RESUMO
Background: Mycoplasma pneumoniae (MP) is a significant cause of community-acquired pneumonia with high macrolide resistance rates. Various COVID-19 pandemic restrictions have impacted the prevalence of MP. Objective: To assess the changes in the pattern of MP infections among children before, during, and after the COVID-19 pandemic. Methods: A total of 36685 enrolled patients, aged 0-18 years, diagnosed with pneumonia and admitted to Children's Hospital of Chongqing Medical University from January 2019 to December 2023, were retrospectively reviewed in this study. The epidemiological characteristics of pediatric MP infection were analyzed. Results: Among 36685 patients, 7610 (20.74%) tested positive for MP. The highest positive rate was observed among children aged over 6 years (55.06%). There was no gender disparity in MP infection across the three phases of the COVID-19 pandemic. Hospital stays were longest for children during the COVID-19 pandemic (P <0.001). MP infection was most prevalent in the summer (29.64%). The lowest positive rate was observed during the pandemic, with the highest rate found after easing the measures across all age groups (P <0.001). There was a surge in the positive rate of MP in the third year after the COVID-19 pandemic. Regression analyses demonstrated a shift in the age range susceptible to MP infection, with children aged 3.8 to 13.5 years post-pandemic compared to the pre-pandemic range of 5.3 to 15.5 years old. Additionally, the average macrolide resistance rate was 79.84%. We observed a higher resistance rate during the pandemic than in the pre- and post-pandemic phases (P <0.001). Conclusion: The restrictive measures implemented during the COVID-19 pandemic have influenced the spread of MP to some extent and altered demographic and clinical characteristics, such as age, age group, season, length of stay, and macrolide resistance. We recommend continuous surveillance of the evolving epidemiological characteristics of MP infection in the post-pandemic period when restrictions are no longer necessary.
Assuntos
COVID-19 , Mycoplasma pneumoniae , Pneumonia por Mycoplasma , SARS-CoV-2 , Humanos , Criança , COVID-19/epidemiologia , Pré-Escolar , China/epidemiologia , Feminino , Masculino , Lactente , Adolescente , Pneumonia por Mycoplasma/epidemiologia , Mycoplasma pneumoniae/efeitos dos fármacos , Mycoplasma pneumoniae/isolamento & purificação , Estudos Retrospectivos , Recém-Nascido , Prevalência , SARS-CoV-2/isolamento & purificação , Hospitalização/estatística & dados numéricos , Pandemias , Macrolídeos/uso terapêutico , Farmacorresistência Bacteriana , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Criança Hospitalizada/estatística & dados numéricos , Estações do Ano , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologiaRESUMO
OBJECTIVES: Mycoplasma pneumoniae (M. pneumoniae) continues to pose a significant disease burden on global public health as a respiratory pathogen. The antimicrobial resistance among M. pneumoniae strains has complicated the outbreak control efforts, emphasizing the need for robust surveillance systems and effective antimicrobial stewardship programs. DESIGN: This review comprehensively investigates studies stemming from previous outbreaks to emphasize the multifaceted nature of M. pneumoniae infections, encompassing epidemiological dynamics, diagnostic innovations, antibiotic resistance, and therapeutic challenges. RESULTS: We explored the spectrum of clinical manifestations associated with M. pneumoniae infections, emphasizing the continuum of disease severity and the challenges in gradating it accurately. Artificial intelligence and machine learning have emerged as promising tools in M. pneumoniae diagnostics, offering enhanced accuracy and efficiency in identifying infections. However, their integration into clinical practice presents hurdles that need to be addressed. Further, we elucidate the pivotal role of pharmacological interventions in controlling and treating M. pneumoniae infections as the efficacy of existing therapies is jeopardized by evolving resistance mechanisms. CONCLUSION: Lessons learned from previous outbreaks underscore the importance of adaptive treatment strategies and proactive management approaches. Addressing these complexities demands a holistic approach integrating advanced technologies, genomic surveillance, and adaptive clinical strategies to effectively combat this pathogen.
Assuntos
Antibacterianos , Surtos de Doenças , Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Humanos , Mycoplasma pneumoniae/efeitos dos fármacos , Mycoplasma pneumoniae/genética , Pneumonia por Mycoplasma/epidemiologia , Pneumonia por Mycoplasma/tratamento farmacológico , Pneumonia por Mycoplasma/microbiologia , Pneumonia por Mycoplasma/diagnóstico , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Inteligência Artificial , Gestão de AntimicrobianosRESUMO
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.
Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Macrolídeos , Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Humanos , Pneumonia por Mycoplasma/tratamento farmacológico , Pneumonia por Mycoplasma/diagnóstico , Macrolídeos/uso terapêutico , Criança , Antibacterianos/uso terapêutico , Mycoplasma pneumoniae/efeitos dos fármacos , Masculino , Feminino , Pré-Escolar , Consenso , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/microbiologiaRESUMO
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.
Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Macrolídeos , Mycoplasma pneumoniae , Pneumonia por Mycoplasma , RNA Ribossômico 23S , Humanos , Pneumonia por Mycoplasma/microbiologia , Pneumonia por Mycoplasma/tratamento farmacológico , Pneumonia por Mycoplasma/epidemiologia , Mycoplasma pneumoniae/genética , Mycoplasma pneumoniae/efeitos dos fármacos , Macrolídeos/farmacologia , Macrolídeos/uso terapêutico , Feminino , Masculino , Farmacorresistência Bacteriana/genética , Pré-Escolar , Criança , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , RNA Ribossômico 23S/genética , Modelos Logísticos , Lactente , Mutação , Fatores de Risco , Estudos RetrospectivosRESUMO
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.
Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Macrolídeos , Mutação , Mycoplasma pneumoniae , Pneumonia por Mycoplasma , RNA Ribossômico 23S , Humanos , Pneumonia por Mycoplasma/tratamento farmacológico , Pneumonia por Mycoplasma/microbiologia , Macrolídeos/uso terapêutico , Macrolídeos/farmacologia , Mycoplasma pneumoniae/genética , Mycoplasma pneumoniae/efeitos dos fármacos , Feminino , Masculino , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Pré-Escolar , Criança , Farmacorresistência Bacteriana/genética , Estudos Retrospectivos , RNA Ribossômico 23S/genética , Lactente , Tempo de Internação , Resultado do Tratamento , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
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.
Assuntos
Biomarcadores , Ferritinas , L-Lactato Desidrogenase , Pneumonia por Mycoplasma , Humanos , Feminino , Masculino , Pneumonia por Mycoplasma/tratamento farmacológico , Pneumonia por Mycoplasma/sangue , Pneumonia por Mycoplasma/diagnóstico , Criança , Ferritinas/sangue , Estudos Retrospectivos , Pré-Escolar , Biomarcadores/sangue , L-Lactato Desidrogenase/sangue , Relação Dose-Resposta a Droga , Adolescente , Mycoplasma pneumoniae/efeitos dos fármacos , Metilprednisolona/administração & dosagem , Glucocorticoides/administração & dosagemRESUMO
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.
Assuntos
Antibacterianos , COVID-19 , Farmacorresistência Bacteriana , Macrolídeos , Mycoplasma pneumoniae , Pneumonia por Mycoplasma , SARS-CoV-2 , Humanos , Taiwan/epidemiologia , Macrolídeos/farmacologia , Macrolídeos/uso terapêutico , Mycoplasma pneumoniae/efeitos dos fármacos , Mycoplasma pneumoniae/genética , Pneumonia por Mycoplasma/epidemiologia , Pneumonia por Mycoplasma/tratamento farmacológico , Pneumonia por Mycoplasma/microbiologia , COVID-19/epidemiologia , Criança , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Pré-Escolar , Pandemias , Masculino , Feminino , Lactente , Adolescente , Testes de Sensibilidade MicrobianaRESUMO
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.
Assuntos
Acetilcisteína , Budesonida , Nomogramas , Pneumonia por Mycoplasma , Humanos , Acetilcisteína/uso terapêutico , Feminino , Masculino , Criança , Pneumonia por Mycoplasma/tratamento farmacológico , Estudos Retrospectivos , Budesonida/uso terapêutico , Budesonida/administração & dosagem , Pré-Escolar , Quimioterapia Combinada , Modelos Logísticos , Mycoplasma pneumoniae/efeitos dos fármacos , Resultado do Tratamento , AdolescenteRESUMO
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 (Pâ = 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.
Assuntos
Antibacterianos , Azitromicina , Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Terbutalina , Humanos , Azitromicina/administração & dosagem , Azitromicina/uso terapêutico , Terbutalina/administração & dosagem , Terbutalina/uso terapêutico , Pneumonia por Mycoplasma/tratamento farmacológico , Criança , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Mycoplasma pneumoniae/efeitos dos fármacos , Quimioterapia Combinada , Administração por Inalação , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Pré-EscolarRESUMO
Currently, there is a nationwide outbreak of Mycoplasma pneumoniae infections. M. pneumoniae is a bacterium that can cause atypical pneumonia, especially in children and young adults, and does not respond to the standard antibiotics prescribed for pneumonia. In addition, the bacterium regularly causes extra-pulmonary symptoms. In our hospitals, we have admitted 100 patients (including 20 children) with M. pneumoniae since the fall of 2023, many of which were young and had severe clinical symptoms. It is important to recognize the clinical picture to start effective antibiotic treatment. In this clinical lesson, we will provide two examples of recently admitted patients and discuss the characteristics of all inpatients who have presented to our hospitals during this epidemic. Finally, we pay attention to antibiotic policy and antibiotic resistance.
Assuntos
Antibacterianos , Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Humanos , Países Baixos/epidemiologia , Antibacterianos/uso terapêutico , Mycoplasma pneumoniae/efeitos dos fármacos , Pneumonia por Mycoplasma/epidemiologia , Pneumonia por Mycoplasma/tratamento farmacológico , Pneumonia por Mycoplasma/história , Criança , Farmacorresistência Bacteriana , Surtos de Doenças , Masculino , Feminino , AdultoRESUMO
To analyze the characteristics of Mycoplasma pneumoniae as well as macrolide antibiotic resistance through whole-genome sequencing and comparative genomics. Thirteen clinical strains isolated from 2003 to 2019 were selected, 10 of which were resistant to erythromycin (MIC >64 µg/mL), including 8 P1-type I and 2 P1-type II. Three were sensitive (<1 µg/mL) and P1-type II. One resistant strain had an AâG point mutation at position 2064 in region V of the 23S rRNA, the others had it at position 2063, while the three sensitive strains had no mutation here. Genome assembly and comparative genome analysis revealed a high level of genome consistency within the P1 type, and the primary differences in genome sequences concentrated in the region encoding the P1 protein. In P1-type II strains, three specific gene mutations were identified: C162A and A430G in L4 gene and T1112G mutation in the CARDS gene. Clinical information showed seven cases were diagnosed with severe pneumonia, all of which were infected with drug-resistant strains. Notably, BS610A4 and CYM219A1 exhibited a gene multi-copy phenomenon and shared a conserved functional domain with the DUF31 protein family. Clinically, the patients had severe refractory pneumonia, with pleural effusion, necessitating treatment with glucocorticoids and bronchoalveolar lavage. The primary variations between strains occur among different P1-types, while there is a high level of genomic consistency within P1-types. Three mutation loci associated with specific types were identified, and no specific genetic alterations directly related to clinical presentation were observed.IMPORTANCEMycoplasma pneumoniae is an important pathogen of community-acquired pneumonia, and macrolide resistance brings difficulties to clinical treatment. We analyzed the characteristics of M. pneumoniae as well as macrolide antibiotic resistance through whole-genome sequencing and comparative genomics. The work addressed primary variations between strains that occur among different P1-types, while there is a high level of genomic consistency within P1-types. In P1-type II strains, three specific gene mutations were identified: C162A and A430G in L4 gene and T1112G mutation in the CARDS gene. All the strains isolated from severe pneumonia cases were drug-resistant, two of which exhibited a gene multi-copy phenomenon, sharing a conserved functional domain with the DUF31 protein family. Three mutation loci associated with specific types were identified, and no specific genetic alterations directly related to clinical presentation were observed.
Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Genoma Bacteriano , Testes de Sensibilidade Microbiana , Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Mycoplasma pneumoniae/genética , Mycoplasma pneumoniae/efeitos dos fármacos , Mycoplasma pneumoniae/classificação , Mycoplasma pneumoniae/isolamento & purificação , Humanos , Antibacterianos/farmacologia , Genoma Bacteriano/genética , Pneumonia por Mycoplasma/microbiologia , Pneumonia por Mycoplasma/tratamento farmacológico , Farmacorresistência Bacteriana/genética , Masculino , Feminino , Sequenciamento Completo do Genoma , Pessoa de Meia-Idade , Macrolídeos/farmacologia , Adulto , Mutação , RNA Ribossômico 23S/genética , Genômica , Idoso , Eritromicina/farmacologiaRESUMO
With the atypical rise of Mycoplasma pneumoniae infection (MPI) in 2023, prompt studies are needed to determine the current epidemic features and risk factors with emerging trends of MPI to furnish a framework for subsequent investigations. This multicentre, retrospective study was designed to analyse the epidemic patterns of MPI before and after the COVID-19 pandemic, as well as genotypes and the macrolide-resistance-associated mutations in MP sampled from paediatric patients in Southern China. Clinical data was collected from 1,33,674 patients admitted into investigational hospitals from 1 June 2017 to 30 November 2023. Metagenomic next-generation sequencing (mNGS) data were retrieved based on MP sequence positive samples from 299 paediatric patients for macrolide-resistance-associated mutations analysis. Pearson's chi-squared test was used to compare categorical variables between different time frames. The monthly average cases of paediatric common respiratory infection diseases increased without enhanced public health measures after the pandemic, especially for influenza, respiratory syncytial virus infection, and MPI. The contribution of MPI to pneumoniae was similar to that in the outbreak in 2019. Compared to mNGS data between 2019-2022 and 2023, the severity of MP did not grow stronger despite higher rates of macrolide-resistance hypervariable sites, including loci 2063 and 2064, were detected in childhood MP samples of 2023. Our findings indicated that ongoing surveillance is necessary to understand the impact of post pandemic on MP transmission disruption during epidemic season and the severity of clinical outcomes in different scenarios.
Assuntos
COVID-19 , Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Humanos , Pneumonia por Mycoplasma/epidemiologia , Pneumonia por Mycoplasma/microbiologia , Mycoplasma pneumoniae/genética , Mycoplasma pneumoniae/isolamento & purificação , Mycoplasma pneumoniae/efeitos dos fármacos , China/epidemiologia , COVID-19/epidemiologia , COVID-19/transmissão , Criança , Estudos Retrospectivos , Pré-Escolar , Masculino , Feminino , Lactente , Macrolídeos/farmacologia , Farmacorresistência Bacteriana , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Adolescente , Sequenciamento de Nucleotídeos em Larga Escala , Antibacterianos/farmacologia , PandemiasRESUMO
OBJECTIVES: In the Asia-Pacific region, Mycoplasma pneumoniae (MP) could be a notable pathogen responsible for adult community-acquired pneumonia (CAP), with varying prevalence rates. This comprehensive review aimed to explore the epidemiology, clinical manifestations, macrolide resistance, and molecular characteristics of MP in adults across several countries in Asia. METHODS: PubMed, Embase, and Google Scholar were searched for relevant articles from 2010-2023 based on the following keywords: adult and Mycoplasma pneumoniae. RESULTS: The prevalence of MP in CAP patients in these countries ranged from 2.1% in Korea to 25.5% in Japan. Macrolide resistance was prominent, particularly in China, with rates ranging 26.9-100%. Clinical manifestations of MP infection included protean extrapulmonary manifestations, and complications such as rhabdomyolysis and thrombocytopenia. Molecular characteristics, especially the multiple locus variable-number tandem-repeat analysis type 4/5/7/2, remained predominant across various countries, emphasising the importance of ongoing surveillance. CONCLUSIONS: This review highlights the urgent need for continued monitoring of MP infections, macrolide resistance, and molecular characteristics to inform effective prevention and treatment strategies in the Asia-Pacific region.
Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Macrolídeos , Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Humanos , Mycoplasma pneumoniae/efeitos dos fármacos , Mycoplasma pneumoniae/genética , Macrolídeos/uso terapêutico , Macrolídeos/farmacologia , Pneumonia por Mycoplasma/epidemiologia , Pneumonia por Mycoplasma/microbiologia , Pneumonia por Mycoplasma/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Ásia/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/tratamento farmacológico , Adulto , Prevalência , Efeitos Psicossociais da DoençaRESUMO
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.
Assuntos
Heparina , Mycoplasma pneumoniae , Polissacarídeos , Animais , Adesinas Bacterianas/metabolismo , Adesinas Bacterianas/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Organismos Aquáticos , Aderência Bacteriana/efeitos dos fármacos , Heparina/farmacologia , Heparina/química , Interações Hospedeiro-Patógeno , Mycoplasma pneumoniae/efeitos dos fármacos , Pneumonia por Mycoplasma/tratamento farmacológico , Pneumonia por Mycoplasma/microbiologia , Polissacarídeos/farmacologia , Polissacarídeos/química , Sulfatos/química , Sulfatos/farmacologiaRESUMO
Objective: To analyze the drug-resistant gene loci of Mycoplasma pneumoniae (MP) using metagenomic next-generation sequencing (mNGS). Methods: From November 2022 to October 2023, 697 clinical samples (including sputum, alveolar lavage fluid and blood) of 686 children with Mycoplasma pneumoniae positive detected by mNGS were retrospectively analyzed. Samples were divided into intensive care unit (ICU) group and non-ICU group, Chi-square test was used to compare groups, and Mann-Kendall trend test was used to analyze the change trend of the detection rate of drug resistance gene loci over time. Results: Of the 697 samples, 164 were from the ICU group and 533 were from the non-ICU group. The detection rate of Mycoplasma pneumoniae resistance gene was 44.3% (309/697), and all detected drug-resistant gene loci of MP were A2063G. The detection rate of Mycoplasma pneumoniae in ICU group was 50.0% (82/164), and the detection rates of Mycoplasma pneumoniae resistance gene loci in sputum, alveolus lavage fluid and blood samples were 75.0% (18/24) and 48.4% (62/128), respectively. The detection rate in sputum was higher than alveolus lavage fluid samples (χ2=5.72,P=0.017). The detection rate of Mycoplasma pneumoniae in non-ICU group was 42.6% (227/533), the detection rate of Mycoplasma pneumoniae resistance gene loci in sputum and alveolar lavage fluid was 40.0% (16/40), 44.3% (201/454), and no detection rate in blood samples (0/12). There was no significant difference in the detection rate of alveolar lavage fluid and sputum (χ2=0.27, P=0.602). From November 2022 to October 2023, the detection rate of submitted samples showed an increasing trend month by month (overall: Z=3.99, ICU inspection group: Z=2.93, non-ICU group: Z=3.01, all P<0.01). Among the bacteria commonly detected with Mycoplasma pneumoniae, Streptococcus pneumoniae accounted for the highest proportion, the detection rate was 15.5% (108/697), and Epstein-Barr virus accounted for the highest proportion of 17.6% (123/697). Conclusions: From November 2022 to October 2023, the detection rate of Mycoplasma pneumoniae drug resistance gene loci showed an increasing trend. The detection rate of drug resistance gene loci in sputum samples of ICU group was higher than alveolus lavage fluid. No new drug resistance site were detected.
Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Sequenciamento de Nucleotídeos em Larga Escala , Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Humanos , Mycoplasma pneumoniae/genética , Mycoplasma pneumoniae/efeitos dos fármacos , Estudos Retrospectivos , Criança , Pneumonia por Mycoplasma/microbiologia , Pneumonia por Mycoplasma/diagnóstico , Pneumonia por Mycoplasma/tratamento farmacológico , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Farmacorresistência Bacteriana/genética , Antibacterianos/farmacologia , Metagenômica/métodos , Escarro/microbiologia , Líquido da Lavagem Broncoalveolar/microbiologia , Testes de Sensibilidade Microbiana , Masculino , Pré-Escolar , FemininoRESUMO
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.
Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Macrolídeos , Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Mycoplasma pneumoniae/efeitos dos fármacos , Mycoplasma pneumoniae/genética , Mycoplasma pneumoniae/isolamento & purificação , Humanos , China/epidemiologia , Macrolídeos/farmacologia , Estudos Retrospectivos , Criança , Antibacterianos/farmacologia , Pré-Escolar , Adolescente , Adulto , Feminino , Masculino , Pneumonia por Mycoplasma/epidemiologia , Pneumonia por Mycoplasma/microbiologia , Pneumonia por Mycoplasma/tratamento farmacológico , Pessoa de Meia-Idade , Adulto Jovem , Testes de Sensibilidade Microbiana , Idoso , Lactente , Prevalência , RNA Ribossômico 23S/genética , Idoso de 80 Anos ou maisAssuntos
Antibacterianos , Farmacorresistência Bacteriana , Macrolídeos , Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Humanos , China/epidemiologia , Pneumonia por Mycoplasma/epidemiologia , Pneumonia por Mycoplasma/tratamento farmacológico , Pneumonia por Mycoplasma/microbiologia , Macrolídeos/uso terapêutico , Macrolídeos/farmacologia , Mycoplasma pneumoniae/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/uso terapêuticoRESUMO
Translation is the fundamental process of protein synthesis and is catalysed by the ribosome in all living cells1. Here we use advances in cryo-electron tomography and sub-tomogram analysis2,3 to visualize the structural dynamics of translation inside the bacterium Mycoplasma pneumoniae. To interpret the functional states in detail, we first obtain a high-resolution in-cell average map of all translating ribosomes and build an atomic model for the M. pneumoniae ribosome that reveals distinct extensions of ribosomal proteins. Classification then resolves 13 ribosome states that differ in their conformation and composition. These recapitulate major states that were previously resolved in vitro, and reflect intermediates during active translation. On the basis of these states, we animate translation elongation inside native cells and show how antibiotics reshape the cellular translation landscapes. During translation elongation, ribosomes often assemble in defined three-dimensional arrangements to form polysomes4. By mapping the intracellular organization of translating ribosomes, we show that their association into polysomes involves a local coordination mechanism that is mediated by the ribosomal protein L9. We propose that an extended conformation of L9 within polysomes mitigates collisions to facilitate translation fidelity. Our work thus demonstrates the feasibility of visualizing molecular processes at atomic detail inside cells.
Assuntos
Microscopia Crioeletrônica , Mycoplasma pneumoniae , Biossíntese de Proteínas , Proteínas Ribossômicas , Ribossomos , Antibacterianos/farmacologia , Mycoplasma pneumoniae/citologia , Mycoplasma pneumoniae/efeitos dos fármacos , Mycoplasma pneumoniae/metabolismo , Mycoplasma pneumoniae/ultraestrutura , Elongação Traducional da Cadeia Peptídica/efeitos dos fármacos , Polirribossomos/efeitos dos fármacos , Polirribossomos/metabolismo , Polirribossomos/ultraestrutura , Biossíntese de Proteínas/efeitos dos fármacos , Proteínas Ribossômicas/metabolismo , Proteínas Ribossômicas/ultraestrutura , Ribossomos/efeitos dos fármacos , Ribossomos/metabolismo , Ribossomos/ultraestruturaRESUMO
Mycoplasma pneumoniae (MPP) induced pneumonia is a common disease of children. Sinomenine (SIN) is an isoquinoline mainly sequestered from Sinomenium acutum. It is a promising drug for treating arthritis, lung, colon, liver and gastric cancer. Hence, the present study investigated the role and mechanism of SIN treatment in MPP induced pneumonia in experimental in-vivo mice model. The BALB/c male mice were separated into four groups (n = 6 mice/group): normal, MPP, MPP + SIN (20 mg/kg bw), and SIN (20 mg/kg bw) alone. Results were expressed as mean ± SD. Data were analyzed using one way Analysis of Variance (ANOVA) with the Dunnett's post hoc test using SPSS v 18.0. P value < 0.05 was considered significant. The total protein, cell count, inflammatory cytokines, MP-IgM, Monocyte chemo attractant protein-1 (MCP-1), and MP-DNA were measured. The protein expressions of Bax/Bcl-2, ERK, JNK, NF-κB were analyzed and histopathology of lungs was examined. SIN treatment significantly (p < 0.05) reduced the total proteins, cell counts in BALF, inflammatory cytokines, MP-IgM, MCP-1, MP-DNA and reversed the histological alterations. SIN attenuated the apoptotic pathway through the modulation of Bax/Bcl-2 expression. SIN alleviated pulmonary inflammatory mediators and apoptosis in MPP-infected mice via suppression of ERK/JNK/NF-κB signaling. SIN administration diminished inflammation and lung fibrosis by inhibiting apoptosis in MPP mice. Hence, SIN is a potential natural protective remedy for MPP.
Assuntos
Sistema de Sinalização das MAP Quinases , Morfinanos , Mycoplasma pneumoniae , NF-kappa B , Pneumonia por Mycoplasma , Animais , Citocinas/metabolismo , Imunoglobulina M , Inflamação , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Morfinanos/farmacologia , Mycoplasma pneumoniae/efeitos dos fármacos , NF-kappa B/metabolismo , Pneumonia por Mycoplasma/tratamento farmacológico , Pneumonia por Mycoplasma/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
BACKGROUND: Mycoplasma pneumoniae is a leading cause of community-acquired respiratory infections. Infantile Feire Kechuan Oral Solution (IFKOS) is effective for treatment of M. pneumoniae infection. The aim of this study was to explore the potential mechanism of IFKOS against M. pneumoniae infection in basal epithelial human lung adenocarcinoma A549 cells. METHODS: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to determine the effects of IFKOS on the viability of A549 cells infected with M. pneumoniae. Optical microscopy was used to observe cell morphology and a Muse cell analyzer was used to assess apoptosis and the cell cycle phase. Enzyme-linked immunosorbent assays were employed to assess the expression levels of interleukin (IL)-4, IL-6, IL-8, IL-17, tumor necrosis factor (TNF)-α, interferon (IFN)-α, and IFN-γ. RESULTS: Under certain conditions, M. pneumoniae infection reduced the viability and inhibited the proliferation of A549 cells, promoted early apoptosis, and arrested cells in the G0/G1 phase, thus shortening the S and G2/M phases (all p < 0.05). M. pneumoniae also upregulated expression of IL-8 and TNF-α and downregulated that of IL-6 (p < 0.05), which switched the immune balance of Th1/Th2 to Th1 cells. IFKOS (5.531 mg/mL) improved the viability and proliferation of M. pneumoniae-infected A549 cells, mitigated early apoptosis, and reversed cell cycle arrest in the G0/G1 phase, thereby extending the S and G2/M phases (all, p < 0.05). IFKOS downregulated expression of IL-8 and TNF-α and upregulated that of IL-6 (p < 0.01), thereby reversing the immune imbalance of Th1/Th2. Secretion of IL-4, IL-17, IFN-α, and IFN-γ was not observed. CONCLUSION: IFKOS played a protective role in the regulation of cell viability, apoptosis, the cell cycle, and Th1/Th2 immune imbalance induced by M. pneumoniae infection and conveyed an anti-inflammatory effect in A549 cells.