Impact of Weight on Treatment Efficacy and Safety in Complicated Skin and Skin Structure Infections and Nosocomial Pneumonia Caused by Methicillin-Resistant Staphylococcus aureus

• Published in: Clinical therapeutics 2013-10, Vol.35 (10), p.1557-1570
• Main Authors: Puzniak, Laura A., PhD, MPH, Morrow, Lee E., MD, Huang, David B., MD, PhD, Barreto, Jason N., PharmD
• Format: Article
• Language: English
• Subjects: Acetamides - administration & dosage; Acetamides - adverse effects; Acetamides - therapeutic use; Adult; Aged; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - therapeutic use; Biological and medical sciences; Body Weight; Clinical trials; Cross Infection - drug therapy; Cross Infection - microbiology; cSSSI; Dose-Response Relationship, Drug; Drug dosages; General aspects; Human infectious diseases. Experimental studies and models; Humans; Infectious diseases; Internal Medicine; Linezolid; Lymphatic system; Male; Medical Education; Medical sciences; Medical treatment; Methicillin-Resistant Staphylococcus aureus - drug effects; Middle Aged; MRSA; Nosocomial infections; nosocomial pneumonia; Obesity; Oxazolidinones - administration & dosage; Oxazolidinones - adverse effects; Oxazolidinones - therapeutic use; Patients; Pharmacology. Drug treatments; Pneumonia, Staphylococcal - drug therapy; Pneumonia, Staphylococcal - microbiology; Skin; Staphylococcal Skin Infections - drug therapy; Staphylococcal Skin Infections - microbiology; Staphylococcus aureus; Staphylococcus infections; Studies; Treatment Outcome; vancomycin; Vancomycin - administration & dosage; Vancomycin - adverse effects; Vancomycin - therapeutic use; weight
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2013.08.001

Abstract Background There are few data on dose optimization and clinical outcomes of antimicrobial agents based on patients’ weight, despite the rising prevalence of obesity. Because there are physiologic, pharmacologic, and dosing differences related to weight, it is important to evaluate the impact of weight on antimicrobial agents to optimize clinical outcomes. Objectives This study compared effects of weight on efficacy and safety in patients treated with linezolid or vancomycin for complicated skin and skin structure infections (cSSSIs) and nosocomial pneumonia (NP) caused by methicillin-resistant Staphylococcus aureus (MRSA). Methods We analyzed data from 2 clinical trials of patients randomized to receive a fixed dose of linezolid or weight-based dosing of vancomycin for the treatment of cSSSIs or NP caused by MRSA. For each study, patients were stratified into quartiles (Q1–4 [lowest to highest weight, respectively]). Clinical success, microbiologic success, and adverse events (AEs) were evaluated. Results The analysis included 632 patients with cSSSIs (linezolid, n = 316; vancomycin, n = 316) and 447 patients with NP (linezolid, n = 224; vancomycin, n = 223). Among patients with cSSSIs, clinical success rates at the study end with fixed-dose linezolid were similar across all weight quartiles and similar to weight-based dosing of vancomycin for Q1–3. Among Q4 (the highest weight quartile [97–295 kg]), clinical success with vancomycin was significantly lower compared with linezolid (69.5% vs 86.2%; P = 0.03). Among patients with NP, no significant differences in success rates between fixed-dose linezolid and weight-based dosing of vancomycin were observed across all quartiles. Frequencies of AEs were consistent across the quartiles for both indications and by treatment. Conclusions Except for Q4 within the vancomycin-treated patients for MRSA cSSSI, the efficacy of fixed-dosed linezolid and weight-based dosing of vancomycin was maintained across all weight quartiles and MRSA infection types. The AEs were consistent with the known safety profiles of each drug regardless of weight quartile. ClinicalTrials.gov identifiers: NCT00087490 and NCT00084266.