Initial treatment failure in non-ICU community-acquired pneumonia: risk factors and association with length of stay, total hospital charges, and mortality

Abstract

Objectives:

To identify risk factors for initial treatment failure in patients with community-acquired pneumonia (CAP) in non-intensive care unit (non-ICU) settings, and to characterize the association between initial treatment failure and length of stay, total hospital charges, and mortality.

Methods:

Retrospective cohort study. Using data from >100 US hospitals, this study identified all adults (age ≥18 years) hospitalized for pneumonia between January 1, 2000 and June 30, 2009 who began antibiotic therapy within 24 h of admission and were treated for at least 48 h if alive; patients admitted to intensive care within the first 24 h in hospital were excluded. Initial therapy was defined as all parenteral antibiotics administered within the first 24 h in hospital. Treatment failure was assessed based on subsequent receipt of new antibiotic(s), excluding agents of similar/narrower spectrum and those begun at discharge. Multivariate logistic regression was used to identify risk factors for treatment failure, and multivariate linear and logistic regression to compare length of stay, total hospital charges, and in-hospital mortality between patients experiencing initial treatment failure and those who did not.

Results:

Among 32,324 patients with non-ICU CAP, 4695 (14.6%) experienced initial treatment failure, most often within 72 h of hospital admission. Significant predictors of initial treatment failure included malnourishment (OR = 1.87; 95% CI = 1.60–2.18), receipt of vasoactive medications within 24 h of admission (1.51 [1.17–1.94]), and renal failure (1.45 [1.32–1.59]). Treatment failure was associated with higher case fatality (8.5% vs 3.3%), longer hospital stays (mean [SD] = 10.1 [8.1] days vs 4.9 [3.3] days), and higher total hospital charges ($37,602 [$71,876] vs $14,371 [$21,633]) (all comparisons, p < 0.01). Study limitations include possible inclusion of patients with healthcare-associated pneumonia (HCAP) in the study sample, our focus on the 40 most commonly used antibiotic regimens, and indirect measurement of treatment failure.

Conclusions:

Approximately one in seven non-ICU CAP patients experience failure of initial antibiotic therapy. Risk of failure is higher for patients with significant comorbidities and/or severe infections. Non-ICU patients who experience initial treatment failure have significantly longer hospital stays, higher total hospital charges, and higher rates of mortality.

Keywords::

• Antibiotics
• Anti-bacterial agents
• Treatment failure
• Pneumonia
• Community-acquired infections

Transparency

Declaration of funding

This study was supported by Forest Research Institute, Inc. Forest Research Institute, Inc. was involved in the design and decision to present these results. Funding for editorial assistance was provided by Forest Research Institute, Inc. Forest Research Institute, Inc. had no involvement in the collection, analysis, or interpretation of data. Data management, processing, and analyses were conducted by AB, JE, and GO. All authors read and approved the final manuscript.

Declaration of financial/other relationships

AB, JE, and GO are employed by Policy Analysis Inc., which received study funding from Forest Laboratories, Inc. DW was a paid consultant to Policy Analysis Inc. on this study. CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

We thank Scientific Therapeutics Information, Inc. (Springfield, New Jersey) for their editorial assistance. Portions of this research were presented previously at the 2010 Annual Meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) (‘Real-World’ Failure of Initial Antibiotic Therapy in Non-ICU Community-Acquired Pneumonia [CAP] in US Hospitals, 2000–2009) (September 12–15, 2010; Boston, MA), and the 2010 Mid-Year Clinical Meeting of the American Society of Health System Pharmacists (ASHP) (Consequences of Failure of Initial Antibiotic Therapy in Patients with Non-ICU Community-Acquired Pneumonia [CAP] in US Hospitals, 2000–2009) (December 5–9, 2010; Anaheim, CA).