Clinical Management and Outcomes of Chlamydia pneumoniae Pneumonia Diagnosed by Targeted Next-Generation Sequencing: A Case Report and Insights

Summary

This report describes targeted NGS-enabled precise diagnosis of C. pneumoniae pneumonia in an adolescent, facilitating successful macrolide therapy and highlighting its utility in atypical respiratory infections.

Abstract

Chlamydia pneumoniae is a significant cause of community-acquired pneumonia, yet its diagnosis remains challenging due to non-specific symptoms and the limitations of traditional methods like serology, which can cause delays. We present the case of a 14-year-old female admitted with cough and right-sided chest pain. Initial laboratory tests were unremarkable, except for a positive C. pneumoniae IgM result. A chest CT scan revealed right upper lobe infiltrates. Despite empirical azithromycin, her improvement was limited. Bronchoscopy was performed, and bronchoalveolar lavage fluid was analyzed by targeted next-generation sequencing (tNGS), which identified C. pneumoniae as the dominant pathogen with a high sequence count (9886), providing strong evidence for the etiology. Targeted macrolide therapy was continued (transitioned to oral doxycycline), leading to marked clinical improvement within 72 h. Longitudinal lab monitoring revealed a self-resolving transaminitis and a rise in Serum Amyloid A post-treatment. This case suggests that tNGS can serve as a valuable adjunctive tool in providing a rapid, culture-independent etiological diagnosis for atypical pneumonias, helping to guide effective therapy in selected patients with complex respiratory infections.

Introduction

Community-acquired pneumonia (CAP) represents a significant global health burden, with a complex and diverse spectrum of causative pathogens that complicates empirical treatment¹. Among the atypical bacteria, Chlamydia pneumoniae is a well-established etiological agent, responsible for an estimated 10%–15% of CAP cases across all age groups². Since its identification as a distinct species in 1986, C. pneumoniae has been recognized not only for causing acute respiratory infections but also for its potential epidemiological links to chronic conditions such as asthma and atherosclero....

Protocol

This study is approved by the Ethics Committee of Yueqing Third People’s Hospital (Approval No. 2026003), ensuring adherence to ethical standards for human research. The primary objective is to obtain a high-quality lower respiratory tract specimen for comprehensive pathogen analysis. Written informed consent was obtained from the patient’s legal guardian for the clinical procedure and the publication of this case report. The following protocol is implemented for the diagnostic evaluation and management of patients with suspected atypical pneumonia, utilizing targeted next-generation sequencing (tNGS) to achieve an etiological diagnosis. The reagents and t....

Results

The implementation of this tNGS-based diagnostic protocol provided critical evidence identifying Chlamydia pneumoniae as the dominant pathogen, guiding precise antimicrobial therapy and favorable clinical outcomes. As detailed in the comprehensive pathogen profile (Figure 2), tNGS analysis of BALF confirmed C. pneumoniae infection with 9,886 sequences, while also identifying Rhinovirus A as a significant co-infection (6,977 sequences). The threshold for clinically relevant .......

Discussion

This case demonstrates the potential utility of targeted next-generation sequencing (tNGS) in assisting the diagnosis of Chlamydia pneumoniae pneumonia. When serological findings prove inconclusive and empirical therapy yields a suboptimal response, tNGS analysis of lower respiratory specimens provides comprehensive pathogen identification, enabling targeted therapeutic intervention.

Compared to traditional methods, tNGS offers significant diagnostic benefits. Unlike microimmunofluore.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
–80°C Ultra-Low Temperature Freezer	Thermo Scientific	905	For long-term storage of specimens and nucleic acids.
Biological Safety Cabinet	Thermo Scientific	1300 Series A2	Provides sterile environment for sample processing.
Bronchoalveolar Lavage (BAL) Catheter	Teleflex	22-160	For instillation and recovery of sterile saline during BAL procedure.
Computer Workstation	Dell	Precision 5860 Tower	High-performance computing for data analysis.
Cryogenic Vial (2.0 mL)	Thermo Scientific	375418	For storage of extracted DNA at controlled temperatures.
DNA/RNA Shield	Zymo Research	R1100	Nucleic acid preservation solution used during sample processing.
Doxycycline Hyclate Capsules	(Local supplier)	100 mg	Tetracycline-class antibiotic for sequential oral therapy.
Fiberoptic Bronchoscope	Olympus	BF-XP190	Used for bronchoalveolar lavage (BAL) under conscious sedation.
High-Speed Centrifuge	Eppendorf	5425 R	For sample preparation and processing.
High-Throughput Sequencer	MGI	MGISEQ-200	Genetic sequencer platform for targeted NGS analysis.
Microcentrifuge Tubes (1.5 mL)	Eppendorf	22431021	Sterile, DNase-/RNase-free tubes for sample handling.
Pathogen Analysis Software	Genseq	Genseq-PM	Bioinformatics pipeline for species-level identification.
Qubit 4.0 Fluorometer	Thermo Fisher Scientific	Q33238	Used for precise library quantification.
Sequencing Reaction Kit	Dian Diagnostics	No. 20240005	Universal kit for sequencing reaction on MGI platform.
Serological Test Kit (C. pneumoniae IgM)	Euroimmun	EI 2390-9601 G	Used for initial serological screening.
Sterile Normal Saline (0.9%)	Baxter	2B2324	Used as lavage fluid during bronchoscopy.
Targeted NGS Enrichment Panel	Dian Diagnostics	Respiratory Pathogen 200+ Panel	Custom panel (Genseq RTI) covering 200+ pathogens.