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FEMS Microbiology Reviews Mar 2024Bacterial pneumonia greatly contributes to the disease burden and mortality of lower respiratory tract infections among all age groups and risk profiles. Therefore,... (Review)
Review
Bacterial pneumonia greatly contributes to the disease burden and mortality of lower respiratory tract infections among all age groups and risk profiles. Therefore, laboratory modelling of bacterial pneumonia remains important for elucidating the complex host-pathogen interactions and to determine drug efficacy and toxicity. In vitro cell culture enables for the creation of high-throughput, specific disease models in a tightly controlled environment. Advanced human cell culture models specifically, can bridge the research gap between the classical two-dimensional cell models and animal models. This review provides an overview of the current status of the development of complex cellular in vitro models to study bacterial pneumonia infections, with a focus on air-liquid interface models, spheroid, organoid, and lung-on-a-chip models. For the wide scale, comparative literature search, we selected six clinically highly relevant bacteria (Pseudomonas aeruginosa, Mycoplasma pneumoniae, Haemophilus influenzae, Mycobacterium tuberculosis, Streptococcus pneumoniae, and Staphylococcus aureus). We reviewed the cell lines that are commonly used, as well as trends and discrepancies in the methodology, ranging from cell infection parameters to assay read-outs. We also highlighted the importance of model validation and data transparency in guiding the research field towards more complex infection models.
Topics: Animals; Humans; Anti-Bacterial Agents; Pneumonia, Bacterial; Streptococcus pneumoniae; Respiratory Tract Infections; Cell Culture Techniques
PubMed: 38409952
DOI: 10.1093/femsre/fuae007 -
Microbiology Spectrum May 2024(MP) is commonly detected in children. However, the epidemiological trends of MP in Northeast (NE) China are unclear. This retrospective study aimed to investigate the...
UNLABELLED
(MP) is commonly detected in children. However, the epidemiological trends of MP in Northeast (NE) China are unclear. This retrospective study aimed to investigate the prevalence of MP infections in this understudied region. The clinical manifestations and bronchoscopic findings observed in hospitalized patients with severe pneumonia (SMPP) were collected from comprehensive data obtained from six tertiary hospitals in NE and Inner Mongolian (IM) China, from 1 January 2017 to 31 December 2023. A total of 5,593,530 children who visited the outpatient and emergency departments, and 412,480 inpatient hospitalized children were included in the study. The positivity rate of MP immunoglobulin M (IgM) in the children who visited the outpatient and emergency departments varied from 7.80% to 10.12%, whereas that of MP infection in hospitalized children ranged from 27.18% to 30.10%. Children hospitalized for MP infection were mainly concentrated in the 1- to 4-year (41.39%) and 4- to 7-year (24.25%) age groups. Before 2020, the season with the highest incidence of MP was winter. After the implementation of non-pharmaceutical interventions (NPIs), the MP epidemic season changed, and the number of children with MP infections decreased; however, the proportion of MP infections in hospitalized children did not change significantly. Starting from August 2023, the MP infection rate in outpatient, emergency, and hospitalized children increased sharply, with SMPP and its complications (e.g., plastic bronchitis and pleural effusion) increasing significantly. MP is prevalent in NE and IM, China. When the NPIs ended, MP infection showed a delayed outbreak trend, and the number of children with severe infection increased significantly.
IMPORTANCE
In Northeastern (NE) and Inner Mongolia (IM), the incidence of (MP) infections, including severe pneumonia (SMPP), is high, posing health risks and imposing substantial economic burdens on the local population. Therefore, it is imperative to prioritize the study of MP prevalence and address the research gaps in MP epidemiology in these areas of China. We obtained a comprehensive collection of pediatric outpatient, emergency, and inpatient data from six public Grade III hospitals. We believe that our study makes a significant contribution to the literature because understanding regional variations in MP infections can help healthcare professionals tailor prevention and treatment strategies, and studying bronchoscopic manifestations can provide insights into the impact of the disease on the respiratory system, potentially leading to a more effective clinical management.
Topics: Humans; China; Pneumonia, Mycoplasma; Child; Mycoplasma pneumoniae; Child, Preschool; Female; Male; Retrospective Studies; Infant; Adolescent; Prevalence; Hospitalization; Incidence; Immunoglobulin M; Seasons
PubMed: 38606996
DOI: 10.1128/spectrum.00097-24 -
Immunity, Inflammation and Disease Oct 2023In recent years, there has been an increase in the number of patients diagnosed with pediatric diseases who have severe Mycoplasma pneumoniae (MP) pneumonia, and there...
BACKGROUND INTRODUCTION
In recent years, there has been an increase in the number of patients diagnosed with pediatric diseases who have severe Mycoplasma pneumoniae (MP) pneumonia, and there has also been an increased attention to serious extrapulmonary complications. However, cases with abdominal pain, acute abdomen, scrotal swelling and pain, and fever as the primary symptoms have been rarely reported.
CASE DESCRIPTION
A 3-years-and-8-months-old male patient diagnosed with pediatric disease was reported with abdominal pain, scrotal swelling and pain, and fever as the primary symptoms in the present study. No respiratory symptoms were observed throughout the disease. Through computed tomography (CT) scanning, the patient was diagnosed with severe MP pneumonia based on the symptoms of abdominal pain and fever, as well as pulmonary infection, pleural effusion, and retroperitoneal exudation. Laboratory tests supported the diagnosis of MP infection, and the diagnosis was confirmed by severe MP pneumonia. The therapeutic effects of azithromycin were poor, and the symptoms were quickly alleviated with the addition of gamma globulin and methylprednisolone. After discharge, azithromycin sequential therapy was administered. The chest CT was normal at the follow-up 1-month later.
CONCLUSION
Severe MP pneumonia in patients with pediatric diseases may include abdominal pain, scrotal swelling and pain, and fever as the primary symptoms. Care should be taken to avoid missed diagnoses and misdiagnoses in clinical practice.
Topics: Child; Humans; Male; Infant; Mycoplasma pneumoniae; Azithromycin; Abdomen, Acute; Pneumonia, Mycoplasma; Abdominal Pain
PubMed: 37904684
DOI: 10.1002/iid3.955 -
Clinical and Experimental Pediatrics Feb 2024Pneumonia is a common pediatric infectious disease that is familiar to pediatricians and a major cause of hospitalization worldwide. Recent well-designed epidemiologic...
Pneumonia is a common pediatric infectious disease that is familiar to pediatricians and a major cause of hospitalization worldwide. Recent well-designed epidemiologic studies in developed countries indicated that respiratory viruses are detected in 30%-70%, atypical bacteria in 7%-17%, and pyogenic bacteria in 2%-8% of children hospitalized with community-acquired pneumonia (CAP). The etiological distribution of CAP varies widely by child age and the epidemiological season of the respiratory pathogen. Moreover, diagnostic tests, particularly for the detection of Streptococcus pneumoniae and Mycoplasma pneumoniae, the 2 major bacterial pathogens involved in pediatric CAP, have several limitations. Therefore, management and empirical antimicrobial therapy for children with CAP should be applied in a stepwise manner based on recent epidemiological, etiological, and microbiological evidence.
PubMed: 37321577
DOI: 10.3345/cep.2022.01452 -
Italian Journal of Pediatrics Sep 2023We investigated changes in microR-29c and microR-146a expression in the serum of children with Mycoplasma pneumoniae pneumonia, analysed their relationship with...
BACKGROUND
We investigated changes in microR-29c and microR-146a expression in the serum of children with Mycoplasma pneumoniae pneumonia, analysed their relationship with inflammatory factors and disease severity, and evaluated their diagnostic significance.
METHODS
Fifty-six children with Mycoplasma pneumoniae pneumonia were enrolled as the Mycoplasma pneumoniae pneumonia group; 37 healthy children were enrolled as the control group. The microR-29c or microR-146a serum expression levels were determined using real-time quantitative reverse transcription polymerase chain reaction. Interleukin-17, tumour necrosis factor-alpha, and interleukin-1 beta levels were detected using enzyme-linked immunosorbent assay. The correlation between serum microR-29c or microR-146a expression and inflammatory factors was analysed using the Pearson's method. Receiver operating characteristic curves were used to evaluate the diagnostic value of serum microR-29c, microR-146a, and their combined detection in Mycoplasma pneumoniae pneumonia.
RESULTS
Compared with that in healthy children, the microR-29c and microR-146a serum levels were significantly downregulated in children with Mycoplasma pneumoniae pneumonia; the decrease was more obvious in children with severe cases than that in those with mild cases. In addition, microR-29c and microR-146a were negatively correlated with increased expression of interleukin-17, tumour necrosis factor-alpha, and interleukin-1 beta. Receiver operating characteristic curves showed that a combination of microR-29c and microR-146a was highly suitable for diagnosing Mycoplasma pneumoniae pneumonia.
CONCLUSION
Serum microR-29c and microR-146a were underexpressed in children with Mycoplasma pneumoniae pneumonia, and diagnostic accuracy was significantly improved with combined microR-29c and microR-146a detection. Therefore, both microR-29c and microR-146a levels can be used as biomarkers for the diagnosis of Mycoplasma pneumoniae pneumonia.
Topics: Child; Humans; Interleukin-17; Interleukin-1beta; Mycoplasma pneumoniae; Tumor Necrosis Factor-alpha; Pneumonia, Mycoplasma
PubMed: 37705091
DOI: 10.1186/s13052-023-01500-0 -
Nature Biotechnology Aug 2023Engineered live bacteria could provide a new modality for treating lung infections, a major cause of mortality worldwide. In the present study, we engineered a...
Engineered live bacteria could provide a new modality for treating lung infections, a major cause of mortality worldwide. In the present study, we engineered a genome-reduced human lung bacterium, Mycoplasma pneumoniae, to treat ventilator-associated pneumonia, a disease with high hospital mortality when associated with Pseudomonas aeruginosa biofilms. After validating the biosafety of an attenuated M. pneumoniae chassis in mice, we introduced four transgenes into the chromosome by transposition to implement bactericidal and biofilm degradation activities. We show that this engineered strain has high efficacy against an acute P. aeruginosa lung infection in a mouse model. In addition, we demonstrated that the engineered strain could dissolve biofilms formed in endotracheal tubes of patients with ventilator-associated pneumonia and be combined with antibiotics targeting the peptidoglycan layer to increase efficacy against Gram-positive and Gram-negative bacteria. We expect our M. pneumoniae-engineered strain to be able to treat biofilm-associated infections in the respiratory tract.
Topics: Humans; Mice; Animals; Anti-Bacterial Agents; Pseudomonas Infections; Pneumonia, Ventilator-Associated; Gram-Negative Bacteria; Gram-Positive Bacteria; Intubation, Intratracheal; Biofilms; Lung
PubMed: 36658340
DOI: 10.1038/s41587-022-01584-9 -
Emerging Microbes & Infections Dec 2024Paediatric pneumonia (MPP) is a heterogeneous disease with a diverse spectrum of clinical phenotypes. No studies have demonstrated the relationship between underlying...
Paediatric pneumonia (MPP) is a heterogeneous disease with a diverse spectrum of clinical phenotypes. No studies have demonstrated the relationship between underlying endotypes and clinical phenotypes as well as prognosis about this disease. Thus, we conducted a multicentre prospective longitudinal study on children hospitalized for MPP between June 2021 and March 2023, with the end of follow-up in August 2023. Blood samples were collected and processed at multiple time points. Multiplex cytokine assay was performed to characterize serum cytokine profiles and their dynamic changes after admission. Cluster analysis based on different clinical phenotypes was conducted. Among the included 196 patients, the levels of serum IL-17A and IL-6 showed remarkable variabilities. Four cytokine clusters based on the two cytokines and four clinical groups were identified. Significant elevation of IL-17A mainly correlated with diffuse bronchiolitis and lobar lesion by airway mucus hypersecretions, while that of IL-6 was largely associated with lobar lesion which later developed into lung necrosis. Besides, glucocorticoid therapy failed to inhibit IL-17A, and markedly elevated IL-17A and IL-6 levels may correlate with lower airway obliterans. Our study provides critical relationship between molecular signatures (endotypes) and clustered clinical phenotypes in paediatric patients with MPP.
Topics: Humans; Child; Mycoplasma pneumoniae; Interleukin-6; Interleukin-17; Prospective Studies; Longitudinal Studies; Pneumonia, Mycoplasma; Cytokines
PubMed: 38407218
DOI: 10.1080/22221751.2024.2324078 -
Frontiers in Cellular and Infection... 2023Omadacycline is a novel tetracycline antibiotic that exhibits good antibacterial activity against atypical pathogens such as . It is approved for the treatment of...
Omadacycline is a novel tetracycline antibiotic that exhibits good antibacterial activity against atypical pathogens such as . It is approved for the treatment of adults with community-acquired bacterial pneumonia. However, the safety and efficacy of omadacycline in pediatric patients under 18 years of age have not yet been established. In the present paper, we report a case of pediatric community-acquired pneumonia in which initial empirical anti-infective therapy had failed. The patient received empirical anti-infective therapy with azithromycin and other antimicrobial agents upon admission but showed a poor clinical response and developed secondary tinnitus and liver dysfunction. After the confirmation of infection through metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid, an antibiotic switch to omadacycline was made. Thereafter, the patient's condition improved, and no adverse reactions were observed. These findings demonstrate that mNGS enables the identification of infection-causing pathogens in patients with unresponsive pneumonia. Omadacycline can be considered as an alternative option for anti-infective therapy in pediatric pneumonia, especially when the presence of bacterial resistance, adverse drug reactions, or organ failure are taken into consideration.
Topics: Adult; Humans; Adolescent; Child; Macrolides; Mycoplasma pneumoniae; Drug Resistance, Bacterial; Anti-Bacterial Agents; Pneumonia, Mycoplasma; Tetracyclines; Community-Acquired Infections
PubMed: 37842004
DOI: 10.3389/fcimb.2023.1244398 -
Infectious Diseases and Therapy Feb 2024Mycoplasma pneumoniae necrotizing pneumonia (MPNP) is an uncommon but increasingly recognized severe complication of pneumonia, and the delayed diagnosis and treatment...
INTRODUCTION
Mycoplasma pneumoniae necrotizing pneumonia (MPNP) is an uncommon but increasingly recognized severe complication of pneumonia, and the delayed diagnosis and treatment are prone to pulmonary sequelae. The aim of this study is to explore independent risk factors for MPNP in children with lung consolidation.
METHODS
A retrospective observational study was conducted on 118 children with MPNP (MPNP group) and 184 children with lung consolidation of Mycoplasma pneumoniae pneumonia (MPP) (control group) admitted to Children's Hospital Affiliated to Zhengzhou University from June 2018 to August 2023. Clinical manifestations and laboratory data were analyzed and the independent risk factors for MPNP in children were analyzed by multivariate logistic regression.
RESULTS
The age of onset, hospitalization days, fever days, proportion of dyspnea, chest pain, complications, and need for fiberoptic bronchoscopic alveolar lavage (FBAL) were higher than those in the control group, and the difference was statistically significant (P < 0.05). The levels of white blood cells (WBC), platelets, neutrophil percentage (N%), neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), fibrinogen (Fbg), D-dimer (D-D), erythrocyte sedimentation rate (ESR), alanine transaminase (ALT), γ-glutamyl transpeptidase (γ-GGT), globulin, lactate dehydrogenase (LDH), α-hydroxybutyrate dehydrogenase (α-HBDH), urea, immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin A (IgA), complement component 3, antistreptolysin O (ASO), serum ferritin, and interleukin-6 (IL-6) in the MPNP group were higher than those in the control group. Red blood cell (RBC), lymphocyte percentage (L%), activated partial thromboplastin time (APTT), alkaline phosphatase (ALP), total protein, albumin, albumin-to-globulin ratio (AGR), creatine kinase (CK), uric acid, natrium, chlorine, calcium, and complement C4 in the MPNP group were lower than those in the control group, and the difference was statistically significant (P < 0.05). The results of multivariate logistic regression analysis showed that age ≥ 83.50 months, fever days ≥ 10.50, ALT ≥ 15.25 U/l, IgM ≥ 1.46 g/l, complement C3 ≥ 1.47 g/l, Fbg ≥ 3.93 g/l, dyspnea and needing FBAL were independent risk factors for MPNP in children.
CONCLUSIONS
Age, fever days, ALT, IgM, complement C3, Fbg, dyspnea, and needing FBAL were independent risk factors for MPNP in children. For children suspected of MPNP, pediatricians should pay close attention to the above indicators, strive for early diagnosis and treatment, and improve prognosis.
PubMed: 38265626
DOI: 10.1007/s40121-023-00914-x -
Emergency Medicine International 2024The study aimed to analyze the clinical characteristics of children with RMPP and to explore the biomarkers for the early prediction of RMPP, thus providing references...
OBJECTIVE
The study aimed to analyze the clinical characteristics of children with RMPP and to explore the biomarkers for the early prediction of RMPP, thus providing references for the clinical diagnosis and treatment of RMPP in children.
METHODS
Baseline clinical characteristics, clinical symptoms, physical examination, chest imaging, and laboratory indicators between children with RMPP and general refractory mycoplasma pneumoniae pneumonia (GMPP) were compared. Multiple logistic regression analysis was used to determine independent risk factors for RMPP. ROC curves were adopted to analyze the predictive values of biomarkers.
RESULTS
The RMPP group had more severe clinical symptoms and manifestations on imaging (including pleural effusion, pulmonary consolidation, and pulmonary atelectasis), a higher incidence of extrapulmonary complications, and a longer duration of hospital stays. Results of multiple logistic regression analysis showed that serum D-dimer (OR = 8.169, < 0.001), C-reactive protein (CRP) (OR = 1.146, < 0.001), and lactate dehydrogenase (LDH) (OR = 1.025, < 0.001) levels were independent risk factors for RMPP. The area under the receiver operating characteristic curve (AUROC) in RMPP prediction was 0.841, 0.870, and 0.893 for serum levels of D-dimer, CRP, and LDH, respectively ( < 0.001), with a cutoff value of 1.47 ng/ml, 39.34 mg/L, and 379 IU/L, respectively.
CONCLUSIONS
Serum D-dimer, CRP, and LDH levels were related to the severity of mycoplasma pneumoniae pneumonia in children and had potential as biomarkers for the early prediction of RMPP, suggesting great applicative values for the early diagnosis and timely intervention of children with RMPP in clinical practice.
PubMed: 38222094
DOI: 10.1155/2024/9328177