Expert consensus on the diagnosis and treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia in children

Background Mycoplasma pneumoniae(M.pneumoniae)is a significant contributor to community-acquired pneumonia among children.Since 1968,when a strain of M.pneumoniae resistant to macrolide antibiotics was initially reported in Japan,macrolide-resistant M.pneumoniae(MRMP)has been documented in many countries worldwide,with varying incidence rates.MRMP infections lead to a poor response to macrolide antibiotics,frequently resulting in prolonged fever,extended antibiotic treatment,increased hospitalization,intensive care unit admissions,and a significantly higher proportion of patients receiving glucocorticoids or second-line antibiotics.Since 2000,the global incidence of MRMP has gradually increased,especially in East Asia,which has posed a serious challenge to the treatment of M.pneumoniae infections in children and attracted widespread attention from pediatricians.However,there is still no global consensus on the diagnosis and treatment of MRMP in children.Methods We organized 29 Chinese experts majoring in pediatric pulmonology and epidemiology to write the world’s first consensus on the diagnosis and treatment of pediatric MRMP pneumonia,based on evidence collection.The evidence searches and reviews were conducted using electronic databases,including PubMed,Embase,Web of Science,CNKI,Medline,and the Cochrane Library.We used variations in terms for“macrolide-resistant”,“Mycoplasma pneumoniae”,“MP”,“M.pneumoniae”,“pneumonia”,“MRMP”,“lower respiratory tract infection”,“Mycoplasma pneumoniae infection”,“children”,and“pediatric”.Results Epidemiology,pathogenesis,clinical manifestations,early identification,laboratory examination,principles of antibiotic use,application of glucocorticoids and intravenous immunoglobulin,and precautions for bronchoscopy are highlighted.Early and rapid identification of gene mutations associated with MRMP is now available by polymerase chain reaction and fluorescent probe techniques in respiratory specimens.Although the resistance rate to macrolide remains high,it is fortunate that M.pneumoniae still maintains good in vitro sensitivity to second-line antibiotics such as tetracyclines and quinolones,making them an effective treatment option for patients with initial treatment failure caused by macrolide antibiotics.Conclusions This consensus,based on international and national scientific evidence,provides scientific guidance for the diagnosis and treatment of MRMP in children.Further studies on tetracycline and quinolone drugs in children are urgently needed to evaluate their effects on the growth and development.Additionally,developing an antibiotic rotation treatment strategy is necessary to reduce the prevalence of MRMP strains.

Effects of Clarithromycin at Sub-Minimum Inhibitory Concentrations on Early <i>erm</i>B Gene Expression, Metabolic Activity and Growth of an <i>erm</i>(B)-Expressing Macrolide-Resistant Strain of <i>Streptococcus pneumoniae</i>

Aim: To investigate the effects of exposure of a macrolide-resistant [erm (B)-expressing] strain of Streptococcus pneumoniae (strain 2507) to clarithromycin (0.5 and 5 mg/L) added at the outset and 6 hours after initiation of culture on early gene expression, energy metabolism, and growth. Methods: Bacterial growth was determined by turbidometric and colony counting procedures, energy metabolism by measurement of ATP, while analysis of gene expression was performed using reverse transcription-PCR and sequencing. Results: Addition of clarithromycin, at either concentration, at the outset of culture, caused transient suppression of growth of 10 - 12 hours duration, while delayed addition of antibiotic (during the logarithmic phase) resulted in an abrupt halt in growth followed by recovery. These inhibitory effects of clarithromycin on bacterial growth were associated with up-regulation of expression of erm(B), decreased ATP and protein synthesis, and were unaffected by inclusion of either catalase (500 and 1000 kunits/L), or competence-stimulating peptide (CSP-1, 0.5 mg/L). The inhibitory effects could, however, be overcome by pre-exposure of the bacteria to the antibiotic. Moreover, clarithromycin appeared to potentiate the antimicrobial actions of ceftriaxone, at sub-MIC concentrations, for strain 2507. Conclusions: Unlike several other common bacterial pathogens, the full expression of erm(B)-mediated macrolide resistance by the pneumococcus has a slow onset, which is associated with transient susceptibility to macrolides and inhibition of growth.