Tropheryma whipplei pneumonia: a retrospective case series of nine patients with treatment response.

BACKGROUND

The detection of Tropheryma whipplei in respiratory specimens has increased with metagenomic next-generation sequencing (mNGS), yet distinguishing colonization from active infection remains challenging. In clinical settings lacking quantitative PCR or pathological confirmation, practical approaches to guide treatment decisions are urgently needed.

METHODS

We retrospectively analyzed nine patients (January 2019-January 2024) with T. whipplei detected by bronchoalveolar lavage fluid (BALF) mNGS. All patients initially received cefoperazone-sulbactam (3.0 g q8h) as empirical therapy for 3-5 days without improvement. Targeted therapy (ceftriaxone or meropenem combined with doxycycline or trimethoprim-sulfamethoxazole) was subsequently initiated. We describe clinical characteristics and treatment outcomes.

RESULTS

Among nine patients (3 male, 6 female; mean age 59 years, range 32-79), six (67%) were immunosuppressed. Primary manifestations included fever (67%), cough with sputum (89%), and dyspnea (78%). Common laboratory findings were anemia (67%), lymphocytopenia (67%), hypoalbuminemia (100%), and elevated inflammatory markers (78%). Chest CT predominantly showed patchy ground-glass opacities. Eight cases (89%) had co-infections. All patients showed no improvement after initial cefoperazone-sulbactam therapy. After targeted therapy was initiated, eight patients (89%) achieved defervescence within 3-5 days, with resolution of pulmonary infiltrates on follow-up CT within 10-14 days. Among these eight responders, one patient (Case 4) underwent repeat BALF mNGS which demonstrated a >99.99% reduction in T. whipplei (from 6,100,499 to 383 reads), reported in the suspected colonizer list rather than the pathogen panel. One non-responder (Case 8) showed a >99% reduction in T. whipplei read count on repeat BALF mNGS after targeted therapy, but ultimately died of polymicrobial sepsis from multidrug-resistant co-pathogens. No relapse occurred during 1-year follow-up.

CONCLUSION

This retrospective case series suggests that rapid improvement after adding targeted anti-T. whipplei therapy is compatible with possible T. whipplei-associated infection in selected mNGS-positive patients, rather than colonization alone. Sequential mNGS showed marked burden reduction in two cases. These observations require prospective validation.