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Yang S, Liu X, Han Y, Wang H, Mei Y, Wang H, Zhang N, Peng Y, Li X. Clinical characteristics and associated factors of macrolide-resistant mycoplasma pneumoniae pneumonia in children: a systematic review and meta-analysis. Eur J Clin Microbiol Infect Dis 2025; 44:1505-1522. [PMID: 40106136 DOI: 10.1007/s10096-025-05101-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2025] [Accepted: 03/06/2025] [Indexed: 03/22/2025]
Abstract
In recent years, the incidence of macrolide-resistant Mycoplasma pneumoniae (MRMP) pneumonia has markedly increased across East Asia, especially in China, Japan, and South Korea, presenting considerable challenges for clinical management. We systematically reviewed and conducted a meta-analysis on the resistance rate, clinical characteristics, and associated factors of MRMP, thereby establishing a foundation for early clinical identification and optimization of treatment strategies. In accordance with the PRISMA 2020 reporting guidelines, six databases including PubMed, Embase, Web of Science, CNKI, VIP, and Wanfang Data were systematically searched for relevant literature up to October 31, 2024. Studies explicitly reporting the clinical characteristics of both MRMP and macrolide-sensitive Mycoplasma pneumoniae (MSMP) pneumonia patients were included, with the population restricted to children. Pooled odds ratio (OR) and mean difference (MD), along with 95% confidence intervals, were calculated using inverse-variance weighting. A significance threshold was set at p < 0.05, and meta-analysis was performed using software such as RevMan, Stata, and R Studio. A total of 65 studies encompassing 20,141 patients were included in this analysis. The meta-analysis revealed that MRMP showed high resistance in East Asia compared to lower resistance in other regions. The overall resistance rate was 61% (95% CI: 54%, 68%), exhibiting notable regional variation. Elevated resistance rates were noted in East Asian countries, specifically China, Japan, and South Korea, reported at 68% (95% CI: 63%, 73%), 61% (95% CI: 43%, 80%), and 63% (95% CI: 42%, 85%), respectively. MRMP resistance was significantly associated with prolonged fever duration (MD: 1.97, 95% CI: 1.10, 2.84), extended hospitalization (MD: 1.96, 95% CI: 1.39, 2.54), elevated log MP-DNA levels (MD: 2.79, 95% CI: 1.54, 4.04), increased proportions of severe (OR: 2.45, 95% CI: 1.75, 3.44) cases and refractory (OR: 3.25, 95% CI: 1.47, 7.17) cases, and the occurrence of complications, particularly intrapulmonary manifestations including pulmonary consolidations (OR: 1.43, 95% CI: 1.14, 1.78), pleural effusions (OR: 2.11, 95% CI: 1.28, 3.49), lobar lesions (OR: 2.03, 95% CI: 1.03, 4.00), mucus plugs (OR: 4.63, 95% CI: 1.66, 12.94), and necrotizing pneumonia (OR: 2.49, 95% CI: 1.19, 5.24), alongside extrapulmonary involvement (OR: 3.08, 95% CI: 2.49, 3.82). No significant differences were observed in peak body temperature (MD: 0.05, 95% CI: -0.11, 0.20) or inflammatory markers including white blood cell count (WBC, MD: 0.28, 95% CI: -0.38, 0.94), C-reactive protein (CRP, MD: 0.71, 95% CI: -2.16, 3.58), Procalcitonin (PCT, MD: -0.11, 95% CI: -0.27, 0.05) and lactate dehydrogenase (LDH, MD: 3.80, 95% CI: -22.92, 30.52). The high resistance rate may be associated with environmental pressure stemming from the widespread use of macrolide antibiotics and increased genetic mutations due to the extensive spread of MP. The observed increase in severe cases, refractory cases, and complications associated with MRMP may be attributed to prolonged colonization resulting from ineffective anti-Mycoplasma pneumoniae treatment, rather than to enhanced virulence or a more severe cytokine storm. PROSPERO registration number CRD42024550871.
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Affiliation(s)
- Shuo Yang
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300381, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China
| | - Xinying Liu
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300381, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China
| | - Yaowei Han
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300381, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China
| | - Huizhe Wang
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300381, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China
| | - Yunzheng Mei
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300381, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China
| | - Haokai Wang
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300381, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China
| | - Na Zhang
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300381, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China
| | - Yingying Peng
- Binhai New Area Hospital of TCM Tianjin, Fourth Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300451, China
| | - Xinmin Li
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300381, China.
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China.
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Li L, Zhang Y, Zhao L, Shi Y. C-reactive protein-induced injury in Mycoplasma pneumoniae-infected lung epithelial cells is mediated by the P38 MAPK/mitochondrial apoptosis pathway. Microbiol Spectr 2025; 13:e0162624. [PMID: 39932324 PMCID: PMC11878036 DOI: 10.1128/spectrum.01626-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Accepted: 12/02/2024] [Indexed: 03/05/2025] Open
Abstract
Patients with Mycoplasma pneumoniae (MP) infections have markedly higher C-reactive protein (CRP). We investigated how CRP contributes to lung epithelial cell death following MP infection. CRP levels were assessed in children diagnosed with Mycoplasma pneumoniae pneumonia (MPP) and A549 lung epithelial cells infected with MP. A549 cells were genetically modified to overexpress CRP. Effects on cell viability, apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨm) were evaluated. The expression of proteins implicated in the p38 MAPK/mitochondrial apoptotic pathway was analyzed. The protective effects of the p38 MAPK inhibitor SB203580 and the mitochondrial protector cyclosporin A (CsA) were assessed. CRP levels were elevated in both MPP patients and MP-infected A549 cells compared to controls. Increased apoptosis and reduced cell viability were observed in MP-infected cells. CRP overexpression led to upregulation of proteins in the p38 MAPK/mitochondrial apoptosis pathway, increased cytoplasmic Cyt C, decreased Tom 20 and ΔΨm, and elevated ROS. Pretreatment with SB203580 or posttreatment with CsA reduced apoptosis and mitochondrial damage and enhanced cell survival. Increased CRP levels during MP infection promote lung epithelial cell death by activating the p38 MAPK/mitochondrial apoptosis pathway. Targeting this pathway could offer therapeutic potential to reduce lung damage in MPP patients.IMPORTANCEThis study provides critical information in understanding the pathophysiological mechanisms for MP infections concerning CRP in mediating lung epithelial cell injury. This study outlines the significant increase in MP-infected patients and shows its direct involvement in cell apoptosis through the p38 MAPK/mitochondrial apoptosis pathway. By explaining this pathway, the possibility of targeting CRP and its connected signaling mechanisms to devise therapeutic interventions for the amelioration of lung damage in MP-infected patients is brought to light. The implications of such data are not merely in the added knowledge for disease pathobiology but also it brings new promise for novel intervention strategies to result in improved clinical outcomes. The elucidation of specific molecular targets inside the apoptosis pathway heralds a new area regarding the direction of future research and clinical application for humanity in general and concerning the broader relevance and impact of this study on respiratory diseases.
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Affiliation(s)
- Lianjia Li
- Department of Pediatrics, Liaocheng Second People’s Hospital, Liaocheng, Shandong, China
| | - Yang Zhang
- Department of Pediatric Surgery, Dongying People’s Hospital, Dongying, Shandong, China
| | - Lin Zhao
- Department of Pediatrics, Weifang People’s Hospital, Weifang, Shandong, China
| | - Yalin Shi
- Department of Pediatric Respiratory Medicine, Sunshine Unlon Hospital, Weifang, Shandong, China
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Jin Y, Wang Y, Xia T, Ma Q. The Predictive Value of Lactate Dehydrogenase for Viral Suppression in Newly Diagnosed People Living With HIV on Antiretroviral Therapy: A Retrospective Cohort Study. Infect Drug Resist 2025; 18:601-611. [PMID: 39902274 PMCID: PMC11789517 DOI: 10.2147/idr.s488220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Accepted: 01/22/2025] [Indexed: 02/05/2025] Open
Abstract
Purpose Rapid initiation of antiretroviral therapy (ART) in people living with HIV (PLWH) is crucial for achieving viral suppression and improving clinical outcomes. Serum lactate dehydrogenase (LDH) levels serve as a readily accessible and rapid clinical biomarker, has significant predictive potential in various viral diseases. This study aims to evaluate the predictive value of LDH levels for viral suppression in the context of rapid ART initiation. Patients and Methods LDH levels were measured in 393 newly diagnosed PLWH who received rapid initiation of ART and were subsequently followed up. The PLWH were stratified based on tertile LDH levels and study endpoints. Kaplan-Meier analysis was conducted to generate survival curves, and Cox regression analysis was utilized to confirm the independent prognostic factors for viral suppression. Results The overall viral suppression rate was 94.1%. Compared to the low LDH tertile, the middle and high LDH tertiles exhibited longer times to first viral suppression (38 vs 84 vs 88 days, respectively, P < 0.001). Kaplan-Meier analysis revealed that PLWH in high LDH tertile showed the worst prognosis for viral suppression (Log rank test, P<0.001). Multivariate Cox regression analysis identified LDH tertile as a significant predictor of viral suppression (HR = 0.714, 95% CI = 0.553-0.922, P = 0.010 for middle vs low tertile; HR = 0.575, 95% CI = 0.443-0.747, P < 0.001 for high vs low tertile). Conclusion LDH levels function as a prognostic indicator for predicting the timing of viral suppression in PLWH on ART. A comprehensive evaluation of LDH levels is beneficial in establishing risk stratification in the context of rapid ART initiation.
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Affiliation(s)
- Yong Jin
- Department of Internal Medicine, Ningbo Yinzhou No.2 hospital, Ningbo, Zhejiang, People’s Republic of China
| | - Yan Wang
- Department of Internal Medicine, Ningbo Yinzhou No.2 hospital, Ningbo, Zhejiang, People’s Republic of China
| | - Ting Xia
- Department of Internal Medicine, Ningbo Yinzhou No.2 hospital, Ningbo, Zhejiang, People’s Republic of China
| | - Qichao Ma
- Department of Dermatology and Venereology, Ningbo Yinzhou No.2 hospital, Ningbo, Zhejiang, People’s Republic of China
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Ma X, Wu Y, De R, Yao H, He F, Wang Y, Wang W, Yan C, Song Q, Guo C, Wen L, Zhao L, Cao L, Zhu C. Impact of co-infections and immune responses on clinical severity of human adenovirus 3 and 7 infections in hospitalized children with lower respiratory tract infections: a comparative study. Front Cell Infect Microbiol 2025; 14:1482787. [PMID: 39850965 PMCID: PMC11754186 DOI: 10.3389/fcimb.2024.1482787] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Accepted: 12/06/2024] [Indexed: 01/25/2025] Open
Abstract
Background The pathogenic distribution of co-infections and immunological status of patients infected with human adenovirus serotypes 3 or 7 (HAdV-3 or HAdV-7) were poorly understood. Methods This study involved a retrospective analysis of respiratory specimens collected from enrolled children with lower respiratory tract infections (LRTIs), positive for HAdV-3 or HAdV-7 from January 2017 to December 2019. Demographic data, clinical features, laboratory and radiographic findings were compared to delineate the impact of co-infections, and immune responses on clinical severity of HAdV-3 or HAdV-7 infections. Results Among 1311cases enrolled, there were 66 infected with HAdV-3 and 58 with HAdV-7. HAdV-7-infected patients exhibited more prolonged fever (100% vs 89.4%, p=0.014), pneumonia (100% vs 89.4%, p=0.014), hypoxia (34.5% vs 12.1%, p=0.003), higher propensity for aspartate aminotransferase exceeding 80U/L (21.1% vs 4.7%, p=0.006), D-Dimer exceeding 1.65mg/L (64.9% vs 12.5%, p<0.001), consolidation (50.0% vs 27.4%, p=0.011), and pleural effusion (32.8% vs 6.5%, p<0.001), co-infections with Mycoplasma pneumoniae (77.1% vs 32.6%, p<0.001), and multiple infections (56.8% vs 41.3%, p=0.007), compared to those with HAdV-3 infections. Immune cell analysis indicated that HAdV-7 infections led to a more pronounced decrease in CD3+ T cells (1596.8 vs 2444.8 cells/𝛍l, p=0.042), CD8+ cytotoxic T cells (668.6 vs 774.0 cells/µl, p=0.045), and increased NK cell percentages (11.5% vs 9.0%, p=0.044) compared to HAdV-3 infections. Conclusions Hospitalized children with HAdV-7-associated LRTIs exhibit greater severity, multiple infections, and significant potential for greater cellular immune dysregulation compared to those with HAdV-3 infection, indicating a more severe clinical course and distinct pathogenic profiles.
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Affiliation(s)
- Xiaolin Ma
- Department of Respiratory Medicine, Children’ s Hospital Affiliated to Capital Institute of Pediatrics, Beijing, China
| | - Yuting Wu
- Department of Respiratory Medicine, Children’ s Hospital Affiliated to Capital Institute of Pediatrics, Beijing, China
| | - Ri De
- Laboratory of Virology, Beijing Key Laboratory of Etiology of Viral Disease in Children, Capital Institute of Pediatrics, Beijing, China
| | - Hailan Yao
- Laboratory of Biochemistry and Immunology, Capital Institute of Pediatrics, Beijing, China
| | - Feng He
- Laboratory of Biochemistry and Immunology, Capital Institute of Pediatrics, Beijing, China
| | - Yi Wang
- Department of Central Laboratory, Capital Institute of Pediatrics, Beijing, China
| | - Wei Wang
- Laboratory of Biochemistry and Immunology, Capital Institute of Pediatrics, Beijing, China
| | - Chao Yan
- Laboratory of Bacteria, Capital Institute of Pediatrics, Beijing, China
| | - Qinwei Song
- Department of Clinical Laboratory, Children’ s Hospital Affiliated to Capital Institute of Pediatrics, Beijing, China
| | - Chunjie Guo
- Department of Respiratory Medicine, Children’ s Hospital Affiliated to Capital Institute of Pediatrics, Beijing, China
| | - Li Wen
- Department of Respiratory Medicine, Children’ s Hospital Affiliated to Capital Institute of Pediatrics, Beijing, China
| | - Linqing Zhao
- Laboratory of Virology, Beijing Key Laboratory of Etiology of Viral Disease in Children, Capital Institute of Pediatrics, Beijing, China
| | - Ling Cao
- Department of Respiratory Medicine, Children’ s Hospital Affiliated to Capital Institute of Pediatrics, Beijing, China
| | - Chunmei Zhu
- Department of Respiratory Medicine, Children’ s Hospital Affiliated to Capital Institute of Pediatrics, Beijing, China
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Kai-Jing Z, Xin-Feng Z, Xiaojuan L, Xiao-Hui H. Predictive value of Ig Mycoplasma pneumoniae-DNA, high-density lipoprotein, natural killer cell, and platelet levels for diagnosing severe M. pneumoniae pneumonia in children. Indian J Med Microbiol 2025; 53:100770. [PMID: 39638043 DOI: 10.1016/j.ijmmb.2024.100770] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 09/29/2024] [Accepted: 12/01/2024] [Indexed: 12/07/2024]
Abstract
OBJECTIVE The present study aimed to assess the predictive value of Ig Mycoplasma pneumoniae (MP)-DNA, high-density lipoprotein (HDL), natural killer (NK) cell, and platelet (PLT) levels for the diagnosis of severe MP pneumonia (SMPP) in children with MP pneumonia (MPP). METHODS Children with MPP admitted to our hospital from August 2022 to February 2024 were selected and assigned to the non-SMPP (NSMPP) and SMPP groups according to whether they had severe pneumonia. The following parameters were analyzed and compared between the two groups by the rank-sum test: age; Ig MP-DNA level; white blood cell, neutrophil (N), and monocyte counts; platelet (PLT), C-reactive protein (CRP), lactate dehydrogenase (LDH), triglycerides, high-density lipoprotein (HDL), low-density lipoprotein, and procalcitonin levels; and levels of T cells, CD4+ T cells, CD8+ T cells, B cells, and NK cells. The chi-square test was used to analyze differences in these variables between genders. One-way analysis of variance was used to select significant variables (P < 0.1) from the abovementioned ones, and the selected variables were analyzed by multivariate analysis of variance to detect independent risk factors. The receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) value were determined for the independent risk factors. RESULTS The two groups showed significant differences in the levels of Ig MP-DNA, N, PLT, CRP, LDH, HDL, CD8+ T cells, and NK cells. PLT and Ig MP-DNA levels were positively correlated with the risk of SMPP development; however, HDL and NK levels showed a negative correlation. The AUC values for Ig MP-DNA + HDL, Ig MP-DNA + NK, Ig MP-DNA + PLT, NK + HDL, NK + PLT, and PLT + HDL were 0.825, 0.812, 0.813, 0.724, 0.717, and 0.701, respectively. CONCLUSION The combination of variables, including Ig MP-DNA + HDL, Ig MP-DNA + NK, and Ig MP-DNA + PLT, can predict whether MPP children would develop SMPP.
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Affiliation(s)
- Zhang Kai-Jing
- Department Hematology of Hangzhou Children's Hospital, Zhejiang University of Traditional Chinese Medicine, Hangzhou, China.
| | - Zhao Xin-Feng
- Laboratory Department of Hangzhou Children's Hospital, Zhejiang University of Traditional Chinese Medicine, Hangzhou, China.
| | - Lv Xiaojuan
- Department Hematology of Hangzhou Children's Hospital, Zhejiang University of Traditional Chinese Medicine, Hangzhou, China.
| | - Huang Xiao-Hui
- Nurse-in-charge, Cardiovascular Department of Hangzhou Children's Hospital, Zhejiang University of Traditional Chinese Medicine, Hangzhou, China.
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Chen Y, Lin C, Huang R, Chen Q, Zhang M, Chen L, Lai X. New Insights on the Clinical Significance of Mycoplasma pneumoniae DNA Load in Mycoplasma pneumoniae Pneumonia. J PEDIAT INF DIS-GER 2024. [DOI: 10.1055/s-0044-1796650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Abstract
Objective This study aimed to assess the consistency of Mycoplasma pneumoniae (MP)-DNA load in the respiratory tracts, its correlation with Mycoplasma pneumoniae pneumonia (MPP) manifestations, and its predictive value for refractory Mycoplasma pneumoniae pneumonia (RMPP).
Methods A retrospective study was performed on a cohort of MPP cases, including 215 patients with positive nasopharyngeal aspirate (NPA) MP-DNA and 59 with positive bronchoalveolar lavage fluid (BALF) MP-DNA. Patients were categorized into two groups based on MP-DNA load: low load (≤106/mL) and high load (>106/mL). The consistency of MP-DNA load in NPA and BALF was determined by Spearman's correlation coefficient. Clinical, laboratory, and radiological data were compared, and the predictive value of NPA MP-DNA for RMPP was evaluated using the receiver operating characteristic curve.
Results A strong correlation was observed between NPA and BALF MP-DNA. High-load groups in both had longer fever durations and more pronounced increases in C-reactive protein, lactate dehydrogenase, and ferritin (p < 0.05). Routine-dose glucocorticoids were more required for patients exhibiting high MP-DNA loads, regardless of the source of the sample. The area under the curve for predicting RMPP using NPA MP-DNA load was 0.861, with 92.9% sensitivity and 67.9% specificity at a cutoff of 9.5 × 105/mL.
Conclusion The NPA MP-DNA load reflects the severity of pulmonary inflammatory response. Increased MP-DNA load in both the upper and lower airways is associated with longer fever and increased inflammation, indicating a need for glucocorticoid therapy. NPA MP-DNA can predict RMPP with high sensitivity.
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Affiliation(s)
- Yu Chen
- Department of Pediatrics, Zhongshan Hospital, Xiamen University, Xiamen, Fujian, People's Republic of China
| | - ChenXi Lin
- Department of Pediatrics, Zhongshan Hospital, Xiamen University, Xiamen, Fujian, People's Republic of China
| | - Rui Huang
- Department of Pediatrics, Zhongshan Hospital, Xiamen University, Xiamen, Fujian, People's Republic of China
| | - Qi Chen
- Department of Pediatrics, Zhongshan Hospital, Xiamen University, Xiamen, Fujian, People's Republic of China
| | - Min Zhang
- Department of Pediatrics, Zhongshan Hospital, Xiamen University, Xiamen, Fujian, People's Republic of China
| | - Ling Chen
- Department of Pediatrics, Zhongshan Hospital, Xiamen University, Xiamen, Fujian, People's Republic of China
| | - XingQian Lai
- Department of Pediatrics, Zhongshan Hospital, Xiamen University, Xiamen, Fujian, People's Republic of China
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Yan X, Fu H, Deng W, Zhang Z, Wang D. Early and rapid diagnosis of Chlamydia psittaci pneumonia by tNGS in six patients: a case series. Front Med (Lausanne) 2024; 11:1491838. [PMID: 39664316 PMCID: PMC11631597 DOI: 10.3389/fmed.2024.1491838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Accepted: 11/11/2024] [Indexed: 12/13/2024] Open
Abstract
Background Psittacosis is a zoonotic infectious disease caused by Chlamydia psittaci (C. psittaci) infection, which can be transmitted by birds, poultry and wild animals. The symptoms and imaging findings of C. psittaci pneumonia are atypical and primarily rely on etiological diagnosis. The incidence of C. psittaci infection has been significantly underestimated because of the low sensitivity and poor timeliness of traditional diagnostic methods. Therefore, early and accurate diagnosis of psittacosis remains a challenge. Case presentation A case series with six pneumonia patients who were admitted to our hospital in the period from January 2023 to June 2023 is presented. These patients exhibited acute onset and symptoms, including fever, cough, poor appetite, dry mouth, dizziness, chills, and chest tightness. Despite comprehensive laboratory and radiological examinations, the cause of the pneumonia remained unidentified. Therefore, a sample of bronchoalveolar lavage fluid (BALF) was tested via target next-generation sequencing (tNGS), which revealed a positive result for C. psittaci. Prompt adjustment of the treatment regimens upon identification of the pathogen led to favorable outcomes in all patients. Conclusion tNGS is a novel diagnostic technology that enables rapid, accurate and cost-effective detection of C. psittaci pneumonia. Early detection of C. psittaci can improve patient outcomes through timely adjustment of therapies.
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Affiliation(s)
- Xinsheng Yan
- Department of Clinical Laboratory, Wuhan Asia General Hospital, Wuhan Asia General Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, China
| | - Huali Fu
- Respiratory and Critical Care Medicine, Wuhan Asia General Hospital, Wuhan Asia General Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, China
| | - Wenjun Deng
- Department of Radiology, Wuhan Asia General Hospital, Wuhan Asia General Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, China
| | - Zhenlu Zhang
- Department of Clinical Laboratory, Wuhan Asia General Hospital, Wuhan Asia General Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, China
| | - Dong Wang
- Department of Clinical Laboratory, Wuhan Asia General Hospital, Wuhan Asia General Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, China
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Li P, Wang W, Zhang X, Pan J, Gong L. Observational retrospective clinical study on clinical features of macrolide-resistant Mycoplasma pneumoniae pneumonia in Chinese pediatric cases. Sci Rep 2024; 14:5632. [PMID: 38453960 PMCID: PMC10920782 DOI: 10.1038/s41598-024-55311-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Accepted: 02/22/2024] [Indexed: 03/09/2024] Open
Abstract
This study aimed to investigate differences in clinical characteristics and laboratory findings between children infected with Macrolide-Sensitive Mycoplasma pneumoniae (MSMP) and Macrolide-Resistant Mycoplasma pneumoniae (MRMP). Additionally, the research sought to identify laboratory markers for rapidly distinguishing refractory Mycoplasma pneumoniae pneumonia (RMPP) from ordinary Mycoplasma pneumoniae pneumonia (OMPP). In total, 265 Mycoplasma pneumoniae (MP) patients were included, with MRMP identified by specific point mutations in domain V of the 23S rRNA gene. A retrospective analysis compared the clinical courses and laboratory data, revealing that MRMP patients experienced prolonged febrile days (P = 0.004), elevated CRP levels (P < 0.001), and higher MP DNA loads than MSMP patients (P = 0.037). Based on clinical symptoms, MRMP was divided into RMPP (n = 56) and OMPP (n = 70), with RMPP demonstrating significantly increased IL-18, community-acquired respiratory distress syndrome (CARDS) toxins in nasopharyngeal aspirate, and serum CRP levels (P < 0.001; P = 0.006; P < 0.001). In conclusion, timely recognition of RMPP is crucial for enhancing prognosis. The identification of MRMP, coupled with proinflammatory cytokines such as IL-18, CARDS toxins, and CRP, emerges as promising markers with the potential to contribute significantly to diagnostic accuracy and prognosis assessment.
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Affiliation(s)
- Peng Li
- Department of Laboratory Medicine, Children's Hospital of Shanxi Province, Taiyuan, China
| | - Wei Wang
- Department of Laboratory Medicine, Shanxi Provincial People's Hospital, Taiyuan, China
| | - Xianhui Zhang
- Department of Laboratory Medicine, Children's Hospital of Shanxi Province, Taiyuan, China
| | - Jie Pan
- Department of Pathology, Stanford University School of Medicine, Palo Alto, CA, 94305, USA
| | - Lina Gong
- Department of Laboratory Medicine, Shanxi Provincial People's Hospital, Taiyuan, China.
- Department of Medical Risk Management, The Third Medical Center of Chinese PLA General Hospital, Beijing, 100039, China.
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Zhang Z, Dou H, Yuan Q, Shi D, Wan R, Tu P, Xin D, Guo S. Proteomic and Phenotypic Studies of Mycoplasma pneumoniae Revealed Macrolide-Resistant Mutation (A2063G) Associated Changes in Protein Composition and Pathogenicity of Type I Strains. Microbiol Spectr 2023; 11:e0461322. [PMID: 37378520 PMCID: PMC10434051 DOI: 10.1128/spectrum.04613-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Accepted: 05/24/2023] [Indexed: 06/29/2023] Open
Abstract
Mycoplasma pneumoniae (MP) is an important respiratory pathogen, the prevalence of macrolide-resistant MP (mainly containing A2063G mutation in 23S rRNA) increased in recent years. Epidemiological studies suggest a higher prevalence of type I resistant (IR) strains than corresponding sensitive (IS/IIS) strains, but not type II resistant (IIR) strains. Here, we aimed to analyze the factors underlying the altered prevalence of IR strains. First, proteomic analyses exhibit the protein compositions were type specific, while more differential proteins were detected between IS and IR (227) than IIS and IIR strains (81). mRNA level detection suggested posttranscriptional regulation of these differential proteins. Differential protein-related phenotypic changes were also detected: (i) P1 abundance was different between genotypes (I < II, IR < IS), the adhesion of MPs showed accordance to P1 abundance within IS and IIS strains; (ii) type I, especially IR, strains had a higher proliferation rate, which is potentially associated with differential proteins participating in glycolysis and one carbon pool metabolisms; (iii) A549 cells infected with IR strains had lower activity of caspase-3 and higher levels IL-8, but the differences were not significant between groups (P > 0.05). Correlations of P1 abundance to caspase-3 activity and proliferation rate to the level of IL-8 were obtained. These results suggest changes in protein composition influenced the pathogenicity of MP, especially in IR strains, which may impact the prevalence of MP strains of different genotypes. IMPORTANCE The prevalence of macrolide-resistant MPs increased the difficulty in treatment of MP infections and posed potential threats to children's health. Epidemiological studies showed a high prevalence of IR-resistant strains (mainly A2063G in 23S rRNA) in these years. However, the trigger mechanisms for this phenomenon are not clear. In this paper, proteomic and phenotypic studies suggest that IR strains have reduced levels of multiple adhesion proteins and increased proliferation rate, which may lead to higher transmission rate of IR strains in the population. This suggests that we should pay attention to the prevalence of IR strains.
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Affiliation(s)
- Zhikun Zhang
- Beijing Tropical Medicine Research Institute, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Department of Pathogenic Biology, School of Basic Medicine Southwest Medical University, Luzhou, China
| | - Haiwei Dou
- Beijing Tropical Medicine Research Institute, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Qing Yuan
- Beijing Tropical Medicine Research Institute, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Dawei Shi
- Beijing Tropical Medicine Research Institute, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Ruijie Wan
- Beijing Tropical Medicine Research Institute, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Peng Tu
- Beijing Tropical Medicine Research Institute, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Deli Xin
- Beijing Tropical Medicine Research Institute, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Shuilong Guo
- Department of Science and Technology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
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Yusuf SO, Chen P. Clinical characteristics of community-acquired pneumonia in children caused by mycoplasma pneumoniae with or without myocardial damage: A single-center retrospective study. World J Clin Pediatr 2023; 12:115-124. [PMID: 37342450 PMCID: PMC10278075 DOI: 10.5409/wjcp.v12.i3.115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Revised: 03/08/2023] [Accepted: 03/30/2023] [Indexed: 06/08/2023] Open
Abstract
BACKGROUND Mycoplasma pneumoniae (MP) is a prevalent pathogen that causes respiratory infections in children and adolescents. AIM To assess the differences in the clinical features of MP-associated community-acquired pneumonia (CAP) in children who presented with mild or severe mycoplasma pneumoniae pneumonia (MPP); to identify the incidence of myocardial damage between the two groups. METHODS This work is a retrospective study. We identified children between 2 mo and 16 years of age with clinical and radiological findings consistent with CAP. We admitted patients to the inpatient department of the Second Hospital of Jilin University, Changchun, China, from January 2019 to December 2019. RESULTS A total of 409 hospitalized patients were diagnosed with MPP. Among them were 214 (52.3%) males and 195 (47.7%) females. The duration of fever and cough was the longest in severe MPP cases. Similarly, plasma levels of highly sensitive C-reactive protein (t = -2.834, P < 0.05), alanine transaminase (t = -2.511, P < 0.05), aspartate aminotransferase (t = -2.939, P < 0.05), and lactate dehydrogenase (LDH) (t = -2.939, P < 0.05) were all elevated in severe MPP cases compared with mild MPP cases, and these elevations were statistically significant (P < 0.05). Conversely, the neutrophil percentage was significantly lower in severe MPP cases than in mild MPP cases. The incidence of myocardial damage was significantly higher in severe MPP cases than in mild MPP cases (χ2 = 157.078, P < 0.05). CONCLUSION Mycoplasma pneumoniae is the main cause of CAP. The incidence of myocardial damage was higher and statistically significant in severe MPP cases than in mild MPP cases.
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Affiliation(s)
- Shukri Omar Yusuf
- Department of Pediatrics, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Peng Chen
- Department of Pediatrics, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
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11
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Liu J, He R, Zhang X, Zhao F, Liu L, Wang H, Zhao S. Clinical features and “early” corticosteroid treatment outcome of pediatric mycoplasma pneumoniae pneumonia. Front Cell Infect Microbiol 2023; 13:1135228. [PMID: 37082710 PMCID: PMC10110948 DOI: 10.3389/fcimb.2023.1135228] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Accepted: 03/10/2023] [Indexed: 04/07/2023] Open
Abstract
BackgroundMany children with mycoplasma pneumoniae (MP) pneumonia (MPP) developed sequelae such as bronchiolitis/bronchitis obliterans (BO). Early corticosteroid therapy might prevent disease progression. This study aimed to use “early” corticosteroid and observe the treatment outcome in patients with MPP.MethodsPatients who had pulmonary infiltrations on chest imaging within 5 days of the disease course and were suspected of having MP infection on admission were enrolled. Among them, patients whose disease course was within 10 days on admission were ultimately enrolled. We analyzed their data including the clinical features, the starting time and dose of corticosteroid therapy, and the treatment outcome. According to chest imaging, we divided patients into two groups (Group A: bronchiolitis-associated lesions or ground-glass opacities; Group B: pulmonary segmental/lobar consolidation).ResultsA total of 210 patients with confirmed MPP were ultimately enrolled. There were 59 patients in Group A and 151 patients in Group B. Patients in Group A were more prone to have allergy histories, hypoxemia, wheezing sound, and wet rales on auscultation than those in Group B. Corticosteroid treatment was initiated between 5 and 10 days of disease onset in all patients and 6–7 days in most patients. Methylprednisolone was prescribed in all patients within 10 days of disease onset, and the highest prescribed dose was at least 2 mg/kg/day. In Group A, methylprednisolone >2 mg/kg/day was prescribed in 22 patients, and among them, 8 patients with diffuse bronchiolitis-associated lesions received high-dose methylprednisolone therapy. After 3 months, lung CT revealed slightly segmental ground-glass opacity in three patients. In Group B, methylprednisolone >2 mg/kg/day was prescribed in 76 patients, and among them, 20 patients with pulmonary lobar consolidation received high-dose methylprednisolone therapy. After 3 months, chest imaging revealed incomplete absorption of pulmonary lesions in seven patients. Among them, five patients with consolidation in more than one pulmonary lobe ultimately had slight BO.ConclusionIn hospitalized patients with MPP, particularly severe MPP, the ideal starting time of corticosteroid treatment might be 5–10 days, preferably 6–7 days, after disease onset. The initial dosage of corticosteroid therapy should be decided according to the severity of the disease. MPP patients with diffuse bronchiolitis-associated lesions/whole lobar consolidation on imaging might require high-dose corticosteroid therapy.
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Affiliation(s)
- Jinrong Liu
- Department of Respiratory Medicine, China National Clinical Research Center of Respiratory Disease, Beijing Children’s Hospital, National Center for Children’s Health, Capital Medical University, Beijing, China
- *Correspondence: Shunying Zhao, ; Jinrong Liu,
| | - Ruxuan He
- Department of Respiratory Medicine, China National Clinical Research Center of Respiratory Disease, Beijing Children’s Hospital, National Center for Children’s Health, Capital Medical University, Beijing, China
| | - Xiaoyan Zhang
- Department of Respiratory Medicine, China National Clinical Research Center of Respiratory Disease, Beijing Children’s Hospital, National Center for Children’s Health, Capital Medical University, Beijing, China
| | - Fei Zhao
- National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, State Key Laboratory of Infectious Disease Prevention and Control, Beijing, China
| | - Liyong Liu
- National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, State Key Laboratory of Infectious Disease Prevention and Control, Beijing, China
| | - Heng Wang
- Department of Respiratory Medicine, China National Clinical Research Center of Respiratory Disease, Beijing Children’s Hospital, National Center for Children’s Health, Capital Medical University, Beijing, China
| | - Shunying Zhao
- Department of Respiratory Medicine, China National Clinical Research Center of Respiratory Disease, Beijing Children’s Hospital, National Center for Children’s Health, Capital Medical University, Beijing, China
- *Correspondence: Shunying Zhao, ; Jinrong Liu,
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12
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Peng QY, Zhang L, Deng H, Ye YM, Huang RL, Liang YQ, Feng SS, Li J, Luo XQ, Peng YL. Poor accuracy of single serological IgM tests in children with suspected acute Mycoplasma pneumoniae infection in Guangzhou, China. J Med Microbiol 2023; 72. [PMID: 36920846 DOI: 10.1099/jmm.0.001673] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/16/2023] Open
Abstract
Introduction. Early and accurate diagnosis of Mycoplasma pneumoniae (MP) infection of children with pneumonia is at the core of treatment in clinical practice.Gap Statement. Serological immunoglobulin M (IgM) tests for MP infection of children in south China have been rarely described.Aim. To assess the diagnostic performance and clinical application of serodiagnosis of MP infection in paediatric pneumonia patients.Methodology. Serum samples from 144 children diagnosed with MP pneumonia were subjected to a particle agglutination (PA)-based IgM assay. Meanwhile, we used an established suspension array as the reference standard method for the detection of MP DNA in bronchoalveolar lavage fluid (BALF) from all patients to assess the reliability of serological assays.Results. When running immunological testing in single serum samples, 80.6 %(79/98) of cases were diagnosed with MP infection, whereas only 55 (56.1 %) cases were positive in MP DNA analysis. Furthermore, single serum tests for IgM during acute MP infection resulted in 85.5 % (47/55) sensitivity and 25.6 % (11/43) specificity. Nevertheless, immunological testing and MP DNA analysis yielded the same results when paired sera were available for MP IgM antibody testing.Conclusion. Paired serological IgM assays are necessary for the determination of an acute MP infection, whereas single serological IgM testing is unreliable. Moreover, even a short interval of two MP serological tests works well.
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Affiliation(s)
- Qiu-Ying Peng
- Department of Pediatrics, Guangzhou Panyu Maternal and Children Health Hospital, Guangzhou Panyu District He Xian Memorial Hospital, Guangzhou, 511499, PR China
| | - Liang Zhang
- Maternal and Child Health Research Institute, Translational Medicine Center, Guangdong Women and Children Hospital, Guangzhou, 511400, PR China
| | - Hua Deng
- Maternal and Child Health Research Institute, Translational Medicine Center, Guangdong Women and Children Hospital, Guangzhou, 511400, PR China
| | - Yu-Ming Ye
- Department of Pediatrics, Guangzhou Panyu Maternal and Children Health Hospital, Guangzhou Panyu District He Xian Memorial Hospital, Guangzhou, 511499, PR China
| | - Rui-Lin Huang
- Department of Pediatrics, Guangzhou Panyu Maternal and Children Health Hospital, Guangzhou Panyu District He Xian Memorial Hospital, Guangzhou, 511499, PR China
| | - Yao-Qiong Liang
- Department of Pediatrics, Guangzhou Panyu Maternal and Children Health Hospital, Guangzhou Panyu District He Xian Memorial Hospital, Guangzhou, 511499, PR China
| | - Su-Shi Feng
- Department of Pediatrics, Guangzhou Panyu Maternal and Children Health Hospital, Guangzhou Panyu District He Xian Memorial Hospital, Guangzhou, 511499, PR China
| | - Juan Li
- Department of Pediatrics, Guangzhou Panyu Maternal and Children Health Hospital, Guangzhou Panyu District He Xian Memorial Hospital, Guangzhou, 511499, PR China
| | - Xue-Qun Luo
- Department of Pediatrics, Guangzhou Panyu Maternal and Children Health Hospital, Guangzhou Panyu District He Xian Memorial Hospital, Guangzhou, 511499, PR China
| | - Yan-Li Peng
- Department of Pediatrics, Guangzhou Panyu Maternal and Children Health Hospital, Guangzhou Panyu District He Xian Memorial Hospital, Guangzhou, 511499, PR China
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Wang G, Wu P, Tang R, Zhang W. Global prevalence of resistance to macrolides in Mycoplasma pneumoniae: a systematic review and meta-analysis. J Antimicrob Chemother 2022; 77:2353-2363. [PMID: 35678262 DOI: 10.1093/jac/dkac170] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 05/03/2022] [Indexed: 02/05/2023] Open
Abstract
OBJECTIVES To determine the prevalence of resistance to macrolides in Mycoplasma pneumoniae worldwide. METHODS Prior to 12 December 2020, PubMed, Web of Science, Scopus and Embase databases were searched for epidemiological studies of M. pneumoniae resistance. Two reviewers independently extracted data from included studies. The extracted data include sampling population, total sampling number, the number of resistant strains and the molecular subtype of resistant strains. The estimate of resistance prevalence was calculated using the random-effects model. RESULTS A total of 17 873 strains were obtained from five continents and reported in 98 investigations between 2000 and 2020, with 8836 strains characterized as macrolide resistant. In summary, macrolide-resistant M. pneumoniae was most common in Asia (63% [95% CI 56, 69]). In Europe, North America, South America and Oceania, the prevalence was 3% [2, 7], 8.6% [6, 11], 0% and 3.3%, respectively. Over the last 20 years, the prevalence of macrolide-resistant M. pneumoniae has remained high in China (81% [73, 87]), with a significant increasing trend in South Korea (4% [1, 9] to 78% [49, 93], P < 0.0001). Furthermore, a point mutation at 2063 from A to G was mostly related to M. pneumoniae macrolide resistance. In terms of clinical outcomes, longer cough (mean difference [MD]: 2.93 [0.26, 5.60]) and febrile days (MD: 1.52 [1.12, 1.92]), and prolonged hospital stays (MD: 0.76 [0.05, 1.46]) might be induced by macrolide-resistant M. pneumoniae pneumonia. CONCLUSIONS The incidence of macrolide-resistant M. pneumoniae varies globally, with eastern Asia having a greater degree of resistance. However, attention is also required in other areas, and antibiotic alternatives should be considered for treatment in high-prevalence countries.
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Affiliation(s)
- Guotuan Wang
- Department of pharmacy, Karamay central hospital of Xinjiang, Karamay, Xinjiang, China
| | - Peng Wu
- Department of emergency, Karamay central hospital of Xinjiang, Karamay, Xinjiang, China
| | - Rui Tang
- Department of pharmacy, West China hospital, Sichuan university, Chengdu, Sichuan, China
| | - Weidong Zhang
- Department of pharmacy, Karamay central hospital of Xinjiang, Karamay, Xinjiang, China
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Choo S, Kim SH, Lee E. Clinical significance of Mycoplasma pneumoniae specific IgM titer in children hospitalized with Mycoplasma pneumoniae pneumonia. BMC Infect Dis 2022; 22:470. [PMID: 35578177 PMCID: PMC9109195 DOI: 10.1186/s12879-022-07456-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Accepted: 05/10/2022] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND The present study aimed to identify the clinical significance of Mycoplasma pneumoniae (MP)-specific immunoglobulin M (IgM) titer, in addition to a diagnosis of MP infection, in children with MP pneumonia. METHODS This study was performed in 155 children hospitalized with MP pneumonia. The clinical features and laboratory and radiographic findings on admission in children with positive or negative MP-specific IgM titers were retrospectively reviewed from the electronic medical records. RESULTS The mean age of the included children was 6.0 years, and 118 (76.1%) of the children were positive for MP-specific IgM. A longer duration between symptom onset and admission (adjusted odds ratio [aOR] 1.47, 95% confidence interval [CI] 1.24-1.75), longer duration of symptoms during the illness (aOR 1.15, 95% CI 1.02-1.30), and development of extra-pulmonary manifestations (aOR 9.16, 95% CI 1.96-42.81) were significantly associated with a positive MP-specific IgM titer. Serum lactate dehydrogenase levels (aOR 1.00, 95% CI 1.00-1.01) and pneumonic infiltration involving > 50% of the total lung volume on chest radiography (aOR 4.68, 95% CI 1.12-19.55) were associated with positive MP-specific IgM in children with MP pneumonia. A poor response to stepwise treatment for MP pneumonia was more common in children with a positive MP-specific IgM titer than those with a negative MP-specific IgM titer on admission. CONCLUSIONS A positive MP-specific IgM titer at diagnosis of MP pneumonia may partially suggest an exaggerated immune response with a higher disease burden compared to children with MP pneumonia with a negative MP-specific IgM titer.
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Affiliation(s)
- Soojeong Choo
- Department of Pediatrics, Chonnam National University Hospital, Chonnam National University Medical School, Jebong-ro, Dong-gu, Gwangju, 61469, Republic of Korea
| | - Seo-Hee Kim
- Department of Pediatrics, Chonnam National University Hospital, Chonnam National University Medical School, Jebong-ro, Dong-gu, Gwangju, 61469, Republic of Korea
| | - Eun Lee
- Department of Pediatrics, Chonnam National University Hospital, Chonnam National University Medical School, Jebong-ro, Dong-gu, Gwangju, 61469, Republic of Korea.
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Mycoplasma pneumoniae and Adenovirus Coinfection Cause Pediatric Severe Community-Acquired Pneumonia. Microbiol Spectr 2022; 10:e0002622. [PMID: 35311565 PMCID: PMC9045297 DOI: 10.1128/spectrum.00026-22] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Consolidation is one complication of pediatric severe community-acquired pneumonia (SCAP) that can respond poorly to conservative medical treatment. We investigated the pathogens that cause pediatric SCAP including cases with persistent consolidation that need bronchoscopy intervention. Alveolar lavage fluid (ALF) samples collected from cases admitted to Children’s Hospital of Fudan University with SCAP during January 2019 to March in 2019 were retrospectively tested by the RespiFinder 2SMART multiplex PCR (multi-PCR) assay targeting 22 respiratory pathogens. A total of 90 cases and 91 samples were enrolled; 80.0% (72/90) of the cases had pulmonary consolidation and/or atelectasis. All samples were positive with targeted pathogens tested by multi-PCR, and 92.3% (84/91) of the samples were co-detected with pathogens. Mycoplasma pneumoniae (MP) and adenovirus (ADV) as the two dominant pathogens, with the positive rates of 96.7% (88/91) and 79.1% (72/91), respectively. Most of the samples were positive with MP and ADV simultaneously. As a control, 78.0% (71/91) of the samples were positive by conventional tests (CT), in which MP had the detection rate of 63.9% (55/86) by a traditional real-time PCR assay, while ADV were positive in 13.1% (12/91) of the samples by a direct immunofluorescence assay (DFA). In cases with persistent pulmonary consolidation, the positive rates of pathogens by multi-PCR and CT were 100% (72/72) and 81.9% (59/72), respectively. There were no significant differences of MP or ADV positive rates between cases with and without pulmonary consolidation. MP and ADV most prevalent in pediatric SCAP cases required fiberscope intervention, and presented with coinfections dominantly. IMPORTANCE Pathogens that cause pediatric severe community-acquired pneumonia (SCAP) requiring bronchoscopy intervention are understudied. Through this study, we explore the etiology of SCAP form alveolar lavage fluid (ALF) samples by the RespiFinder 2SMART multi-PCR assay. It is observed that high mixed detection rates of Mycoplasma pneumoniae and adenovirus in ALF samples collected from hospitalized SCAP children experienced bronchoscopy intervention. Eighty percent of the cases had pulmonary consolidation and/or atelectasis. The presence of possible coinfection of these two pathogens might contribute to poor clinical anti-infection response. The results of this study might be helpful for the selection of clinical strategies for the empirical treatment of such pediatric SCAP cases.
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Guo H, Zhang H, Li F. Based on the Auxiliary Effect of X-Ray in the Treatment of Severe Pneumonia in Children with Arterial and Venous Blood Gas. JOURNAL OF HEALTHCARE ENGINEERING 2022; 2022:5786630. [PMID: 35399849 PMCID: PMC8986414 DOI: 10.1155/2022/5786630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 03/03/2022] [Accepted: 03/04/2022] [Indexed: 11/25/2022]
Abstract
Pediatric severe pneumonia clinical is a conceptual term for the diagnosis and treatment of pediatric clinical diseases. At present, domestic and foreign standards for clinical diagnosis of severe pneumonia, which is a childhood disease, are still inconsistent. At present, the first book of the main pediatric medical textbook in the society interprets the clinical definition of severe pneumonia in children as follows: severe pneumonia refers to pulmonary function in heart failure or other comorbidities in other important organs except the lung. This article is based on X-ray medical film and television examinations, through the analysis of arterial and venous blood gas in children with severe pneumonia to play a certain role in adjuvant therapy for children with pneumonia. Prospective clinical studies have found significant changes in the function of auxiliary coagulation and blood fibrinolysis indicators in patients with severe pneumonia in late childhood. The obvious difference between the pretreatment and the late-stage treatment for 1 week and the direct influence on the blood gas quantitative analysis and liver function of advanced patients provide a scientific basis for the diagnosis of typical advanced childhood severe pneumonia patients with adjuvant anticoagulant therapy. The data analysis of the clinical laboratory found that the blood coagulation and fibrinolysis functions of the typical patients with severe pneumonia in the typical late stage of childhood were significantly activated, and the anticoagulant antibody substances were significantly reduced, fibrinolytic coagulation inhibitors and anticoagulants are significantly increased, fibrinolytic activators are significantly reduced, and the body is in a procoagulant state for a long time. Adjuvant anticoagulation therapy through quantitative analysis of blood gas in patients can not only effectively increase the success rate of early treatment of typical late-stage severe pneumonia in children by 64.28% but also significantly reduce the inflammatory coagulation indexes of patients with late-stage severe pneumonia in children. The functions of coagulation, anticoagulation, and coagulation fibrinolysis have been significantly restored. The advantages of X-ray-based adjuvant treatment of severe pneumonia in children with arteriovenous blood gas are good contrast, clear imaging, and clear development of fine lesions or thick parts, and objective records are kept for comparison during review and consultation and discussion. The disadvantage is that the operation is more complicated, and it is not convenient to observe the activity function of the organ.
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Affiliation(s)
- Hui Guo
- Department of Pediatric, Ji'an Matemal and Child Health Hospital, Jian 343000, Jiangxi, China
| | - Hua Zhang
- Department of Pediatric, Ji'an Matemal and Child Health Hospital, Jian 343000, Jiangxi, China
| | - Fuping Li
- Department of Radiology, Ji'an Matemal and Child Health Hospital, Jian 343000, Jiangxi, China
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Lu J, Zhang J, Wang G, Zhang X, Li Z. Effects of bronchoalveolar lavage on Mycoplasma Pneumoniae pneumonia: A propensity score matched-cohort study. Front Pediatr 2022; 10:1066640. [PMID: 36683805 PMCID: PMC9846808 DOI: 10.3389/fped.2022.1066640] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 12/12/2022] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND The purpose of this study was to evaluate the efficacy and safety of BAL in treating MPP. METHODS From January 2013 to January 2019, 1,689 pediatric patients with MPP were analyzed retrospectively. Patients were subdivided into BAL group and non-BAL group according to whether they received BAL treatment within seven days after admission. The propensity score matching method matched patients' baseline characteristics (1:1). The primary outcomes were hospital stays and the cure rate. Secondary outcomes included mortality, co-infection, repeat hospitalization within 30 days, and total cost of treatment. RESULTS After matching, 524 patients (BAL: 262; control: 262) were recorded. The BAL group had significantly shorter hospital stays (OR: 0.5, 95% CI: 0.4-0.7). Meanwhile, BAL did not significantly modify the cost, co-infection rate, and mortality. In subgroup analyses, the group with BAL intervention within three days had a significantly shorter hospital stay (OR: 0.4, 95% CI: 0.3-0.5) compared with the group with BAL intervention three days after admission. CONCLUSIONS Early BAL intervention is a better treatment than conventional drug therapy alone, and no significant complications were seen in this study. BAL intervention has an excellent clinical benefit. The earlier the intervention, the better the effect.
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Affiliation(s)
- Jinmiao Lu
- Department of Pharmacy, National Children's Medical Center, Children's Hospital of Fudan University, Shanghai, China
| | - Junqi Zhang
- Department of Pharmacy, National Children's Medical Center, Children's Hospital of Fudan University, Shanghai, China
| | - Guangfei Wang
- Department of Pharmacy, National Children's Medical Center, Children's Hospital of Fudan University, Shanghai, China
| | - Xiaobo Zhang
- Department of Respiratory Disease, National Children's Medical Center, Children's Hospital of Fudan University, Shanghai, China
| | - Zhiping Li
- Department of Pharmacy, National Children's Medical Center, Children's Hospital of Fudan University, Shanghai, China
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Hill V, Akarsu H, Barbarroja RS, Cippà VL, Kuhnert P, Heller M, Falquet L, Heller M, Stoffel MH, Labroussaa F, Jores J. Minimalistic mycoplasmas harbor different functional toxin-antitoxin systems. PLoS Genet 2021; 17:e1009365. [PMID: 34673769 PMCID: PMC8562856 DOI: 10.1371/journal.pgen.1009365] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 11/02/2021] [Accepted: 09/29/2021] [Indexed: 11/19/2022] Open
Abstract
Mycoplasmas are minute bacteria controlled by very small genomes ranging from 0.6 to 1.4 Mbp. They encompass several important medical and veterinary pathogens that are often associated with a wide range of chronic diseases. The long persistence of mycoplasma cells in their hosts can exacerbate the spread of antimicrobial resistance observed for many species. However, the nature of the virulence factors driving this phenomenon in mycoplasmas is still unclear. Toxin-antitoxin systems (TA systems) are genetic elements widespread in many bacteria that were historically associated with bacterial persistence. Their presence on mycoplasma genomes has never been carefully assessed, especially for pathogenic species. Here we investigated three candidate TA systems in M. mycoides subsp. capri encoding a (i) novel AAA-ATPase/subtilisin-like serine protease module, (ii) a putative AbiEii/AbiEi pair and (iii) a putative Fic/RelB pair. We sequence analyzed fourteen genomes of M. mycoides subsp. capri and confirmed the presence of at least one TA module in each of them. Interestingly, horizontal gene transfer signatures were also found in several genomic loci containing TA systems for several mycoplasma species. Transcriptomic and proteomic data confirmed differential expression profiles of these TA systems during mycoplasma growth in vitro. While the use of heterologous expression systems based on E. coli and B. subtilis showed clear limitations, the functionality and neutralization capacities of all three candidate TA systems were successfully confirmed using M. capricolum subsp. capricolum as a host. Additionally, M. capricolum subsp. capricolum was used to confirm the presence of functional TA system homologs in mycoplasmas of the Hominis and Pneumoniae phylogenetic groups. Finally, we showed that several of these M. mycoides subsp. capri toxins tested in this study, and particularly the subtilisin-like serine protease, could be used to establish a kill switch in mycoplasmas for industrial applications.
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Affiliation(s)
- Virginia Hill
- Institute of Veterinary Bacteriology, University of Bern, Bern, Switzerland
- Graduate School for Biomedical Science, University of Bern, Bern, Switzerland
| | - Hatice Akarsu
- Institute of Veterinary Bacteriology, University of Bern, Bern, Switzerland
| | | | - Valentina L. Cippà
- Institute of Veterinary Bacteriology, University of Bern, Bern, Switzerland
| | - Peter Kuhnert
- Institute of Veterinary Bacteriology, University of Bern, Bern, Switzerland
| | - Martin Heller
- Friedrich-Loeffler-Institute—Federal Research Institute for Animal Health, Jena, Germany
| | - Laurent Falquet
- Biochemistry Unit, University of Fribourg and Swiss Institute of Bioinformatics, Fribourg, Switzerland
| | - Manfred Heller
- Proteomics and Mass Spectrometry Core Facility, Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland
| | - Michael H. Stoffel
- Division of Veterinary Anatomy, Department of Clinical Research and Veterinary Public Health, University of Bern, Bern, Switzerland
| | - Fabien Labroussaa
- Institute of Veterinary Bacteriology, University of Bern, Bern, Switzerland
| | - Joerg Jores
- Institute of Veterinary Bacteriology, University of Bern, Bern, Switzerland
- * E-mail:
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Li H, Li T, Cai Q, Wang X, Liao Y, Cheng Y, Zhou Q. Development and Validation of a Radiomics Nomogram for Differentiating Mycoplasma Pneumonia and Bacterial Pneumonia. Diagnostics (Basel) 2021; 11:1330. [PMID: 34441265 PMCID: PMC8392308 DOI: 10.3390/diagnostics11081330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 07/17/2021] [Accepted: 07/20/2021] [Indexed: 11/16/2022] Open
Abstract
OBJECTIVES To develop and validate a radiological nomogram combining radiological and clinical characteristics for differentiating mycoplasma pneumonia and bacterial pneumonia with similar CT findings. METHODS A total of 100 cases of pneumonia patients receiving chest CT scan were retrospectively analyzed, including 60 patients with mycoplasma pneumonia and 40 patients with bacterial pneumonia. The patients were divided into the train set (n = 70) and the test set (n = 30). The features were extracted from chest CT images of each patient by AK analysis software, then univarite analysis, spearman correlation analysis, and least absolute shrinkage and selection operator (LASSO) were utilized for dimension reduction in training set. A radiomics model was built by multivariable logistic regression based on the selected features, and a radiomics-clinical multivariable logistic regression model was built by combining imaging radiomics and clinical risk factors (age and temperature). ROC, AUC, sensitivity, specificity, and accuracy were calculated to validate the two models. The nomogram of the radiomics-clinical was built and evaluated by calibration curve. The clinical benefit of the two models was measured by using decision curve. RESULTS A total of 396 texture features were extracted from each chest CT image, and 10 valuable features were screened out. In the radiomics model, the AUC, sensitivity, specificity, and accuracy for the train set is 0.877, 0.762, 0.821, 78.6%, and for the test set it is 0.810, 0.667, 0.750 and 70.0%, respectively. In the radiomics-clinical model, the AUC, sensitivity, specificity, and accuracy for the train set is 0.905, 0.976, 0.714, 87.1%, and for the test set is is 0.847, 0.889, 0.667 and 80.0%, respectively. Decision curve analysis shows that both the two models increase the clinical benefits of the patients, and the radiomics-clinical model gains higher clinical benefits, compared to the radiomics model. CONCLUSION The radiomics-clinical nomogram had good performance in identifying mycoplasma pneumonia and bacterial pneumonias, which would be helpful in clinical decision-making.
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Affiliation(s)
- Honglin Li
- Department of Radiology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510000, China; (H.L.); (Q.C.); (X.W.)
| | - Ting Li
- Department of Respiratory Medicine, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510000, China;
| | - Qinxin Cai
- Department of Radiology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510000, China; (H.L.); (Q.C.); (X.W.)
| | - Xiaozhuan Wang
- Department of Radiology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510000, China; (H.L.); (Q.C.); (X.W.)
| | | | - Yuanxiong Cheng
- Department of Respiratory Medicine, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510000, China;
| | - Quan Zhou
- Department of Radiology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510000, China; (H.L.); (Q.C.); (X.W.)
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20
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Liu J, Shen R, Feng L, Cheng S, Chen J, Xiao T, Zhao S. Proteomics study of Mycoplasma pneumoniae pneumonia reveals the Fc fragment of the IgG-binding protein as a serum biomarker and implicates potential therapeutic targets. Front Med 2021; 16:378-388. [PMID: 34241785 DOI: 10.1007/s11684-021-0840-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 11/24/2020] [Indexed: 10/20/2022]
Abstract
Macrolide and corticosteroid resistance has been reported in patients with Mycoplasma pneumoniae (MP) pneumonia (MPP). MP clearance is difficult to achieve through antibiotic treatment in sensitive patients with severe MPP (SMPP). SMPP in children might progress to airway remodeling and even bronchiolitis/bronchitis obliterans. Therefore, identifying serum biomarkers that indicate MPP progression and exploring new targeted drugs for SMPP treatment require urgency. In this study, serum samples were collected from patients with general MPP (GMPP) and SMPP to conduct proteomics profiling. The Fc fragment of the IgG-binding protein (FCGBP) was identified as the most promising indicator of SMPP. Biological enrichment analysis indicated uncontrolled inflammation in SMPP. ELISA results proved that the FCGBP level in patients with SMPP was substantially higher than that in patients with GMPP. Furthermore, the FCGBP levels showed a decreasing trend in patients with GMPP but the opposite trend in patients with SMPP during disease progression. Connectivity map analyses identified 25 possible targeted drugs for SMPP treatment. Among them, a mechanistic target of rapamycin kinase (mTOR) inhibitor, which is a macrolide compound and a cell proliferation inhibitor, was the most promising candidate for targeting SMPP. To our knowledge, this study was the first proteomics-based characterization of patients with SMPP and GMPP.
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Affiliation(s)
- Jinrong Liu
- Department of Respiratory Medicine, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China
| | - Rongfang Shen
- State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Lin Feng
- State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Shujun Cheng
- State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Jun Chen
- Beijing Engineering Research Center of Pediatric Surgery, Engineering and Transformation Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.
| | - Ting Xiao
- State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
| | - Shunying Zhao
- Department of Respiratory Medicine, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.
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21
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Liu J, Li Y. Thrombosis associated with mycoplasma pneumoniae infection (Review). Exp Ther Med 2021; 22:967. [PMID: 34335909 PMCID: PMC8290426 DOI: 10.3892/etm.2021.10399] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 06/18/2021] [Indexed: 12/12/2022] Open
Abstract
Mycoplasma pneumoniae is a common pathogen causing respiratory infections in children and adults. In addition to respiratory diseases, Mycoplasma pneumoniae is also involved in numerous extrapulmonary diseases. Thrombosis is an extrapulmonary manifestation associated with Mycoplasma pneumoniae infection. In recent years, an increasing number of case reports have been published identifying thrombosis secondary to Mycoplasma pneumoniae infection. In the present study, the available relevant literature in English available on PubMed, Medline and Web of Science was consulted. The results of the present study demonstrated that in patients with thrombosis caused by Mycoplasma pneumoniae infection, some of the factors causing thrombosis are transient and some are due to hereditary thrombophilia. Following timely treatment, the majority of patients recovered completely but some patients had a poor prognosis. The present review focuses on the pathogenesis, clinical features, treatment and prognosis of this crucial issue, which contributes toward the understanding of the disease.
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Affiliation(s)
- Jingwei Liu
- Department of Pediatrics Intensive Care Unit, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Yumei Li
- Department of Pediatrics Intensive Care Unit, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
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Esposito S, Argentiero A, Gramegna A, Principi N. Mycoplasma pneumoniae: a pathogen with unsolved therapeutic problems. Expert Opin Pharmacother 2021; 22:1193-1202. [PMID: 33544008 DOI: 10.1080/14656566.2021.1882420] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
INTRODUCTION Despite the amount of new information, the most effective approach for the diagnosis and treatment of Mycoplasma pneumoniae infections is not established. In this narrative review the pharmacological options for macrolide-resistant (ML) M. pneumoniae infections in children are discussed. AREAS COVERED Despite significant improvement in the diagnosis and in the definition of diseases potentially associated with this pathogen, not all the problems related to M. pneumoniae infection are solved. True epidemiology of M. pneumoniae diseases and the real role of this pathogen in extra-respiratory manifestations is still unestablished. This reflects on therapy. It is not known whether antibiotics are really needed in all the cases, independently of severity and localization. The choice of antibiotic therapy is debated as it is not known whether ML resistance has clinical relevance. Moreover, not precisely defined is the clinical importance of corticosteroids for improvement of severe cases, including those associated with ML-resistant strains. EXPERT OPINION Improvement in M. pneumoniae identification is mandatory to reduce antibiotics overuse , especially in the presence of ML-resistant strains. Priority for future studies includes the evaluation of the true benefit of therapeutic approaches including corticosteroids in patients with severe CAP and in those with extra-respiratory M. pneumoniae diseases.
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Affiliation(s)
- Susanna Esposito
- Pediatric Clinic, Pietro Barilla Children's Hospital, University of Parma, Parma, Italy
| | - Alberto Argentiero
- Pediatric Clinic, Pietro Barilla Children's Hospital, University of Parma, Parma, Italy
| | - Andrea Gramegna
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Internal Medicine Department, Respiratory Unit and Cystic Fibrosis Adult Center, Milan, Italy.,Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy
| | - Nicola Principi
- Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy
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Ma Y, Li R, Wang J, Jiang W, Yuan X, Cui J, Wang C. ITIH4, as an inflammation biomarker, mainly increases in bacterial bloodstream infection. Cytokine 2020; 138:155377. [PMID: 33348064 DOI: 10.1016/j.cyto.2020.155377] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 11/13/2020] [Accepted: 11/17/2020] [Indexed: 12/17/2022]
Abstract
Bloodstream infection (BSI) is usually accompanied with the changes of varieties of inflammation proteins. In our previous study, we identified that inter-α-trypsin inhibitor heavy chain H4 (ITIH4) was highly expressed in the infection arms than the normal control arm. However, the correlated verification and mechanism remain obscure. Escherichia coli infected mice model and clinical serum samples were used to validate the concentration of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), as well as ITIH4, in ELISA method. Cytokines (IL-6, TNF-α, IL-10 and lipopolysaccharide (LPS)) were used to stimulate the HepG2 cell model to explore which cytokines influence the expression of ITIH4. JAK/STAT inhibitor was treated before IL-6 and LPS stimulation. Westernblot, as well as real-time PCR were performed to detect the expression of ITIH4 in liver tissue from protein and transcription levels. Immunohistochemistry analysis was used to observe the expression of ITIH4 in mice liver tissue. In mice model, IL-6, TNF-α, as well as IL-10 increased in the infection arms than the normal control arm. ITIH4 in serum and liver tissue of mice model increased from 1 h to 128 h, which were remarkably different from that of the normal control arm. Besides, ITIH4 increased in the bacterial infection arm greatly than the fungemia arm, mycoplasma pneumoniae (MP) arm and febrile arm in clinical serum samples. Furthermore, using the HepG2 cell line, we demonstrated that ITIH4 was up-regulated at both protein and mRNA levels upon dose- and time- response treatments with IL-6, as well as LPS. Moreover, IL-6 or LPS mediated induction of ITIH4 expression could be significantly decreased by treatment with an JAK/STAT inhibitor in protein or mRNA level. No changes were observed after TNF-α or IL-10 stimulation. ITIH4 might be a critical inflammatory biomarker which correlated with the development of BSI, especially with bacterial bloodstream infection. It is expected that this study would provide some insights into potential functional mechanisms underlying BSI.
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Affiliation(s)
- Yating Ma
- Department of Laboratory Medicine, Chinese PLA General Hospital, Beijing 100853, China; Nankai University School of Medicine, Nankai University, Tianjin 300071, China
| | - Ruibing Li
- Department of Laboratory Medicine, Chinese PLA General Hospital, Beijing 100853, China
| | - Jianan Wang
- Department of Laboratory Medicine, Chinese PLA General Hospital, Beijing 100853, China
| | - Wencan Jiang
- Department of Laboratory Medicine, Chinese PLA General Hospital, Beijing 100853, China
| | - Xiaozhou Yuan
- Department of Laboratory Medicine, Chinese PLA General Hospital, Beijing 100853, China
| | - Jiayue Cui
- Department of Laboratory Medicine, Chinese PLA General Hospital, Beijing 100853, China
| | - Chengbin Wang
- Department of Laboratory Medicine, Chinese PLA General Hospital, Beijing 100853, China; Nankai University School of Medicine, Nankai University, Tianjin 300071, China.
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