title: Impact of weight on treatment efficacy and safety in complicated skin and skin structure infections and nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Pfizer Inc, Collegeville, Pennsylvania.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Puzniak
authors.forename: Lee E
authors.initials: LE
authors.lastname: Morrow
authors.forename: David B
authors.initials: DB
authors.lastname: Huang
authors.forename: Jason N
authors.initials: JN
authors.lastname: Barreto
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001835:Body Weight; D003428:Cross Infection / Q000188:drug therapy* / Q000382:microbiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D000069349:Linezolid; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008875:Middle Aged; D023303:Oxazolidinones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011023:Pneumonia, Staphylococcal / Q000188:drug therapy* / Q000382:microbiology; D013207:Staphylococcal Skin Infections / Q000188:drug therapy* / Q000382:microbiology; D016896:Treatment Outcome; D014640:Vancomycin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D014640:Vancomycin; D000069349:Linezolid
keywords: MRSA; cSSSI; linezolid; nosocomial pneumonia; vancomycin; weight