PMID- 24011955
OWN - NLM
STAT- MEDLINE
DCOM- 20140507
LR  - 20151119
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 35
IP  - 10
DP  - 2013 Oct
TI  - Impact of weight on treatment efficacy and safety in complicated skin and skin 
      structure infections and nosocomial pneumonia caused by methicillin-resistant 
      Staphylococcus aureus.
PG  - 1557-70
LID - S0149-2918(13)00823-0 [pii]
LID - 10.1016/j.clinthera.2013.08.001 [doi]
AB  - 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.
CI  - (c) 2013 Elsevier HS Journals, Inc. All rights reserved.
FAU - Puzniak, Laura A
AU  - Puzniak LA
AD  - Pfizer Inc, Collegeville, Pennsylvania.
FAU - Morrow, Lee E
AU  - Morrow LE
FAU - Huang, David B
AU  - Huang DB
FAU - Barreto, Jason N
AU  - Barreto JN
LA  - eng
SI  - ClinicalTrials.gov/NCT00084266
SI  - ClinicalTrials.gov/NCT00087490
PT  - Clinical Trial, Phase IV
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20130903
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Acetamides)
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Oxazolidinones)
RN  - 6Q205EH1VU (Vancomycin)
RN  - ISQ9I6J12J (Linezolid)
SB  - IM
MH  - Acetamides/administration & dosage/adverse effects/*therapeutic use
MH  - Adult
MH  - Aged
MH  - Anti-Bacterial Agents/administration & dosage/adverse effects/*therapeutic use
MH  - *Body Weight
MH  - Cross Infection/*drug therapy/microbiology
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Linezolid
MH  - Male
MH  - Methicillin-Resistant Staphylococcus aureus/*drug effects
MH  - Middle Aged
MH  - Oxazolidinones/administration & dosage/adverse effects/*therapeutic use
MH  - Pneumonia, Staphylococcal/*drug therapy/microbiology
MH  - Staphylococcal Skin Infections/*drug therapy/microbiology
MH  - Treatment Outcome
MH  - Vancomycin/administration & dosage/adverse effects/*therapeutic use
OTO - NOTNLM
OT  - MRSA
OT  - cSSSI
OT  - linezolid
OT  - nosocomial pneumonia
OT  - vancomycin
OT  - weight
EDAT- 2013/09/10 06:00
MHDA- 2014/05/08 06:00
CRDT- 2013/09/10 06:00
PHST- 2013/03/09 00:00 [received]
PHST- 2013/06/21 00:00 [revised]
PHST- 2013/08/01 00:00 [accepted]
PHST- 2013/09/10 06:00 [entrez]
PHST- 2013/09/10 06:00 [pubmed]
PHST- 2014/05/08 06:00 [medline]
AID - S0149-2918(13)00823-0 [pii]
AID - 10.1016/j.clinthera.2013.08.001 [doi]
PST - ppublish
SO  - Clin Ther. 2013 Oct;35(10):1557-70. doi: 10.1016/j.clinthera.2013.08.001. Epub 
      2013 Sep 3.