Mycoplasma pneumoniae is known to cause upper respiratory tract infections and pneumonia, especially in children 5–15 years of age (1). Although mostly sporadic, M. pneumoniae infections may occur as successive epidemics every few years (1). The precedent outbreak was observed during the 2019–2020 cold season, simultaneously in several countries, just before onset the COVID-19 pandemic (2). Then, the number of cases observed worldwide decreased markedly during this pandemic. However, although the resurgence of most respiratory pathogens was gradually observed from 2021, incidence of M. pneumoniae remained particularly low until June 2023, when a major resurgence of cases was reported worldwide (2–3).

We describe M. pneumoniae respiratory infections diagnosed in Marseille, France, university hospitals during January 1, 2014–February 15, 2024. We analyzed retrospectively all respiratory samples tested with 1 of the following specific quantitative PCRs (qPCRs) for M. pneumoniae: qPCR carried out by point-of-care laboratories using the Biofire FilmArray Respiratory Panel 2 Plus Assay (bioMérieux, https://www.biomerieux.com); qPCR performed routinely at the core laboratory using the FTD Respiratory Pathogens 21 Assay (Siemens Healthineers, https://www.siemens-healthineers.com); or an in-house specific qPCR (4). We used OpenEpi version 3.01 (https://www.openepi.com) for statistical analyses and considered differences significant at p<0.05.

Overall, 98,401 samples from 74,355 patients were tested for M. pneumoniae as part of the diagnosis of respiratory infections during 2014–2024. Median patient age was 30 years (range 0–108 years); 52% were male and 48% female. M. pneumoniae was detected in 449 patients (0.6%). Median age of positive patients was 10 years (range 0–101 years); 57% were male and 43% female.

We observed a few M. pneumoniae outbreaks in Marseille during 2014–2020, with a peak in early 2020 (Figure). Incidence then declined until a resurgence was observed beginning in 2023. Initially, 9 cases were observed in January 2023, followed by 6 cases during February–May. Then, a major increase in diagnoses was observed during June 1, 2023–February 15, 2024 (203 total with a peak of 48 cases in December 2023). From January 2023 through mid-February 2024, we diagnosed 218 M. pneumoniae infections (0.8% of 26,449 patients tested), compared with 231 cases (0.3% of 71,952 patients tested) during January 2014–December 2022 (p<0.0001). Median age was significantly lower for patients diagnosed since 2023 than for previous years (8 vs. 15 years; p<0.0001) (Table). Concurrent presence of >1 respiratory viruses was found for 114/316 (36%) M. pneumoniae–positive patients. The prevalence of co-infections was significantly higher in children <5 years of age than in other age groups (p<0.0001). The most common co-infections were with rhinovirus (n = 49), influenza A virus (n = 13), respiratory syncytial virus (n = 12), human coronavirus OC43 (n = 10), influenza B virus (n = 9) and metapneumovirus (n = 9) (Appendix Figure 1). Co-infections were significantly less frequent in patients diagnosed during 2014–2022 (45/164 [27%]) compared with those diagnosed since 2023 (69/152 [45.4%]; p = 0.0008).

The increase of M. pneumoniae infection cases observed in our center are in line with observations from surveillance networks in France and throughout Europe (i.e., detection of the first epidemic sign in June 2023 until a peak reaching in December 2023) (2). High percentages of positivity (up to 50%) have been reported in China (5). In Marseille, we observed a lower percentage (1.8%), similar to the 0.89% observed in the United States since September 2023 (6). Most previous studies reported an increased incidence of M. pneumoniae infection particularly in school-age children and young adults (3,7). In Marseille, children <15 years were more affected during 2023–2024 than in previous seasons. However, we observed a switch regarding the population affected by the epidemic; adults became more affected beginning in January 2024 (Appendix Figure 2), possibly because of a massive transmission of the bacterium from infected children. We also observed a high rate of co-infections (≈50%), compared with 18% in the Netherlands (3). A high rate of co-infection with M. pneumoniae and other pathogens has also been previously reported in 65% of children and 34% of adults with acute respiratory infections in the United States (8). M. pneumoniae carriage ranging from 21% to 56% has also been reported in asymptomatic children (9). Interactions during co-detected microorganisms are complex, making it difficult to clearly define the contribution of each to respiratory infection. A high rate of asymptomatic carriers suggests a critical role for the nasopharyngeal microbiota in the clinical expression of respiratory infection.

There are several hypotheses for this re-emergence of M. pneumoniae, including the emergence of a new strain or a decline in individual and collective immunity. The current outbreak could be the usual periodic recurrence marked by an exacerbation resulting from a period of low exposure linked to restrictive measures during the COVID-19 pandemic. We did not investigate macrolide resistance, but reported resistance is low in Europe (10), and most studies described favorable outcomes after macrolide treatment (7). The number of M. pneumoniae infection cases is probably underestimated, particularly because patients with mild symptoms are not systematically tested. The high prevalence of co-infections with respiratory viruses justifies the use of a syndromic diagnostic strategy.