Pneumonia--Bacterial

A literature search was conducted to evaluate the pharmacokinetic and pharmacodynamic profile of the respiratory fluoroquinolones (gemifloxacin, levofloxacin and moxifloxacin) and their efficacy and safety in the management of community-acquired pneumonia (CAP). Data show that CAP is a common presentation in primary care practice, and is associated with high rates of morbidity and mortality, particularly in the elderly. Although the causative pathogens differ depending on treatment setting and patient factors, Streptococcus pneumoniae is the primary pathogen in all treatment settings. As a class, the respiratory fluoroquinolones have a very favorable pharmacokinetic and pharmacodynamic profile. Pharmacodynamic criteria suggest that moxifloxacin and gemifloxacin are more potent against S. pneumoniae, which may have the added benefit of reducing resistance selection and enhancing bacterial eradication. The respiratory fluoroquinolones are also generally well tolerated, and are first-line options for outpatient treatment of CAP in patients with comorbidities or previous antibiotic use.

Topics: Ambulatory Care; Anti-Bacterial Agents; Aza Compounds; Clinical Trials as Topic; Community-Acquired Infections; Drug Resistance, Bacterial; Fluoroquinolones; Gemifloxacin; Humans; Levofloxacin; Moxifloxacin; Naphthyridines; Ofloxacin; Pneumonia, Bacterial; Primary Health Care; Quinolines; Streptococcus pneumoniae

Community-acquired pneumonia (CAP) is the leading cause of death due to bacterial infection. It accounts for 10 million physician office visits in the USA annually. However, 80% of these are managed in the community, usually with oral antibiotic therapy. Typically, such courses have lasted 10 days or longer. Streptococcus pneumoniae accounts for 25% of all CAP infections; resistance among S. pneumoniae to all classes of antibiotics, including fluoroquinolones, poses new and shifting challenges to the primary care physician. Gemifloxacin is a potent agent, active against pneumococci and atypical pathogens. Administered once daily for 5 days, gemifloxacin is highly efficacious and well tolerated. Gemifloxacin administered for 5-7 days is a cost effective and safe alternative to both parenteral and oral antimicrobials, which may not cover the emerging resistant respiratory pathogens.

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Drug Resistance, Bacterial; Fluoroquinolones; Gemifloxacin; Humans; Naphthyridines; Pneumonia, Bacterial

Newer fluoroquinolones have become an important therapeutic choice in the treatment of community-acquired pneumonia (CAP). Gemifloxacin is one of the newest members of this class of antibiotics and has performed favourably in this indication.. To analyse the microbiological activity, pharmacokinetic/pharmacodynamic properties and clinical activity of gemifloxacin in CAP, as well as the safety reported in controlled clinical studies.. Literature research of English publications in the last 10 years addressing all aspects of gemifloxacin in CAP.. Gemifloxacin is microbiologically the most active fluoroquinolone against Streptococcus pneumoniae--the leading pathogen of CAP. In several comparative studies gemifloxacin was highly effective and well tolerated in the treatment of mild-to-moderate severe CAP.

Topics: Anti-Bacterial Agents; Clinical Trials as Topic; Community-Acquired Infections; Fluoroquinolones; Gemifloxacin; Humans; Naphthyridines; Pneumonia, Bacterial

Gemifloxacin is a synthetic fluoroquinolone antimicrobial agent exhibiting potent activity against most gram-negative and gram-positive organisms, such as the important community-acquired respiratory pathogens Streptococcus pneumoniae (including multidrug-resistant S. pneumoniae), Haemophilus influenzae , and Moraxella catarrhalis . The agent's mechanism of action involves dual targeting of two essential bacterial enzymes: DNA gyrase and topoisomerase IV. Gemifloxacin was approved by the Food and Drug Administration in April 2003 for treatment of community-acquired pneumonia and acute bacterial exacerbation of chronic bronchitis. The drug has an oral bioavailability of approximately 71%. Approximately 20-35% of gemifloxacin is excreted unchanged in the urine after 24 hours. The elimination half-life of gemifloxacin is 6-8 hours in patients with normal renal function, supporting once-daily dosing. The 24-hour free-drug area under the plasma concentration-time curve:minimum inhibitory concentration ratio (fAUC(0-24):MIC) associated with efficacy, based on results from in vitro and animal models of infection, is approximately 30. With a mean fAUC(0-24) of approximately 3 microg*hour/ml (35% of total AUC(0-24) of 8.4) and a median S. pneumoniae MIC for 90% of tested strains of 0.03, a fAUC(0-24):MIC ratio of 100 would be expected after standard dosing (320 mg once/day). In clinical studies involving both hospitalized and outpatient populations, gemifloxacin has been highly effective in the treatment of community-acquired pneumonia and acute exacerbation of chronic bronchitis. Clinical success rates ranged from 93.9-95.9% in patients with community-acquired pneumonia and 96.1-97.5% in those with acute exacerbation of chronic bronchitis. Gemifloxacin is well tolerated; the frequency of adverse events with this agent is low. Most adverse events are mild-to-moderate in severity, with diarrhea (< 4%), nausea and rash (< 3%), and headache (< 2%) most commonly reported. Drug interactions with gemifloxacin are not common, although absorption is greatly reduced when given with divalent and trivalent cation-containing compounds, such as antacids. Due to its potent activity against many common gram-positive and gram-negative respiratory pathogens, its proven clinical efficacy, and its favorable safety profile, gemifloxacin is a highly effective empiric treatment for community-acquired lower respiratory tract infections.

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Drug Interactions; Drug Resistance, Bacterial; Fluoroquinolones; Gemifloxacin; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Naphthyridines; Pneumonia, Bacterial; Randomized Controlled Trials as Topic; Respiratory Tract Infections

Community-acquired lower respiratory tract infections (LRTIs) are more prevalent in the elderly than in children and younger adults and form a significant proportion of all consultations and hospital admissions in this older age group. Furthermore, in a world of increasing life expectancy the trend seems unlikely to be reversed. Antimicrobial treatment of community-acquired pneumonia (CAP) must cover Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, and in many circumstances should also cover the intracellular (atypical) pathogens. In contrast, acute exacerbations of chronic bronchitis (AECB) are mainly associated with H. influenzae and S. pneumoniae and not with atypical bacteria: in severe cases, other Gram-negative bacteria may be involved. Frequently in LRTIs, the aetiology of the infection cannot be identified from the laboratory specimens and treatment has to be empirical. In such situations it is important to not only to use an antibiotic that covers all likely organisms, but also one that has good activity against these organisms given the local resistance patterns. Gemifloxacin is a new quinolone antibiotic that targets pneumococcal DNA gyrase and topoisomerase IV and is highly active against S. pneumoniae including penicillin-, macrolide- and many ciprofloxacin-resistant strains, as well as H. influenzae and the atypical pathogens. In clinical trials in CAP and AECB, gemifloxacin has been shown to be as effective a range of comparators and demonstrated an adverse event profile that was in line with the comparator agents. In one long-term study in AECB significantly more patients receiving gemifloxacin than clarithromycin remained free of recurrence after 26 weeks. The improved potency, broad spectrum of activity and proven clinical and bacteriological efficacy and safety profile should make it a useful agent in the 21st century battle against community-acquired LRTIs.

Topics: Anti-Bacterial Agents; Bronchitis; Chlamydophila Infections; Community-Acquired Infections; Fluoroquinolones; Gemifloxacin; Gram-Negative Bacterial Infections; Haemophilus Infections; Humans; Legionnaires' Disease; Moraxellaceae Infections; Naphthyridines; Pneumococcal Infections; Pneumonia, Bacterial; Pneumonia, Mycoplasma; Staphylococcal Infections

Topics: Adult; Anti-Bacterial Agents; Bacteria; Costs and Cost Analysis; Economics, Pharmaceutical; Female; Fluoroquinolones; Gemifloxacin; Humans; Male; Naphthyridines; Pneumonia, Bacterial; Treatment Outcome

Short-course therapy has been advocated for the treatment of community-acquired pneumonia (CAP). We compared the efficacy and safety of 5 and 7 day courses of gemifloxacin for outpatient treatment of mild-moderate CAP.. In a multicentre, double-blind, parallel group study, patients were randomized to receive 320 mg of oral gemifloxacin once daily for 5 or 7 days. Over 95% of all patients in each cohort had a Fine score of

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Community-Acquired Infections; Double-Blind Method; Drug Administration Schedule; Female; Fluoroquinolones; Gemifloxacin; Humans; Male; Middle Aged; Naphthyridines; Pneumonia, Bacterial; Pneumonia, Pneumococcal; Streptococcus pneumoniae; Treatment Outcome

An open-label, non-comparative study assessed the clinical and bacteriological efficacy of gemifloxacin (320 mg, once-daily for 7 days) in lower respiratory tract infections (LRTI). Patients with acute exacerbation of chronic bronchitis (AECB, n=261) or community-acquired pneumonia (CAP, n=216) were enrolled into the study. Clinical success rates at follow-up (days 21-28) in the intent-to-treat (ITT) population were high, 83.1% in AECB patients (95% CI: 77.9, 87.4) and 82.9% in CAP patients (95% CI: 77.0, 87.5). High bacteriological success rates were achieved (bacteriological ITT population), 91.2% (52/57) in AECB patients (95% CI: 80.0, 96.7) and 77.9% (60/77) in CAP patients (95% CI: 66.8, 86.3). Gemifloxacin was well tolerated with a low incidence of adverse events. Gemifloxacin treatment resulted in high clinical and bacteriological success rates and is a well-tolerated therapy for the treatment of LRTIs.

Topics: Adult; Aged; Anti-Infective Agents; Bronchitis; Chronic Disease; Community-Acquired Infections; Drug Administration Schedule; Female; Fluoroquinolones; Gemifloxacin; Gram-Negative Bacterial Infections; Haemophilus Infections; Humans; Klebsiella Infections; Male; Middle Aged; Naphthyridines; Pneumococcal Infections; Pneumonia, Bacterial; Staphylococcal Infections; Treatment Failure

This multicentre, randomized, double blind, parallel group study compared the efficacy and safety of gemifloxacin (320 mg once daily) with trovafloxacin (200 mg once daily) in 571 patients with community-acquired pneumonia (CAP). Although treatment was given routinely for 7 days it could be extended to 14 days; two-thirds of patients were treated for 7 days. High clinical success rates were noted at follow-up in the per-protocol population in both the gemifloxacin group (95.8%) and the trovafloxacin group (93.6%), non-inferiority with 95% CI. In the intent-to-treat population, the clinical success rate at follow-up was significantly superior for gemifloxacin (87.6%) compared with trovafloxacin (81.1%; 95% CI 0.5, 12.4). The pathogens identified most commonly at presentation were Mycoplasma pneumoniae and Streptococcus pneumoniae. Gemifloxacin eradicated 100% of S. pneumoniae. One bacteraemic isolate of S. pneumoniae was associated with clinical failure in the trovafloxacin group (MIC of trovafloxacin 8 mg/L). Gemifloxacin was well tolerated and the incidence of transient liver function abnormalities was very low. Gemifloxacin is an effective and well-tolerated treatment for patients with CAP.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Community-Acquired Infections; Double-Blind Method; Drug Resistance, Microbial; Female; Fluoroquinolones; Gemifloxacin; Humans; Male; Middle Aged; Naphthyridines; Pneumonia, Bacterial

Several medical-specialty professional societies have suggested that combination therapy with a beta -lactam plus a macrolide or doxycycline or monotherapy with a "respiratory quinolone" (i.e., levofloxacin, gatifloxacin, moxifloxacin, or gemifloxacin) are optimal first-line therapy for patients hospitalized with community-acquired pneumonia. These recommendations are based predominantly on retrospective studies that suggest improved rates of morbidity and mortality and hospital length of stay among patients treated in such a fashion. Well-designed, prospective, randomized studies confirming this tenet of therapy have not been published, although numerous prospective studies have provided indirect confirmation. The biological rationale for such a differential response (i.e., favoring combination therapy or fluoroquinolone therapy) includes the immunomodulatory effects of macrolides or more-optimal treatment of primary infection or coinfection with atypical pathogens. Well-designed, prospective, randomized trials are required to best define the effectiveness of combination therapy with a beta -lactam plus macrolide or doxycycline or with a respiratory quinolone in hospitalized patients with community-acquired pneumonia.

Topics: Anti-Infective Agents; Aza Compounds; Community-Acquired Infections; Doxycycline; Drug Therapy, Combination; Fluoroquinolones; Gatifloxacin; Gemifloxacin; Hospitalization; Humans; Levofloxacin; Macrolides; Moxifloxacin; Naphthyridines; Ofloxacin; Outcome Assessment, Health Care; Pneumonia, Bacterial; Quinolines; Retrospective Studies

Topics: Anti-Bacterial Agents; Clinical Trials as Topic; Community-Acquired Infections; Fees, Pharmaceutical; Fluoroquinolones; Gastrointestinal Diseases; Gemifloxacin; Naphthyridines; Pneumonia, Bacterial