Gemifloxacin use in the treatment of acute bacterial exacerbation of chronic bronchitis.

The newest generation of fluoroquinolones have proven efficacy against bacterial organisms associated with acute exacerbation of chronic bronchitis (AECB). Gemifloxacin, as one of the quinolones in this class, exhibits many of the pharmacokinetic and pharmacodynamic characteristics of the class with a few notable differences. Against Streptococccus pneumoniae it has a lower minimal inhibitory concentration (MIC) than the other respiratory fluoroquinolones and it has activity against both bacterial DNA gyrase and topoisomerase IV. The increased activity of gemifloxacin against both enzymes may be associated with decreased rates of resistance. Clinically, gemifloxacin has been shown to have positive effects on length of hospitalization and increased success at long-term follow-up in AECB patients. These associations were observed in noninferiority comparison studies. Although an advantage with the use of gemifloxacin in AECB is suggested, there are no comparison data is available to conclude that gemifloxacin is superior to the other respiratory fluoroquinolones. Gemifloxacin is generally well tolerated, but is associated with a characteristic rash and gastrointestinal upset as its most common observed side effects.

Addition of inhaled tobramycin to ciprofloxacin for acute exacerbations of Pseudomonas aeruginosa infection in adult bronchiectasis.

RATIONALE: Pseudomonas aeruginosa lung infection in patients with bronchiectasis, a chronic airway disease that is characterized by episodes of exacerbation, is associated with more severe disease and a higher utilization of health-care resources. Inhaled tobramycin solution reduces the number of acute exacerbations in patients with cystic fibrosis (CF)-related bronchiectasis with P aeruginosa infection but remains untested in the treatment of exacerbations in patients with non-CF bronchiectasis. OBJECTIVES: This study tested the effect of adding inhaled tobramycin solution to oral ciprofloxacin (Cip) for the treatment of acute exacerbations of non-CF bronchiectasis in patients with P aeruginosa infection. METHODS: A double-blind, randomized, active comparator, parallel-design study conducted at 17 study centers (5 in the United Kingdom, and 12 in the United States) compared 2 weeks of therapy with Cip with either an inhaled tobramycin solution or placebo in 53 adults with known P aeruginosa infection who were having acute exacerbations of bronchiectasis. MEASUREMENTS: Clinical symptoms, pulmonary function, clinical efficacy, and sputum microbiology were investigated prospectively. MAIN RESULTS: An inhaled solution of Cip with tobramycin, compared to placebo, achieved greater microbiological response but no statistically significant difference in clinical efficacy at days 14 or 21. Clinical and microbiological outcomes at the test of cure (ie, the clinical outcome assessment at day 21) were concordant when an inhaled tobramycin solution was added to therapy with Cip and compared to placebo (p = 0.01). Both subject groups had similar overall adverse event rates, but subjects receiving therapy with an inhaled tobramycin solution reported an increased frequency of wheeze (50%; placebo group, 15%). CONCLUSIONS: The addition of an inhaled tobramycin solution to therapy with oral Cip for the treatment of acute exacerbations of bronchiectasis due to P aeruginosa improved microbiological outcome and was concordant with clinical outcome; the inability to demonstrate an additional clinical benefit may have been due to emergent wheeze resulting from treatment.

Appropriate outpatient macrolide use in community-acquired pneumonia.

PURPOSE: To review current guidelines concerning the outpatient management of community-acquired pneumonia (CAP), to discuss antibiotic resistance and its relation to outcomes, and to define the appropriate use of newer macrolides in CAP. DATA SOURCES: Comprehensive review of the scientific literature, comparison of published clinical practice guidelines, and expert opinion. CONCLUSIONS: Despite increasing knowledge regarding its etiology and pathogenesis, CAP remains the seventh leading cause of death in the United States. Although 80% of all patients with CAP are treated as outpatients, over 1 million hospital admissions due to CAP occur each year. From an employer perspective, total annual employer costs were fivefold greater for patients with pneumonia than for those who were not affected. Appropriate antimicrobial choices should lead to improved outcomes. Reports of increasing resistance of pathogens associated with CAP, increasing frequency of atypical pathogens, and the availability of an increasing number of antimicrobials have made treatment decisions more involved. IMPLICATIONS FOR PRACTICE: In an effort to improve outcomes, several guidelines have been published recommending appropriate antimicrobial agents to treat CAP in different patient populations. All guidelines base treatment recommendations on the hospitalization status of the patient, and all agree that coverage of atypical pathogens as part of an initial empirical regimen is important. Comorbidity and modifying factors that may increase the risk of infection with resistant organisms also are taken into account. Controversy exists regarding the use of newer macrolides versus newer fluoroquinolones as initial empirical therapy. The applicability of the reported increasing resistance of common pneumonia pathogens to outcomes in regimens containing newer macrolides is a subject of debate. Defining appropriate antimicrobial use in different patient groups should help achieve better outcomes and allay the development of resistance.

Efficacy and tolerability of gatifloxacin in community treatment of acute exacerbations of chronic bronchitis.

BACKGROUND: Recognizing acute exacerbations of chronic bronchitis (AECB) and selecting appropriate antibiotic treatment for patients who would benefit most is a challenge for community-based physicians. OBJECTIVE: The Tequin Clinical Experience Study, an open-label, noncomparative, postmarketing trial, assessed the efficacy and tolerability of gatifloxacin, an 8-methoxy fluoroquinolone, in the treatment of AECB in the community-practice setting. METHODS: Consecutive patients with respiratory tract infections in community-based settings were eligible for participation. Treated patients (N = 2512) included 1107 men (44.1%) and 1405 women (55.9%) aged > or =18 years with a clinical diagnosis of chronic bronchitis. All participants received oral gatifloxacin 400 mg once daily for 7 to 10 days. Clinical response was determined via telephone contact conducted by the investigator or study coordinator using case-report forms or during an office visit after the last dose. The investigator or coordinator collected expectorated or induced sputum specimens that were then smeared on a microscope slide, stored in a tube, and transported to a central reference laboratory for Gram-staining and culture. Of 1388 pretreatment sputum specimens submitted, pathogens were isolated from 424. RESULTS: The most frequently detected pathogens were Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. All H. influenzae and 99% of S. pneumoniae isolates tested were susceptible to gatifloxacin. Of the 2267 patients with a determinable clinical response, 2084 (91.9% [95% CI, 90.8%-93.0%]) were cured (all acute symptoms improved or returned to baseline level, no new symptoms present, no additional antibiotic required). The 95.8% cure rate in 166 patients with H. influenzae included 100% of those with beta-lactamase-positive strains. Overall, 89.2% of 111 patients with M. catarrhalis were cured; rates were similar regardless of beta-lactamase production. The clinical cure rate in 74 patients with S. pneumoniae was 98.6% and was independent of the degree of penicillin resistance (minimum inhibitory concentration > or =2.0 microg/ mL). All 6 patients infected with S. pneumoniae fully resistant to penicillin were cured. Gatifloxacin was generally well tolerated, and the majority of adverse events were mild to moderate; only 11 drug-related adverse events in 10 patients (0.4%) were serious. Drug-related nausea (3.0%), dizziness (1.5%), diarrhea (1.2%), and vomiting (0.9%) were the most common adverse events. CONCLUSIONS: The high clinical cure rate and favorable tolerability support gatifloxacin as a rational choice for the treatment of AECB in patients such as those in this community-based study.