Macrolide-Resistant Mycoplasma pneumoniae Infections among Children before and during COVID-19 Pandemic, Taiwan, 2017-2023.

Before the COVID-19 pandemic, Mycoplasma pneumoniae infections emerged during spring to summer yearly in Taiwan, but infections were few during the pandemic. M. pneumoniae macrolide resistance soared to 85.7% in 2020 but declined to 0% during 2022-2023. Continued molecular surveillance is necessary to monitor trends in macrolide-resistant M. pneumoniae.

In vitro and in vivo study of andrographolide nanoparticles for the treatment of Mycoplasma pneumoniae pneumonia.

OBJECTIVE(S): The emergence of antibiotic resistance has led to suboptimal treatment outcomes for Mycoplasma pneumoniae pneumonia (MPP). Exploring naturally occurring drug components that are both effective against MPP and non-toxic may be a promising choice. This study aimed to investigate the therapeutic effect of andrographolide nanoparticles on pneumonia caused by Mycoplasma pneumoniae infection. METHODS: Andrographolide alginate-poloxamer nanoparticles (AND-ALG-POL/NPs) were obtained by wet medium grinding, and the characterization and in vitro release of the prepared andrographolide nanoparticles were examined by high performance liquid chromatography, particle size analyzer, zeta potential meter and transmission electron microscopy. The cytotoxicity and anti-inflammatory effects of AND-ALG-POL/NPs were evaluated in vitro by MP-infected lung epithelial cells BEAS-2B. Symptoms of pneumonia, total cell count, total protein content and inflammatory factor levels in BALF were assessed by MP-induced pneumonia in BALB/c mice treated with AND-ALG-POL/NPs, and histopathological studies were performed on lung tissues from experimental animals. RESULTS: The results showed that the prepared AND-ALG-POL/NPs were homogeneous spherical with a diameter of 180 ± 23 nm, a zeta potential of (-14.4 ± 2.1) mV, an average encapsulation rate of 87.74 ± 0.87 %, and an average drug loading of 13.17 ± 0.54 %. AND-ALG-POL/NPs were capable of slow release in vitro and showed significant inhibitory ability against MP (P < 0.001). However, AND-ALG-POL/NPs were not cytotoxic to normal cells and alleviated MP infection-induced apoptosis and elevated inflammatory factors. In the in vivo experiments, AND-ALG-POL/NPs alleviated the symptoms of pneumonia in MPP mice, reduced the abnormally elevated total cell count, total protein content and inflammatory factor levels in BALF, and alleviated lung tissue edema, inflammatory cell infiltration and apoptosis (P < 0.001). Meanwhile, the therapeutic effects of AND-ALG-POL/NPs on MPP were similar to those of azithromycin (AZM) and higher than those of andrographolide (AND) free monotherapy (P < 0.001). CONCLUSION: In summary, the prepared AND-ALG-POL/NPs can effectively inhibit MPP in vitro and in vivo, and the effect is similar to that of AZM. Therefore, AND- ALG - POL/NPs have the potential to replace AZM as a potential drug for the treatment of MPP.

Molecular epidemiology of Mycoplasma pneumoniae pneumonia in children, Wuhan, 2020-2022.

BACKGROUND: Mycoplasma pneumoniae (M. pneumoniae) is an important pathogen of community-acquired pneumonia in children. The factors contributing to the severity of illness caused by M. pneumoniae infection are still under investigation. We aimed to evaluate the sensitivity of common M. pneumoniae detection methods, as well as to analyze the clinical manifestations, genotypes, macrolide resistance, respiratory microenvironment, and their relationship with the severity of illness in children with M. pneumoniae pneumonia in Wuhan. RESULTS: Among 1,259 clinical samples, 461 samples were positive for M. pneumoniae via quantitative polymerase chain reaction (qPCR). Furthermore, we found that while serological testing is not highly sensitive in detecting M. pneumoniae infection, but it may serve as an indicator for predicting severe cases. We successfully identified the adhesin P1 (P1) genotypes of 127 samples based on metagenomic and Sanger sequencing, with P1-type 1 (113/127, 88.98%) being the dominant genotype. No significant difference in pathogenicity was observed among different genotypes. The macrolide resistance rate of M. pneumoniae isolates was 96% (48/50) and all mutations were A2063G in domain V of 23S rRNA gene. There was no significant difference between the upper respiratory microbiome of patients with mild and severe symptoms. CONCLUSIONS: During the period of this study, the main circulating M. pneumoniae was P1-type 1, with a resistance rate of 96%. Key findings include the efficacy of qPCR in detecting M. pneumoniae, the potential of IgM titers exceeding 1:160 as indicators for illness severity, and the lack of a direct correlation between disease severity and genotypic characteristics or respiratory microenvironment. This study is the first to characterize the epidemic and genomic features of M. pneumoniae in Wuhan after the COVID-19 outbreak in 2020, which provides a scientific data basis for monitoring and infection prevention and control of M. pneumoniae in the post-pandemic era.

The role of LDH and ferritin levels as biomarkers for corticosteroid dosage in children with refractory Mycoplasma pneumoniae pneumonia.

BACKGROUND: This study explored the relationship between inflammatory markers and glucocorticoid dosage upon admission. METHODS: We conducted a retrospective analysis of 206 patients with refractory Mycoplasma pneumoniae pneumonia (RMPP) admitted to a Children's Hospital from November 2017 to January 2022. Patients were categorized into three groups based on their methylprednisolone dosage: low-dose (≤ 2 mg/kg/d), medium-dose (2-10 mg/kg/d), and high-dose (≥ 10 mg/kg/d). We compared demographic data, clinical manifestations, laboratory findings, and radiological outcomes. Spearman's rank correlation coefficient was used to assess relationships between variables. RESULTS: The median age was highest in the low-dose group at 7 years, compared to 5.5 years in the medium-dose group and 6 years in the high-dose group (P < 0.001). The body mass index (BMI) was also highest in the low-dose group at 16.12, followed by 14.86 in the medium-dose group and 14.58 in the high-dose group (P < 0.001). More severe radiographic findings, longer hospital stays, and greater incidence of hypoxia were noted in the high-dose group (P < 0.05). Additionally, significant increases in white blood cells, C-reactive protein, procalcitonin, lactate dehydrogenase (LDH), alanine transaminase, aspartate transaminase, ferritin, erythrocyte sedimentation rate, and D-dimer levels were observed in the high-dose group (P < 0.05). Specifically, LDH and ferritin were markedly higher in the high-dose group, with levels at 660.5 U/L and 475.05 ng/mL, respectively, compared to 450 U/L and 151.4 ng/mL in the medium-dose group, and 316.5 U/L and 120.5 ng/mL in the low-dose group. Correlation analysis indicated that LDH and ferritin levels were significantly and positively correlated with glucocorticoid dose (Spearman ρ = 0.672 and ρ = 0.654, respectively; P < 0.001). CONCLUSIONS: Serum LDH and ferritin levels may be useful biomarkers for determining the appropriate corticosteroid dosage in treating children with RMPP.

Clinical characteristics and logistic regression analysis of macrolide-resistant Mycoplasma pneumoniae pneumonia in children.

PURPOSE: To investigate macrolide-resistant Mycobacterium pneumoniae (MRMP) pneumonia in children and construct a logistic regression model for mutations in the Mycoplasma pneumoniae drug-resistant gene. METHODS: Clinical data of 281 children were analyzed. Sequencing confirmed a mutation at the A2063G locus of the 23 S rRNA gene in 227 children (A2063G group); 54 children showed no mutations (non-MRMP [NMRMP] group). We compared clinical features, laboratory tests, imaging, and bronchoscopy results and constructed a multifactorial logistic regression model to analyze risk and protective factors. RESULTS: The A2063G group had longer durations of fever and hospitalization before admission, a higher proportion of treatment with sodium methylprednisolone succinate (MPS)/dexamethasone, longer time to discontinue hormones, and higher probability of combined infections. Monocyte percentage was significantly higher in the A2063G group. Imaging suggested a higher incidence of infections in the right lung compared to both lungs. Univariate analysis revealed fever duration before admission, hormone dose and duration, monocyte percentage, and mixed infections as risk factors for Mycoplasma pneumoniae infection with the A2063G mutation. The logistic regression model showed that mixed infections were an independent risk factor for the A2063G locus mutation, whereas hormone dose was a protective factor. CONCLUSION: A prevalence of macrolide resistance of 80.8% among children was observed in the region. Logistic regression analysis revealed that co-infection with other respiratory pathogens is an independent risk factor for the development of resistance genes, while the use of hormone dosage acts as a protective factor.

Outbreak of Mycoplasma pneumoniae pneumonia in hospitalized patients: Who is concerned? Nord Franche-Comté Hospital, France, 2023-2024.

We report an outbreak of confirmed Mycoplasma pneumoniae community-acquired pneumonia (CAP) in Nord Franche-Comté Hospital, France, from 14 November 2023 to 31 January 2024. All 13 inpatients (11 adults with a mean age of 45.5 years and 2 children) were diagnosed with positive serology and/or positive reverse transcription polymerase chain reaction (RT-PCR) on respiratory specimens. All patients were immunocompetent and required oxygen support with a mean duration of oxygen support of 6.2 days. Two patients were transferred to the intensive care unit (ICU) but were not mechanically ventilated. Patients were treated with macrolides (n = 12, 92.3%) with recovery in all cases. No significant epidemiological link was reported in these patients.

Azithromycin sequential therapy plus inhaled terbutaline for Mycoplasma Pneumoniae pneumonia in children: a systematic review and meta-analysis.

BACKGROUND: An improper host immune response to Mycoplasma pneumoniae generates excessive inflammation, which leads to the impairment of pulmonary ventilation function (PVF). Azithromycin plus inhaled terbutaline has been used in the treatment of Mycoplasma pneumoniae pneumonia (MPP) in children with impaired pulmonary function, but previous randomized controlled trials (RCTs) showed inconsistent efficacy and safety. This study is aimed to firstly provide a systematic review of the combined therapy. METHODS: This study was registered at the International Prospective Register of Systematic Reviews (PROSPERO CRD42023452139). A PRISMA-compliant systematic review and meta-analysis was performed. Six English and four Chinese databases were comprehensively searched up to June, 2023. RCTs of azithromycin sequential therapy plus inhaled terbutaline were selected. The revised Cochrane risk of bias tool for randomized trials (RoB2) was used to evaluate the methodological quality of all studies, and meta-analysis was performed using Stata 15.0 with planned subgroup and sensitivity analyses. Publication bias was evaluated by a funnel plot and the Harbord' test. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation recommendations. RESULTS: A total of 1,938 pediatric patients from 20 RCTs were eventually included. The results of meta-analysis showed that combined therapy was able to significantly increase total effectiveness rate (RR = 1.20, 95%CI 1.15 to 1.25), forced expiratory volume in one second (SMD = 1.14, 95%CIs, 0.98 to 1.29), the ratio of forced expiratory volume in one second/forced vital capacity (SMD = 2.16, 95%CIs, 1.46 to 2.86), peak expiratory flow (SMD = 1.17, 95%CIs, 0.91 to 1.43). The combined therapy was associated with a 23% increased risk of adverse reactions compared to azithromycin therapy alone, but no significant differences were found. Harbord regression showed no publication bias (P = 0.148). The overall quality of the evidence ranged from moderate to very low. CONCLUSIONS: This first systematic review and meta-analysis suggested that azithromycin sequential therapy plus inhaled terbutaline was safe and beneficial for children with MPP. In addition, the combined therapy represented significant improvement of PVF. Due to lack of high-quality evidence, our results should be confirmed by adequately powered RCTs in the future.

Clinical efficacy of macrolide antibiotics in mycoplasma pneumoniae pneumonia carrying a macrolide-resistant mutation in the 23 S rRNA gene in pediatric patients.

BACKGROUND: The global prospective surveillance data showed the re-emergence of mycoplasma pneumoniae pneumonia (MPP) in Europe and Asia after the coronavirus disease 2019 pandemic. We sought to observe the effect of macrolide antibiotics in the treatment of MPP carrying a macrolide-resistant mutation gene and the potential of targeted next-generation sequencing (tNGS) as a front-line diagnostic in MPP patients. METHODS: The baseline characteristics of 91 children with MPP hospitalized from January to October 2023 were retrospectively analyzed. They were divided into two groups according to whether carrying the macrolide-resistant mutation or not. The logistic and linear regression analyses were used to determine whether the mutation was a standalone predictive predictor of the duration of fever and hospital length of stay. RESULTS: First, no patients had a fever for ≥ 7 days after macrolide treatment. But length of stay and hormone concentration were significantly different between the two groups (P < 0.05). There were also no statistical association between the mutation and the duration of fever and hospital length of stay. CONCLUSION: Macrolides can be administered to MPP children carrying a macrolide-resistant mutation. tNGS can be seen as a front-line diagnostic in MPP.

A comparative study of general and severe mycoplasma pneumoniae pneumonia in children.

OBJECTIVES: The increasing prevalence of severe Mycoplasma pneumoniae pneumonia (SMPP) poses a significant threat to the health of children. This study aimed to characterise and assess the outcomes in children with SMPP. METHODS: We retrospectively analysed children hospitalised for M. pneumoniae pneumonia (MPP) between January and December 2022. Retrospectively, demographic, clinical, underlying diseases, laboratory and radiological findings, and treatment outcomes were collected and analysed. Disease severity was defined as severe or general according to the Guideline for diagnosis and treatment of community-acquired pneumonia in children (2019 version). RESULTS: Over a 12-month observation period, 417 children with MPP were enrolled, 50.6% (211/417) of whom had SMPP, with the peak incidence observed in winter. Of the 211 children with SMPP, 210 were treated and discharged with improvement, while one child with congenital heart disease died of cardioembolic stroke. A significantly higher proportion of patients with SMPP had underlying diseases, extrapulmonary complications (myocardial and digestive system involvement), and bacterial co-infection. A total of 25 (12%) children with SMPP received mechanical ventilation. The median duration of mechanical ventilation was 3 days. All children were treated with macrolide antibiotic. A significantly higher proportion of patients with SMPP received antibiotic other than macrolides, methylprednisolone sodium succinate, intravenous immunoglobulin and anticoagulation, compared with patients with general MPP (GMPP). Children with SMPP had significantly higher levels of white blood cells, neutrophil percentage, C-reactive protein, procalcitonin, interferon-γ, interleukin (IL)-2, IL-5, IL-6, IL-8, IL-10 and significantly lower percentages of lymphocytes, monocytes, and natural killer cells, compared with GMPP group. CONCLUSION: Our findings suggest that severely ill children have more pronounced inflammatory reaction and extrapulmonary complications. For effective management of children with SMPP, hormonal, prophylactic, anticoagulant therapy, as well as the use of antibiotics other than macrolides for bacterial co-infections, could be incorporated into treatment regimens.

Macrolide resistance of Mycoplasma pneumoniae in several regions of China from 2013 to 2019.

This paper retrospectively analysed the prevalence of macrolide-resistant Mycoplasma pneumoniae (MRMP) in some parts of China. Between January 2013 and December 2019, we collected 4,145 respiratory samples, including pharyngeal swabs and alveolar lavage fluid. The highest PCR-positive rate of M. pneumoniae was 74.5% in Beijing, the highest resistance rate was 100% in Shanghai, and Gansu was the lowest with 20%. The highest PCR-positive rate of M. pneumoniae was 74.5% in 2013, and the highest MRMP was 97.4% in 2019; the PCR-positive rate of M. pneumoniae for adults in Beijing was 17.9% and the MRMP was 10.48%. Among the children diagnosed with community-acquired pneumonia (CAP), the PCR-positive and macrolide-resistant rates of M. pneumoniae were both higher in the severe ones. A2063G in domain V of 23S rRNA was the major macrolide-resistant mutation, accounting for more than 90%. The MIC values of all MRMP to erythromycin and azithromycin were ≥ 64 µg/ml, and the MICs of tetracycline and levofloxacin were ≤ 0.5 µg/ml and ≤ 1 µg/ml, respectively. The macrolide resistance varied in different regions and years. Among inpatients, the macrolide-resistant rate was higher in severe pneumonia. A2063G was the common mutation, and we found no resistance to tetracycline and levofloxacin.

New-generation tetracyclines for severe macrolide-resistant Mycoplasma pneumoniae pneumonia in children: a retrospective analysis.

BACKGROUND: Macrolide-resistant Mycoplasma pneumoniae (MRMP) strains are increasingly prevalent, leading to a rise in severe Mycoplasma pneumoniae pneumonia incidence annually, which poses a significant threat to children's health. This study aimed to compare the effectiveness and safety of oral minocycline and doxycycline for the treatment of severe MRMP pneumonia in children. METHODS: This retrospective analysis included children treated for severe MRMP pneumonia at the Pediatric Department of Tongji Hospital, Shanghai, China, between September 2023 and January 2024 using minocycline and doxycycline. The patients were divided into four groups according to treatment: oral doxycycline alone (DOX group), oral minocycline alone (MIN group), oral doxycycline with intravenous glucocorticoids (DOXG group), and oral minocycline with intravenous glucocorticoids (MING group). Student's t-test, Mann-Whitney U test, and χ2 or Fisher's exact tests were used for group comparisons. RESULTS: A total of 165 patients were included in this study: 84 received minocycline, and 81 received doxycycline. The DOX group had higher fever resolution rates within 24, 48, and 72 h compared to the MIN group (63.2% vs. 31.8%, 79.0% vs. 63.6%, and 100% vs. 90.9%, respectively; all p < 0.05). The DOXG group showed higher fever resolution rates within 24 and 48 h than the MING group (92.3% vs. 83.4%, 100% vs. 92.7%, all p > 0.05). There were no statistically significant differences in time to imaging improvement, cough improvement, and disappearance of wet rales between groups, regardless of glucocorticoid combination. The longer the duration of fever prior to tetracycline therapy, the greater the likelihood of hypoxemia (p = 0.039) and a greater than two-fold elevation in the D-dimer level (p = 0.004).Univariate binary logistic regression model analysis revealed that CRP and erythrocyte sedimentation rate at disease onset were associated with defervescence within 24 h after treatment with tetracyclines alone (p = 0.020, p = 0.027), with erythrocyte sedimentation rate also influencing defervescence within 48 h (p = 0.022). CONCLUSION: Doxycycline treatment resulted in a higher rate of defervescence than minocycline. Prompt treatment reduced the probability of pleural effusion, hypoxemia, pulmonary atelectasis, and D-dimer levels > 2 times the reference value.

Challenges in the treatment of pediatric Mycoplasma pneumoniae pneumonia.

Mycoplasma pneumoniae (MP) is an important cause of community-acquired pneumonia in children and young adolescents. Despite macrolide antibiotics effectiveness as a first-line therapy, persistence of fever and/or clinical deterioration sometimes may complicate treatment and may even lead to severe systemic disease. To date, there is no consensus on alternative treatment options, optimal dosage, and duration for treating severe, progressive, and systemic MP pneumonia after macrolide treatment failure. Macrolide-resistant MP pneumonia and refractory MP pneumonia are the two major complex conditions that are clinically encountered. Currently, the vast majority of MP isolates are resistant to macrolides in East Asia, especially China, whereas in Europe and North America, whereas in Europe and North America prevalence is substantially lower than in Asia, varying across countries. The severity of pneumonia and extrapulmonary presentations may reflect the intensity of the host's immune reaction or the dissemination of bacterial infection. Children infected with macrolide-resistant MP strains who receive macrolide treatment experience persistent fever with extended antibiotic therapy and minimal decrease in MP-DNA load. Alternative second-line agents such as tetracyclines (doxycycline or minocycline) and fluoroquinolones (ciprofloxacin or levofloxacin) may lead to clinical improvement after macrolide treatment failure in children. Refractory MP pneumonia reflects a deterioration of clinical and radiological findings due to excessive immune response against the infection. Immunomodulators such as corticosteroids and intravenous immunoglobulin (IVIG) have shown promising results in treatment of refractory MP pneumonia, particularly when combined with appropriate antimicrobials. Corticosteroid-resistant hyperinflammatory MP pneumonia represents a persistent or recrudescent fever despite corticosteroid therapy with intravenous methylprednisolone at standard dosage. CONCLUSION:  This report summarizes the clinical significance of macrolide-resistant and refractory MP pneumonia and discusses the efficacy and safety of alternative drugs, with a stepwise approach to the management of MP pneumonia recommended from the viewpoint of clinical practice. WHAT IS KNOWN: • Although MP pneumonia is usually a benign self-limited infection with response macrolides as first line therapy, severe life-threatening cases may develop if additional treatment strategies are not effectively implemented. • Macrolide-resistant and refractory MP pneumonia are two conditions that may complicate the clinical course of MP pneumonia, increasing the risk for exacerbation and even death. WHAT IS NEW: • This report summarizes the clinical relevance of macrolide-resistant and refractory MP pneumonia and discusses the efficacy and safety of alternative drug therapies. • A practical stepwise approach to the management of MP pneumonia is developed based on a comprehensive analysis of existing evidence and expert opinion.

Efficacy of azithromycin combined with intravenous immunoglobulin in the treatment of refractory mycoplasma pneumoniae pneumonia in children: a meta-analysis.

BACKGROUND: The incidence of refractory Mycoplasma pneumoniae pneumonia (RMPP) in children is increasing, posing a serious threat to life safety. Intravenous immunoglobulin (IVIG) has demonstrated the ability to modulate the immune system and has shown the potential to treat RMPP. This study evaluated the clinical efficacy and safety of azithromycin combined with IVIG in the treatment of RMPP in children through a meta-analysis. METHODS: A comprehensive search was conducted in seven databases including PubMed and Cochrane Library, and the studies on the treatment of RMPP in children with azithromycin combined with IVIG were screened. After data extraction, meta-analysis and sensitivity analysis were performed to assess heterogeneity and stability. RESULTS: Thirteen randomized controlled trials and two cohort studies were included, totaling 1,142 children. The results of meta-analysis showed a higher clinical efficacy rate (RR = 1.18, 95% CI: 1.11-1.25, P < 0.01) and shorter time to defervescence (MD = -2.12, 95% CI: -2.69--1.55), time to disappearance of pulmonary rales (MD = -2.90, 95% CI: -3.57--2.23), time to disappearance of cough (MD = -3.59, 95% CI: -4.51--2.67), and hospital length of stay (MD = -5.72, 95% CI: -8.80--2.64) in the experimental group receiving azithromycin combined with IVIG treatment compared to the control group treated with azithromycin alone. Additionally, there was no significant publication bias in this meta-analysis. CONCLUSION: Treatment with azithromycin combined with IVIG is more effective than treatment with azithromycin alone for children with RMPP. CLINICAL TRIAL NUMBER: Not applicable.

Marine-Derived Sulfated Glycans Inhibit the Interaction of Heparin with Adhesion Proteins of Mycoplasma pneumoniae.

Mycoplasma pneumoniae, a notable pathogen behind respiratory infections, employs specialized proteins to adhere to the respiratory epithelium, an essential process for initiating infection. The role of glycosaminoglycans, especially heparan sulfate, is critical in facilitating pathogen-host interactions, presenting a strategic target for therapeutic intervention. In this study, we assembled a glycan library comprising heparin, its oligosaccharide derivatives, and a variety of marine-derived sulfated glycans to screen the potential inhibitors for the pathogen-host interactions. By using Surface Plasmon Resonance spectroscopy, we evaluated the library's efficacy in inhibiting the interaction between M. pneumoniae adhesion proteins and heparin. Our findings offer a promising avenue for developing novel therapeutic strategies against M. pneumoniae infections.

Influence Factors of the Therapeutic Effect of Budesonide Combined with N-Acetylcysteine in Children with Mycoplasma Pneumoniae Infection Analyzed by Lasso-Logistic and Construction of a Nomogram Prediction Model.

Objective: This study aims to analyze the factors influencing the efficacy of budesonide (BUD) combined with N-acetylcysteine (NAC) treatment in children with Mycoplasma pneumoniae (MP) infection through Lasso-Logistic analysis, construct a Nomogram predictive model, and provide personalized treatment plans for clinicians. Additionally, it aims to fill the knowledge gap regarding the treatment of MP-infected children with BUD combined with NAC. Methods: We retrospectively analyzed clinical data from 96 children treated with BUD and NAC for MP infection at our hospital from January 2022 to May 2023. Treatment outcomes were categorized as good or poor. Logistic regression and Lasso-Logistic analysis were used to identify independent factors influencing outcomes and construct a predictive Nomogram model, which was validated through ROC curve analysis. Results: Logistic regression identified prolonged fever (≥7 days), high fever, and elevated levels of TNF-α, IL-6, and CRP as independent risk factors for poor outcomes. The Nomogram model, based on these factors, demonstrated excellent predictive accuracy with a C-index of 0.992 and AUC values of 0.987 and 0.948 in the modeling and validation cohorts, respectively. Conclusion: The developed Nomogram model provides clinicians with a reliable tool to predict poor treatment outcomes in children with MP infection treated with BUD and NAC, supporting more personalized and effective treatment plans.

Increase of respiratory illnesses among children in Beijing, China, during the autumn and winter of 2023.

In 2023, through an ongoing respiratory pathogen surveillance system, we observed from mid-September onwards, an increase of respiratory illness among children aged ≤ 15 years presenting at hospital outpatient clinics in Beijing, China. Data indicated that illness was caused by multiple pathogens, predominantly Mycoplasma pneumoniae. Seasonality, periodicity and high prevalence of resistance to macrolide (30 of 30 strains sequenced with the A2063G mutation) were important characteristics of the M. pneumoniae epidemic, which resulted in a rise in consultations at specialised paediatric hospitals.

Mycoplasma pneumoniae epidemic in Denmark, October to December, 2023.

We report a surge of patients, especially children and adolescents, with respiratory disease caused by Mycoplasma pneumoniae in Denmark since October 2023. While the surge has reached an epidemic level, no impact on hospital capacity has been observed; only 14% (446/3,195) of cases, primarily adults, required hospitalisation. Macrolide resistance was detected in less than 2% of samples tested. Timely monitoring of hospitalisations linked to M. pneumoniae infections has been established to inform the healthcare system, decisionmakers and the public.

Are Mycoplasma pneumoniae coinfections frequent in COVID-19 patients? A systematic review.

Understanding the proportion of SARS-CoV-2 patients with Mycoplasmapneumoniae coinfection is crucial for treating patients suffering from coronavirus disease (COVID-19), help to ensure responsible use of antibiotics and minimize the negative consequences of overuse. In addition, this knowledge could have an impact on empirical antibiotic management guidelines for patients with COVID-19. This systematic review aimed to identify the prevalence of M. pneumoniae in patients with coronavirus disease 2019 (COVID-19). A bibliographic search of studies published in Spanish or English was conducted using the PubMed search engine. Fourteen articles from different continents (America, Asia and Europe) were included, involving a total of 5855 patients in these studies. The mean age of COVID-19 patients with M. pneumoniae was 48 years old (range 1-107), most of whom were male. The detection of laboratory-confirmed M. pneumoniae infection varied between 0 and 33.3%. Most of patients referred fever, cough, and dyspnea, and received empirical antibiotic treatment. Bacterial coinfection was not associated with increased ICU admission and mortality. The prevalence of coinfection showed extremely dissimilar figures according to the population studied and diagnostic criteria. However, it is important to develop Latin American studies, given the heterogeneity observed in the studies conducted in different countries. Standardized definitions should be developed in order to be able to assess the impact of coinfections in patients with a diagnosis of COVID-19.

Polydatin alleviates mycoplasma pneumoniae-induced injury via inhibition of Caspase-1/GSDMD-dependent pyroptosis.

Mycoplasma pneumoniae (MP) is one of the main pathogens causing community acquired pneumonia (CAP) in children and adults. Previous pharmacological and clinical studies have shown that Polydatin (PD) exerts anti-inflammatory action by conferring protective benefit in MP pneumonia. However, the mechanism underlying the of PD on MP infection remains unclear. It was found that PD alleviated MP-induced injury by inhibiting caspase-1/gasdermin D (GSDMD)-mediated epithelial pyroptosis. The results demonstrated that PD inhibited the transformation of GSDMD to N-terminal gasdermin-N (GSDMD-N) by decreasing caspase-1 activation, as well as suppressed the formation and secretion of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18), reversed Na, K-ATPase reduction, and suppressed LDH release both in vitro and vivo. Taken together, epithelial pyroptosis in BEAS-2B cells and lung injury in mice were prevented by PD. In conclusion, PD suppressed pulmonary injury triggered by MP infection, by inhibiting the caspase-1/GSDMD-mediated epithelial pyroptosis signaling pathway. Thus, PD may be regarded as a potential therapy for MP-induced inflammation.

miRNA, lncRNA and circRNA: targeted molecules with therapeutic promises in Mycoplasma pneumoniae infection.

Mycoplasma pneumoniae (MP) is primarily recognized as a respiratory pathogen that causes community-acquired pneumonia, which can lead to acute upper and lower airway inflammation and extrapulmonary syndrome. Refractory pneumonia caused by MP can cause severe complications and even be life-threatening, particularly in infants and the elderly. It is well-known that non-coding RNAs (ncRNAs) represented by miRNAs, lncRNAs and circRNAs have been manifested to be widely involved in the regulation of gene expression. Growing evidence indicates that these ncRNAs have distinct differentiated expression in MP infection and affect multiple biological processes, playing an indispensable role in the initiation and promotion of MP infection. However, the epigenetic mechanisms involved in the development of MP infection remain unclear. This article reviews the mechanisms by which miRNAs, lncRNAs, and circRNAs mediate MP infection, such as inflammatory responses, apoptosis and pulmonary fibrosis. Focusing on miRNAs, lncRNAs and circRNAs associated with MP infection could provide new insights into this disease's early diagnosis and therapeutic approaches.