Comparing the cost-effectiveness of linezolid to trimethoprim/sulfamethoxazole plus rifampicin for the treatment of methicillin-resistant Staphylococcus aureus infection: a healthcare system perspective.

OBJECTIVE: Few industry-independent studies have been conducted to compare the relative costs and benefits of drugs to treat methicillin-resistant Staphylococcus aureus (MRSA) infection. We performed a stochastic cost-effectiveness analysis comparing two treatment strategies-linezolid versus trimethoprim-sulfamethoxazole plus rifampicin-for the treatment of MRSA infection. METHODS: We used cost and effectiveness data from a previously conducted clinical trial, complementing with other data from published literature, to compare the two regimens from a healthcare system perspective. Effectiveness was expressed in terms of quality-adjusted life-years (QALYs). Several sensitivity analyses were performed using Monte Carlo simulation, to measure the effect of potential parameter changes on the base-case model results, including potential differences related to type of infection and drug toxicity. RESULTS: Treatment of MRSA infection with trimethoprim-sulfamethoxazole plus rifampicin and linezolid were found to cost on average €146 and €2536, and lead to a gain of 0.916 and 0.881 QALYs, respectively. Treatment with trimethoprim-sulfamethoxazole plus rifampicin was found to be more cost-effective than linezolid in the base case and remained dominant over linezolid in most alternative scenarios, including different types of MRSA infection and potential disadvantages in terms of toxicity. With a willingness-to-pay threshold of €0, €50 000 and €200 000 per QALY gained, trimethoprim-sulfamethoxazole plus rifampicin was dominant in 100%, 96% and 85% of model iterations. A 95% discount on the current purchasing price of linezolid would be needed when it goes off-patent for it to represent better value for money compared with trimethoprim-sulfamethoxazole plus rifampicin. CONCLUSIONS: Combined treatment of trimethoprim-sulfamethoxazole plus rifampicin is more cost-effective than linezolid in the treatment of MRSA infection.

Randomized non-inferiority trial to compare trimethoprim/sulfamethoxazole plus rifampicin versus linezolid for the treatment of MRSA infection.

OBJECTIVES: The therapeutic arsenal for MRSA infections is limited. The aim of this study was to assess the non-inferiority of a combination of trimethoprim/sulfamethoxazole plus rifampicin versus linezolid alone for the treatment of MRSA infection. METHODS: We conducted a randomized, open-label, single-centre, non-inferiority trial comparing trimethoprim/sulfamethoxazole (160 mg/800 mg three times daily) plus rifampicin (600 mg once a day) versus linezolid (600 mg twice a day) alone in adult patients with various types of MRSA infection. Patients were allocated 1:1 to either regimen. The primary outcome was clinical cure at 6 weeks after the end of treatment (non-inferiority margin 20%) assessed by both ITT and PP analyses. Secondary outcomes included the microbiologically documented persistence of MRSA in clinical cultures, mortality and adverse events. The study protocol has been registered with ClinicalTrials.gov (NCT00711854). RESULTS: Overall, 150 patients were randomized to one of the two treatment arms between January 2009 and December 2013 and were included in the ITT analysis. Of these 56/75 (74.7%) in the linezolid group and 59/75 (78.7%) in the trimethoprim/sulfamethoxazole and rifampicin group experienced clinical success (risk difference 4%, 95% CI -9.7% to 17.6%). The results were confirmed by the PP analysis, with 54/66 (81.8%) cured patients in the linezolid group versus 52/59 (88.1%) in the trimethoprim/sulfamethoxazole and rifampicin group (risk difference 6.3%, 95% CI -6.8% to 19.2%). There were no statistically significant differences between the two groups in any of the secondary outcomes, including microbiologically documented failure. Four adverse drug reactions attributed to the study medication occurred in the linezolid group versus nine in the trimethoprim/sulfamethoxazole and rifampicin group. CONCLUSIONS: Compared with linezolid, trimethoprim/sulfamethoxazole and rifampicin seems to be non-inferior in the treatment of MRSA infection.

Burden of meticillin-resistant Staphylococcus aureus infections at a Swiss University hospital: excess length of stay and costs.

BACKGROUND: Meticillin-resistant Staphylococcus aureus (MRSA) infections increase hospital costs primarily by prolonging patient length of stay (LOS). AIM: To estimate the health-economic burden of MRSA infections at a Swiss University hospital using different analytical approaches. METHODS: Excess LOS was estimated by: (i) multistate modelling comparing MRSA-infected and MRSA-free patients with MRSA infection as time-dependent exposure; (ii) matching MRSA-infected patients with a cohort of MRSA-uninfected patients. The economic impact was assessed by: (i) comparing cost estimates between MRSA-infected and MRSA-free patients and multiplying excess LOS by bed-day cost; (ii) comparing real costs between MRSA-infected and MRSA-colonized non-infected patients. FINDINGS: The crude mean LOS was 37.3, 33.0 and 8.8 days for MRSA-infected, MRSA-colonized and MRSA-free patients, respectively. Excess LOS attributable to MRSA infection was 11.5 [95% confidence interval (CI): 7.9-15] or 15.3 days according to multistate modelling and matched analysis, respectively. The likelihood of discharge after MRSA infection was significantly reduced (adjusted hazard ratio: 0.69; 95% CI: 0.59-0.81). Average bed-day costs for MRSA-infected patients were 1.49- and 1.26-fold higher than for the general population hospitalized in acute wards and MRSA-colonized patients, respectively. MRSA infection resulted in an average additional cost of about 800 Swiss francs per day. CONCLUSIONS: This analysis emphasizes the financial impact of MRSA infections, demonstrates the importance of accounting for time-dependent bias and confirms that multistate modelling is a valid strategy for estimating excess LOS and costs after MRSA infection.

Invasive fusariosis with prolonged fungemia in a patient with acute lymphoblastic leukemia: case report and review of the literature.

Fusariumspp are rare but important opportunistic pathogens in immunocompromised patients. Disseminated fusarial infections occur mostly in patients with hematologic malignancies with myelosuppressive chemotherapy or in patients with severe immunodeficiency. Although more frequent than Aspergillus fungemia, Fusarium fungemia remains a rare event. We describe the case of a female patient with febrile neutropenia and persistent fungemia due to Fusarium solani, treated with posaconazole and liposomal amphotericin B. A review of the literature for Fusariumspp fungemia was carried out.