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      Critical combination of initial markers for predicting refractory Mycoplasma pneumoniae pneumonia in children: a case control study

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          Abstract

          Background

          It is unclear whether the responses of refractory and common Mycoplasma pneumoniae (MP) pneumonia to macrolides differ. Hence, this study aimed to identify biomarkers that may be used to distinguish refractory and common pneumonias caused by MP in children at hospital admission.

          Methods

          The study included 123 children divided into five groups according to infection agent and treatment protocol: Group I included those with MP infection without documented viral infection, treated with only macrolides; Group II included those with MP infection without documented viral infection, treated with a combination of macrolides and methylprednisolone; Group III included those with MP infection and documented viral infection, treated with only macrolides; Group IV included those with viral pneumonia without documented MP infection; Group V was the control group composed of admitted children without MP or a documented viral infection. These five groups were further subdivided into Groups A (including Groups I, III, IV, and V) and B (Group II) according to the responses to macrolide treatment. Concentrations of cytokines interleukin 6, interleukin 17, interleukin 18, and tumor necrosis factor-α, and lactate dehydrogenase, and ferritin of all children were evaluated, and these levels were compared among the groups. Statistical comparisons were made using Kruskal Wallis test and Mann-Whitney U test.

          Results

          Serum lactate dehydrogenase, interleukin 18, and ferritin concentrations were significantly higher in Group II than in Groups I, III, IV, and V and were significantly higher in Group B than in Group A. When the serum lactate dehydrogenase concentration was 350 IU/L or higher, the sensitivity and specificity for diagnosing refractory MP pneumonia were 73 and 80%, respectively. When the interleukin 18 level was 360 pg/mL or higher, the sensitivity and specificity for diagnosing refractory MP pneumonia were 93 and 70%, respectively. When the ferritin level was 230 pg/mL or higher, the sensitivity and specificity for diagnosing refractory MP pneumonia were 67 and 67%, respectively.

          Conclusion

          These results suggest that serum lactate dehydrogenase, interleukin 18, and ferritin constitute the critical combination of biomarkers useful for predicting refractory MP pneumonia in children at hospital admission.

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          Most cited references24

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          Methylprednisolone pulse therapy for refractory Mycoplasma pneumoniae pneumonia in children

          Summary Objectives To determine the efficacy of methylprednisolone pulse therapy for children with Mycoplasma pneumoniae pneumonia (MP) that is refractory to antibiotic treatment. Methods Refractory patients were defined as cases showing clinical and radiological deterioration despite appropriate antibiotic therapy for 7 days or more. We identified 6 such children (male/female: 3/3) aged 3–9 years who were treated between 1998 and 2006. During the same period, 190 children with MP were admitted to our institution. Results Common laboratory findings of the patients included cytopenia, elevated serum lactate dehydrogenase and ferritin levels, and elevated urine β2-microglobulin levels, suggesting complication of hypercytokinemic condition. We initiated intravenous methylprednisolone at a dose of 30 mg/kg on 10.2 ± 2.8 clinical days and administered it once daily for 3 consecutive days. Fever subsided 4–14 h after initiation of steroid pulse therapy in all patients. This dramatic effect was accompanied by rapid improvement of radiological abnormalities including infiltrates and pleural effusion, followed by improvement of laboratory abnormalities. There were no adverse events of steroid therapy. Conclusions This is the first case-series study showing an effect of 3-day methylprednisolone pulse therapy on refractory MP in children. This therapy is apparently an efficacious and well-tolerated treatment for refractory MP.
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            Role of prednisolone treatment in severe Mycoplasma pneumoniae pneumonia in children.

            Mycoplasma pneumoniae pneumonia (MP) is responsible for 10-40% of cases of pediatric community-acquired pneumonia. Occasionally, progression to severe pneumonia occurs despite appropriate antibiotic therapy. We retrospectively evaluated the effect of prednisolone in 15 children with MP whose clinical and radiographic course worsened despite broad-spectrum antibiotics, including appropriate macrolides. The mean ( +/- SD) age was 6.1 +/- 1.9 years, and 10 were boys. All children had received macrolides at presentation, but they had persistent fever and progressively worsening radiographic findings. In addition to broad-spectrum antimicrobial therapy, we added prednisolone (1 mg/kg for 3-7 days, then tapered over 7 days) on day 6 (+/-1.5 days) of admission. Fourteen children became afebrile within 24 hr, and their clinical status and radiographic findings improved over several days. The white blood cell count at presentation was 7,500 +/- 2,000/mm3, with a proportion demonstrating lymphopenia (lymphocyte differential, 19.7 +/- 5.7%). In conclusion, corticosteroid treatment appeared to be temporally associated with clinical and radiographic improvement, and may be helpful for reducing morbidity in children with macrolide-nonresponsive severe MP. Further studies may be warranted. (c) 2006 Wiley-Liss, Inc.
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              Mycoplasma pneumoniae pneumonia in children

              Mycoplasma pneumoniae (MP), the smallest self-replicating biological system, is a common cause of upper and lower respiratory tract infections, leading to a wide range of pulmonary and extra-pulmonary manifestations. MP pneumonia has been reported in 10 to 40% of cases of community-acquired pneumonia and shows an even higher proportion during epidemics. MP infection is endemic in larger communities of the world with cyclic epidemics every 3 to 7 years. In Korea, 3 to 4-year cycles have been observed from the mid-1980s to present. Although a variety of serologic assays and polymerase chain reaction (PCR) techniques are available for the diagnosis of MP infections, early diagnosis of MP pneumonia is limited by the lack of immunoglobulin (Ig) M antibodies and variable PCR results in the early stages of the infection. Thus, short-term paired IgM serologic tests may be mandatory for an early and definitive diagnosis. MP infection is usually a mild and self-limiting disease without specific treatment, and if needed, macrolides are generally used as a first-choice drug for children. Recently, macrolide-resistant MP strains have been reported worldwide. However, there are few reports of apparent treatment failure, such as progression of pneumonia to acute respiratory distress syndrome despite macrolide treatment. The immunopathogenesis of MP pneumonia is believed to be a hyperimmune reaction of the host to the insults from MP infection, including cytokine overproduction and immune cell activation (T cells). In this context, immunomodulatory treatment (corticosteroids or/and intravenous Ig), in addition to antibiotic treatment, might be considered for patients with severe infection.
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                Author and article information

                Contributors
                +82 31 560 2254 , jaewonoh@hanyang.ac.kr
                Journal
                Respir Res
                Respir. Res
                Respiratory Research
                BioMed Central (London )
                1465-9921
                1465-993X
                23 August 2019
                23 August 2019
                2019
                : 20
                : 193
                Affiliations
                [1 ]ISNI 0000 0004 0647 3212, GRID grid.412145.7, Department of Pediatrics, College of Medicine, , Hanyang University Guri Hospital, ; 249-1 Kyomun-Dong, Guri, Kyunggi-Do, Seoul, 471-701 South Korea
                [2 ]ISNI 0000 0001 1364 9317, GRID grid.49606.3d, Department of Medicine, , Graduate School of Hanyang University, ; Seoul, South Korea
                Author information
                http://orcid.org/0000-0003-2714-0065
                Article
                1152
                10.1186/s12931-019-1152-5
                6706904
                31443650
                536fa9a2-aa0e-42bd-acac-021fff99677f
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 17 January 2019
                : 5 August 2019
                Categories
                Research
                Custom metadata
                © The Author(s) 2019

                Respiratory medicine
                biomarkers,mycoplasma pneumoniae,refractory mycoplasma pneumoniae pneumonia

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