Macrolide-Resistant Mycoplasma pneumoniae Infections in Children, Ohio, USA

Mariana M. Lanata; Huanyu Wang; Kathy Everhart; Melisa Moore-Clingenpeel; Octavio Ramilo; Amy Leber


Emerging Infectious Diseases. 2021;27(6):1588-1597. 

In This Article

Abstract and Introduction


Emergence of macrolide-resistant Mycoplasma pneumoniae (MRMp) challenges empiric macrolide therapy. Our goal was to determine MRMp rates and define characteristics of children infected with macrolide-sensitive M. pneumoniae (MSMp) versus MRMp in Ohio, USA. We cultured PCR-positive M. pneumoniae specimens and sequenced M. pneumoniae–positive cultures to detect macrolide resistance mutations. We reviewed medical records to compare characteristics of both groups. We identified 14 (2.8%) MRMp and 485 (97.2%) MSMp samples. Patients in these groups had similar demographics and clinical characteristics, but patients with MRMp had longer hospitalizations, were more likely to have received previous macrolides, and were more likely to have switched to alternative antimicrobial drugs. MRMp-infected patients also had ≈5-fold greater odds of pediatric intensive care unit admission. Rates of MRMp infections in children in central Ohio are low, but clinicians should remain aware of the risk for severe illness caused by these pathogens.


Mycoplasma pneumoniae is a major pathogen that accounts for up to 40% of the total number of community-acquired pneumonias (CAPs) in children and up to 19% of the pediatric CAPs that require hospitalization,[1,2] yet those numbers might not reflect its actual clinical impact because testing for M. pneumoniae is not performed routinely. M. pneumoniae infection has a wide range of manifestations, from asymptomatic infection to severe pneumonia requiring admission to the intensive care unit.[3,4] Because it lacks a cell wall, M. pneumoniae is not susceptible to β-lactam antimicrobial drugs, which are first-line therapy for CAP in children.[5]

Macrolides are considered the antimicrobial drugs of choice for the treatment of M. pneumoniae infections in children;[5] however, in the past few decades, macrolide-resistant M. pneumoniae (MRMp) has emerged. Rates of resistance are highest in Asia, as high as 100%, and reported rates in the United States vary from 3.5% to 13.2%.[3,6–13] No published data are available from Ohio, where we conducted our study.

Macrolide resistance is conveyed by single base mutations in the V region of 23S rRNA, which codes for the binding site of macrolides in the M. pneumoniae ribosome. The most common mutations include the change of A to C/G/T at location A2063 or at location A2064.[14,15] These are the 2 mutations associated with macrolide resistance that have been reported in the United States.[3,6]

M. pneumoniae is a slow-growing, fastidious organism, making routine culture and phenotypic antimicrobial drug sensitivity testing impractical for clinical use and limiting the use of these techniques mainly to research purposes. Since molecular assays were developed, diagnosis of M. pneumoniae infections has shifted from serology to molecular detection using PCR, resulting in improved sensitivity and specificity. However, even with molecular detection, most clinicians have no information regarding antimicrobial sensitivity of M. pneumoniae. Therefore, as in many other settings, we currently have no data on local rates of MRMp, and most children diagnosed with M. pneumoniae infection are treated initially with macrolides. If clinical concerns for macrolide resistance occur while children are receiving therapy, clinicians sometimes choose to switch antimicrobial therapy to another agent, although there are no established clinical parameters or guidelines concerning when to consider potential resistance to macrolide antimicrobial drugs.

Studies, emerging mainly from Asia, have reported increased disease severity in adults and children infected with MRMp. More consistently, studies have demonstrated longer duration of fever in patients infected with MRMp and longer duration of hospitalization. Other studies have reported more frequent pulmonary complications and the need for changing antimicrobial drug therapy.[16–19] Chen et al. recently published a meta-analysis further consolidating the evidence for longer duration of fever and hospitalization in patients with MRMp, but no differences were reported in clinical presentation, laboratory results, or chest radiograph findings.[20] Data about MRMp infection in children in the United States remain limited.

The primary objective of this study was to determine the rate of MRMp infections in children in central Ohio, USA. Our second objective was to examine the clinical characteristics, antimicrobial drug treatment, and outcomes in this cohort; to identify potential differences between patients infected with macrolide-sensitive M. pneumoniae (MSMp) and those infected with MRMp; and to determine whether infection with MRMp was associated with worse clinical outcomes than infection with MSMp.