Pid10: Effects of Linezolid on Hospital Length of Stay in Methicillin-Resistant Staphylococcus Infections Estimated From Multivariate Survival Analysis

Abstract

OBJECTIVES: To estimate differences in adjusted hospital length of stay (LOS) between linezolid and vancomycin using multivariate survival analysis. Linezolid's bioequivalent IV and oral formulations may enable earlier hospital discharge compared to vancomycin treatment. METHODS: 460 hospitalized patients with suspected/confirmed methicillin‐resistant Staphylococcus infections were treated with either linezolid (LZD) or vancomycin (VAN) in a randomized controlled trial. Covariate imbalances between treatment groups were tested using t‐tests and chi‐square tests. Multivariate Cox proportional hazards and several parametric models for LOS were tested for best fit using the Akaike Information Criteria and log‐likelihood ratio statistics. The Cox proportional hazards assumption was rejected (p < .05); log‐logistic survival models fit best. The log‐logistic estimates are used to create two alternative adjusted survivorship functions, one based on individual corrections to LOS (Individual correction), and the other based on means of the predicted survivorship function for each individual (Mean survivorship). Adjusted LOS at quartiles of % discharged for each function was compared with unadjusted LOS using Kaplan‐Meier method. RESULTS: Hospital unit type at randomization and number of comorbidities both differed significantly between groups and significantly affected LOS. With covariate controls in the log‐logistic model, linezolid treatment significantly reduced LOS (p = .04). Adjusted/unadjusted LOS at quartiles of % discharged were: CONCLUSIONS: When adjusted for covariate differences, median LOS for linezolid patients was at least 2 days shorter than for vancomycin patients. Other differences in the LOS distribution are evident and may be important to decision‐makers but off‐median estimates may be sensitive to the adjustment method used. Methodologic considerations are explored further. % discharged Adjusted LOS (days) Unadjusted LOS Individual correction Mean survivorship Kaplan‐Meier LZDVANLZDVANLZDVAN25610696850 (median)14161316141575262828292929

Linezolid versus vancomycin for the treatment of Gram-positive bacterial infections: meta-analysis of randomised controlled trials

“…1). Of these studies, seven RCTs were excluded because they only studied the length of hospital stay and economic variables [20][21][22][23][24][25][26], four RCTs were excluded because they were part of RCTs already included in the meta-analysis and the data from these reports were used if additional useful information could be extracted [27][28][29][30], one RCT was excluded because it was written in Russian [31], one RCT was excluded because it was done in cancer patients [32] and one RCT was excluded because it had heterogeneity with other RCTs [33]. Thus, nine RCTs were included in the meta-analysis [34][35][36][37][38][39][40][41][42].…”

Linezolid reduces length of stay and duration of intravenous treatment compared with vancomycin for complicated skin and soft tissue infections due to suspected or proven methicillin-resistant Staphylococcus aureus (MRSA)

“…As in many health outcomes analyses, LOS was chosen as the primary endpoint in this analysis since it has significant implications for healthcare costs [7,15]. Increased resource use and costs associated with the treatment of methicillinresistant Gram-positive infections, particularly those caused by MRSA, are largely due to increased LOS and/or complications of therapy [7,8,21,22].…”

“…Estimates of the mean and median LOS for the two treatment arms were obtained from Kaplan-Meier survival curves (duration analysis), a standard method for analysis of duration data that was also used in an earlier study [15], taking into account the censored LOS data. Differences between the survival curves for the two treatment arms were tested using the Wilcoxon Rank Sum Test.…”

Clinical results of linezolid in arthroplasty and trauma related infections

“…Further studies have also demonstrated reduction of length of hospital stay in patients with MRSA treated with linezolid [9,23] . Staphylococcus aureus is the single most common organism causing osteomyelitis secondary to trauma, surgery or insertion of a joint [24] . Chronic infection is notoriously difficult to treat.…”