A controlled, double-blind, multicenter study comparing clarithromycin extended-release tablets and levofloxacin tablets in the treatment of community-acquired pneumonia

doi:10.1016/S0149-2918(02)85148-7

Clinical Therapeutics

Volume 24, Issue 5, May 2002, Pages 736-751

https://doi.org/10.1016/S0149-2918(02)85148-7 Get rights and content

Abstract

Background: Macrolides and fluoroquinolones are frequently used for the empiric treatment of community-acquired pneumonia (CAP).

Objective: The aim of the study was to compare the safety profile and efficacy of clarithromycin extended-release (ER) tablets with those of levofloxacin tablets for the treatment of CAP in ambulatory adult patients.

Methods: In a Phase III, double-blind, randomized, parallel-group, multicenter study, ambulatory adult patients (≥18 years) with signs and symptoms of CAP received a 7-day course of treatment with either clarithromycin ER (two 500-mg tablets once daily) or levofloxacin (two 250-mg tablets once daily). A diagnosis of CAP was confirmed by radiography of the chest and physical examination, and sputum samples were analyzed to identify etiologic pathogen(s). Tolerability was assessed through subjective reports of adverse events and through changes in physical findings, concomitant medications, and laboratory values.

Results: There were no statistically significant differences between treatment groups in terms of sex, age, race, or body weight. The mean age was 50 years (range, 18–91 years). Of 299 patients randomized and treated, 252 were clinically evaluable (128 clarithromycin ER, 124 levofloxacin). The 95% CI for the difference between cure rates demonstrated equivalence of the 2 treatments. Among clinically evaluable patients at the test-of-cure visit, clinical cure rates were 88% (113/128) and 86% (107/124), and radiographic success rates were 95% (117/123) and 88% (104/118) for clarithromycin ER and levofloxacin, respectively. Both treatment regimens were effective in resolving and improving clinical signs and symptoms of CAP. Among clinically and bacteriologically evaluable patients, bacteriologic cure rates were 86% (80/93) and 88% (85/97) for clarithromycin ER and levofloxacin, respectively. No statistically significant differences were observed between the 2 treatment groups in the overall incidence of adverse events.

Conclusions: Clarithromycin ER demonstrated equivalent efficacy and tolerability to the fluoroquinolone levofloxacin in a group of ambulatory adult patients with CAP. Clarithromycin ER also appeared to be safe in the population studied.

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Cited by (46)

Macrolides for better resolution of community-acquired pneumonia: A global meta-analysis of clinical outcomes with focus on microbial aetiology
2023, International Journal of Antimicrobial Agents
This meta-analysis examined the effect of macrolides on resolution of community-acquired pneumonia (CAP) and interpretation of clinical benefit according to microbiology; emphasis is given to data under-reported countries (URCs).
This meta-analysis included 47 publications published between 1994 and 2022. Publications were analysed for 30-d mortality (58 759 patients) and resolution of CAP (6465 patients). A separate meta-analysis was done for the prevalence of respiratory pathogens in URCs.
Mortality after 30 d was reduced by the addition of macrolides (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.51–0.82). The OR for CAP resolution when macrolides were added to the treatment regimen was 1.23 (95% CI 1.00–1.52). In the CAP resolution analysis, the most prevalent pathogen was Streptococcus pneumoniae (12.68%; 95% CI 9.36–16.95%). Analysis of the pathogen epidemiology from the URCs included 12 publications. The most prevalent pathogens were S. pneumoniae (24.91%) and Klebsiella pneumoniae (12.90%).
The addition of macrolides to the treatment regimen led to 35% relative decrease of 30-d mortality and to 23% relative increase in resolution of CAP.
Mortality and clinical cure rates for pneumonia: a systematic review, meta-analysis, and trial sequential analysis of randomized control trials comparing bactericidal and bacteriostatic antibiotic treatments
2022, Clinical Microbiology and Infection
Citation Excerpt :
Thus, we excluded this study. Forty-three trials were included in the final analysis, as shown in the Preferred Reporting Items for Systematic Reviews and Meta-analysis flow chart (Table S1, Fig. 1) [34–76]. Fifteen of 43 trials were open-label studies, resulting in a significant risk of performance bias [34,36,38,42,45,46,51,53,56,60,64,66,69,71,76].
Bactericidal antibiotics are generally assumed to be superior to bacteriostatic antibiotics as first-line treatment for pneumonia.
We performed a systematic review, meta-analysis, and trial sequential analysis (TSA) of randomized controlled trials (RCTs) of bactericidal versus bacteriostatic antibiotics to ascertain clinical superiority. Clinical cure rate was the primary outcome. Secondary outcomes included all-cause mortality, microbiological eradication, treatment failure, and relapse rates.
PubMed, Cochrane Library, Embase, and MedRxiv
Randomized control trials.
Adult patients with bacterial pneumonia treated with antibiotics in the community or in-hospital.
Bacteriostatic versus bactericidal antibiotics.
The Cochrane Collaboration assessing risk of bias 2 tool.
Data on dichotomous outcomes are presented as risk ratio (RR). A random-effects model with the generic Mantel–Haenszel method was used for integrating RRs for generalizability of findings. The I² method was used to assess the magnitude of variation secondary to heterogeneity.
Forty-three RCTs involving 10 752 patients met the eligibility criteria. The clinical cure rate (42 studies, 10 312 patients; RR: 1.02; 95% CI, 0.99–1.05; I²: 37%; TSA-adjusted CI, 0.99–1.05), all-cause mortality (25 studies, 8302 patients; RR: 1.07; 95% CI, 0.81–1.42; I²: 57%), microbiological eradication (24 studies, 2776 patients; RR: 1.00; 95% CI, 0.97–1.03; I²: 0%), treatment failure (31 studies, 7296 patients; RR: 0.96; 95% CI, 0.83–1.11; I²: 42%), and relapse rate (5 studies, 1111 patients; RR: 1.15; 95% CI, 0.50–2.63; I²: 0%) were similar between bactericidal and bacteriostatic antibiotic treatments.
Bactericidal agents are not associated with any statistical difference in clinical cure rates, mortality, microbiological eradication, treatment failure, or relapse rates compared with bacteriostatic antibiotics in the treatment of pneumonia.
Macrolides vs. quinolones for community-acquired pneumonia: Meta-analysis of randomized controlled trials
2013, Clinical Microbiology and Infection
The relative efficacy, safety and ecological implications of macrolides vs. quinolones in the treatment of community-acquired pneumonia (CAP) are debatable. We performed a systematic review and meta-analysis of randomized controlled trials comparing any macrolide vs. any quinolone for the treatment of CAP among adult inpatients or outpatients, as monotherapy or both in combination with a beta-lactam. We did not limit inclusion by pneumonia severity, publication status, language or date of publication. The primary outcomes assessed were 30-day all-cause mortality and treatment failure. Two authors independently extracted the data. Fixed effect meta-analysis of risk ratios (RRs) with 95% confidence intervals was performed. Sixteen trials (4989 patients) fulfilling inclusion criteria were identified, mostly assessing outpatients with mild to moderate CAP. All-cause mortality was not significantly different for macrolides vs. quinolones, RR 1.03 (0.63–1.68, seven trials), with a low event rate (2%). Treatment failure was significantly lower with quinolones, RR 0.78 (0.67–0.91, 16 trials). The definition of failure used in the primary studies was not clearly representative of patients’ benefit. Microbiological failure was lower with quinolones, RR 0.63 (0.49–0.81, 13 trials). All adverse events, adverse events requiring discontinuation and any premature antibiotic discontinuation were significantly more frequent with macrolides, mainly on account of gastrointestinal adverse events. Resistance development was not assessed in the trials. Randomized controlled trials show an advantage of quinolones in the treatment of CAP with regard to clinical cure without need for antibiotic modification at end of treatment and gastrointestinal adverse events. The clinical significance of this advantage is unclear.
Review of Macrolides (Azithromycin, Clarithromycin), Ketolids (Telithromycin) and Glycylcyclines (Tigecycline)
2011, Medical Clinics of North America
Citation Excerpt :
In a comparative trial between 5 days of gemifloxacin and 7 days of clarithromycin, clinical and bacteriologic cures were similar, but significantly more patients in the gemifloxacin group remained free of AECB recurrences.96 For the outpatient treatment of community-acquired pneumonia, equivalent efficacy has been shown between (1) clarithromycin 500 mg twice daily for 10 days and moxifloxacin or gatifloxacin and (2) clarithromycin extended-release tablets (2 × 500 mg tablets once daily for 7 days) and levofloxacin or trovafloxacin.97–100 Azithromycin (500 mg on day 1 followed by 250 mg daily for 4 days) was equivalent to cefaclor in patients with outpatient community-acquired pneumonia.101
Macrolides, Ketolides, and Glycylcyclines: Azithromycin, Clarithromycin, Telithromycin, Tigecycline
2009, Infectious Disease Clinics of North America
Antibiotherapy for acute CAP in adults
2006, Medecine et Maladies Infectieuses
Les pneumopathies communautaires sont une des infections les plus fréquentes. Les germes en cause sont multiples et sous l'effet de l'antibiothérapie, leurs sensibilités aux antibiotiques se modifient. Parallèlement, de nouveaux antibiotiques voient le jour dans cette indication. Il est donc nécessaire de refaire une mise à jour sur les molécules utilisables au cours de ce type d'infection. Nous avons refait le point sur l'épidémiologie bactérienne et sur l'évolution des résistances. Nous nous sommes penchés sur les nouveaux antibiotiques comme la lévofloxacine, la moxifloxacine, la télithromycine, mais aussi d'anciens comme la pristinamycine. Toutes ces molécules sont actives sur les germes retrouvés dans les infections communautaires. Il n'y a pour le moment quasiment pas d'évolution des résistances de Streptococcus pneumoniae vis-à-vis de ces molécules. Cependant, pour les fluoroquinolones, les mutations ne sont pas faciles à détecter en routine. Il n'existe pas au travers des études cliniques de différences entre la moxifloxacine et la lévofloxacine. Cependant, les études bactériologiques et pharmacologiques vont plutôt dans le sens d'une utilisation de la moxifloxacine et/ou d'une augmentation de la posologie de la lévofloxacine. Les molécules de références pour l'infection à Legionella pneumophila sont les nouvelles fluoroquinolones. En ce qui concerne l'infection à Streptococcus pneumoniae, l'amoxicilline reste la molécule de référence, même pour ceux qui possède une sensibilité diminuée à la pénicilline. Par ailleurs, faut-il traiter systématiquement les infections liées à des germes intracellulaires ? Il n'existe pour le moment pas de réponse dans la littérature.
Community acquired pneumonia is one of the most frequent infections. With time, bacterial epidemiology and bacterial resistance evolve and new antibiotics become available. So an up-date on adequate antibiotic use is necessary. We reviewed the epidemiology of pneumonia and the evolution of bacterial resistance. We also collected data on new antibiotics which can be used for this infection such as levofloxacin, moxifloxacin, telithromycin, and pristinamycin. All these drugs are effective on bacteria involved in pneumonia. At this time, only few Streptococcus pneumoniae strains have developed resistance to these drugs. However, resistance to fluoroquinolones is not easily detected with common laboratory techniques. There is no effectiveness difference between the 2 new fluoroquinolones (levofloxacin, moxifloxacin) in clinical studies. However, in bacteriological and pharmacological studies, moxifloxacin seems to be more effective than levofloxacin (500 mg/day). For the treatment of pneumonia due to Legionella pneumophila, fluoroquinolones are now widely recommended. For Streptococcus pneumonia, amoxicillin remain the drug of choice, even for bacteria with a decreased susceptibility to penicillin. The importance of treating atypical pathogens remains to be documented.

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Clinical Therapeutics

Abstract

References (23)

Antimicrobial resistance in Streptococcus pneumoniae: Implications for patients with community-acquired pneumonia

Mayo Clin Proc

A multicenter study of grepafloxacin and clarithromycin in the treatment of patients with community-acquired pneumonia

Chest

Sparfloxacin versus clarithromycin in the treatment of community-acquired pneumonia

Clin Ther

An update on community-acquired pneumonia in adults

Compr Ther

Antibiotic usage for respiratory tract infections in an era of rising resistance and increased cost pressure

Am J Managed Care

Etiology of community-acquired pneumonia: Impact of age, comorbidity, and severity

Am J Respir Crit Care Med

Importance of atypical pathogens of community-acquired pneumonia

Clin Infect Dis

Prospective study of community-acquired pneumonia of bacterial etiology in adults

Eur J Clin Microbiol Infect Dis

Practice guidelines for the management of community-acquired pneumonia in adults. Infectious Diseases Society of America

Clin Infect Dis

Guidelines for the management of adults with community-acquired pneumonia. Diagnosis, assessment of severity, antimicrobial therapy, and prevention

Am J Respir Crit Care Med

Canadian guidelines for the initial management of community-acquired pneumonia: An evidence-based update by the Canadian Infectious Diseases Society and the Canadian Thoracic Society

Clin Infect Dis

Cited by (46)

Macrolides for better resolution of community-acquired pneumonia: A global meta-analysis of clinical outcomes with focus on microbial aetiology

Mortality and clinical cure rates for pneumonia: a systematic review, meta-analysis, and trial sequential analysis of randomized control trials comparing bactericidal and bacteriostatic antibiotic treatments

Macrolides vs. quinolones for community-acquired pneumonia: Meta-analysis of randomized controlled trials

Review of Macrolides (Azithromycin, Clarithromycin), Ketolids (Telithromycin) and Glycylcyclines (Tigecycline)

Macrolides, Ketolides, and Glycylcyclines: Azithromycin, Clarithromycin, Telithromycin, Tigecycline

Antibiotherapy for acute CAP in adults