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Serum peak sulfamethoxazole concentrations demonstrate difficulty in achieving a target range: a retrospective cohort
Bao D Dao1, Jason N Barreto2, Robert C Wolf2
1Department of Pharmacy Services, Mayo Clinic, Rochester, Minnesota ; Current affiliation: Department of Clinical Pharmacy, University of California San Francisco, San Francisco, California.
Objectives:
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.
Insights
Achieving target serum peak concentrations of sulfamethoxazole (SMX) with trimethoprim/sulfamethoxazole (TMP/SMX) dosing guidelines was low. Many patients exceeded the therapeutic SMX range, suggesting the dosing algorithm may be too aggressive.
Area of Science:
- Pharmacology
- Clinical Pharmacy
- Infectious Diseases
Background:
- Trimethoprim/sulfamethoxazole (TMP/SMX) exhibits significant interindividual variability in drug levels.
- Therapeutic drug monitoring (TDM) is a strategy to optimize TMP/SMX dosing.
- A target peak serum SMX concentration of 100–150 μg/mL has been proposed for optimal efficacy.
Purpose of the Study:
- To evaluate the success rate of a TMP/SMX dosing guideline in achieving the target peak SMX concentration range.
- To compare low-dose versus high-dose TMP/SMX therapy regarding SMX concentration attainment.
Main Methods:
- Retrospective cohort study of 305 hospitalized adult patients receiving TMP/SMX.
- Patients were categorized into low-dose (TMP <15 mg/kg/d) and high-dose (TMP >15 mg/kg/d) groups.
- Serum peak SMX concentrations were measured and analyzed using logistic regression.
Main Results:
- Target peak SMX concentrations (100–150 μg/mL) were achieved in only 29% (peak cohort) and 26% (modified peak cohort) of patients.
- The median peak SMX concentration was 144 μg/mL.
- A high proportion of patients had above-target SMX peak concentrations (44% and 46% in the respective cohorts).
Conclusions:
- The TMP/SMX dosing guideline demonstrated a low success rate in achieving the intended target SMX concentration range.
- No significant difference in target attainment was observed between low-dose and high-dose TMP/SMX cohorts.
- The high incidence of above-target SMX levels suggests the current dosing algorithm may be overly aggressive.
