Linezolid for the Treatment of Multidrug‐Resistant, Gram‐Positive Infections: Experience from a Compassionate‐Use Program

Abstract

Linezolid was provided for treatment of multidrug-resistant, gram-positive infections through a compassionate-use program. Patients (n=796) received 600 mg of linezolid intravenously or orally every 12 h (828 treatment courses). Bacteremia was present in 46% of infections, endocarditis was present in 10.6%, and line-related infections were present in 31.1%. Other infections included intraabdominal infections (15.1%), complicated skin and skin-structure infections (13.3%), and osteomyelitis (10.7%). Causative pathogens included vancomycin-resistant enterococci (66.3%) and methicillin-resistant staphylococci (22.1%). Clinical intent-to-treat (ITT) outcomes in the evaluable population were as follows: cure, 73.3%; failure, 6.8%; and indeterminate, 19.9%. Microbiological ITT outcomes in evaluable patients were as follows: cure, 82.4%; failure, 14.1%; and indeterminate, 3.5%. At the test of cure assessment, the clinical cure and microbiological success rates were 91.5% and 85.8%, respectively. The most common adverse events possibly related to linezolid use were gastrointestinal disturbances (9.8% of cases), thrombocytopenia (7.4% of cases), decreased hemoglobin/hematocrit levels (4.1% of cases), and cutaneous reactions (4.0% of cases). Linezolid provided high rates of clinical cure and microbiological success in this complicated patient population, with very good overall tolerance.

Linezolid induced optic neuropathy, a serious yet reversible adverse effect: a case report

“…[12,13] Prolonged use outside the recommended safe period is often undertaken but has previously been associated with optic and peripheral neuropathies. [2,[4][5][6][7] In this case the patient had already been on linezolid 600 mg once daily for fourteen months before she developed symptoms due to its toxicity.…”

Treating Central Catheter–Associated Bacteremia Due to Methicillin-Resistant Staphylococcus aureus: Beyond Vancomycin

“…6,9 Recent research supports use of alternative agents for MRSA bacteremia, but the use of these agents is often reserved for patients who cannot tolerate vancomycin, have persistent bacteremia during treatment with vancomycin, or have MRSA infections for which vancomycin MICs are elevated. 6,9,22,23,25,26,38 Daptomycin has the most data to support its use as an alternative agent in MRSA bacteremia in both the IDSA 2009 CLABSI and 2011 MRSA guidelines. Linezolid should be reserved for salvage therapy.…”

“…6 Available data do support use of linezolid as an alternative agent in MRSA bacteremia. The effectiveness of linezolid as definitive treatment for MRSA bacteremia was shown in an observational compassionate use program 25 as well as a pooled analysis 26 of data from 5 randomized controlled trials that showed similar clinical cure rates for vancomycin and linezolid (46% vs 56%; odds ratio, 1.47; 95% CI, 0.50-4.31). Additionally, findings of an open-label randomized controlled study 27 published in 2009 indicated that linezolid and vancomycin treatment of MRSA CLABSIs had similar successful clinical outcomes (79% vs 76%; 95% CI, -21 to 27).…”

Novel pharmaceutical molecules against emerging resistant gram-positive cocci

“…The following antibacterial agents have been approved during the last five years: quinupristin/dalfopristin, [29][30][31][32] linezolid, 33,34 daptomycin, [35][36][37] and tigecycline. 38,39 Novel lipoglycopeptide agents under study include dalbavancin, 40 telavancin, and oritavancin.…”