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Respiratory fluoroquinolones for the treatment of community-acquired pneumonia: a meta-analysis of randomized controlled trials.

ABSTRACT: BACKGROUND: We investigated whether the use of respiratory fluoroquinolones was associated with better clinical outcomes compared with the use of macrolides and beta- lactams among adults with pneumonia. METHODS: We searched PubMed, Current Contents, Scopus, EMBASE, ClinicalTrials.gov and Cochrane with no language restrictions. Two reviewers independently extracted data from published trials that compared fluoroquinolones (levofloxacin, moxifloxacin, gemifloxacin) with macrolides or beta-lactams or both. A meta-analysis was performed with the clinical outcomes of mortality, treatment success and adverse outcomes. RESULTS: We included 23 trials in our meta-analysis. There was no difference in mortality among patients who received fluoroquinolones or the comparator antibiotics (OR 0.85, 95% CI 0.65-1.12). Pneumonia resolved in more patients who received fluoroquinolones compared with the comparator antibiotics for the included outcomes in the intention-to-treat population (OR 1.17, 95% CI 1.00-1.36), clinically evaluable population (OR 1.26, 95% CI 1.06-1.50) and the microbiologically assessed population (OR 1.67, 95% CI 1.28-2.20). Fluoroquinolones were more effective than a combination of beta-lactam and macrolide (OR 1.39, 95% CI 1.02-1.90). They were also more effective for patients with severe pneumonia (OR 1.84, 95% CI 1.02-3.29), those who required admission to hospital (OR = 1.30, 95% CI 1.04-1.61) and those who required intravenous therapy (OR = 1.44, 15% CI 1.13-1.85). Fluoroquinolones were more effective than beta-lactam and macrolide in open-label trials (OR = 1.35, 95% CI 1.08-1.69) but not in blinded randomized controlled trials (OR = 1.13, 95% CI 0.85-1.50). INTERPRETATION: Fluoroquinolones were associated with higher success of treatment for severe forms of pneumonia; however, a benefit in mortality was not evident. A randomized controlled trial that includes patients with severe pneumonia with or without bacteremia is needed.

SUBMITTER: Vardakas KZ

PROVIDER: S-EPMC2585120 | biostudies-other | 2008 Dec

REPOSITORIES: biostudies-other

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Respiratory fluoroquinolones for the treatment of community-acquired pneumonia: a meta-analysis of randomized controlled trials.

Vardakas Konstantinos Z KZ Siempos Ilias I II Grammatikos Alexandros A Athanassa Zoe Z Korbila Ioanna P IP Falagas Matthew E ME

CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 20081201 12

<h4>Background</h4>We investigated whether the use of respiratory fluoroquinolones was associated with better clinical outcomes compared with the use of macrolides and beta- lactams among adults with pneumonia.<h4>Methods</h4>We searched PubMed, Current Contents, Scopus, EMBASE, ClinicalTrials.gov and Cochrane with no language restrictions. Two reviewers independently extracted data from published trials that compared fluoroquinolones (levofloxacin, moxifloxacin, gemifloxacin) with macrolides or ...[more]

PMID: 19047608

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Project description:Community-acquired pneumonia (CAP) is the third-leading infectious cause of death worldwide. The standard treatment of CAP has not changed for the past fifty years and its mortality and morbidity remain high despite adequate antimicrobial treatment. Systemic corticosteroids have anti-inflammatory effects and are therefore discussed as adjunct treatment for CAP. Available studies show controversial results, and the question about benefits and harms of adjunct corticosteroid therapy has not been conclusively resolved, particularly in the non-critical care setting.This randomized multicenter study compares a treatment with 7 days of prednisone 50 mg with placebo in adult patients hospitalized with CAP independent of severity. Patients are screened and enrolled within the first 36 hours of presentation after written informed consent is obtained. The primary endpoint will be time to clinical stability, which is assessed every 12 hours during hospitalization. Secondary endpoints will be, among others, all-cause mortality within 30 and 180 days, ICU stay, duration of antibiotic treatment, disease activity scores, side effects and complications, value of adrenal function testing and prognostic hormonal and inflammatory biomarkers to predict outcome and treatment response to corticosteroids. Eight hundred included patients will provide an 85% power for the intention-to-treat analysis of the primary endpoint.This largest to date double-blind placebo-controlled multicenter trial investigates the effect of adjunct glucocorticoids in 800 patients with CAP requiring hospitalization. It aims to give conclusive answers about benefits and risks of corticosteroid treatment in CAP. The inclusion of less severe CAP patients will be expected to lead to a relatively low mortality rate and survival benefit might not be shown. However, our study has adequate power for the clinically relevant endpoint of clinical stability. Due to discontinuing glucocorticoids without tapering after seven days, we limit duration of glucocorticoid exposition, which may reduce possible side effects.7 September 2009 on ClinicalTrials.gov: NCT00973154.

Project description:BackgroundThe presumed superiority of newer fluoroquinolones for the treatment of acute bacterial sinusitis is based on laboratory data but has not yet been established on clinical grounds.MethodsWe performed a meta-analysis of randomized controlled trials comparing the effectiveness and safety of fluoroquinolones and beta-lactams in acute bacterial sinusitis.ResultsWe identified 8 randomized controlled trials investigating the newer "respiratory" fluoroquinolones moxifloxacin, levofloxacin and gatifloxacin. In the primary effectiveness analysis involving 2133 intention-to-treat patients from 5 randomized controlled trials, the extent of clinical cure and improvement did not differ between fluoroquinolones and beta-lactams (odds ratio [OR] 1.09, 95% confidence interval [CI] 0.85-1.39) at the test-of-cure assessment, which varied from 10 to 31 days after the start of treatment. Fluoroquinolones were associated with an increased chance of clinical success among the clinically evaluable patients in all of the randomized controlled trials (OR 1.29, 95% CI 1.03-1.63) and in 4 blinded randomized controlled trials (OR 1.45, 95% CI 1.05-2.00). There was no statistically significant difference between fluoroquinolones and amoxicillin-clavulanate (OR 1.24, 95% CI 0.93-1.65). Eradication or presumed eradication of the pathogens isolated before treatment was more likely with fluoroquinolone treatment than with beta-lactam treatment (OR 2.11, 95% CI 1.09-4.08). In the primary safety analysis, adverse events did not differ between treatments (OR 1.17, 95% CI 0.86-1.59). However, more adverse events occurred with fluoroquinolone use than with beta-lactam use in 2 blinded randomized controlled trials. The associations described here were generally consistent when we included 3 additional studies involving other fluoroquinolones (ciprofloxacin and sparfloxacin) in the analysis.InterpretationIn the treatment of acute bacterial sinusitis, newer fluoroquinolones conferred no benefit over beta-lactam antibiotics. The use of fluoroquinolones as first-line therapy cannot be endorsed.

Project description:BACKGROUND:Guidelines recommend macrolides and fluoroquinolones in patients hospitalized with community-acquired pneumonia (CAP), but their use has been associated with cardiac events. We quantified associations between macrolide and fluoroquinolone use and cardiac events in patients hospitalized with CAP in non-ICU wards. METHODS:This was a post-hoc analysis of a cluster-randomized trial as a cohort study; including patients with a working diagnosis of CAP admitted to non-ICU wards without a cardiac event on admission. We calculated cause-specific hazard ratio's (HR's) for effects of time-dependent macrolide and fluoroquinolone exposure as compared to beta-lactam monotherapy on cardiac events, defined as new or worsening heart failure, arrhythmia, or myocardial ischemia during hospitalization. RESULTS:Cardiac events occurred in 146 (6.9%) of 2107 patients, including heart failure (n =?101, 4.8%), arrhythmia (n =?53, 2.5%), and myocardial ischemia (n =?14, 0.7%). These occurred in 11 of 207 (5.3%), 18 of 250 (7.2%), and 31 of 277 (11.2%) patients exposed to azithromycin, clarithromycin, and erythromycin for at least one day, and in 9 of 234 (3.8%), 5 of 194 (2.6%), and 23 of 566 (4.1%) exposed to ciprofloxacin, levofloxacin, and moxifloxacin, respectively. HR's for erythromycin, compared to beta-lactam monotherapy, on any cardiac event and heart failure were 1.60 (95% CI 1.09;2.36) and 1.89 (95% CI 1.22;2.91), respectively. HR's for levofloxacin and moxifloxacin, compared to beta-lactam monotherapy, on any cardiac event were 0.40 (95% CI 0.18;0.87)and 0.56 (95% CI 0.36;0.87), respectively. Findings remained consistent after adjustment for confounders and/or in a sensitivity analysis of radiologically confirmed CAP (n =?1604, 76.1%). CONCLUSIONS:Among patients with CAP hospitalized to non-ICU wards, erythromycin use was associated with a 68% increased risk of hospital-acquired cardiac events, mainly heart failure. Levofloxacin and moxifloxacin were associated with a lower risk of heart failure. Although our study does not fully exclude confounding bias, findings remained largely unchanged in crude, adjusted, and sensitivity analyses. These findings may caution the use of erythromycin as empirical therapy in these patients. TRIAL REGISTRATION:The original trial was retrospectively registered under ClinicalTrials.gov Identifier NCT01660204 on August 8th, 2012.

Project description:BackgroundSystemic corticosteroids have anti-inflammatory effects, whereas macrolides also have immunomodulatory activity in addition to their primary antimicrobial actions. We aimed to evaluate the potential interaction effect between corticosteroids and macrolides on the systemic inflammatory response in patients with severe community-acquired pneumonia to determine if combining these two immunomodulating agents was harmful, or possibly beneficial.MethodsWe performed a post-hoc exploratory analysis of a randomized clinical trial conducted in three tertiary hospitals in Spain. This trial included patients with severe community-acquired pneumonia with high inflammatory response (C-reactive protein [CRP] >15 mg/dL) who were randomized to receive methylprednisolone 0.5 mg/kg/tpd or placebo. The choice of antibiotic treatment was at the physician's discretion. One hundred and six patients were classified into four groups according to antimicrobial therapy combination (?-lactam plus macrolide or ?-lactam plus fluoroquinolone) and corticosteroid arm (placebo or corticosteroids). The primary outcome was treatment failure (composite outcome of early treatment failure, or of late treatment failure, or of both early and late treatment failure).ResultsThe methylprednisolone with ?-lactam plus macrolide group had more elderly patients, with comorbidities, and higher pneumonia severity index (PSI) risk class V, but a lower proportion of intensive care unit admission, compared to the other groups. We found non differences in treatment failure between groups (overall p = 0.374); however, a significant difference in late treatment failure was observed (4 patients in the placebo with ?-lactam plus macrolide group (31%) vs. 9 patients in the placebo with ?-lactam plus fluoroquinolone group (24%) vs. 0 patients in the methylprednisolone with ?-lactam plus macrolide group (0%) vs. 2 patients [5%] in the methylprednisolone with ?-lactam plus fluoroquinolone group overall p = 0.009). We found a significant difference for In-hospital mortality in the per protocol population (overall p = 0.01). We did not find significant differences in treatment failure, early or late; or In-hospital mortality after adjusting for severity (PSI), year and centre of enrolment.ConclusionsIn this exploratory analysis, we observed that the glucocorticosteroids and macrolides combination had no statistically significant association with main clinical outcomes compared with other combinations in patients with severe community acquired pneumonia and a high inflammatory response after taking account potential confounders.Trial registrationClinicaltrials.gov NCT00908713.

Project description:BACKGROUND: Streptococcus pneumoniae is the leading cause of community-acquired pneumonia (CAP). High global incidence of macrolide and penicillin resistance has been reported, whereas fluoroquinolone resistance is uncommon. Current guidelines for suspected CAP in patients with co-morbidity factors and recent antibiotic therapy recommend initial empiric therapy using one fluoroquinolone or one macrolide associated to other drugs (amoxicillin, amoxicillin/clavulanate, broad-spectrum cephalosporins). Resistance to fluoroquinolones is determined by efflux mechanisms and/or mutations in the parC and parE genes coding for topoisomerase IV and/or gyrA and gyrB genes coding for DNA gyrase. No clinical cases due to fluoroquinolone-resistant S. pneumoniae strains have been yet reported from Italy. CASE PRESENTATION: A 72-year-old patient with long history of chronic obstructive pulmonary disease and multiple fluoroquinolone treatments for recurrent lower respiratory tract infections developed fever, increased sputum production, and dyspnea. He was treated with oral levofloxacin (500 mg bid). Three days later, because of acute respiratory insufficiency, the patient was hospitalized. Levofloxacin treatment was supplemented with piperacillin/tazobactam. Microbiological tests detected a S. pneumoniae strain intermediate to penicillin (MIC, 1 mg/L) and resistant to macrolides (MIC >256 mg/L) and fluoroquinolones (MIC >32 mg/L). Point mutations were detected in gyrA (Ser81-Phe), parE (Ile460-Val), and parC gene (Ser79-Phe; Lys137-Asn). Complete clinical response followed treatment with piperacillin/tazobactam. CONCLUSION: This is the first Italian case of community-acquired pneumonia due to a fluoroquinolone-resistant S. pneumoniae isolate where treatment failure of levofloxacin was documented. Molecular analysis showed a group of mutations that have not yet been reported from Italy and has been detected only twice in Europe. Treatment with piperacillin/tazobactam appears an effective means to inhibit fluoroquinolone-resistant strains of S. pneumoniae causing community-acquired pneumonia in seriously ill patients.

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Respiratory fluoroquinolones for the treatment of community-acquired pneumonia: a meta-analysis of randomized controlled trials.

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Respiratory fluoroquinolones for the treatment of community-acquired pneumonia: a meta-analysis of randomized controlled trials.

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