# Emergence of Clinically Macrolide-Unresponsive Mycoplasma pneumoniae Segmental/Lobar Pneumonia and COVID-19 Pneumonia in Children in Taiwan, 2024–2025

**Authors:** Hao-Yuan Lee, Chien-Chin Chen, Shu-Hua Ko, Yu-Ling Huang, En-Pen Chang, Cheng-Yi Hsu, Jia Ru Wu, Wei-Hsin Chen, Yu-Chau Hsu, Meng-Yen Li, Yu-Lung Hsu, Wen-Yuan Lee, Chyi-Liang Chen

PMC · DOI: 10.3390/antibiotics15030292 · Antibiotics · 2026-03-13

## TL;DR

This study compares the clinical features of Mycoplasma pneumonia and COVID-19 pneumonia in children, finding that Mycoplasma pneumonia is often unresponsive to macrolide antibiotics and has distinct symptoms.

## Contribution

The study is the first to compare clinical characteristics of Mycoplasma pneumonia subtypes and COVID-19 pneumonia in children during a specific variant wave.

## Key findings

- Mycoplasma pneumonia in children aged 6–11 years was associated with prolonged fever and elevated inflammatory markers.
- Children with Mycoplasma segmental/lobar pneumonia showed higher rates of macrolide non-response compared to other groups.
- Clinical indicators like lymphocytopenia and elevated CRP levels were strongly linked to macrolide non-response in Mycoplasma pneumonia.

## Abstract

Background: To date, no study has compared the clinical characteristics of Mycoplasma pneumoniae-associated segmental/lobar pneumonia, Mycoplasma bronchopneumonia, and COVID-19 pneumonia primarily caused by the NB.1.8.1 variant in children. Methods: We examined the epidemiologic trends of pneumonia, segmental/lobar pneumonia, and COVID-19 pneumonia at a teaching hospital from 2015 to 2025. In addition, we compared the clinical characteristics of children hospitalized with Mycoplasma segmental/lobar pneumonia, Mycoplasma bronchopneumonia, and COVID-19 pneumonia during the NB.1.8.1 variant wave in 2024–2025. Results: Between 2015 and 2024, 10,601 pneumonia cases were identified, including 525 cases of segmental/lobar pneumonia and 162 cases of COVID-19 pneumonia. An outbreak of segmental/lobar M. pneumoniae pneumonia and COVID-19 pneumonia occurred in Taiwan during 2024–2025. Starting in early 2025, monthly Mycoplasma positivity rates among children with segmental/lobar pneumonia and bronchopneumonia exceeded 60%. Mycoplasma pneumonia predominantly affected children aged 6–11 years, whereas COVID-19 pneumonia mainly occurred in those younger than 3 years of age. Fever, cough, and rhinorrhea were the most common symptoms in all groups, limiting clinical differentiation. Children with segmental/lobar Mycoplasma pneumonia were more likely to present with prolonged fever (>5 days), lymphocytopenia, a neutrophil-to-lymphocyte ratio (NLR) ≥ 3, and elevated C-reactive protein (CRP) levels, each of which was strongly associated with macrolide non-response (all p < 0.001). Conclusions: Children with segmental/lobar Mycoplasma pneumonia demonstrated more severe clinical manifestations. Segmental/lobar involvement and inflammatory markers, such as lymphocytopenia, elevated NLR, and increased CRP levels, were associated with macrolide non-response. These indicators may help guide therapeutic decision-making in pediatric M. pneumoniae pneumonia.

## Linked entities

- **Diseases:** bronchopneumonia (MONDO:0005682)

## Full-text entities

- **Genes:** N (nucleocapsid phosphoprotein) [NCBI Gene 43740575], CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, ORF1ab (ORF1a polyprotein;ORF1ab polyprotein) [NCBI Gene 43740578], E (envelope protein) [NCBI Gene 43740570]
- **Diseases:** gastrointestinal symptoms (MESH:D012817), tachypnea (MESH:D059246), viral infections (MESH:D014777), Lymphocytopenia (MESH:D008231), acquired pneumonia (MESH:D000077299), symptoms (MESH:D012816), infectious disease (MESH:D003141), Fever (MESH:D005334), diarrhea (MESH:D003967), sore throat (MESH:D010612), Cough (MESH:D003371), CAP (MESH:D003147), pleural effusion (MESH:D010996), influenza (MESH:D007251), COVID-19 Infections (MESH:D000086382), inflammation (MESH:D007249), M. pneumoniae infection (MESH:C566367), Thrombocytopenia (MESH:D013921), Mycoplasma (MESH:D009175), vomiting (MESH:D014839), IPD (MESH:D011008), abdominal pain (MESH:D015746), infection (MESH:D007239), MP infection (MESH:D011019), leukocytosis (MESH:D007964), respiratory infections (MESH:D012141), M. pneumoniae bronchopneumonia (MESH:D001996), injury to (MESH:D014947), NLR (MESH:D015467), Rhinorrhea (MESH:D012818), death (MESH:D003643), MPP (MESH:D011014), pneumococcal pneumonia (MESH:D011018), Anemia (MESH:D000740), necrotizing pneumonia (MESH:D000071067), lung involvement (MESH:D008171), difficulty breathing (MESH:D004417), atelectasis (MESH:D001261)
- **Chemicals:** Macrolide (MESH:D018942), doxycycline (MESH:D004318), fluoroquinolones (MESH:D024841), pneumococcal conjugate vaccine (-), tetracyclines (MESH:D013754), azithromycin (MESH:D017963)
- **Species:** Mycoplasmoides pneumoniae (Filterable agent of primary atypical pneumonia, species) [taxon 2104], Mus musculus (house mouse, species) [taxon 10090], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Coronaviridae (family) [taxon 11118], Gallus gallus (bantam, species) [taxon 9031], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** CMUH114 — Homo sapiens (Human), Transformed cell line (CVCL_D326)

## Full text

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## Figures

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## References

41 references — full list in the complete paper: https://tomesphere.com/paper/PMC13024332/full.md

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Source: https://tomesphere.com/paper/PMC13024332