The global resurgence of Mycoplasma pneumoniae after the lifting of COVID pandemic restrictions offered a unique opportunity for researchers to examine its epidemiology and pathophysiology, advancing the understanding of M pneumoniae infections in children in the process, according to findings presented at the European Academy of Paediatrics (EAP) 2025 and published in Current Opinion in Infectious Diseases.

Although the 2023-2024 resurgence took a similar length of time compared with other outbreaks of M pneumoniae, levels of endemic infection during the COVID protocols were substantially lower, which could have resulted in an absence of population-level immunity, the researchers wrote.

The review underscores “the urgent need for improved diagnostics to correctly manage patients and make informed decisions regarding the patients who would benefit from macrolides,” said Michael L. Beeton, PhD, microbiologist at Cardiff Metropolitan University in Cardiff, Wales, who was not involved in writing the paper. “This is an important need in the context of growing concerns around macrolide resistance.”

‘Unique Epidemiologic Behavior’

According to Annemarie M.C. van Rossum, MD, PhD, and Ruben C.A. de Groot, MD, PhD, from the Erasmus MC University Medical Center in Rotterdam, Netherlands, following the lifting of COVID restrictions, M pneumoniae infections resurged globally from 2023 to 2024. 

Recent findings from the European Society of Clinical Microbiology and Infectious Diseases Study Group for Mycoplasma and Chlamydia Infections show the recent epidemiologic behavior of M pneumoniae is “likely explained by its slow rate of replication, long incubation period, and possibly reduced population immunity following years of low circulation,” de Groot said. The researchers postulated that low levels of endemic circulation could provide some population-level immunity, which could have been absent during the current resurgence.

Overall, the studies analyzed, including ones from Spain, Portugal, and China, produced mixed results on disease severity and failed to provide strong enough evidence to conclude that M pneumoniae infections were more severe than in previous upsurges, the authors noted.

Diagnosing M pneumoniae infection also remains challenging, van Rossum said, “because current tests cannot reliably distinguish between active infection and asymptomatic carriage in children, underscoring the need for more accurate and timely diagnostic tools; this is not unique for respiratory tract infections by this bacterium but also the case for many other respiratory pathogens.”

Knowledge Gaps

Another key takeaway involved treatment of M pneumoniae, van Rossum said, which is often not required and can generally be postponed, as it typically causes mild, self-limiting illness.

Whether antibiotics support recovery and/or prevent complications or extrapulmonary manifestations — such as Mycoplasma-induced rash and mucositis [MIRM] and Guillain-Barré syndrome — remains unclear, “highlighting the need for high-quality clinical studies on the effect of antibiotics on M pneumoniae infections,” de Groot said. “Overuse of macrolides results in macrolide resistance, which is present at different levels around the world and has a high incidence in East Asia.” The researchers wrote that tetracyclines and quinolones are emerging as useful alternatives for children.

Moreover, additional studies are necessary to determine the exact role of immunomodulatory treatment and what subset of patients might benefit from these interventions, the researchers wrote. “International collaboration during the 2023-2024 resurgence has proven to be pivotal in advancing our understanding of M pneumoniae infection in children,” they wrote.

Vigilance Required

Beeton said it is important to continue with international surveillance of M pneumoniae detections and to gain a better understanding of the specific types that are in circulation. Beeton also stressed clinicians must be vigilant during outbreaks of M pneumoniae, particularly when it comes to the awareness of the extrapulmonary complications that can occur, “such as MIRM or M pneumoniae-triggered reactive infectious mucocutaneous eruptions. Although macrolide-resistant M pneumoniae is generally uncommon outside of Asia, resistance can occur, and nonmacrolide antibiotics may need to be considered.”

Van Rossum, de Groot, and Beeton reported having no relevant financial conflicts of interest.

Brian Ellis is a freelance writer and editor who lives in Southwest Virginia.