Treatment failure rates and health care utilization and costs among patients with community-acquired pneumonia treated with levofloxacin or macrolides in an outpatient setting: A retrospective claims database analysis

doi:10.1016/j.clinthera.2008.01.023

Clinical Therapeutics

Volume 30, Issue 2, February 2008, Pages 358-371

https://doi.org/10.1016/j.clinthera.2008.01.023 Get rights and content

Abstract

Background: Macrolide antibiotics and fluoroquinolones are extensively used in the treatment of community-acquired pneumonia (CAP).

Objective: This analysis was conducted to compare treatment failure rates and health care utilization and cost outcomes among patients with CAP treated with levo-floxacin (500 or 750 mg) or macrolides (azithromycin, clarithromycin, or erythromycin) in an outpatient setting.

Methods: This was a retrospective analysis of claims data from a large US health plan. Patients were aged ≥18 years and had a primary diagnosis of CAP that was treated with oral levofloxacin or a macrolide in an outpatient setting (including physicians' offices, outpatient clinics, urgent care centers, and large ambulatory health centers). Patients were followed for 30 days after the index drug date to measure study outcomes. Multivariate regression analysis and a propensity score technique were used to compare rates of treatment failure and CAP-related health care utilization and costs. Two post hoc subgroup analyses were conducted in patients aged ≥50 and ≥65 years.

Results: Of the 7526 patients meeting the inclusion criteria, 2968 (39.4%) were treated with levofloxacin and 4558 (60.6%) with a macrolide. Unadjusted rates of treatment failure were 21.1% and 22.7% in the levofloxacin and macrolide cohorts, respectively. After adjustment for demographic characteristics, baseline comorbidities, and severity of illness, levofloxacin recipients were significantly less likely to experience treatment failure than macrolide recipients (odds ratio [OR] = 0.84; 95% CI, 0.75-0.94, P = 0.003). The likelihood of treatment failure was significantly lower in levofloxacin recipients aged ≥50 years (OR = 0.79; 95% CI, 0.66–0.94; P = 0.007) and ≥65 years (OR = 0.65; 95% CI, 0.43–1.00; P = 0.049) compared with the corresponding subgroups of macrolide recipients. The magnitude of this difference was greatest in the subgroup aged ≥65 years, which had a 35% reduced risk of treatment failure compared with the corresponding group of macrolide-treated patients. The rate of CAP-related emergency department visits was significantly lower among patients receiving levofloxa-cin (OR = 0.68; 95% CI, 0.51–0.91; P = 0.009); there were no differences in CAP-related hospitalizations or total CAP-related health care costs between levofloxa-cin and macrolide recipients.

Conclusions: Multivariate-adjusted rates of treatment failure in outpatients with CAP were significantly lower in those treated with levofloxacin relative to those treated with a macrolide. The lower rates of treatment failure with levofloxacin were consistently observed across all patients and in the subgroups aged ≥50 and ≥65 years. Rates of emergency department visits were also significantly lower among levofloxacin-treated patients, whereas overall CAP-related hospitali-zations and costs did not differ significantly between the 2 treatment groups.

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Cited by (42)

Macrolides vs. quinolones for community-acquired pneumonia: Meta-analysis of randomized controlled trials
2013, Clinical Microbiology and Infection
Citation Excerpt :
In a retrospective study of patients with Legionella pneumophila CAP, time to clinical stability and length of hospital stay were in favour of levofloxacin, without achieving statistical significance [6]. Among outpatients with CAP, a retrospective study showed that levofloxacin recipients were significantly less likely to experience treatment failure than macrolide recipients (adjusted odds ratio 0.84, 95% CI 0.75–0.94) [7]. Selection bias in observational studies limits the validity of these results.
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.
Multidisciplinary guidelines for the management of community-acquired pneumonia
2013, Medicina Clinica
La neumonía adquirida en la comunidad (NAC) es una enfermedad infecciosa respiratoria aguda que tiene una incidencia que oscila entre 3 y 8 casos por 1.000 habitantes por año. Esta incidencia aumenta con la edad y las comorbilidades. El 40% de los pacientes con NAC requieren ingreso hospitalario y alrededor del 10% necesitan ser admitidos en una Unidad de Cuidados Intensivos (UCI). La mortalidad global de la NAC está alrededor del 10%. Diversos estudios han sugerido que la implementación de guías clínicas mejora la evolución del paciente tanto en mortalidad como en estancia hospitalaria. Las guías clínicas más recientes y más utilizadas son la de la Infectious Diseases Society of America/American Thoracic Society, publicada en 2007, la de la British Thoracic Society, publicada en 2009, y la de la European Respiratory Society en colaboración con la European Society of Clinical Microbiology and Infectious Diseases, publicada en 2011. En España, la más reciente es la normativa de la Sociedad Española de Neumología y Cirugía Torácica, publicada en el año 2010. La presente guía clínica GNAC es multidisciplinar y ha contado con la ayuda del Centro Cochrane Iberoamericano (CCIB) para la síntesis de las guias previas y la selección de la bibliografía.
Esta guía clínica está diseñada para ser utilizada por todos los profesionales que pueden participar en el proceso asistencial de la NAC en sus vertientes diagnóstica, de caracterización de la gravedad, de tratamiento y de prevención.
Para cada uno de los siguientes apartados se han desarrollado tablas con recomendaciones donde se clasifica su evidencia, la fortaleza de la misma y su aplicabilidad práctica según la clasificación Grading of Recommendations of Assessment Development and Evaluations (GRADE):
- 1.
  Epidemiología, etiología microbiana y resistencias microbianas.
- 2.
  Diagnóstico clínico y microbiológico.
- 3.
  Escalas pronósticas y decisión de ingreso hospitalario.
- 4.
  Criterios de ingreso en la UCI.
- 5.
  Tratamiento antibiótico empírico y tratamiento antibiótico definitivo.
- 6.
  Falta de respuesta al tratamiento antibiótico.
- 7.
  Vacunaciones en la prevención de la NAC.
Community-acquired pneumonia (CAP) is an infectious respiratory disease with an incidence that ranges from 3 to 8 cases per 1,000 inhabitants per year. This incidence increases with age and comorbidities. Forty per cent of CAP patients require hospitalization and around 10% of these patients are admitted in an Intensive Care Unit (ICU). Several studies have suggested that the implementation of clinical guidelines has a positive impact in the outcome of patients including mortality and length of stay. The more recent and used guidelines are those from Infectious Diseases Society of America/American Thoracic Society, published in 2007, the 2009 from the British Thoracic Society, and that from the European Respiratory Society/European Society of Clinical Microbiology and Infectious Diseases, published in 2010. In Spain, the most recently released guideline is the Sociedad Española de Neumología y Cirugía Torácica-2011 guideline.
The present guidelines GNAC are designed to be used by the majority of health-care professionals that can participate in the care of CAP patients including diagnosis, decision of hospital and ICU admission, treatment and prevention. The Centro Cochrane Iberoamericano (CCIB) has participated in summarizing the previous guidelines and in the bibliography search.
For each one of the following sections the panel of experts has developed a table with recommendations classified according to its evidence, strength and practical applicability using the Grading of Recommendations of Assessment Development and Evaluations (GRADE) system:
- 1.
  Epidemiology, microbiological etiology and antibiotic resistances.
- 2.
  Clinical and microbiological diagnosis.
- 3.
  Prognostic scales and decision of hospital admission.
- 4.
  ICU admission criteria.
- 5.
  Empirical and definitive antibiotic treatment.
- 6.
  Treatment failure.
- 7.
  Prevention.
What Is the Best Approach to the Nonresponding Patient with Community-Acquired Pneumonia?
2013, Infectious Disease Clinics of North America
Citation Excerpt :
The presence of unusual microorganisms in CAP is a cause of treatment failure because these microorganisms are not adequately covered by the recommended initial empiric therapy (Mycobacteria, Nocardia spp, anaerobes, fungi, Pneumocystis jiroveci). One example is community-acquired MRSA, which may carry a cytotoxin (Panton-Valentine leukocidin) that causes severe necrotizing pneumonia with resistance to β-lactam antibiotics.3,15–17 Other infectious causes of nonresponse to treatment are complications of CAP, such as empyema (see Figs. 1–4), endocarditis, arthritis, pericarditis, meningitis, or peritonitis, and necrotizing pneumonia (abscess).3,6,18
Guideline adherence and macrolides reduced mortality in outpatients with pneumonia
2012, Respiratory Medicine
Citation Excerpt :
To our knowledge, this is the largest prospective study investigating the impact of guideline-concordant antibiotic use in outpatients with pneumonia, as well as the first to report a clinical benefit with either guideline concordance or macrolide use. Previous studies in outpatients with pneumonia were either relatively small, retrospective, or had limited clinical data for multivariable adjustment.5,24,25 Gleason et al. prospectively looked at 864 outpatients and found that antibiotic treatments concordant with the 1993 ATS guidelines did not improve outcomes, perhaps because these guidelines did not recommend routine coverage for atypical organisms.24
For outpatients with pneumonia, guidelines recommend empiric antibiotics and some suggest macrolides are preferred agents. We hypothesized that both guideline-concordant antibiotics and macrolides would be associated with reduced mortality.
All outpatients with pneumonia assessed at 7 Emergency Departments in Edmonton, Alberta, Canada were enrolled in a population-based registry that included clinical-radiographic data, Pneumonia Severity Index (PSI) and treatments. Guideline-concordant regimens included macrolides and respiratory fluoroquinolones; other regimens were “discordant”. Main outcome was 30-day all-cause mortality.
The study included 2973 outpatients; mean age 51 years, 47% female, most had mild pneumonia (73% PSI Class I–II). Over 30-days, 38 (1%) patients died, 228 (8%) were hospitalized, and 253 (9%) reached the endpoint of death or hospitalization. Most (2845 [96%]) patients received guideline-concordant antibiotics. Compared to patients receiving discordant antibiotics, those receiving guideline-concordant antibiotics were less likely to die within 30-days (8 [6%] versus 30 [1%], adjusted OR 0.23, 95% CI 0.09–0.59, p = 0.002). Within the guideline-concordant subgroup, compared to the 947 (33%) patients treated with fluoroquinolones, those receiving macrolides [1847 (64%)] were less likely to die (25 [3%] versus 4 [0.2%], adjusted OR 0.28, 95% CI 0.09–0.86, p = 0.03).
In outpatients with pneumonia, treatment with guideline-concordant antibiotics and macrolides were both associated with mortality reduction.
Suspect Screening and Semi-Quantification of Macrolide Antibiotics in Municipal Wastewater by High-Performance Liquid Chromatography—Precursor Ion Scan Tandem Mass Spectrometry
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Macrolide Treatment Failure Due to Drug–Drug Interactions: Real-World Evidence to Evaluate a Pharmacological Hypothesis
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View all citing articles on Scopus

^*: Express Track online publication February 4, 2008.

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Treatment failure rates and health care utilization and costs among patients with community-acquired pneumonia treated with levofloxacin or macrolides in an outpatient setting: A retrospective claims database analysis*

Abstract

Clin Ther

Chest

Am J Med

J Emerg Med

J Chronic Dis

J Clin Epidemiol

Chest

Clin Ther

Med Clin North Am

Chest

Deaths: Preliminary data for 2004

Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults

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

2004 National Hospital Discharge Survey

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

Principles of antibiotic treatment of community-acquired pneumonia in the outpatient setting

Am J Med

Advances in antimicrobial therapy of community-acquired pneumonia

Curr Opin Infect Dis

Comparative antimicrobial susceptibility of respiratory tract pathogens

Chemotherapy

International guidelines for the treatment of community-acquired pneumonia in adults: The role of macrolides

Drugs

World surveillance of antibiotic resistance among clinical isolates of Streptococcus pneumoniae and Streptococcus pyogenes during 1999/2000

Abstr Intersci Conf Antimicrob Agents Chemother

Hidden epidemic of macrolide-resistant pneumococci

Emerg Infect Dis

Quality of care, process, and outcomes in elderly patients with pneumonia

JAMA

Associations between initial antimicrobial therapy and medical outcomes for hospitalized elderly patients with pneumonia

Arch Intern Med