To Treat or Not to Treat? Mycoplasma and Its Controversies
PHM 2025 Session Recap
In a unique session at PHM 2025, an intensivist, a hospitalist, and two infectious disease specialists provided an update on Mycoplasma pneumoniae from the lens of their different specialties (Y. Katharine Chang, MD, Elizabeth Lloyd, MD, Christine Mikesell, MD, and Alison Tribble, MD, MSCE). Dr. Mikesell, pediatric intensive care, began the presentation by discussing the typical presentation of Mycoplasma pneumoniae. Classically, it has been associated with respiratory illnesses and “walking pneumonia”. Rates of illness due to Mycoplasma rose dramatically in the past year following a period of low incidence during the COVID-19 pandemic. While school-aged children have the highest prevalence of infection, outbreaks have been rising across all ages and countries. Mycoplasma pneumoniae is an infrequent pathogen identified in adults hospitalized for community-acquired pneumonia, with rates varying from 1.8% to 13%. Higher rates of hospitalization and ICU admissions have been seen in recent outbreaks in Europe. In all ages, patients with underlying chronic conditions such as cardiovascular disease, abnormal pulmonary imaging, or extrapulmonary manifestations are at the highest risk for severe disease.
With the rise in mycoplasma, Dr. Chang, pediatric hospital medicine, discussed the increase in non-respiratory manifestations, such as dermatologic, neurologic, and hematologic manifestations, seen in about 12% of hospitalized cases. After the COVID-19 pandemic, dermatologic manifestations such as erythema multiforme and Steven’s Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are seen in about 3% of adults hospitalized with Mycoplasma pneumoniae infection. While rarer in adults compared to children and adolescents, reactive infectious mucocutaneous eruption (RIME), formally mycoplasma-induced rash with mucositis, is another unique type of dermatologic manifestation separate from SJS/TEN. It is thought to be an inflammatory response rather than an illness caused by the bacteria. Typically, patients present with mucocutaneous signs such as oral, ocular, and urogenital lesions, potentially without a known prior infection. The prognosis is generally excellent, but consultation with ophthalmology and urology to provide supportive care to prevent ocular or genital lesions is critical to avoid long-term morbidity. Unfortunately, there is no robust evidence for correct treatment. Steroids and antibiotics, generally azithromycin, are often used, but it is unknown if either improves outcomes. In the case of recurrence, evidence for repeat courses of antibiotics is lacking.
Another uncommon manifestation Dr. Chang discussed is central nervous system (CNS) disease. CNS involvement most frequently presents as meningoencephalitis but can also include acute cerebellar ataxia or opsoclonus-myoclonus. CNS manifestations are also thought to be an inflammatory response, but antibiotics are prescribed in this case as well, and immunomodulatory therapy can be considered in severe cases. Doxycycline or levofloxacin is the preferred antibiotic for treatment, as azithromycin has poor penetration into the CNS.
Dr. Lloyd, a pediatric infectious disease specialist, described the conundrum with testing for Mycoplasma and explained why testing can be particularly problematic. The Infectious Diseases Society of America (IDSA) recommends polymerase chain reaction (PCR)-based molecular assays and serologic tests (IgM and IgG ELISA) as the best diagnostic tests. PCR-based tests have the highest sensitivity and specificity in both adults and children, but notably require a high-quality specimen, with some data suggesting that oropharyngeal swabs may be more sensitive than nasopharyngeal swabs. At this time, the Centers for Disease Control and Prevention recommends that either method is acceptable. In the hospital setting with onsite testing, turnaround time is rapid, and sensitivity and specificity are high, making PCR testing potentially helpful to guide management. Though a positive PCR test may seem helpful, in children, asymptomatic carriage can occur for weeks to months after illness, leading to a high false positive rate of 17-25% making diagnosis difficult. Additionally, as symptoms can be highly nonspecific, identification of a positive PCR test does not guarantee disease. Serologic ELISA IgM tests vary in sensitivity and specificity based on age. While sensitivity is similar to PCR in children, specificity is lower in adolescents; conversely, ELISA IgM sensitivity is low in adults, but specificity is higher.
Dr. Tribble, a pediatric infectious disease expert, added to the dilemma by discussing the lack of evidence that treating for mycoplasma is beneficial in relieving symptoms or shortening the length of stay, even in the most critically ill. In the case of suspicion for Mycoplasma, IDSA guidelines currently recommend the addition of a macrolide for Mycoplasma coverage if Mycoplasma is a consideration, as the current evidence indicates that it provides benefit to adult patients. It is unclear, though, why hospitalized adults benefit from azithromycin, as it may have either an anti-microbial or anti-inflammatory effect. For pediatric patients, the evidence at this time does not demonstrate clinical benefit in adding a macrolide for most patients, though trials in hospitalized children are ongoing.
Risks of therapy must also be considered, as Dr. Tribble also brought up the need for antimicrobial stewardship. Outside of common side effects from azithromycin, such as gastrointestinal distress and risk for QT prolongation, increasing use of azithromycin has led to large increases in resistance to macrolides. As azithromycin resistance continues to increase, treating for mild disease may not be advisable. Macrolide resistance also contributes to increasing resistance to beta lactams and tetracyclines. For example, rising azithromycin resistance in chlamydia, salmonella, and other bacteria typically treatable by macrolides is now requiring more broad-spectrum antibiotics for management.
With the increase in mycoplasma resistance to azithromycin, for patients with severe disease in which mycoplasma is thought to be a significant factor, alternative antibiotics are available. Doxycycline is generally a good alternative, and levofloxacin can be used, though judiciously given the very broad coverage that it provides. Resistance is increasing, particularly in Southeast Asia, so travel history may be an indicator that doxycycline or a fluoroquinolone may be more appropriate. At this time, macrolides are still recommended as the first-line therapy in the United States to avoid increasing doxycycline resistance.
Mycoplasma remains an infection to consider in the differential, though determining if the patient’s symptoms are truly from Mycoplasma can be difficult. With the rise in mycoplasma and the particularly severe extrapulmonary manifestations, hospitalists should consider the risks and benefits of treatment. Supportive care is generally adequate for less severe disease. For hospitalized patients, we will need to monitor for resistance and consider broadening therapy in patients who have more severe disease not responsive to first-line management.
Key Takeaways
- Mycoplasma pneumoniae can present with extra-pulmonary symptoms that are likely due to an inflammatory reaction
- Resistance to macrolides is rising, particularly in Southeast Asia
- Azithromycin is still the first-line treatment for Mycoplasma in the U.S.
Dr. Skoczylas
Dr Skoczylas is a pediatric hospitalist, clinical assistant professor, and medical director of the Well Newborn Nursery at the University of Michigan C.S. Mott Children’s Hospital, Ann Arbor.
Dr. Jacobson
Dr. Jacobson is an assistant professor of internal medicine and pediatrics and associate program director of the pediatric hospital medicine fellowship program at the University of Michigan Medical School in Ann Arbor.