Trimethoprim-sulfamethoxazole dosing and outcomes of pulmonary nocardiosis

Abstract

Background: Nocardia often causes pulmonary infection among those with chronic pulmonary disease or immunocompromising conditions. Trimethoprim-sulfamethoxazole (TMP-SMX) is recommended as first-line treatment, though little data exists regarding outcomes of different dosing regimens.

Methods: We performed a multicenter retrospective cohort study of adult patients with non-disseminated pulmonary nocardiosis initially treated with TMP-SMX monotherapy. Patients' initial TMP-SMX dosing was categorized as high- (> 10 mg/kg/day), intermediate- (5-10 mg/kg/day) or low-dose (< 5 mg/kg/day). Outcomes included one-year mortality, post-treatment recurrence, and dose adjustment or early discontinuation of TMP-SMX. SMX serum concentrations and their effect on management were also assessed. Inverse probability of treatment weighting was applied to Cox regression analyses.

Results: Ninety-one patients were included with 24 (26.4%), 37 (40.7%), and 30 (33.0%) treated with high-, intermediate-, and low-dose TMP-SMX, respectively. Patients who initially received low-dose (HR 0.07, 95% CI 0.01-0.68) and intermediate-dose TMP-SMX (HR 0.27, 95% CI 0.07-1.04) had lower risk of one-year mortality than the high-dose group. Risk of recurrence was similar between groups. Nineteen patients had peak SMX serum concentrations measured which resulted in 7 (36.8%) dose changes and was not associated with one-year mortality or recurrence. However, 66.7% of the high-dose group required TMP-SMX dose adjustment/discontinuation compared to 24.3% of the intermediate-dose and 26.7% of the low-dose groups (p = 0.001).

Conclusions: Low- and intermediate-dose TMP-SMX for non-disseminated pulmonary nocardiosis were not associated with poor outcomes compared to high-dose therapy, which had a higher rate of dose adjustment/early discontinuation. Historically used high-dose TMP-SMX may not be necessary for management of isolated pulmonary nocardiosis.

Keywords: Nocardia; Bactrim; Bronchiectasis; Dose; Sulfonamide.

Fig. 1

Histogram and density plot of initial, weight-based trimethoprim doses after adjusting for baseline creatinine clearance. The bars represent the number of patients with specific trimethoprim-sulfamethoxazole doses, with a bin width of 0.5 mg/kg/day of trimethoprim

Fig. 2

Love plot displaying averaged standardized mean differences of propensity score variables between trimethoprim-sulfamethoxazole dosing categories before and after inverse probability of treatment weighting (IPTW)

Fig. 3

Kaplan-Meier curves illustrating the occurrence of one-year mortality (A) and all-time recurrence (B). The p-values were calculated via the log-rank test and the vertical hash marks represent censored patients

Fig. 4

Kaplan-Meier curves illustrating one-year mortality in those with chronic pulmonary disease (A) and receiving immunocompromising medications (B), as well as all-time recurrence in those with chronic pulmonary disease (C) and receiving immunocompromising medications (D). The p-values were calculated via the log-rank test and the vertical hash marks represent censored patients