# Whole genome sequencing confirmed the de novo development of macrolide resistance in a child with Mycoplasma pneumoniae infection receiving azithromycin treatment

**Authors:** Huanyu Wang, Sophonie J. Oyeniran, Kathy Everhart, Amy L. Leber

PMC · DOI: 10.1128/asmcr.00088-25 · ASM Case Reports · 2025-07-02

## TL;DR

A child's Mycoplasma pneumoniae infection developed resistance to azithromycin during treatment, confirmed through genome sequencing.

## Contribution

This case confirms de novo macrolide resistance development in MPN during azithromycin treatment using whole genome sequencing.

## Key findings

- A mutation conferring macrolide resistance was detected after azithromycin treatment but not before.
- Whole genome sequencing showed only one SNP difference between pre- and post-treatment isolates, confirming the same strain.
- The case demonstrates rapid de novo resistance development during macrolide therapy.

## Abstract

Mycoplasma pneumoniae (MPN) is a major pathogen of community-acquired respiratory tract infections, and macrolides are the drug of choice for treating MPN infections. Macrolide resistance in our patient population has been low; however, an increase in resistance rates was observed during a recent resurgence.

A previously healthy 11-year-old male was diagnosed with MPN infection and received azithromycin treatment. His symptoms continued after two courses of azithromycin, and he tested positive for MPN DNA three times. Sanger sequencing of samples collected after his first course of azithromycin revealed a mutation conferring macrolide resistance, while the sample collected before the initiation of antibiotics did not. Additionally, whole genome sequencing (WGS) and single-nucleotide polymorphism (SNP) analysis demonstrated that samples collected before and after receiving azithromycin differed by one SNP, indicating that the two isolates are the same strain, and the development of macrolide resistance occurred de novo during treatment.

Our case utilized WGS to confirm that the development of de novo macrolide resistance can occur rapidly following macrolide use. Clinicians should be vigilant for macrolide treatment failure and consider alternative drugs if symptoms persist or there are signs of clinical deterioration.

## Linked entities

- **Chemicals:** azithromycin (PubChem CID 447043)

## Full-text entities

- **Diseases:** MPN infection (MESH:D011019), respiratory tract infections (MESH:D012141)
- **Chemicals:** azithromycin (MESH:D017963), Macrolide (MESH:D018942)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mycoplasmoides pneumoniae (Filterable agent of primary atypical pneumonia, species) [taxon 2104]

## Full text

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## Figures

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## References

18 references — full list in the complete paper: https://tomesphere.com/paper/PMC12530247/full.md

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Source: https://tomesphere.com/paper/PMC12530247