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      The timing of azithromycin treatment is not associated with the clinical prognosis of childhood Mycoplasma pneumoniae pneumonia in high macrolide-resistant prevalence settings

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      PLoS ONE
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          Abstract

          Background

          Mycoplasma pneumoniae infection is a major cause of community-acquired pneumonia in children. We performed a retrospective study to evaluate the clinical impact of the timing of azithromycin treatment in children with Mycoplasma pneumoniae pneumonia in high macrolide-resistant prevalence settings.

          Methods and findings

          A total of 623 patients were enrolled in this study and were divided into 2 groups according to the timing of azithromycin therapy. Children who received azithromycin within 3 days (72 hours) after the onset of Mycoplasma pneumoniae pneumonia were classified into the early azithromycin treatment group (n = 174), whereas the late azithromycin treatment group (n = 449) comprised children treated with azithromycin more than 72 hours after symptom onset. We evaluated clinical prognosis according to demographic, clinical and laboratory characteristics. Although the early azithromycin treatment group exhibited a longer fever duration after azithromycin administration (7.17±4.12 versus 4.82±3.99 days, P<0.01), the total fever duration exhibited no significant difference (9.02±4.58 versus 9.57±4.91 days, P = 0.212). After azithromycin therapy, the two groups exhibited no significant differences with respect to improvements in the laboratory and radiological findings (all P>0.05).

          Conclusion

          The timing of azithromycin treatment is not associated with the clinical prognosis of Mycoplasma pneumoniae pneumonia in children in high macrolide-resistant Mycoplasma pneumoniae prevalence settings.

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          Most cited references27

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          Mycoplasma pneumoniae and its role as a human pathogen.

          Mycoplasma pneumoniae is a unique bacterium that does not always receive the attention it merits considering the number of illnesses it causes and the degree of morbidity associated with it in both children and adults. Serious infections requiring hospitalization, while rare, occur in both adults and children and may involve multiple organ systems. The severity of disease appears to be related to the degree to which the host immune response reacts to the infection. Extrapulmonary complications involving all of the major organ systems can occur in association with M. pneumoniae infection as a result of direct invasion and/or autoimmune response. The extrapulmonary manifestations are sometimes of greater severity and clinical importance than the primary respiratory infection. Evidence for this organism's contributory role in chronic lung conditions such as asthma is accumulating. Effective management of M. pneumoniae infections can usually be achieved with macrolides, tetracyclines, or fluoroquinolones. As more is learned about the pathogenesis and immune response elicited by M. pneumoniae, improvement in methods for diagnosis and prevention of disease due to this organism may occur.
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            Epidemiology and clinical characteristics of community-acquired pneumonia in hospitalized children.

            The precise epidemiology of childhood pneumonia remains poorly defined. Accurate and prompt etiologic diagnosis is limited by inadequate clinical, radiologic, and laboratory diagnostic methods. The objective of this study was to determine as precisely as possible the epidemiology and morbidity of community-acquired pneumonia in hospitalized children. Consecutive immunocompetent children hospitalized with radiographically confirmed lower respiratory infections (LRIs) were evaluated prospectively from January 1999 through March 2000. Positive blood or pleural fluid cultures or pneumolysin-based polymerase chain reaction assays, viral direct fluorescent antibody tests, or viral, mycoplasmal, or chlamydial serologic tests were considered indicative of infection by those organisms. Methods for diagnosis of pneumococcal pneumonia among study subjects were published by us previously. Selected clinical characteristics, indices of inflammation (white blood cell and differential counts and procalcitonin values), and clinical outcome measures (time to defervescence and duration of oxygen supplementation and hospitalization) were compared among groups of children. One hundred fifty-four hospitalized children with LRIs were enrolled. Median age was 33 months (range: 2 months to 17 years). A pathogen was identified in 79% of children. Typical respiratory bacteria were identified in 60% (of which 73% were Streptococcus pneumoniae), viruses in 45%, Mycoplasma pneumoniae in 14%, Chlamydia pneumoniae in 9%, and mixed bacterial/viral infections in 23%. Preschool-aged children had as many episodes of atypical bacterial LRIs as older children. Children with typical bacterial or mixed bacterial/viral infections had the greatest inflammation and disease severity. Multivariate logistic-regression analyses revealed that high temperature (> or = 38.4 degrees C) within 72 hours after admission (odds ratio: 2.2; 95% confidence interval: 1.4-3.5) and the presence of pleural effusion (odds ratio: 6.6; 95% confidence interval: 2.1-21.2) were significantly associated with bacterial pneumonia. This study used an expanded diagnostic armamentarium to define the broad spectrum of pathogens that cause pneumonia in hospitalized children. The data confirm the importance of S pneumoniae and the frequent occurrence of bacterial and viral coinfections in children with pneumonia. These findings will facilitate age-appropriate antibiotic selection and future evaluation of the clinical effectiveness of the pneumococcal conjugate vaccine as well as other candidate vaccines.
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              The Definition of Pneumonia, the Assessment of Severity, and Clinical Standardization in the Pneumonia Etiology Research for Child Health Study

              To develop a case definition for the Pneumonia Etiology Research for Child Health (PERCH) project, we sought a widely acceptable classification that was linked to existing pneumonia research and focused on very severe cases. We began with the World Health Organization’s classification of severe/very severe pneumonia and refined it through literature reviews and a 2-stage process of expert consultation. PERCH will study hospitalized children, aged 1–59 months, with pneumonia who present with cough or difficulty breathing and have either severe pneumonia (lower chest wall indrawing) or very severe pneumonia (central cyanosis, difficulty breastfeeding/drinking, vomiting everything, convulsions, lethargy, unconsciousness, or head nodding). It will exclude patients with recent hospitalization and children with wheeze whose indrawing resolves after bronchodilator therapy. The PERCH investigators agreed upon standard interpretations of the symptoms and signs. These will be maintained by a clinical standardization monitor who conducts repeated instruction at each site and by recurrent local training and testing.
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                Author and article information

                Contributors
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SoftwareRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: SoftwareRole: Writing – original draft
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                29 January 2018
                2018
                : 13
                : 1
                : e0191951
                Affiliations
                [1 ] Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China
                [2 ] The First People’s Hospital of Wenling, Wenling, Zhejiang, P.R. China
                University of Kentucky, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-5160-7502
                Article
                PONE-D-17-08207
                10.1371/journal.pone.0191951
                5788379
                29377957
                c5ce4175-07c4-4b31-82cf-28989150cba3
                © 2018 Yang et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 23 March 2017
                : 15 January 2018
                Page count
                Figures: 0, Tables: 3, Pages: 7
                Funding
                Funded by: Wenling science and technology project fund
                Award ID: 2012WLCA0057
                Award Recipient :
                This work was supported by grant 2012WLCA0057 from the Wenling Science and Technology Project Fund ( http://new.wl.gov.cn/col/col1402190/index.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Linghong Chen received the funding.
                Categories
                Research Article
                Biology and Life Sciences
                Microbiology
                Medical Microbiology
                Microbial Pathogens
                Bacterial Pathogens
                Mycoplasma Pneumoniae
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Pathogens
                Microbial Pathogens
                Bacterial Pathogens
                Mycoplasma Pneumoniae
                Biology and Life Sciences
                Organisms
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                Mycoplasma
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                Medicine and Health Sciences
                Pulmonology
                Pneumonia
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                Diagnostic Medicine
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                Fevers
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                Pathology and Laboratory Medicine
                Signs and Symptoms
                Fevers
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
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                Neutrophils
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                Cell Biology
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                Animal Cells
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                Prognosis
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                Retrospective Studies
                Medicine and Health Sciences
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                Pleural Effusion
                Medicine and Health Sciences
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