Cotrimoxazole Versus Vancomycin for Invasive Methicillin-resistant Staphylococcus Aureus Infections

• Status: Completed
• Trial end date: 2014-06-01
• Target enrollment: 0
• Participant gender: All

Summary

Methicillin-resistant Staphylococcus aureus (SA) is a major pathogen causing mainly health-care associated infections and, lately, also community acquired infections. Few treatment choices exist to treat these infections. The currently recommended antibiotics for these infections are glycopeptides (vancomycin or teicoplanin). Glycopeptide treatment hs several disadvantages. It is a last resort antibiotic family that should be reserved for the future; Vancomycin is less effective that beta-lactam drugs for SA infections susceptible to both agents; treatment can only be given intravenously; and use of vancomycin has led to the development of SA strains with partial or complete resistance to vancomycin. Cotrimoxazole is an old antibiotic active against most strains of MRSA, depending on local epidemiology.

Study hypothesis: The purpose of this study is to show that cotrimoxazole is as effective as treatment with vancomycin for invasive MRSA infections.

We plan a randomized controlled trial comparing treatment with cotrimoxazole vs. vancomycin for invasive MRSA infections. The primary efficacy outcome we will assess will be Improvement or cure with or without antibiotic modifications, defined as: survival at 7 days post randomization with resolution of fever (<38 for two consecutive days) and resolution of hypotension (>90 systolic without need for vasopressor support); and physician's assessment that the primary infection was improved or cured. The primary safety outcome will be all-cause 30-day survival.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Rabin Medical Center
• Treatments: Methicillin; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

Criteria

Inclusion Criteria:

• Adults >18 years

• providing signed informed consent or, if unable, having a legal guardian or a caretaker that will sign informed consent

• Patients with documented MRSA infections:

• MRSA bacteremia

• Other microbiologically documented MRSA infections defined as a clinical source of infection (CDC criteria) plus microbiological documentation of MRSA from the source of infection

• Patients with highly probable MRSA infections, prior to microbiological documentation of the pathogen:

• Suspected neurosurgical meningitis (including VP-shunt meningitis)

• Sepsis during hemodialysis

• Ventilator-associated pneumonia with prior antibiotic treatment within 48 hours

• Catheter-related or suspected catheter-related infections

• Surgical site infection in the presence of a foreign body

Exclusion Criteria:

Exclusion before randomization:

• Previous antibiotic treatment directed against MRSA >48 hours (including vancomycin, fucidic acid, rifampicin or cotrimoxazole)

• Known allergy to either study drug

• Acute leukemia and/ or BMT with neutropenia <500/mm3 or <1000/mm3 and expected to decrease below 500/mm3

• Pregnancy, lactation

• Previous enrollment in this study

• Concurrent participation in another trial

Exclusions after randomization:

• Documented Staphylococcal infection resistant to cotrimoxazole or VISA or VRSA

• Documented MSSA

• Documented left-sided endocarditis