The CARDS toxin of Mycoplasma pneumoniae induces a positive feedback loop of type 1 immune response.

Background: Within the past 3-5 years, Mycoplasma pneumoniae has become a major pathogen of community-acquired pneumonia in children. The pathogenic mechanisms involved in M. pneumoniae infection have not been fully elucidated. Methods: Previous protein microarray studies have shown a differential expression of CXCL9 after M. pneumoniae infection. Here, we conducted a hospital-based study to explore the clinical significance of the type 1 immune response inflammatory factors interferon (IFN)-γ and CXCL9 in patients with M. pneumoniae pneumonia (MPP). Then, through in vitro experiments, we explored whether CARDS toxin stimulated F-DCs (dendritic cells incubated with Flt3L) to promote Th-cell differentiation; we also investigated the IFN-γ-induced CXCL9 secretion pathway in macrophages and the role of CXCL9 in promoting Th1 cell migration. Results: The CXCL9 expression level was upregulated among patients with a higher fever peak, fever duration of greater than 7 days, an imaging manifestation of lobar or segmental, or combined pleural effusion (P<0.05). The peripheral blood levels of IFN-γ and CXCL9, which were higher in patients than in the healthy control group, were positively correlated with each other (r=0.502, P<0.05). In patients, the CXCL9 expression level was significantly higher in the bronchoalveolar lavage fluid (BALF) than in the peripheral blood, and the BALF CXCL9 expression level was higher than that in the healthy control group (all P<0.05). Our flow cytometry analysis revealed that M1-phenotype macrophages (CD16 + CD64 + CD163-) were predominant in the BALF from children with MPP. In in vitro experiments, F-DCs stimulated with CARDS toxin promoted the differentiation of CD4 + IFN-γ + Th (Th1) cells (P<0.05). Moreover, IFN-γ induced high levels of CXCL9 expression in M1-type macrophages in a dose-dependent and time-dependent manner. Additionally, macrophages transfection with STAT1-siRNA-1 downregulated the expression of CXCL9 (P<0.05), and CXCL9 promoted Th1 cell migration (P<0.05). Conclusions: Our findings suggest that CARDS toxin induces a type 1 immune response positive feedback loop during M. pneumoniae infection; this putative mechanism may be useful in future investigations of immune intervention approaches for M. pneumoniae pneumonia.

Mycoplasma pneumoniae among Chinese Outpatient Children with Mild Respiratory Tract Infections during the Coronavirus Disease 2019 Pandemic.

Mycoplasma pneumoniae is a common pathogen causing respiratory disease in children. We sought to investigate the epidemiology of M. pneumoniae among outpatient children with mild respiratory tract infections (RTIs) during the coronavirus disease 2019 (COVID-19) pandemic. Eligible patients were prospectively enrolled from January 2020 to June 2021. Throat swabs were tested for M. pneumoniae RNA. M. pneumoniae IgM was tested by a colloidal gold assay. Macrolide resistance and the effect of the COVID-19 countermeasures on M. pneumoniae prevalence were assessed. Symptom scores, treatments, and outcomes were evaluated. Eight hundred sixty-two eligible children at 15 centers in China were enrolled. M. pneumoniae was detected in 78 (9.0%) patients. Seasonally, M. pneumoniae peaked in the first spring and dropped dramatically to extremely low levels over time until the next summer. Decreases in COVID-19 prevalence were significantly associated with decreases in M. pneumoniae prevalence (r = 0.76, P = 0.001). The macrolide resistance rate was 7.7%. The overall sensitivity and specificity of the colloidal gold assay used in determining M. pneumoniae infection were 32.1% and 77.9%, respectively. No more benefits for improving the severity of symptoms and outcomes were observed in M. pneumoniae-infected patients treated with a macrolide than in those not treated with a macrolide during follow-up. The prevalences of M. pneumoniae and macrolide resistance in outpatient children with mild RTIs were at low levels in the early stage of the COVID-19 pandemic but may have rebounded recently. The colloidal gold assay for M. pneumoniae IgM may be not appropriate for diagnosis of M. pneumoniae infection. Macrolides should be used with caution among outpatients with mild RTIs. IMPORTANCE This is the first and largest prospective, multicenter, active, population-based surveillance study of the epidemiology of Mycoplasma pneumoniae among outpatient children with mild respiratory tract infections (RTIs) during the COVID-19 pandemic. Nationwide measures like strict face mask wearing and restrictions on population movement implemented to prevent the spread of COVID-19 might also effectively prevent the spread of M. pneumoniae. The prevalence of M. pneumoniae and the proportion of drug-resistant M. pneumoniae isolates in outpatient children with mild RTIs were at low levels in the early stage of the COVID-19 pandemic but may have rebounded recently. The colloidal gold assay for M. pneumoniae IgM may be not appropriate for screening and diagnosis of M. pneumoniae infection. Macrolides should be used with caution among outpatients with mild RTIs.

The effects of magainin 2-derived and rationally designed antimicrobial peptides on Mycoplasma pneumoniae.

Combating the spread of antimicrobial resistance (AMR) among bacteria requires a new class of antimicrobials, which desirably have a narrow spectrum because of their low propensity for the spread of AMR. Antimicrobial peptides (AMPs), which target the bacterial cell membrane, are promising seeds for novel antimicrobials because the cell membrane is essential for all cells. Previously, we reported the antimicrobial and haemolytic effects of a natural AMP, magainin 2 (Mag2), isolated from the skin of Xenopus laevis (the African clawed frog), four types of synthesised Mag2 derivatives, and three types of rationally designed AMPs on gram-positive and gram-negative bacteria. To identify novel antimicrobial seeds, we evaluated the effect of AMPs on Mycoplasma pneumoniae, which also exhibits AMR. We also evaluated the antimicrobial effects of an AMP, NK2A, which has been reported to have antimicrobial effects on Mycoplasma bovis, in addition to Mag2 and previously synthesised seven AMPs, on four strains of M. pneumoniae using colorimetric, biofilm, and killing assays. We found that three synthesised AMPs, namely 17base-Ac6c, 17base-Hybrid, and Block, had anti-M. pneumoniae (anti-Mp) effect at 8-30 µM, whereas others, including NK2A, did not have any such effect. For the further analysis, the membrane disruption activities of AMPs were measured by propidium iodide (PI) uptake assays, which suggested the direct interaction of AMPs to the cell membrane basically following the colorimetric, biofilm, and killing assay results. PI uptake assay, however, also showed the NK2A strong interaction to cell membrane, indicating unknown anti-Mp determinant factors related to the peptide sequences. Finally, we conclude that anti-Mp effect was not simply determined by the membrane disruption activities of AMPs, but also that the sequence of AMPs were important for killing of M. pneumoniae. These findings would be helpful for the development of AMPs for M. pneumoniae.

Biomarkers of Mycoplasma pneumoniae pneumonia in children by urine metabolomics based on Q Exactive liquid chromatography/tandem mass spectrometry.

RATIONALE: Mycoplasma pneumoniae has become one of the common pathogens causing pediatric respiratory infections. In clinical diagnosis, throat swabs are very difficult to obtain from children, and there is a possibility of false positive results; hence, there are few clinically available diagnostic methods. METHODS: In this study, Q Exactive liquid chromatography/tandem mass spectrometry was used to analyze the metabolites in the urine of healthy children (HC) and M. pneumoniae pneumonia in children (MPPC) patients. A multivariate statistical analysis was performed to screen the differential metabolites. Based on the HMDB and KEGG, the possible metabolic pathways subject to biological alteration were identified. RESULTS: Compared with HC, 73 different metabolites in MPPC patients disrupted nine metabolic pathways through different change trends; after integrating various parameters, 20 significantly different metabolites were identified as MPPC potential biomarkers. Through the above two analysis modes, acetylphosphate and 2,5-dioxopentanoate were both screened out and used as potential biomarkers for the early diagnosis of MPPC for the first time. CONCLUSIONS: The characterization of 20 potential biomarkers provides a scientific basis for predicting and diagnosing MPPC. This article further indicates that urine metabolic profiling has great potential in diagnosing MPPC and can effectively prevent the disease from causing further deterioration.

Attenuated lncRNA NKILA Enhances the Secretory Function of Airway Epithelial Cells Stimulated by Mycoplasma pneumoniae via NF-κB.

The secretory function of airway epithelial cells is important in the pathogenesis of Mycoplasma pneumoniae pneumonia (MPP). To investigate the regulatory function of NKILA (nuclear factor-κB (NF-κB) interacting long noncoding RNA (lncRNA)) in MPP, we first detected NKILA as well as the concentration of interleukin 8 (IL-8) and tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid of children with MPP. Then, NKILA was knocked down in epithelial cells to investigate its effect on their secretory function. The results suggested that NKILA was downregulated in children with MPP, while IL-8 and TNF-α levels increased. Knockdown of NKILA in vitro promoted the inflammatory effects of Mycoplasma pneumoniae (MP) in epithelial A549 and BEAS-2B cells. Knockdown of NKILA promoted inhibitor of κBα (IκBα) phosphorylation and degradation, and NF-κB p65 nuclear translocation. Furthermore, RNA immunoprecipitation showed that NKILA could physically bind to IκBα in MP-treated A549 cells. Collectively, our data demonstrated that attenuation of NKILA enhances the effects of MP-stimulated secretory functions of epithelial cells via regulation of NF-κB signaling.

Correlations between Serum P2X7, Vitamin A, 25-hydroxy Vitamin D, and Mycoplasma Pneumoniae Pneumonia.

BACKGROUND: Identifying new molecular diagnostic markers for Mycoplasma Pneumoniae Pneumonia (MPP) has always been an essential topic since MPP cases have increased every year, especially among children. Here, we examined the correlation between serum level of Purinergic receptor P2X7, vitamin A, and 25-hydroxy vitamin D (25(OH)D) and the severity of MPP, aiming to identify molecules that have the potential to become diagnostic markers. METHODS: This study was conducted on 186 cases aged 1-14 (136 MPP and 50 non-MPP patients). Serum levels of Purinergic receptor P2X7, vitamin A, 25(OH)D, and multiple inflammatory and immune factors were measured, compared, and tested for statistical significance. RESULTS: Serum P2X7, tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) levels were significantly increased in severe MPP patients, while serum vitamin A, 25(OH)D, IgA, and IgG levels were significantly decreased. CONCLUSION: Our results demonstrated a positive correlation between serum P2X7 level and the severity of MPP, and negative correlations between serum levels of vitamin A and 25(OH)D and the severity of MPP, suggesting that high serum levels of P2X7 and low serum levels of vitamin A and 25(OH)D may indicate relatively severer MPP.

High ratio of C-reactive protein/procalcitonin predicts Mycoplasma pneumoniae infection among adults hospitalized with community acquired pneumonia.

There is limited data on serum biomarkers in distinguishing Mycoplasma pneumoniae (MP) from Streptococcus pneumoniae (SP) and viral pneumoniae (VP) etiologies of community-acquired pneumonia (CAP). A retrospective study of inpatients diagnosed with CAP at the First Affiliated Hospital of Dali University (Dali, Yunnan, China) between January 2018 and June 2020 was conducted. The demographic, clinical and laboratory data of the patients with CAP were analyzed. Univariate analyses identified predictors for MP infections. The discriminative power of C-reactive protein (CRP), procalcitonin (PCT), CRP/PCT and CRP/PCT >350 µg/ng was assessed by area under the curve (AUC) of the receiver operating characteristic (ROC) curves. A total of 552 CAP patients, including 247 (44.7%) with MP, 152 (27.6%) with SP and 153 (27.7%) with influenza A and B viruses, were enrolled. When comparing MP with SP, cough and CRP/PCT >350 µg/ng (odds ratio [OR]) 2.88, p < .001) were predictors for MP. CRP/PCT >350 µg/ng had 76% sensitivity and 100% specificity (AUC = 0.89, p < .001, 95% confidence interval [CI]:0.81-0.94) to predict MP infections. Furthermore, similar results were again obtained when comparing MP with VP. CRP/PCT >350 µg/ng present better information (OR: 4.70; AUC = 0.92, p < .001, 87% sensitivity and 100% specificity). In addition, comparing MP and non-MP (SP and VP combined), CRP/PCT >350 µg/ng exhibited excellent performance (AUC = 0.90, 95%CI 0.83-0.95, p < .001, 76% sensitivity and 100% specificity). CRP/PCT ratio may be a potential index to distinguish MP-CAP from non-MP-CAP.

Modelling persistent Mycoplasma pneumoniae biofilm infections in a submerged BEAS-2B bronchial epithelial tissue culture model.

Introduction. Infections with the respiratory pathogen Mycoplasma pneumoniae are often chronic, recurrent and resistant, persisting after antibiotic treatment. M. pneumoniae grown on glass forms protective biofilms, consistent with a role for biofilms in persistence. These biofilms consist of towers of bacteria interspersed with individual adherent cells.Hypothesis/Gap Statement. A tissue culture model for M. pneumoniae biofilms has not been described or evaluated to address whether growth, development and resistance properties are consistent with persistence in the host. Moreover, it is unclear whether the M. pneumoniae cells in the biofilm towers and individual bacterial cells have distinct roles in disease.Aim. We evaluated the properties of biofilms of M. pneumoniae grown on the immortalized human bronchial epithelial cell line BEAS-2B in relation to persistence in the host. We observed nucleation of biofilm towers and the disposition of individual cells in culture, leading to a model of how tower and individual cells contribute to infection and disease.Methodology. With submerged BEAS-2B cells as a substrate, we evaluated growth and development of M. pneumoniae biofilms using scanning electron microscopy and confocal laser scanning microscopy. We characterized resistance to erythromycin and complement using minimum inhibitory concentration assays and quantification of colony forming units. We monitored biofilm tower formation using time-lapse microscopic analysis of host-cell-free M. pneumoniae cultures.Results. Bacteria grown on host cells underwent similar development to those grown without host cells, including tower formation, rounding and incidence of individual cells outside towers. Erythromycin and complement significantly reduced growth of M. pneumoniae. Towers formed exclusively from pre-existing aggregates of bacteria. We discuss a model of the M. pneumoniae biofilm life cycle in which protective towers derive from pre-existing aggregates, and generate individual cytotoxic cells.Conclusion . M. pneumoniae can form protective biofilms in a tissue culture model, implicating biofilms in chronic infections, with aggregates of M. pneumoniae cells being important for establishing infections.

Mycoplasma pneumoniae biofilms grown in vitro: traits associated with persistence and cytotoxicity.

The atypical bacterial pathogen Mycoplasma pneumoniae is a leading etiological agent of community-acquired pneumonia in humans; infections are often recalcitrant, recurrent and resistant to antibiotic treatment. These characteristics suggest a mechanism that facilitates long-term colonization in hosts. In an in vitro setting, M. pneumoniae forms biofilms that are unusual in that motility plays no more than a very limited role in their formation and development. Given the unusual nature of M. pneumoniae biofilms, open questions remain concerning phenotypes associated with persistence, such as what properties might favour the bacteria while minimizing host damage. M. pneumoniae also produces several cytotoxic molecules including community-acquired respiratory distress syndrome (CARDS) toxin, H2S and H2O2, but how it deploys these agents during growth is unknown. Whereas several biochemical techniques for biofilm disruption were ineffective, sonication was required for disruption of M. pneumoniae biofilms to generate individual cells for comparative studies, suggesting unusual physical properties likely related to the atypical cell envelope. Nonetheless, like for other bacteria, biofilms were less susceptible to antibiotic inhibition and complement killing than dispersed cells, with resistance increasing as the biofilms matured. CARDS toxin levels and enzymatic activities associated with H2S and H2O2 production were highest during early biofilm formation and decreased over time, suggesting attenuation of virulence in connection with chronic infection. Collectively, these findings result in a model of how M. pneumoniae biofilms contribute to both the establishment and propagation of M. pneumoniae infections, and how both biofilm towers and individual cells participate in persistence and chronic disease.

Assessment of serum sialic acid correlated with C3 in children with Mycoplasma pneumoniae pneumonia.

BACKGROUND: Different from the diagnosis of bacterial infections, Mycoplasma pneumoniae pneumonia (MPP) is still lacking of convenient non-specific laboratory parameters. METHOD: A total of 125 children with MPP were included in the MPP group and 89 children with Mycoplasma-negative pneumonia were included in the control group, and the sera were collected from the children at both the acute and recovery stages in the two groups. RESULTS: The sialic acid and C3 in the MPP group were significantly higher than those in the control group both at the acute and at the recovery stage. On the other hand, the sialic acid and C3 at the acute stage were significantly higher than those at the recovery stage in the MPP group. However, in the control group, the sialic acid and C3 demonstrated IgG exhibited no significant change between the acute stage and the recovery stage. Lastly, positive correlations between sialic acid level and C3 level were identified in the MPP group at both acute and recovery stages. CONCLUSION: Our study demonstrated that the serum sialic acid correlated with C3 specifically increased in children with MPP, indicating that it might be the important non-specific parameters in the diagnosis of MPP.

Epidemiology of Mycoplasma pneumoniae prevalence in Iranian patients: a systematic review and meta-analysis.

Introduction. Mycoplasma pneumoniae is regarded as the important infectious agent of acute respiratory infections (ARIs) in the world. However, there is little knowledge about the prevalence of M. pneumoniae in Iran. Therefore, the aim of this study was to investigate the prevalence of M. pneumoniae in Iran through a meta-analysis of included studies.Methods. A systematic search was done by using electronic databases from papers that were published by Iranian authors to the end of February 2019. Then, 12 publications, which met our inclusion criteria, were enrolled for data extraction and analysis by using the 'metaprop program' in stata version 14.0.Results. The pooled prevalence of M. pneumoniae was 9 % (95 % confidence intervals: 5-16 %) ranging from 1 to 26 %. There was a significant heterogeneity among the 12 studies (X2=128.29; P<0.001; I 2=91.43 %). The funnel plot for publication bias showed no evidence of asymmetry.Conclusions. The frequency of M. pneumoniae in Iran is comparable with other parts of the world. Although the overall prevalence of M. pneumoniae was low, awareness about the distribution of these agent is very important because of higher infection rates in susceptible groups. In addition, these results showed the rates of M. pneumoniae had variation based on location, type of infection and sample, gender and detection rate and there was evidence of publication bias.

Correlation between chest radiographic findings and clinical features in hospitalized children with Mycoplasma pneumoniae pneumonia.

BACKGROUND: Radiologic evaluation of children with Mycoplasma pneumoniae is important for diagnosis and management. OBJECTIVE: To investigate the correlation between chest radiographic findings and the clinical features in children with Mycoplasma pneumoniae pneumonia. MATERIALS AND METHODS: This study included 393 hospitalized children diagnosed with M. pneumoniae pneumonia between January 2000 and August 2016. Their clinical features and chest radiographs were reviewed. Radiographic findings were categorized and grouped as consolidation group (lobar or segmental consolidation) and non-consolidation group (patchy infiltration, localized reticulonodular infiltration, or parahilar peribronchial infiltration). RESULTS: Lobar or segmental consolidation (37%) was the most common finding, followed by parahilar or peribronchial infiltration (27%), localized reticulonodular infiltration (21%) and patchy infiltration (15%). The consolidation group was more frequently accompanied by pleural effusions (63%), compared to the non-consolidation group (16%). Compared with patients in the non-consolidation group, those in the consolidation group were associated with a significantly higher rate of hypoxia, tachypnea, tachycardia, extrapulmonary manifestations, prolonged fever, and longer periods of anti-mycoplasma therapy and hospitalization. Lobar or segmental consolidation was significantly more frequent in children ≥5 years old (44%) compared with children 2-5 years old (34%) and <2 years old (13%). Parahilar peribronchial infiltration was significantly more frequent in children <2 years old (56%) compared with children 2-5 years old (32%) and ≥5 years old (18%). CONCLUSION: The chest radiographic findings of children with M. pneumoniae pneumonia correlate well with the clinical features. Consolidative lesions were frequently observed in older children and were associated with more severe clinical features.

Interleukin 1 Receptor-Like 1 (IL1RL1) Promotes Airway Bacterial and Viral Infection and Inflammation.

Interleukin 1 receptor-like 1 (IL1RL1), also known as suppression of tumorigenicity 2 (ST2), is the receptor for interleukin 33 (IL-33) and has been increasingly studied in type 2 inflammation. An increase in airway IL-33/ST2 signaling in asthma has been associated with eosinophilic inflammation, but little is known about the role of ST2 in neutrophilic inflammation. Airway Mycoplasma pneumoniae and human rhinovirus (HRV) infections are linked to neutrophilic inflammation during acute exacerbations of asthma. However, whether ST2 contributes to M. pneumoniae- and HRV-mediated airway inflammation is poorly understood. The current study sought to determine the functions of ST2 during airway M. pneumoniae or HRV infection. In cultured normal human primary airway epithelial cells, ST2 overexpression (OE) increased the production of neutrophilic chemoattractant IL-8 in the absence or presence of M. pneumoniae or HRV1B infection. ST2 OE also enhanced HRV1B-induced IP-10, a chemokine involved in asthma exacerbations. In the M. pneumoniae-infected mouse model, ST2 deficiency, in contrast to sufficiency, significantly reduced the levels of neutrophils following acute (≤24 h) infection, while in the HRV1B-infected mouse model, ST2 deficiency significantly reduced the levels of proinflammatory cytokines KC, IP-10, and IL-33 in bronchoalveolar lavage (BAL) fluid. Overall, ST2 overexpression in human epithelial cells and ST2 sufficiency in mice increased the M. pneumoniae and HRV loads in cell supernatants and BAL fluid. After pathogen infection, ST2-deficient mice showed a higher level of the host defense protein lactotransferrin in BAL fluid. Our data suggest that ST2 promotes proinflammatory responses (e.g., neutrophils) to airway bacterial and viral infection and that blocking ST2 signaling may broadly attenuate airway infection and inflammation.

Hypersensitivity reactions to antiepileptic drugs in children.

BACKGROUND: Antiepileptic drugs (AEDs) can cause hypersensitivity reactions in children. These reactions are mainly cutaneous, self-limiting, and benign, but life-threatening severe cutaneous adverse reactions can occur. Infections can lead to skin eruptions and mimic drug hypersensitivity reactions, if a drug is taken at the same time. The aims of our study were to confirm or rule out the diagnosis of hypersensitivity reactions to AEDs in children and to detect an infection which mimics these reactions. METHODS: A prospective survey was conducted in a group of 100 children with histories of hypersensitivity reactions to AEDs by performing patch tests, delayed-reading intradermal test, and, in case of negative results, challenge test. In all children, a study was performed to detect infections by viruses or Mycoplasma pneumoniae. RESULTS: Maculopapular exanthema and delayed-appearing urticaria were the most reported hypersensitivity reactions to AEDs. Sixty-six (66%) of 100 children had confirmed hypersensitivity reactions to AEDs. Fifty-nine children had positive patch test. No children had positive challenge tests. The most common AEDs causing hypersensitivity reactions were carbamazepine (45.4%) and lamotrigine (43.6%). Thirty-two children had positive tests for viruses or M pneumoniae, and nine of them had also a positive allergy work-up. CONCLUSION: Considering that there are no specific tests to distinguish between a viral infection and hypersensitivity reactions to AEDs in the acute phase, a diagnostic work-up should be performed in all children with suspected hypersensitivity reactions to AEDs, as well as infectious agent study, to remove a false label of hypersensitivity.

Atypical and Typical Bacteria in Children with Community Acquired Pneumonia.

This study seeks to determine the pathogens in respiratory specimens and blood serum obtained from children who present with community acquired pneumonia (CAP) diagnosed on the basis of clinical and radiological evidence. The study group consisted of 46 hospitalized children aged 1-11 years. The material for research consisted of pharyngeal swabs and samples of blood serum. One hundred and thirty eight pharyngeal swabs were examined for the presence of C. pneumoniae antigen, C. pneumoniae DNA, and for typical pathogens. C. pneumoniae DNA was detected in pharyngeal swabs with nested PCR. Classical microbiological culture was used for detection of typical bacteria. ELISA test were used for detection anti-C. pneumoniae and anti-M. pneumoniae antibodies in the serum. C. pneumoniae DNA was identified in 10.9% of children. Positive culture for typical pathogens was observed in 8.7% of children. Specific anti-C. pneumoniae IgM antibodies were found in 8.7% of children, and IgG and IgA antibodies in 1 child each. Specific anti-M. pneumoniae IgG antibodies were found in 13.1% of children and IgM antibodies in 1 child. We conclude that the underlying bacterial etiology of CAP is rather rarely conclusively confirmed in children. Nonetheless, determining the etiology of CAP is essential for the choice of treatment to optimize the use and effectiveness of antimicrobials and to avoid adverse effect. Due to considerable variations in the power of detection of the type of atypical bacteria causing CAP, the search for the optimum diagnostic methods continues.

Phase-shifting of the transmissibility of macrolide-sensitive and resistant Mycoplasma pneumoniae epidemics in Hong Kong, from 2015 to 2018.

Mycoplasma pneumoniae is a threat to public health. This pathogen caused an epidemic in Hong Kong during the years 2015-2018. The reproduction number during the initial epidemic was estimated to be 1.7 for macrolide-resistant M. pneumoniae (MRMP) and 1.4 for macrolide-sensitive M. pneumoniae (MSMP). During 2016-2018, the reproduction number remained stable at around 1.0 for both MRMP and MSMP. Phase-shifting and changes in the leading-status between the transmissibilities of MSMP and MRMP were found.

Comparison of high-dose and low-dose corticosteroid therapy for refractory Mycoplasma pneumoniae pneumonia in children.

BACKGROUND: Mycoplasma pneumoniae pneumonia (MPP) is generally a self-limiting disease, but it may become refractory. It is thought that refractory MPP is linked to the excessive immunologic responses of the host. Consequently, the use of adjunctive systemic corticosteroids may have beneficial effects. In this study, we compared the effects of high- and low-dose corticosteroid therapy in a pediatric population with refractory MPP. METHODS: We retrospectively collected data from 91 pediatric MPP patients treated with adjunctive systemic corticosteroids between April 2014 and October 2016. The patients were divided into the following two groups: high-dose corticosteroid group (2 mg/kg/day or more of prednisolone equivalents; n = 38) and low-dose corticosteroid group (<2 mg/kg/day; n = 53). Additionally, we compared the number of febrile days post-corticosteroid administration. We used 25 paired patients in a propensity score matching analysis to correct for confounding factors both by age and by days (from onset till corticosteroid therapy initiation). RESULTS: We observed that in the high-dose corticosteroid group defervescence following corticosteroid therapy initiation was achieved significantly earlier and length of hospitalization was significantly shorter (0.8 ± 1.0 vs. 1.5 ± 1.4 days and 8.2 ± 2.4 vs. 10.7 ± 2.7 days, respectively). In the propensity score matching, we observed that significant differences in the length of fever following corticosteroid therapy initiation and hospitalization were still present. Further, neither of the groups developed corticosteroid-related adverse events. CONCLUSION: Our results suggest that patients with refractory MPP treated with high-dose corticosteroid could achieve defervescence earlier and have a shorter hospitalization.

M. pneumoniae and C. pneumoniae are no relevant pathogens in critically ill patients with hospital-acquired respiratory tract infections.

PURPOSE: To assess the incidence of Mycoplasma pneumoniae and Chlamydia pneumoniae in the pathogenesis of hospital-acquired respiratory tract infections (RTIs) in critically ill patients. METHODS: This is a retrospective cohort study of all ICU-patients ≥ 18 years with RTI who underwent conventional culture techniques and PCR testing for both M. pneumoniae and C. pneumoniae from respiratory tract specimens (bronchoalveolar lavage or tracheobronchial aspirates) between January 2013 to May 2017 at the Jena University Hospital. RESULTS: In total, 314 patients were included in the analysis. Of these, 210 (66.9%) patients were diagnosed with HAP, 65 (20.7%) with VAP and 39 (12.4%) with VAT. Overall, 73 (30.7%) patients were on mechanical ventilation on the day of microbiological examination. PCR-testing for M. pneumoniae was positive in two patients (0.6%) and for C. pneumoniae in zero patients. CONCLUSIONS: Our study shows that the incidence of M. pneumoniae and C. pneumoniae in the pathogenesis of hospital-acquired RTIs in critically ill patients is negligible. The results support the recommendations of the guidelines not to perform empiric therapy covering these pathogens.

Increased Total Serum Immunoglobulin E in Children Developing Mycoplasma pneumoniae-related Extra-pulmonary Diseases.

Mycoplasma pneumoniae has been recognized to be involved in several extra-pulmonary diseases, but the underlying immunologic mechanisms are still largely unknown. Recently, we observed a significant elevation of serum Immunoglobulin E (IgE) in a small group of these children. Here, we assessed total serum IgE levels in children affected with Mycoplasma pneumoniae-related extra-pulmonary diseases. We prospectively collected the data of 162 children admitted to the hospital (because of respiratory infections or extra-pulmonary diseases) who were evaluated for Mycoplasma pneumoniae serology and total serum IgE levels, concomitantly. Based upon clinical and serology aspects, 3 groups of children were identified: I) with non-mycoplasma respiratory disease; II) with mycoplasma-related respiratory diseases; III) with extra-pulmonary diseases related to concomitant/recent Mycoplasma pneumoniae infection. Interestingly, children with Mycoplasma pneumoniae-related extra-pulmonary diseases showed a significant elevation of total serum IgE. In particular, patients developing Mycoplasma pneumoniae-related extra-pulmonary diseases (group III) showed significantly higher level of IgE than both previous groups (p<0.001 vs. group I; p<0.01 vs. group II). In conclusion, hospitalized children diagnosed with Mycoplasma pneumoniae-related extra-pulmonary diseases resulted to have significantly increased serum IgE compared to children developing respiratory illnesses only.