Brief research report on toxicity-guided TMP-SMX dose reduction in disseminated nocardiosis.

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Frontiers in Medicine Published April 24, 2026 Medically reviewed April 24, 2026 DOI ↗ By Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

Key Takeaway

Consider that temporary TMP-SMX dose reduction may be a bridge in severe toxicity, but durable cure remains unconfirmed.

This is a brief research report detailing a single case of disseminated nocardiosis with central nervous system involvement in a 55-year-old male gold miner with pneumoconiosis and chronic corticosteroid use. The report describes a toxicity-guided dose modification of trimethoprim-sulfamethoxazole (TMP-SMX), de-escalating from 15 mg·kg⁻¹·d⁻¹ to 11.25 mg·kg⁻¹·d⁻¹, then maintaining at 7.5 mg·kg⁻¹·d⁻¹, in combination with imipenem and amikacin, following initial failure of empirical meropenem.

The authors report clinical improvement observed at Day 120. However, durable cure remains unconfirmed. The patient experienced grade III gastrointestinal toxicity (CTCAE v5.0), leading to TMP-SMX de-escalation.

Key limitations noted by the authors include that the approach falls below current recommendations and requires robust therapeutic drug monitoring. The practice relevance is framed cautiously: temporary TMP-SMX dose reduction with intensive monitoring may be feasible as a bridge to complete guideline-concordant therapy in extreme circumstances of severe dose-limiting toxicity. The report does not provide a sample size beyond the single case, and follow-up was at Day 120.

Study Details

Study typeGuideline

EvidenceLevel 5

PublishedApr 2026

View Original Abstract ↓

BackgroundOptimal antimicrobial strategies for disseminated nocardiosis with central nervous system (CNS) involvement remain poorly defined, particularly regarding trimethoprim-sulfamethoxazole (TMP-SMX) dosing in immunocompromised patients with severe drug intolerance.MethodsThis observational case study analyzed the clinical course and pharmacological management of a 55-year-old male gold miner with pneumoconiosis and chronic corticosteroid use who developed Nocardia farcinica brain abscess. Diagnosis was established via metagenomic next-generation sequencing (mNGS) and phenotypic culture. An individualized antimicrobial regimen was designed based on toxicity monitoring.ResultsDiagnosis of N. farcinica was confirmed by mNGS within 48 h. The patient initially failed empirical meropenem but responded to combination therapy with imipenem, amikacin, and TMP-SMX. Due to grade III gastrointestinal toxicity (CTCAE v5.0), TMP-SMX was de-escalated from 15 mg·kg−1·d−1–11.25 mg·kg−1·d−1, with maintenance at 7.5 mg·kg−1·d−1. Clinical improvement was observed at Day 120, though durable cure remains unconfirmed.ConclusionIn extreme circumstances of severe dose-limiting toxicity, temporary TMP-SMX dose reduction with intensive monitoring may be feasible as a bridge to complete guideline-concordant therapy, though this approach falls below current recommendations and requires robust therapeutic drug monitoring. Species-directed antimicrobial selection and early molecular diagnosis facilitated initial clinical resolution in this high-risk immunocompromised host.