Elsevier

Clinical Therapeutics

Volume 36, Issue 9, 1 September 2014, Pages 1233-1243.e1
Clinical Therapeutics

Health Economic Evaluation of Patients Treated for Nosocomial Pneumonia Caused by Methicillin-resistant Staphylococcus aureus: Secondary Analysis of a Multicenter Randomized Clinical Trial of Vancomycin and Linezolid

https://doi.org/10.1016/j.clinthera.2014.06.029Get rights and content

Abstract

Purpose

Results from studies comparing health care resource use (HCRU), costs of treatment, and cost-effectiveness of linezolid compared with vancomycin therapy in the treatment of hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia are limited in the published literature. We therefore conducted an analysis to compare the HCRU, costs of treatment, and cost-effectiveness of linezolid compared with vancomycin in the treatment of hospitalized patients with MRSA nosocomial pneumonia using data from a Phase IV clinical trial. The economic effect of moderate to severe adverse events (MSAEs) and the development of renal failure were also evaluated.

Methods

We performed a post hoc analysis of data from a Phase IV, double-blind, randomized, comparator-controlled, multicenter trial that compared linezolid and vancomycin treatment in patients with MRSA nosocomial pneumonia. HCRU and costs were compared based on treatment, development of MSAEs, and development of renal failure using data from the modified intent-to-treat population. Predictors of costs were evaluated using generalized linear models. A piggyback cost-effectiveness analysis was conducted to assess the incremental cost-effectiveness ratio of linezolid versus vancomycin, given the significantly higher clinical success of linezolid compared with vancomycin found in the trial.

Findings

Overall, HCRU and costs were similar between the linezolid and vancomycin treatment groups; drug costs were significantly higher and dialysis costs significantly lower for linezolid- compared with vancomycin-treated patients. Total treatment costs were approximately $8000 higher (P = .046) for patients who developed renal failure compared with those who did not. Renal failure occurred more commonly in patients randomized to receive vancomycin (15%) compared with linezolid (4%; P < .001). Region, ventilator-associated pneumonia, clinical failure, and development of renal failure were associated with significantly higher total costs. The point estimate incremental cost-effectiveness ratio for linezolid compared with vancomycin was $16,516 per treatment success, with linezolid dominant in 24% and dominated in <2% of bootstrapped samples.

Implications

This phase 4 clinical trial conducted in patients with MRSA-confirmed nosocomial pneumonia reveals that linezolid- compared with vancomycin-treated patients had similar HCRU and total overall costs. Fewer patients developed renal failure during the study while taking linezolid compared with vancomycin, and patients with a documented MSAE or renal failure had increased HCRU and costs. In summary, linezolid may be a cost-effective treatment strategy in MRSA-confirmed nosocomial pneumonia.

Introduction

More than a quarter of hospital-acquired pneumonias were caused by Staphylococcus aureus, and of these, more than half are caused by methicillin-resistant S aureus (MRSA).1 Vancomycin is the mainstay of treatment for patients with serious MRSA infections, such as hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP).2 Recommendations are to achieve vancomycin trough concentration of 15 to 20 mg/L in patients with HAP and VAP to improve tissue penetration and patient outcomes and increase the probability of achieving optimal serum drug levels.2, 3

Historically, increased serum vancomycin trough concentrations were implicated as a cause of nephrotoxicity in patients treated with vancomycin.3 Recent data suggest that vancomycin trough levels of ≥15 mg/L may be an independent risk factor for nephrotoxicity.4, 5, 6, 7 A few studies have examined renal failure among patients treated with vancomycin.8, 9 However, the renal adverse events and associated economic burden of vancomycin in treating patients with nosocomial pneumonia caused by MRSA are unclear.

Linezolid is another treatment option for patients with MRSA nosocomial pneumonia. Linezolid, an oxazolidinone, was approved in 2000 by the US Food and Drug Administration for the treatment of gram-positive infections, including those caused by MRSA.10

To our knowledge, few publications from randomized clinical studies have compared health care resource use (HCRU), costs of treatment, and cost-effectiveness between linezolid and vancomycin in the treatment of hospitalized patients with confirmed MRSA nosocomial pneumonia. We therefore conducted an analysis to compare HCRU, costs of treatment, and cost-effectiveness of intravenous linezolid relative to intravenous vancomycin therapy for MRSA nosocomial pneumonia using data from the ZEPHyR study (Linezolid in the Treatment of Subjects with Nosocomial Pneumonia Proven to Be Due to Methicillin-Resistant Staphylococcus aureus).11 In this analysis, we also assessed the economic effect associated with the development of moderate to severe adverse events and renal failure.

Section snippets

Patient Populations

We conducted this post hoc analysis using data for the modified intent-to-treat population (mITT) from the ZEPHyR study.11 The complete methods for the ZEPHyR study are described in detail elsewhere.11 Briefly, patients were randomly assigned in a 1:1 ratio to either vancomycin 15 mg/kg IV every 12 hours or linezolid 600 mg IV every 12 hours for 7 to 14 days. The end of treatment visit was conducted within 5 days of end of therapy; the end of study (EOS) visit was conducted 7 to 30 days after

Results

A complete description of patient disposition and characteristics, clinical and microbiologic response, and tolerability outcomes for the ZEPHyR study is available in the published literature.11 Briefly, of the 1225 patients randomized to receive either linezolid (n = 618) or vancomycin treatment (n = 607), a total of 448 patients comprised the mITT population (linezolid, n = 224; vancomycin, n = 224). Demographic and clinical characteristics were similar between the treatment groups, except

Discussion

This study provides recent information regarding HCRU and costs associated with treating patients with MRSA-confirmed nosocomial pneumonia. Results from this post hoc clinical trial analysis revealed that linezolid treatment was associated with a lower incidence of renal failure and similar total costs compared with vancomycin treatment in patients with nosocomial pneumonia. Furthermore, this study is the first, to our knowledge, to report that that the cost of treating a patient with renal

Conclusions

This study provides updated information assessing overall HCRU and the effect of adverse events and renal failure on HCRU outcomes and associated costs in patients with MRSA nosocomial pneumonia. Study analyses were based on results from a randomized, double-blind, multicenter, clinical study designed to directly compare linezolid and vancomycin therapy in patients with proven MRSA nosocomial pneumonia. In addition to the significantly higher clinical response at EOS associated with linezolid

Conflicts of Interest

Pharmerit International received consulting fees from Pfizer Inc in connection with this study and development of this manuscript. C.T. Solem, Y. Wan, and X. Gao are employees of Pharmerit International. J.M. Stephens is an employee and shareholder of Pharmerit International. M. Niederman received an honorarium from Pfizer Inc in connection with his work on this study and has received research grants, has been an advisory board member, and participated in medical education activities organized

Acknowledgments

We thank Richard Chambers of Pfizer Inc and Professor Ben van Hout of the University of Sheffield for their contribution to study conceptualization, analysis plan, and review and interpretation of results. Medical writing support was provided by Beth Lesher, PharmD, BCPS, at Pharmerit International and was funded by Pfizer Inc.

M.S. Niederman and J. Chastre contributed to study conceptualization and design. C.T. Solem, Y. Wan, J.M. Stephens and X. Gao developed the analysis plan, methodology and

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