Sparfloxacin versus clarithromycin in the treatment of community-acquired pneumonia

doi:10.1016/S0149-2918(00)88271-5

Clinical Therapeutics

Volume 21, Issue 1, January 1999, Pages 103-117

https://doi.org/10.1016/S0149-2918(00)88271-5 Get rights and content

Abstract

Community-acquired pneumonia remains a significant health concern despite the availability of effective antibiotics. Ibis randomized, double-masked, double-dummy, multicenter comparative trial was undertaken to compare the efficacy and safety of sparfloxacin with those of clarithromycin in the treatment of community-acquired pneumonia. In 54 centers throughout the United States, 342 patients aged ≥18 years with community-acquired pneumonia were enrolled in this trial. A total of 167 patients, 98 males and 69 females with a mean age of 51.0 years (range, 18-87), received a 400-mg loading dose of sparfloxacin on the first day, followed by 200 mg once daily for a total of 10 days. A total of 175 patients, 85 males and 90 females with a mean age of 51.3 years (range, 18–91), received clarithromycin 250 mg twice daily for 10 days. In the intent-to-treat population, 133 (79.6%) patients in the sparfloxacin group and 145 (82.9%) in the clarithromycin group were cured or improved (the 95% confidence interval [CI] for the differences in success rate between sparfloxacin and clarithromycin was −11.5% to 5.1%). Success rates for the per-protocol patients were 88.7% (133/150) in the sparfloxacin group and 88.9% (144/162) in the clarithromycin groups (95% CI, −7.2% to 6.8%). There were no significant differences in success rate between treatment groups based on age ≥65 years. The overall bacteriologic response rates in the bacteriologically assessable population were 97.0% (64/66 isolates) in the sparfloxacin group and 91.4% (74/81 isolates) in the clarithromycin group. Recurrence occurred in 6.0% of per-protocol patients in the sparfloxacin group and 6.3% of patients in the clarithromycin group. The overall frequency of adverse events was 56.3% in the sparfloxacin group and 65.1% in the clarithromycin group. Gastrointestinal disturbances were the most common adverse event in both groups. Abnormal taste related to study drug was reported by 17 patients (9.7%) treated with clarithromycin, versus 3 patients (1.8%) treated with sparfloxacin (P = 0.002). Photosensitivity reactions were reported in 10 patients (6.0%) treated with sparfloxacin, versus 1 patient (0.6%) treated with clarithromycin (P = 0.002). QT-interval prolongation was documented in 4 patients (2.4%) in the sparfloxacin group and no patients in the clarithromycin group. Thus sparfloxacin was as well tolerated and as effective as clarithromycin in the treatment of community-acquired pneumonia.

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Cited by (52)

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 :
Bacteriostatic antimicrobial therapeutics included tigecycline, oxazolidinones, macrolides, sulphonamides, and tetracyclines (Table S3). Twenty-three trials included patients with community-acquired pneumonia who were admitted to the hospital [34,36–38,40–42,44,45,47,49,51,52,56,59–61,65,66,71–73,75], whereas 10 trials included patients with nosocomial pneumonia [43,46,48,50,53,54,56,57,59,62]. The remaining 10 studies reported in- and outpatients with acute bacterial pneumonia as lower respiratory infections [35,63,64,67–70,73,74,76].
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.
Cardiac tolerance of moxifloxacin: clinical experience from a large observational French study in usual medical practice (IMMEDIAT study)
2006, Medecine et Maladies Infectieuses
La moxifloxacine (IZILOX^®) est indiquée dans les infections bactériennes respiratoires. Au cours de son développement clinique, un allongement de QTc, d'environ 6 ms en moyenne, a été observé. Cet effet est susceptible d'être à l'origine de torsades de pointes. Cependant la tolérance de la moxifloxacine a été bonne au cours du développement. Afin de confirmer, sur un large échantillon de patients, le bon profil de tolérance de la moxifloxacine au terme des études de développement, l'étude IMMEDIAT* a été mise en place en France en médecine de ville.
Cette étude observationnelle, prospective, non contrôlée mais monitorée a été conduite chez 13 578 patients ayant une infection des voies respiratoires traitée par moxifloxacine à la dose de 400 mg/j pendant cinq à dix jours conformément à l'AMM. Les événements indésirables (EI) pouvant correspondre à une manifestation clinique d'un trouble du rythme ventriculaire (évènements dits « critiques ») ont été recueillis puis évalués par un Comité scientifique chargé de déterminer l'origine potentiellement cardiaque de l'évènement détecté et d'estimer l'imputabilité au traitement.
Sur les 13 578 patients recrutés, 1046 événements indésirables (678 patients [5 %]) ont été rapportés, dont 854 (564 patients [4,15 %]) ont été considérés comme liés au traitement. Parmi ces 1046 événements indésirables (EI), 95 (62 patients [0,46 %]) étaient des EI graves. Un total de 189 EI critiques (159 patients [1,2 %]) ont été validé par le Comité scientifique. Après analyse, 34 EI (28 patients [0,21 %]) ont été considérés comme potentiellement d'origine cardiaque. Parmi ces 34 EI, seul 25 (19 patients [0,14 %]) étaient considérés comme possiblement reliés à la moxifloxacine : palpitations (13 patients), tachycardie (quatre patients), malaise (quatre patients), vertige (trois patients) et pâleur (un patient). Tous ces événements ont été transitoires et ont eu une évolution favorable.
Cette étude post-AMM confirme, dans les conditions d'usage en pratique de ville, le bon profil de tolérance de la moxifloxacine suggéré par les études pré-AMM sans mise en évidence d'évènements indésirables inattendus.
Moxifloxacin (Izilox^®) is prescribed for bacterial respiratory tract infections. ECG analysis done in clinical trials showed a mean QT prolongation at 6 ms that could lead to Torsades de Pointe. However, Izilox^® was well tolerated during clinical trials. To confirm the correct safety profile of Izilox^® in a large sample of patients, a French PMS study — MMEDIAT — was carried out in usual medical practice.
This prospective observational uncontrolled and monitored study was conducted in 13,578 patients with respiratory tract infection and treated with moxifloxacin 400 mg daily (duration: 5 to 10 days in accordance to the Market Authorization). Any clinical event being potentially a surrogate of a ventricular rhythm disorder (“critical event”) were collected and analyzed by a Scientific Committee in charge to determine the potential cardiac origin of the reported event and to establish a causal relationship with the treatment.
Among 13,578 patients, 1046 adverse events (678 patients [5%]) were reported, including 854 drug related events (564 patients [4.15%]). Of these 1046 adverse events, 95 (62 patients [0.46%]) were serious.
A total of 189 critical adverse events (159 patients [1.2%]) were reviewed by the Scientific Committee. After analysis, 34 adverse events (28 patients [0.21%]) were assessed from potential cardiac origin. Of these 34 adverse events, 25 (19 patients [0.14%]) were assessed as drug-related: palpitations [13 patients], tachycardia [4 patients], malaise [4 patients], vertigo [3 patients] and pallor [1 patient]. All adverse events were transient and had favourable outcome.
This PMS study confirmed that Izilox^® is well-tolerated in usual medical practice, in adequation with the safety data obtained in clinical trials.
Clarithromycin in 2003: Sustained efficacy and safety in an era of rising antibiotic resistance
2004, International Journal of Antimicrobial Agents
Data from surveillance studies show increasing prevalence of respiratory pathogens resistant to commonly used antibiotics. Thus, a Medline search was conducted to identify studies of clarithromycin, especially those addressing macrolide resistance. Changing trends of in vitro susceptibility have not affected clinical efficacy with clarithromycin. Over the last 12 years, clarithromycin study results have shown consistent rates of clinical cure and bacteriological eradication, which are similar to those observed with comparator agents. The incidence of clarithromycin treatment failure in patients infected with Streptococcus pneumoniae is substantially less than that predicted by macrolide resistance rates from surveillance programmes. In summary, despite widespread use since its introduction, clarithromycin remains active both in vitro and in vivo against clinically relevant respiratory tract pathogens.
Telithromycin 800 mg once daily for seven to ten days is an effective and well-tolerated treatment for community-acquired pneumonia
2003, Clinical Microbiology and Infection
This open, multinational study examined the efficacy and tolerability of telithromycin (HMR 3647), the first ketolide antibacterial agent, at an oral dose of 800 mg once daily for seven to ten days (further validated using pharmacokinetic analysis) as an empiric therapy in adults with mild to moderate community-acquired pneumonia (CAP).
A total of 240 patients (aged 18–79 years; median 40 years) with clinical signs and symptoms of CAP (radiologically confirmed) were enrolled in the study and received at least one dose of study medication. Sputum and blood samples for bacteriologic documentation were collected within 48 h prior to enrollment. Clinical and bacteriological outcomes were assessed 17–21 days (test of cure visit) and 31–36 days (late post-therapy visit) after treatment initiation. Adverse events were assessed by spontaneous reporting and investigator observation.
At the test of cure visit, 92.9% (95% CI: 88.4–96.1; n = 197) of patients achieved clinical cure in the per-protocol (PP) population. In the modified intent-to-treat (mITT) population, the cure rate was 79.6% (95% CI: 73.9–84.5; n = 240), including 12.5% of undetermined cases categorized as failures. Clinical cure (PP population) remained high in patients ≥65 years (85.7%), and in patients with a Fine score ≥III (92.1 %). Among those patients for whom bacteriologic data were available, the majority had a satisfactory outcome (88.9% in the bacteriologic PP; n = 45). Bacterial eradication rates were similarly high (85.5% and 82.7% for the mITT and PP populations, respectively). All patients with infections as a result of atypical/intracellular pathogens Chlamydophila (Chlamydia) pneumoniae, Mycoplasma pneumoniae or Legionella pneumophila had a clinical outcome of cure. Treatment was well tolerated. Adverse events were mainly gastrointestinal in origin and mild in intensity.
An oral dose of telithromycin 800 mg once daily for seven to ten days is an effective and well-tolerated first-line treatment for mild to moderate CAP in adults.

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Sparfloxacin versus clarithromycin in the treatment of community-acquired pneumonia

Abstract

Clin Ther

Diagn Microbiol Infect Dis

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

Am Rev Respir Dis

Community-acquired pneumonia: An update

Clevel Clin J Med

Community-acquired pneumonia

NEJM

Influence of age on symptoms at presentation in patients with community-acquired pneumonia

Arch Intern Med

Prospective study of epidemiology and prognostic factors in community-acquired pneumonia

Eur J Clin Microbiol Infect Dis

Prognosis, outcomes of patients with community-acquired pneumonia. A meta-analysis

JAMA

Community-acquired pneumonia in adults: Initial antibiotic therapy

Am Fam Phys