title: Serum peak sulfamethoxazole concentrations demonstrate difficulty in achieving a target range: a retrospective cohort study.
abstract: OBJECTIVE
  Trimethoprim (TMP)/sulfamethoxazole (SMX) has consistently demonstrated great interindividual variability. Therapeutic drug monitoring may be used to optimize dosing. Optimal peak SMX concentration has been proposed as 100 to 150 μg/mL. The objective of our work was to determine the success rate of a TMP/SMX dosing guideline in achieving a targeted serum peak SMX concentration range.
  
  
  METHODS
  Our retrospective cohort study enrolled 305 adult hospitalized patients who received treatment with TMP/SMX and underwent serum peak SMX concentration monitoring from January 2003 to November 2011. Patients receiving low-dose TMP/SMX therapy (TMP <15 mg/kg/d) were compared with those receiving high-dose therapy (TMP >15 mg/kg/d).
  
  
  RESULTS
  Patients were classified into peak and modified peak SMX concentration cohorts based on time between TMP/SMX dose and SMX quantification. The association between dosing group and the outcome of the SMX level within the goal range was measured using logistic regression models. The primary outcome measured was serum peak SMX concentration 100 to 150 μg/mL. Serum peak SMX concentrations were attained within range for the peak and modified peak cohort 29% and 26% of the time, respectively. The median peak SMX concentration was 144 μg/mL (range 25-471 μg/mL). The low daily dose cohort demonstrated a trend toward improvement in the odds of target peak concentration range attainment. The results were similar regardless of the method used to adjust for baseline characteristics. The pure peak and modified peak cohorts had 44% and 46% of patients with above-target SMX peak concentrations, respectively.
  
  
  CONCLUSIONS
  Attainment of the intended target concentration range was low with no difference in attainment between the low-dose and high-dose cohorts. Higher proportions of patients had an above-target SMX peak, which may indicate that the dosing algorithm is overly aggressive in obtaining the therapeutic goal.
authors.affiliation: Department of Pharmacy Services, Mayo Clinic, Rochester, Minnesota ; Current affiliation: Department of Clinical Pharmacy, University of California San Francisco, San Francisco, California.
authors.forename: Bao D
authors.initials: BD
authors.lastname: Dao
authors.affiliation: Department of Pharmacy Services, Mayo Clinic, Rochester, Minnesota.
authors.forename: Jason N
authors.initials: JN
authors.lastname: Barreto
authors.affiliation: Department of Pharmacy Services, Mayo Clinic, Rochester, Minnesota.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Wolf
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Ross A
authors.initials: RA
authors.lastname: Dierkhising
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Plevak
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Pritish K
authors.initials: PK
authors.lastname: Tosh
keywords: Serum peak concentration; Sulfamethoxazole; Therapeutic drug monitoring; Trimethoprim