key: cord-0780516-uv8eura6 authors: Hess, Gregory; Hill, Jerrold W.; Raut, Monika K.; Fisher, Alan C.; Mody, Samir; Schein, Jeff R.; Chen, Chi-Chang title: Comparative antibiotic failure rates in the treatment of community-acquired pneumonia: Results from a claims analysis date: 2010-08-26 journal: Adv Ther DOI: 10.1007/s12325-010-0062-1 sha: f8221cd6d3960c4901166814528f9373a657b78e doc_id: 780516 cord_uid: uv8eura6 INTRODUCTION|: Antibiotic treatment failure contributes to the economic and humanistic burdens of community-acquired pneumonia (CAP) by increasing morbidity, mortality, and healthcare costs. This study compared treatment failure rates of levofloxacin with those of other antibiotics in a large US sample. METHODS|: Medical and pharmacy claims in the nationally representative SDI database were used to identify adults with a new outpatient diagnosis of CAP receiving a study antibiotic (levofloxacin, amoxicillin/clavulanate, azithromycin, moxifloxacin) between September 1, 2005 and March 31, 2008. Treatment failure was defined as ≥1 of the following events ≤30 days after index date: a refill for the index antibiotic after completed days of therapy, a different antibiotic dispensed >1 day after the index prescription, or hospitalization with a pneumonia diagnosis or emergency department visit >3 days postindex. Cohorts were propensity score matched for demographic and clinical characteristics. Treatment failure rates were compared between pairs of cohorts for the full sample and for high-risk patients (age ≥65 and/or on Medicaid). RESULTS|: Among the 3994 study patients, the numbers of dispensed index prescriptions were 268 for amoxicillin/clavulanate, 1609 for azithromycin, 1460 for levofloxacin, and 657 for moxifloxacin. Unadjusted treatment failure rates for the sample were 20.8% for levofloxacin, 23.9% for amoxicillin/clavulanate, 23.9% for azithromycin, and 19.9% for moxifloxacin. For high-risk patients, unadjusted treatment failure rates were 19.1% for levofloxacin, 26.1% for amoxicillin/clavulanate, 26.3% for azithromycin, and 24.3% for moxifloxacin. Propensity score-matched treatment failure rates were significantly lower with levofloxacin than azithromycin (19.8% vs. 24.5%, odds ratio [OR] comparator vs. levofloxacin 1.38; 95% CI: 1.14, 1.67), a difference amplified in high-risk patients (19.0% vs. 26.4%, OR 1.61; 95% CI: 1.22, 2.13). No significant differences were observed for other paired comparisons. CONCLUSION|: In a large US sample, treatment failure in CAP appeared to be less likely with quinolones (such as levofloxacin) than azithromycin, an effect particularly marked in high-risk patients (age ≥65 and/or on Medicaid). The medical claims database, established in 1999, includes more than 600,000 annual claims (CMS-1500 forms) containing diagnosis and visit information and represents activity of more than 450,000 physicians per month. This study was exempt from institutional review board approval as it was retrospective, did not involve an intervention, and utilized anonymized data. The study included patients ≥18 years old given a primary or secondary diagnosis of pneumonia (based on CMS-1500 medical claims) ( The primary outcome of interest was the treatment failure rate. Treatment failure was defined, in a manner consistent with the medical literature, 6,10-12,15 as ≥1 of the following events Propensity scores (predicted probabilities) were estimated from each of the three logistic regression models, and levofloxacin patients were then matched 1:1 by propensity score to patients with the comparator antibiotic using nearest-neighbor matching within a predefined caliper. Treatment failure rates were compared using Bowker's test for paired observations. The third method compared treatment failure rates in the propensity score-matched treatment cohorts using logistic regression analyses. Odds ratios (OR) for the likelihood of treatment failure with each comparator antibiotic versus levofloxacin and 95% CIs were calculated. The analyses described above, which were done in the full patient sample, were also conducted for a subset of patients considered to be at high risk for treatment failure. The highrisk subset was defined as being ≥65 years old and/or on Medicaid. 16 In both the sample as a whole and the high- Of 1 (Figure 3) . No other significant differences were found in propensity scorematched treatment failure rates in either the full sample or the high-risk subset (Figure 3 ). Patients treated with azithromycin were 38% more likely to experience treatment failure Moxi oxacin, 24.3% n=325 Figure 2 . Unadjusted treatment failure rates in the full sample and the high-risk subset. *P<0.05 vs. levofloxacin. Table 3 . Treatment failure in CAP is associated with heightened risk of morbidity and mortality and The results of this study are also consistent with data from a retrospective, claims-based analysis of patients with CAP treated in an outpatient setting in a large US health plan. 15 In a propensity score-adjusted analysis, patients with CAP treated with levofloxacin (n=2520) were significantly less likely than those treated with a macrolide (n=2520) to experience treatment failure, defined as a second antibiotic claim after the index prescription date or hospital admission with a primary or secondary diagnosis of CAP. Moreover, the incidence of CAP-related emergency department visits was 22% lower among levofloxacin-treated patients than macrolide-treated patients although significant differences were not observed for CAP-related hospitalizations or total CAP-related healthcare costs. In that study, 15 as in the current study, benefits of levofloxacin were particularly marked in patients aged ≥65 years. Whereas levofloxacin was associated with a 16% lower risk of treatment failure than macrolides in the sample as a whole, levofloxacin was associated with a 35% lower risk of treatment failure in patients aged ≥65 The reason for the lower treatment failure rates with levofloxacin compared with azithromycin (and with macrolides generally in the study reported above) 15 In the current study, the benefit of levofloxacin over azithromycin with respect to treatment failure was manifested both in the unadjusted data and in the propensity score- show that levofloxacin was associated with a significantly lower rate of treatment failure than azithromycin in both the sample as a whole and a high-risk subset of patients who were ≥65 years old and/or on Medicaid. The results of this study show that the treatment failure rate tended to be lower in the levofloxacin group compared with the amoxicillin/clauvulanate group or the moxifloxacin group although the differences were not statistically significant. Community-acquired pneumonia Deaths: final data for Ambulatory 3. medical care utilization estimates for National hospital discharge survey Antibiotics 5. for community acquired pneumonia in adult outpatients Community-acquired pneumonia: 6. the US perspective the clinic. Community-acquired 7. pneumonia Treatment failure in 8. community-acquired pneumonia Causes and factors associated with early failure in hospitalized patients with community-acquired pneumonia Risk 10. factors of treatment failure in community acquired pneumonia: implications for disease outcome Early and late treatment 11. failure in community-acquired pneumonia Paladino JJ. 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Antimicrobial susceptibility of pathogens isolated from more than 10,000 patients with infectious respiratory diseases: a 25-year longitudinal study Increase in pneumococcus 20. macrolide resistance, United States International guidelines for the 21. treatment of community-acquired pneumonia in adults: the role of macrolides Hidden epidemic of 22. macrolide-resistant pneumococci A case series of macrolide treatment failures in community acquired pneumonia The authors acknowledge Jane Saiers, PhD