Prevention and Treatment of Mycoplasma pneumoniae Requires Long-term Attention

Mycoplasma pneumoniae is a major etiological agent of community-acquired pneumonia that accounts for 10% to 40% of community-acquired pneumonia and exhibits distinct cyclic epidemic patterns that recur at 3- to 7-year intervals.[1–4] Nonpharmaceutical interventions (NPIs) against coronavirus disease 2019 (COVID-19) that were used by countries worldwide during the pandemic significantly reduced the prevalence of M. pneumoniae.[5] After the lifting of COVID-19 pandemic restrictions, M. pneumoniae gradually grew globally.[6] To provide a better understanding of the growth of M. pneumoniae in 2023, we explored the hazards, incidence, diagnosis, and antibiotic resistance of M. pneumoniae. 1. The hazards of M. pneumoniae infection cannot be ignored M. pneumoniae is one of the smallest self-replicating organisms. It lacks a cell wall and has a generation time of 6 hours.[1] Patients with M. pneumoniae infection and asymptomatic infected individuals are sources of infection. M. pneumoniae can be transmitted from person to person through droplets or aerosol particles from secretions of coughs, sneezes, and runny noses. M. pneumoniae infection is a self-limiting disease that has a wide range of manifestations from asymptomatic infection to severe pneumonia. The primary symptoms of M. pneumoniae infection are fever and cough; moreover, cough may persist for 1 to 2 weeks after fever subsides.[1]M. pneumoniae can cause upper and lower respiratory tract infections. Compared with influenza and respiratory syncytial virus, M. pneumoniae causes a higher incidence of pneumonia. M. pneumoniae infection can develop into severe or life-threatening conditions, such as severe lower respiratory tract disease with chest tightness, chest pain, shortness of breath, and difficulty breathing in some patients.[7] Furthermore, extrapulmonary complications of M. pneumoniae infection may occur in the brain, blood system, heart, kidneys, musculoskeletal system, stomach, intestines, and skin.[8] The most common extrapulmonary complications of M. pneumoniae infection occur in the central nervous system and are occasionally life-threatening. M. pneumoniae infection is associated with chronic lung disease and bronchial asthma.[9] 2. A high incidence of M. pneumoniae was observed worldwide after the COVID-19 pandemic The specific epidemic pattern of M. pneumoniae is characterized by epidemics every few years owing to reduced herd immunity.[10] In the past several years, the use of NPIs to control the spread of COVID-19 worldwide has resulted in a drastically reduced incidence of multiple respiratory tract infections, such as influenza, respiratory syncytial virus, and M. pneumoniae.[11,12] The worldwide incidence of M. pneumoniae before the COVID-19 pandemic (between April 1, 2017, and March 31, 2020) was 8.61%.[12] The incidence of M. pneumoniae decreased to 1.69% following the implementation of NPIs, between April 1, 2020, and March 31, 2021.[10,13] The mean incidence of M. pneumoniae was 0.7% in 20 countries in Europe, Asia, the Americas, and Oceania between 2021 and 2022.[10] Global prospective surveillance indicated that the incidence of M. pneumoniae was 0.82% between April 1, 2022, and March 31, 2023.[5] A surveillance survey conducted from April 1 to 30 September 30, 2023, showed the re-emergence of M. pneumoniae after the lifting of the COVID-19 pandemic restrictions. The incidence of M. pneumoniae was 4.12% higher than that in previous years after the introduction of COVID-19 pandemic restrictions.[6] The lifting of COVID-19 restrictions and waning herd immunity may have contributed to the earlier arrival of M. pneumoniae’s cyclical epidemic peak. The use of NPIs caused a dramatic drop in the prevalence of M. pneumoniae in 2020. However, since 2023, a high worldwide incidence of M. pneumoniae has been observed.[14] 3. The difficulties and challenges in diagnosing M. pneumoniae The atypical early-stage symptoms of M. pneumoniae infection make diagnosis difficult. The imaging manifestations of M. pneumoniae are complex and varied and can lead to misdiagnosis. The diagnostic capacity of M. pneumoniae is insufficient. Many medical institutions (especially primary medical institutions) continue to rely on routine blood and serum antibody examinations to diagnose M. pneumoniae. The gap in detection technology leads to failure in rapidly identifying the pathogen or misdiagnosis. Experimental or incorrect medication can increase antimicrobial resistance and the risk to patient safety. Moreover, mixed infections of M. pneumoniae with other pathogens is common. The prevalence of coinfection ranges from 5.7% to 38.4%.[15] Primary medical institutions cannot differentially diagnose respiratory tract infections, complicating the implementation of graded diagnosis and treatment. 4. Currently, antibiotic resistance is the toughest issue associated with M. pneumoniae in China For several decades, macrolides were widely used to treat M. pneumoniae infection and are used as first-line antibiotics. Azithromycin, clarithromycin, erythromycin, and acetylkitasamycin are recommended in children, and azithromycin is commonly used. Intravenous injection followed by sequential oral use can be considered in particularly severe cases. New tetracycline drugs including doxycycline and minocycline are effective against drug-resistant M. pneumoniae in adults and children older than 8 years who are resistant to macrolides; however, long-term use (>21 days) in children younger than 8 years may cause adverse effects such as yellowing of teeth and enamel dysplasia. Therefore, physicians must cautiously evaluate the benefits and adverse effects of these drugs. Moreover, quinolones including levofloxacin, moxifloxacin, and tosufloxacin are effective antibiotics for the treatment of M. pneumoniae infection in adults without QT prolongation. However, a full evaluation of the benefits and drawbacks of quinolones in children and adolescents younger than 18 years is required prior to administration, given the risk of cartilage damage and tendon rupture.[16–18] In severe cases associated with acute onset and rapid disease development, corticoid therapy is considered effective for controlling inflammation. Children with suspected mucus plug occlusion should undergo bronchoscopy as soon as possible; bronchoscopy and alveolar lavage are helpful for local lavage and airway clearance, which can reduce the risk of complications and improve sequelae. In severely ill children, intravenous human immunoglobulin G may be effective in regulating immune response and fighting infection.[16–18] The excessive use of antibiotics increases the likelihood of macrolide resistance in M. pneumoniae.[4] Macrolide-resistant M. pneumoniae was first reported in Japan in 2000 and subsequently became a global problem. The prevalence of macrolide-resistant M. pneumoniae significantly differs across countries. Current data suggest that the global prevalence of macrolide-resistant M. pneumoniae is approximately 28%.[19,20] However, significant geographical variation is observed. The prevalence rates of macrolide-resistant M. pneumoniae are approximately 12%, 5%, 10%, and greater than 50% in Canada, Europe, the United States, and Japan, respectively.[19,20] In China, the prevalence of macrolide-resistant M. pneumoniae increased from 80% to 90%,[20,21] which is significantly higher than that in Europe, the United States, and Japan. Macrolide-resistance may be one of the main causes of severe M. pneumoniae pneumonia, refractory M. pneumoniae pneumonia, and macrolide-unresponsive M. pneumoniae pneumonia. Resistance leads to poor curative effects, repeat hospital visits, long treatment cycles, and an increase in the number of outpatient consultations and hospital admissions. Resistance can also lead to cross-infection with other pathogens such as influenza, chlamydia, severe acute respiratory syndrome coronavirus 2, and respiratory syncytial virus during the epidemic season, further complicating diagnosis and treatment. 5. The prevention and control of M. pneumoniae requires long-term attention and investment in the future To manage future prevalence, strengthening the etiological and syndromic surveillance of respiratory infections is warranted. Using surveillance to identify M. pneumoniae epidemics is achievable. Measures should be taken to address the M. pneumoniae epidemic. Nonpharmaceutical interventions can be implemented in high-risk populations, and the ability of medical institutions to identify M. pneumoniae should be strengthened to allow early antibiotic treatment. Medical institutions are encouraged to build microbiology laboratory capacity with a focus on improving their diagnostic molecular biology facilities to diagnose M. pneumoniae. To ensure high-quality inspection, rapid, sensitive, and specific M. pneumoniae pathogen detection should be performed in primary health care institutions, outpatient and emergency departments where fever is detected, and pediatric outpatient and emergency departments. Vaccines that prevent M. pneumoniae infection are currently unavailable; therefore, accelerating the development of an effective vaccine to prevent M. pneumoniae infections is urgently required. The value of new antibacterial drugs such as omadacycline and lefamulin in combating M. pneumoniae infection should be appropriately increased. Research and development of innovative antibiotics are crucial for avoiding drug resistance. Most importantly, new effective drugs with fewer adverse effects must be developed and acquired for use in children younger than 8 years.

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