Azithromycin Effectiveness in Children with Mutated Mycoplasma Pneumoniae Pneumonia.

Objective: Mycoplasma pneumoniae (MP) is highly resistant to macrolides in China. However, macrolides still exhibit clinical effectiveness in some macrolide-resistant patients. We tend to explore azithromycin effectiveness in Mycoplasma pneumoniae pneumonia (MPP) children with A2063/2064G mutation. Methods: This retrospective observational cohort study was conducted at the Children's Hospital of the Chongqing Medical University. Children with macrolide-resistant mutations (A2063/2064G) diagnosed as MPP were retrospectively enrolled. Receiver operating characteristic (ROC) curves and logistic regression analysis were used to evaluate and identify independent risk factors for treatment failure (progress to refractory Mycoplasma pneumoniae pneumonia [RMPP]) in macrolide-unresponsive Mycoplasma pneumoniae pneumonia (MUMPP) children with the A2063/2064G mutation. Results: One hundred fifty-five children were retrospectively enrolled. More than 20% (36/155, 23.23%) of patients experienced defervescence within 3 days of azithromycin treatment. RMPP was diagnosed in 54 patients (54/155, 34.84%) and the incidence of RMPP during hospitalization was 22.72 per 1000 person-days. Logistic regression analysis showed that lactate dehydrogenase (LDH) ≥ 399 (U/L) was an independent risk factor for RMPP (odds ratio [OR] 4.66, 95% confidence interval [CI] 1.31-17.10, P=0.017). During the year followed, RMPP patients had a significantly higher incidence of bronchiolitis obliterans and bronchiectasis than non-RMPP patients (16.67% vs 1.98%, P=0.001; 9.26% vs 0.00%, P=0.005, respectively). Conclusion: Azithromycin was effective in children with MPP with the A2063/2064G mutation. For MUMPP children with A2063/2064G mutation, children with LDH ≥ 399 (U/L) had significant higher risk for progression to RMPP, and should consider to be treated with alternative antibiotics (eg tetracyclines, and fluoroquinolones).

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OBJECTIVES: To investigate the role of calprotectin S100 A8/A9 complex in evaluating the condition of children with severe Mycoplasma pneumoniae pneumonia (SMPP). METHODS: A prospective study was conducted among 136 children with Mycoplasma pneumoniae pneumonia (MPP) and 30 healthy controls. According to the severity of the condition, the children with MPP were divided into mild subgroup (40 children) and SMPP subgroup (96 children). The levels of S100 A8/A9 complex and related inflammatory factors were compared between the MPP group and the healthy control group, as well as between the two subgroups of MPP. The role of S100 A8/A9 in assessing the severity of MPP was explored. RESULTS: The MPP group had a significantly higher level of S100 A8/A9 than the healthy control group, with a significantly greater increase in the SMPP subgroup (P<0.05). The multivariate logistic regression analysis showed that the increases in serum C reactive protein (CRP) and S100A8/A9 were closely associated with SMPP (P<0.05). The receiver operating characteristic (ROC) curve analysis showed that the combined measurement of serum S100 A8/A9 and CRP had an area under the ROC curve of 0.904 in predicting SMPP, which was significantly higher than the AUC of S100 A8/A9 or CRP alone (P<0.05), with a specificity of 0.718 and a sensitivity of 0.952. CONCLUSIONS: S100 A8/A9 is closely associated with the severity of MPP, and the combination of S100 A8/A9 with CRP is more advantageous for assessing the severity of MPP in children.

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.

Efficacy and safety of Lianhua Qingwen granule combined with azithromycin for mycoplasma pneumoniae pneumonia in children: a systematic review with meta-analysis and trial sequential analysis.

Background: Lianhua Qingwen (LHQW) granule, a botanical drug preparation, is frequently utilized as an adjuvant treatment for mycoplasma pneumoniae pneumonia (MPP). Nevertheless, the clinical efficacy and safety of this treatment remain uncertain. Purpose: This study aims to evaluate the efficacy and safety of LHQW granule combined with azithromycin (AZM) in treating MPP in children. Method: To identify all randomized controlled trials (RCTs) of LHQW granule plus AZM, a search was conducted in eight Chinese and English databases (CNKI, Wan Fang, VIP, Sinomed, PubMed, Embase, Web of Science, and Cochrane Library) from their inception until 25 December 2023. Meta-regression and subgroup analysis were employed to investigate heterogeneity. Sensitivity analysis and trial sequential analysis (TSA) were conducted to assess the robustness of the findings. Additionally, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was utilized to evaluate the quality of evidence. Results: A total of 15 RCTs involving 1909 participants were included in this study. The meta-analysis results indicated combination therapy of LHQW granule and AZM is significant different from AZM alone in both efficacy and safety, which are specifically observed in the following outcomes: response rate (RR = 1.17, 95% CI: 1.12 to 1.22, p < 0.01), antipyretic time (MD = -1.32, 95% CI: -1.66 to -0.98, p < 0.01), cough disappearance time (MD = -1.76, 95% CI: -2.47 to -1.05, p < 0.01), pulmonary rale disappearance time (MD = -1.54, 95% CI: -2.06 to -1.02, p < 0.01), c-reactive protein (CRP) (MD = -5.50, 95% CI: -6.92 to -4.07, p < 0.01), procalcitonin (PCT) (MD = -0.31, 95% CI: -0.38 to -0.24, p < 0.01), interleukin 6 (IL-6) (MD = -5.97, 95% CI: -7.39 to -4.54, p<0.01), tumor necrosis factor α (TNF-α) (MD = -5.74, 95% CI: -7.44 to -4.04, p < 0.01), forced vital capacity (FVC) (SMD = 0.48, 95% CI: 0.34 to 0.62, p < 0.01), forced expiratory volume in the first second (FEV1) (SMD = 0.55, 95% CI: 0.44 to 0.67, p < 0.01), FEV1/FVC (SMD = 0.49, 95% CI: 0.32 to 0.67, p < 0.01), CD4+ T lymphocyte (CD4+) (MD = 4.04, 95% CI: 3.09 to 4.98, p < 0.01), CD8+ T lymphocyte (CD8+) (MD = -3.32, 95% CI: 4.27 to 2.38, p < 0.01) and adverse events (RR = 0.65, 95% CI: 0.43 to 0.96, p < 0.01). Conclusion: The combination therapy of LHQW granule and AZM may be a better strategy to treat MPP in children. However, the clinical efficacy and safety of LHQW granule require further validation. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/.

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.

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.

Current Mycoplasma pneumoniae outbreak: Don't forget its role in Bickerstaff encephalitis.

Mycoplasma pneumoniae is a common cause of community-acquired pneumonia in children and young adults. It is responsible of a broad array of extrapulmonary manifestations, the most severe affecting the central nervous system. We report a challenging diagnosis of macrolide-resistant M. pneumoniae-induced Bickerstaff encephalitis in a 16-year-old man.

Position statement of the Spanish Society of Paediatric Infectious diseases on the diagnosis and treatment of Mycoplasma pneumoniae infection.

Mycoplasma pneumoniae (M. pneumoniae) is a bacterium with particular characteristics that give rise to a broad clinical spectrum, being respiratory infection the most frequent presentation. Infection by M. pneumoniae occurs in cyclical epidemics, and paediatricians in Spain have noticed an increase in cases since January 2024, establishing hospital registers to collect surveillance data (as it is not a notifiable disease in Spain). The diagnosis of infection by M. pneumoniae is made through serological testing and/or the detection of genetic material by means of polymerase chain reaction (PCR). Neither methods can differentiate between colonization and active infection, so a precise diagnosis is not possible and testing should only be requested in the case of high clinical suspicion. The role of antibiotherapy in infection by M. pneumoniae in its different clinical variants is not well defined. Most infections are self-limiting and mild, and there is insufficient evidence to support the use of antibiotherapy in these cases. Antibiotic treatment is justified in patients with risk factors for the development of severe disease (Down syndrome, anatomical or functional asplenia, immunosuppression), in hospitalized patients with respiratory infection and in patients with moderate or severe extrapulmonary forms. Taking into account aspects concerning the rational use of antimicrobials, the treatment of choice would be clarithromycin, with azithromycin as an alternative, reserving the use of doxycycline and levofloxacin for cases of antimicrobial resistance and/or infections of the central nervous system.

Epidemiologic trends and changes in humoral immunity and lymphocyte subsets levels among hospitalized children with Mycoplasma pneumoniae infection during 2019-2023.

PURPOSE: To understand the changes in humoral immunity and lymphocyte subsets levels among hospitalized children with Mycoplasma pneumoniae (MP) infection from 2019 to 2023. METHODS: This study retrospectively analyzed inpatients aged 0-14 years who were diagnosed with MP infection or MP pneumonia in a tertiary hospital from January 2019 to December 2023. The children were divided into three groups: before the implementation of nonpharmaceutical interventions (NPIs), during the implementation of NPIs, and after the NPIs being lifted. RESULTS: A total of 4103 patients were enrolled in this study, of whom 2125 were diagnosed with MP infection and 1978 were diagnosed with MP pneumonia. The number of MP infection cases dramatically decreased early during the implementation of NPIs, and the previous epidemic trend resumed after the NPIs were lifted, with the number of cases during the period 2019-2023 peaked in November 2023. In children aged < 5 years, the levels of IgA and IgM and the percentages of total T cells and cytotoxic T cells in the "before the implementation of NPIs" group were greater than those in the other groups, and the percentage of total B cells was lower than that in the other groups. In children aged ≥ 5 years, the IgM level in the "before the implementation of NPIs" group was greater than that in the other groups. CONCLUSION: The number of MP-infected hospitalized children decreased significantly after NPI implementation and reached its highest peak during 2019-2023 in November 2023. After the NPIs were lifted, the level of humoral immunity was decreased and balance lymphocyte subsets were disrupted, especially in children aged < 5 years. We should pay close attention to and prevent MP infection in a timely manner after epidemics caused by large respiratory pathogens.

Effectiveness of the six-step approach guided online training program to improve knowledge of Mycoplasma pneumoniae pneumonia among pediatricians: a pretest-posttest study.

Background: In 2023, China witnessed an earlier and more widespread outbreak of Mycoplasma pneumoniae pneumonia (MPP). To address this situation, an online training program was designed to enhance the knowledge of MPP among pediatricians in Shanghai, China. Methods: An online training program on the diagnosis and treatment of MPP, guided by Kern's six-step approach, was developed by the Shanghai Pediatric Clinical Quality Control Center. A pre- and post-training survey was conducted using a 20-item self-administered questionnaire to investigate the pediatricians' knowledge of MPP. A linkage mechanism was established to match pretest/posttest questionnaires using personal identifiers. Paired t-tests and McNemar tests were performed to measure the differences, as appropriate, between pre- and post-training groups. A higher survey score indicated better knowledge. Results: There were 289 participants performed pre- and post-tests. The average age of the respondents was 38.7 years (standard deviation: 8.9). Over 80% of the participants were primary (32.5%) and intermediate (47.8%) pediatricians. Those from specialized hospitals accounted for the highest proportion (41.5%). The post-training group achieved significantly higher total scores than the pre-training group (91.3 vs. 67.7, t=22.48, P<0.001), regardless of the professional titles or hospital levels (all P<0.001). The accuracy rates of each question increased significantly in the post-training group (all P<0.001). Conclusions: The online training program effectively enhanced pediatricians' understanding of diagnosing and treating MPP. It is recommended to maintain continuous education and training targeting all healthcare providers.

Intracardiac and Cerebral Thrombosis Complicated With Mycoplasma Pneumonia.

A seven-year-old girl developed multiposition thrombosis after fever and respiratory symptoms. Chest computed tomography (CT) scan demonstrated bilateral infiltrates, consolidation of the right lower lobe, and pleural effusion in the right lung field. Brain magnetic resonance imaging (MRI) showed multiple abnormal signals in the brain with limited diffusion, and cerebral infarction could not be excluded. Echocardiography revealed hypoechoic mitral valve tips, which are likely to be suspected as vegetation. Mycoplasma pneumoniae infection was clarified by a four-fold increase in IgG antibodies to M. pneumoniae sera. D-dimer levels were elevated increasingly. We found and reported this rare pediatric case of an M. pneumoniae-induced severe pneumonia complicated with intracardiac and cerebral thrombosis. We investigate the clinical characteristics, diagnosis, and treatment of refractory mycoplasma pneumonia complicated with intracardiac and cerebral thrombosis in children.

Mycoplasma pneumoniae pneumonia-associated thromboembolism with plastic bronchitis: a series of five case reports and literature review.

BACKGROUND: Mycoplasma pneumoniae pneumonia is a common respiratory infection among children. However, the occurrence of thromboembolism with plastic bronchitis in association with Mycoplasma pneumoniae pneumonia is extremely rare. This case series presents five cases of children with Mycoplasma pneumoniae pneumonia who developed thromboembolism and plastic bronchitis. The clinical presentation, diagnostic approach, and management strategies are discussed. METHODS: A retrospective analysis was conducted on medical records from a pediatric hospital. Patient demographics, clinical features, laboratory findings, imaging results, treatment modalities, and outcomes were collected. RESULTS: The patients in our case series presented with varying degrees of respiratory distress, cough, and fever. Imaging studies revealed evidence of thromboembolism based on pulmonary artery occlusion. Bronchial casts were observed by bronchoscopy. Laboratory tests demonstrated elevated D-dimer levels and fibrinogen degradation products. All patients received a combination of low molecular weight heparin anticoagulation and supportive care. CONCLUSION: Thromboembolism with plastic bronchitis associated with Mycoplasma pneumoniae pneumonia is a rare but potentially serious complication in children. Prompt recognition and management are crucial for improving patient outcomes. This case series highlights the diverse clinical presentations, diagnostic challenges, and treatment strategies for this unique clinical entity. Further research is needed to better understand the pathogenesis and optimal management of this condition.

Study on the Correlation Between the Expression of NF-Ƙb in the Alveolar Lavage Fluid of Children with Severe Mycoplasma Pneumoniae Pneumonia, Its Clinical Characteristics, and Cellular Immunity.

Objective: This study explored the level of nuclear factor-ƙB (NF-ƙB) in the bronchoalveolar lavage fluid (BALF) of children with severe Mycoplasma Pneumoniae pneumonia (SMPP) and the correlation between NF-ƙB, cellular immunity, and clinical characteristics. Methods: A total of 41 hospitalized children diagnosed with SMPP were selected and included in the SMPP group, and 13 bronchial foreign bodies (FB) without infection during the same period were included in the FB group. The NF-ƙB in the BALF of participants was detected by enzyme-linked immunosorbent assay. The correlation between NF-ƙB and laboratory findings, cellular immunity, and the clinical features in children with SMPP was analyzed. The differences in chest imaging and bronchoscopy in children with SMPP were observed. Results: The levels of NF-ƙB were significantly increased in the SMPP group compared with the FB group (P < 0.001). There were correlations between different NF-ƙB pairs in the SMPP group (P < 0.01). Nuclear factor-ƙB (NF-ƙB) correlated with IL-6, the mycoplasma load in BALF, fever peak, length of hospital stay, and sputum suppository (P < 0.05). The higher the intracellular NF-ƙB level in BALF, the lower the CD3+ CD4+ value in peripheral blood (P < 0.05). Intracellular NF-ƙB and total NF-ƙB correlated with pleural effusion, pericardial effusion, and extrapulmonary complications (P < 0.05). Conclusion: NF-ƙB is involved in airway inflammation changes in children with SMPP. The higher the level of NF-ƙB in the airway, the more severe the clinical manifestations, and the longer the length of hospital stay is likely to be.

Mycoplasma pneumoniae detections in children with lower respiratory infection before and during the COVID-19 pandemic: a large sample study in China from 2019 to 2022.

BACKGROUND: Nonpharmaceutical interventions (NPIs) implemented to reduce the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have suppressed the spread of other respiratory viruses during the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to explore the epidemiological trends and clinical characteristics of Mycoplasma pneumoniae (MP) infection among inpatient children with lower respiratory tract infection (LRTI) before and during the COVID-19 pandemic, and investigate the long-term effects of China's NPIs against COVID-19 on the epidemiology of MP among inpatient children with LRTI. METHODS: Children hospitalised for LRTI at the Department of Pulmonology, The Children's Hospital, Zhejiang University School of Medicine (Hangzhou, China) between January 2019 and December 2022 were tested for common respiratory pathogens, including Mycoplasma pneumoniae (MP), Chlamydia trachomatis (CT) and other bacteria. Clinical data on age, sex, season of onset, disease spectrum, and combined infection in children with MP-induced LRTI in the past 4 years were collected and analysed. RESULTS: Overall, 15909 patients were enrolled, and MP-positive cases were 1971 (34.0%), 73 (2.4%), 176 (5.8%), and 952 (20.6%) in 2019, 2020, 2021, and 2022, respectively, with a significant statistical difference in the MP-positive rate over the 4 years (p <0.001). The median age of these children was preschool age (3-6 years), except for 2022, when they were school age (7-12 years), with statistical differences. Comparing the positive rates of different age groups, the school-age children (7-12 years) had the highest positive rate, followed by the preschoolers (3-6 years) in each of the 4 years. Compared among different seasons, the positive rate of MP in children with LRTI was higher in summer and autumn, whereas in 2020, it was highest in spring. The monthly positive rate peaked in July 2019, remained low from 2020 to 2021, and rebounded until 2022. Regarding the disease spectrum, severe pneumonia accounted for the highest proportion (46.3%) pre-pandemic and lowest (0%) in 2020. CONCLUSION: Trends in MP detection in children with LRTIs suggest a possible correlation between COVID-19 NPIs and significantly reduced detection rates. The positivity rate of MP gradually rose after 2 years. The epidemic season showed some differences, but school-age children were more susceptible to MP before and during the COVID-19 pandemic.

Necrotizing pneumonia associated with macrolide-resistant Mycoplasma in a child.

We reported a pediatric case of necrotizing pneumonia due to macrolide-resistant Mycoplasma pneumoniae, an uncommon presentation of a common disease. Acquisition of resistance does not increase virulence, but it leads to more difficult treatment and potential complications. Macrolide-resistant M. pneumoniae requires extended antibiotic therapy with the addition of a second-line agent and an immunomodulator to promote clinical improvement with minimal sequelae.

Identification of Mycoplasma pneumoniae proteins interacting with NOD2 and their role in macrophage inflammatory response.

Mycoplasma pneumoniae (M. pneumoniae, Mp) is a cell wall-deficient microorganism known to cause chronic respiratory infections in both children and adults. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is an intracellular pattern recognition receptor primarily responsible for identifying muramyl dipeptide (MDP) found in bacterial cell walls. Previous experiments have demonstrated that Mycoplasma ovipneumoniae induces macrophage autophagy through NOD2. In this study, we conducted RNA-seq analysis on macrophages infected with M. pneumoniae and observed an up-regulation in the expression of genes associated with the NOD2 signaling pathway. Mechanistic investigations further revealed the involvement of the NOD2 signaling pathway in the inflammatory response of macrophages activated by M. pneumoniae. We utilized GST pull-down technology in conjunction with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to pinpoint the M. pneumoniae proteins that interact with NOD2. Additionally, co-immunoprecipitation (Co-IP) and immunofluorescence co-localization techniques were used to confirm the interaction between DUF16 protein and NOD2. We found that DUF16 protein can enter macrophages and induce macrophage inflammatory response through the NOD2/RIP2/NF-κB pathway. Notably, the region spanning amino acids 13-90 was identified as a critical region necessary for DUF16-induced inflammation. This research not only broadens our comprehension of the recognition process of the intracellular receptor NOD2, but also deepens our understanding of the development of M. pneumoniae infection.

Efficacy and inflammatory levels (IL-6, IL-10) of adjuvant application of vitamin-A in the treatment of pediatric Mycoplasma pneumoniae pneumonia: a systematic review and meta-analysis.

Objective: The purpose of this study is to evaluate the efficacy of Vitamin A (VitA) as an adjuvant therapy for pediatric Mycoplasma Pneumoniae Pneumonia (MPP) through meta-analysis, and to investigate its impact on inflammation levels (IL-6, IL-10), in order to explore the role of VitA in pediatric MPP. Methods: Using a systematic literature search method, relevant research literature is searched, and RCT studies that meet the requirements are selected based on preset inclusion and exclusion criteria. Then, a quality evaluation was conducted on the included literature, and meta-analysis was used to calculate the combined effect values of mortality rate, hospital stay, lung rale disappearance time, cough duration, fever duration, IL-6 and IL-10 levels, and heterogeneity analysis was conducted. The levels of IL-6 and IL-10 represent the inflammatory levels in pediatric MPP patients, and exploring their changes has significant implications for the anti-inflammatory effect of treatment. Results: A total of 10 RCT studies were included, with a total sample size of 1,485, including 750 cases in the control group and 735 cases in the observation group. The meta-analysis results of this study showed that there was a significant difference in the total clinical efficacy of using VitA adjuvant therapy compared to the control group without VitA [OR = 3.07, 95%CI = (2.81, 4.27)], P < 0.05. However, there was no significant difference in the adverse reaction rate between the use of VitA as an adjuvant therapy and the control without VitA [OR = 1.17, 95%CI = (0.61, 2.27)], P > 0.05. At the same time, the hospitalization time [MSD = -0.86, 95% CI = (-1.61, -0.21)], lung rale disappearance time [MSD = -0.78, 95%CI = (-1.19,-0.51)], cough duration [MSD = -1.07, 95%CI = (-1.41, -0.71)], and fever duration [MSD = -0.47, 95%CI = (-0.72, -0.23)] using VitA as an adjuvant treatment were obviously lower. In addition, the meta-analysis outcomes also showed that the use of VitA adjuvant therapy can significantly reduce IL-6 [MSD = -1.07, 95%CI = (-1.81, -0.27)] and IL-10 [MSD = -0.13, 95%CI = (-0.31, 0.12)] levels. This indicates that the application of VitA in pediatric MPP also has the effect of reducing inflammatory response. Conclusion: Based on the meta-analysis results, VitA adjuvant therapy can significantly improve the clinical symptoms of pediatric MPP patients, shorten hospitalization time, promote the disappearance of lung rales, and alleviate cough and fever symptoms. In addition, VitA adjuvant therapy can effectively reduce inflammation levels, indicating its potential role in inhibiting inflammatory responses. In clinical practice, VitA adjuvant therapy for pediatric MPP can be promoted as a potential treatment option.

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.

Structure-Based Virtual Screening, ADMET Properties Prediction and Molecular Dynamics Studies Reveal Potential Inhibitors of Mycoplasma pneumoniae HPrK/P.

Mycoplasma pneumoniae pneumonia (MPP) is a frequent cause of community-acquired pneumonia (CAP) in children. The incidence of childhood pneumonia caused by M. pneumoniae infection has been rapidly increasing worldwide. M. pneumoniae is naturally resistant to beta-lactam antibiotics due to its lack of a cell wall. Macrolides and related antibiotics are considered the optimal drugs for treating M. pneumoniae infection. However, clinical resistance to macrolides has become a global concern in recent years. Therefore, it is imperative to urgently identify new targets and develop new anti-M. pneumoniae drugs to treat MMP. Previous studies have shown that deficiencies in HPrK/P kinase or phosphorylase activity can seriously affect carbon metabolism, growth, morphology, and other cellular functions of M. pneumoniae. To identify potential drug development targets against M. pneumoniae, this study analyzed the sequence homology and 3D structure alignment of M. pneumoniae HPrK/P. Through sequence and structure analysis, we found that HPrK/P lacks homologous proteins in the human, while its functional motifs are highly conserved in bacteria. This renders it a promising candidate for drug development. Structure-based virtual screening was then used to discover potential inhibitors among 2614 FDA-approved drugs and 948 bioactive small molecules for M. pneumoniae HPrK/P. Finally, we identified three candidate drugs (Folic acid, Protokylol and Gluconolactone) as potential HPrK/P inhibitors through molecular docking, molecular dynamics (MDs) simulations, and ADMET predictions. These drugs offer new strategies for the treatment of MPP.