Macrolide-Resistant Mycoplasma pneumoniae Infections in Pediatric Community-Acquired Pneumonia

Abstract

M ycoplasma pneumoniae is a common causative pathogen in community-acquired pneumonia (CAP) during childhood. In the post-pneumococcal conjugate vaccine (PCV) 13 era, the epidemiology of pediatric pneumonia has changed. In some countries where PCV13 is already included in national immunization program, M. pneumoniae has become the leading pathogen in pediatric CAP (1,2).The clinical manifestations of M. pneumoniae infection are usually mild and self-limited. However, life-threatening pneumonia or even acute respiratory distress syndrome requiring extracorporeal membrane oxygen has been reported (3). Furthermore, some extrapulmonary symptoms, such as mucositis, hepatitis, encephalitis, hemolysis, or erythema multiforme, have linked M. pneumoniae infection to the formation of autoimmunity or immune complexes. The association between M. pneumoniae and refractory asthma has also been mentioned (4).Macrolides are the first-line therapy for M. pneumoniae. Because of high oral bioavailability and oncedaily formulation, macrolides have been widely used in outpatient settings. During the past 10 years, however, macrolide-resistant Mycoplasma pneumoniae (MRMP) has emerged worldwide. The most prevalent area is Asia, where prevalence rates are 13.6%-100% (5). In Japan and China, resistance rates are >90% in some epidemic years (5,6).The treatment of MRMP has become challenging. Although 1 report showed more complications in managing MRMP infections (7), the association between severe disease and resistance remains inconsistent and unclear. We conducted a systematic review and meta-analysis to examine the effect of macrolide resistance on the manifestations, outcomes, and clinical judgment of M. pneumoniae infection. Methods Search StrategyWe conducted a systematic literature search in PubMed, Embase, and the Cochrane Library database using the keywords Mycoplasma pneumoniae, macrolide, antibiotic resistance, and drug resistance. There was no language restriction in our search. We reviewed eligible full texts and the reference lists of the relevant studies. The last update of the study was on December 1, 2019.Two independent reviewers (Y.-C.C. and T.-H.C.) screened all titles and abstracts for eligibility. Studies were eligible for inclusion if the study population was restricted to children (<18 years of age) with community-acquired pneumonia; macrolide

Clinical Efficacy of Doxycycline for Treatment of Macrolide-Resistant Mycoplasma pneumoniae Pneumonia in Children

“…Additionally, there were no differences in laboratory findings, including anemia, leukocytosis, thrombocytopenia, LFT elevation, or CRP elevation (data not shown). These results correlate with previous reports, including a systemic review on the effect of macrolide resistance on clinical features in children [ 9 , 11 , 12 , 13 , 14 ]. Therefore, it is difficult to distinguish MSMP and MRMP cases based on clinical characteristics.…”

“…Doxycycline was used initially in a small number of cases among children of older ages in the 2019–2020 cohort based on the consideration of the high local macrolide resistance rate of up to 84.5%; there have been reports on the efficacy and safety of doxycycline in children and current recommendations are that children with moderate to severe disease may benefit from macrolides or tetracyclines (for children >7 years) [ 1 , 7 , 9 ]. The majority of cases which switched from macrolide to doxycycline were also in 2019–2020 ( Table S1 ).…”

Low-Dose Corticosteroid Treatment in Children With Mycoplasma pneumoniae Pneumonia: A Retrospective Cohort Study

“…Third, we did not determine the macrolide resistance for all of the patients, as it is not a determinant of clinical severity in MRMP pneumonia (44). However, patients infected with MRMP had a longer febrile period, length of hospital stay, antibiotic drug courses, and defervescence time after macrolide treatment compared with patients infected with macrolidesensitive Mycoplasma pneumoniae (MSMP) (45). In the MRMP era, problems to use antibiotics for patients with MPP in children become more obvious, and corticosteroids might be critical for reducing morbidity on MP infection.…”

Mycoplasma pneumoniae Infections: Pathogenesis and Vaccine Development

“…Failure in antibiotic treatment has caused an increase in mortality rate during recent years [ 28 ]. Although the clinical outcomes of infections caused by macrolide-susceptible and -resistant M. pneumoniae isolates are not significantly different, patients infected with macrolide-resistant isolates had a longer febrile period (1.71 days), length of hospital stay (1.61 day), antibiotic drug courses (2.93 days), and defervescence time after macrolide treatment (2.04 days) compared to patients infected with macrolide-sensitive isolates [ 29 ]. Furthermore, macrolide-resistant strains may be associated with more extrapulmonary complications, and severe clinical and radiological features [ 24 , 30 ].…”