Objective:

To report two pediatric cases of severe Mycoplasma pneumoniae pneumonia (MPP) complicated by massive pleural effusion and to explore the diagnostic utility of targeted next-generation sequencing (tNGS) in identifying pathogens, emphasizing its potential impact on treatment decisions.

Key Findings:

• Both patients had massive pleural effusion unresponsive to initial anti-mycoplasma therapy, highlighting the need for tailored treatment approaches. tNGS detected macrolide-resistant Mycoplasma pneumoniae and TTV in pleural fluid from both cases, which informed subsequent treatment adjustments. Patients recovered after closed thoracic drainage and adjusted anti-mycoplasma therapy.

Interpretation:

The detection of TTV in pleural fluid may indicate immune perturbation or disease severity rather than being a confirmed pathogenic factor, given its high prevalence in humans, suggesting a need for cautious interpretation in clinical settings.

Limitations:

• The clinical significance of TTV detection remains uncertain due to the absence of control samples, which limits the ability to draw definitive conclusions about its role in disease pathology. The study is based on only two cases, limiting the generalizability of findings.

Conclusion:

Broader pathogen testing in pleural fluid may enhance diagnostic evaluation in complex infections, but further controlled studies are needed to clarify the role of TTV and validate the findings presented.