Differentiation of Pneumocystis jirovecii pneumonia from colonization: a clinical decision framework incorporating risk stratification and next-generation sequencing thresholds.

Abstract

Objective: To delineate the clinical differences between Pneumocystis jirovecii pneumonia (PJP) and colonization, identify independent risk factors associated with PJP development, and construct a multidimensional diagnostic model to address the ongoing clinical challenge of accurately distinguishing P. jirovecii infection status in practice.

Materials and methods: This retrospective study analyzed the clinical characteristics, imaging findings, and laboratory parameters of patients who tested positive for P. jirovecii by next-generation sequencing (NGS) at the First Hospital of Jilin University between January 2014 and October 2024. Multivariable logistic regression was performed to determine independent predictors of PJP.

Results: Of the 292 patients included in the analysis (210 diagnosed with PJP and 82 classified as colonized), those with PJP had significantly higher rates of immunosuppression (64.4% vs. 9.9%, P < 0.001) and markedly increased P. jirovecii sequence counts from NGS (median: 1,686 vs. 4, P < 0.001).Human immunodeficiency virus coinfection, decreased lymphocyte count, elevated BDG levels, and increased LDH levels were identified as independent risk factors for PJP. A diagnostic model incorporating these four variables demonstrated excellent predictive capability, yielding an area under the receiver operating characteristic curve of 0.892 (P < 0.001; 95% confidence interval: 0.855-0.929). The optimal NGS sequence count threshold for differentiating PJP from colonization was determined to be 37, achieving a sensitivity of 91% and a specificity of 87.8% (area under the receiver operating characteristic curve: 0.964).

Conclusions: The developed risk prediction model-comprising lymphocyte count, BDG, and LDH levels-facilitates rapid, pre-NGS clinical risk stratification for PJP, enabling prompt and informed therapeutic decision-making. When NGS results yield a P. jirovecii-specific sequence reads below the cutoff value of 37, a definitive diagnosis of PJP is unlikely. However, such findings should be interpreted in the context of the patient's clinical presentation and assessed using the diagnostic model to ensure an accurate evaluation of infection status.