Diagnose und Therapie der Pneumonie bei Kindern und Jugendlichen

Die Mutter eines 10-jährigen Mädchens meldete sich wegen Husten und hohem Fieber beim Hausarzt. Die Symptome bestanden seit 4 Tagen. Das Mädchen war bisher gesund und hatte alle empfohlenen Impfungen erhalten. Aufgrund der Anamnese wurde eine Pneumonie vermutet

Childhood community-acquired pneumonia

Community-acquired pneumonia (CAP) is a common disease in children, and its aetiological and clinical diagnosis are challenging for physicians in both private practice and hospitals. Over the past three decades, conjugate vaccines have successfully reduced the burden of the former main causes of CAP, Streptococcus pneumoniae and Haemophilus influenzae type b. Today, viruses are by far the most commonly detected pathogens in children with CAP.  Conclusion: New insights into the aetiology and treatment of CAP in children in recent years have influenced management and are the focus of this review. In addition to reducing diagnostic uncertainty, there is an urgent need to reduce antibiotic overuse and antimicrobial resistance in children with CAP. What is Known: • Conjugate vaccines against Streptococcus pneumoniae and Haemophilus influenzae type b have shifted the epidemiology of childhood CAP to predominantly viral pathogens and Mycoplasma pneumoniae. • Clinical, laboratory, and radiological criteria cannot reliably distinguish between bacterial and viral aetiology in children with CAP. What is New: • Test results and epidemiological data must be carefully interpreted, as no single diagnostic method applied to non-pulmonary specimens has both high sensitivity and high specificity for determining pneumonia aetiology in childhood CAP. • This review provides a simple and pragmatic management algorithm for children with CAP to aid physicians in providing optimal and safe care and reducing antibiotic prescribing

Antibody responses to Mycoplasma pneumoniae: protecting against and triggering disease

_Mycoplasma pneumoniae_ (_Mp_) is a major bacterial cause of community-acquired pneumonia (CAP) in children and is even becoming a more important pathogen since the introduction of the pneumococcal conjugate vaccine. In light of the global increase in antibiotic resistance of _Mp_, the main goal is to clarify the pathogenesis of this infection to better understand the need and efficacy of antimicrobial treatment for this CAP and to develop diagnostic and therapeutic strategies for _Mp_-associated disease. Vaccination may be a promising alternative to antibiotics. However, to develop optimal approaches to vaccination against _Mp_ it is critical to understand the immune mechanisms that may contribute to protection and/or immunopathology. The main objective of this thesis was to determine the role of antibodies to _Mp_ in respiratory tract carriage, pulmonary infection, and extrapulmonary nervous system disease (encephalitis and Guillain-Barré syndrome), where an antibody-mediated pathogenesis has been suggested. We demonstrated in this thesis that the infection-induced _Mp_-specific antibody response is essential to clear pulmonary _Mp_ infection, but has a limited effect on _Mp_ carriage in the URT. Our data indicate that the humoral response to _Mp_ derived glycolipids is redundant for pulmonary clearance of _Mp_. The hypothesis that the _Mp_-induced IgG response against the major myelin glycolipid galactocerebroside (GalC) response turns autoimmune is not only of importance to understand _Mp_-associated immune-mediated diseases as encephalitis and Guillain-Barré syndrome, but also to construct _Mp_-targeting vaccines, as based on these findings such vaccines may include _Mp_-derived protein antigens rather than lipids thereby avoiding the induction of potential autoimmune anti-glycolipid antibodies. Overall, the results in this thesis pave the way for improved d

Impact of rapid enterovirus polymerase chain reaction testing on management of febrile young infants < 90 days of age with aseptic meningitis

BACKGROUND Diagnostic evaluation of febrile young infants is challenging. Empirical antimicrobial treatment is therefore common practice in this setting despite high percentage of causative viral infections. The objective of this study was to investigate the impact of rapid enterovirus cerebrospinal fluid polymerase chain reaction (CSF EV PCR) test on hospital length of stay (LOS) and antimicrobial treatment duration in young febrile infants. METHODS Retrospective observational study comparing duration of antimicrobial treatment and hospital LOS before (May 1, 2014 - May 30, 2015, untested group) and after (June 1, 2015 - June 30, 2017, tested group) the introduction of rapid CSF EV PCR testing in infants < 90 days of age presenting with fever and CSF pleocytosis at the University Children's Hospital Zurich. Additionally, the same variables were compared after test introduction between CSF EV PCR positive and negative children. RESULTS One hundred twenty-eight children were enrolled in the study, 58 before and 70 after the introduction of rapid CSF EV PCR testing. Duration of antimicrobial treatment was significantly shortened in EV positive (n = 42) compared to both EV negative (n = 28) (median 18 h and 48 h, respectively, p < 0.001) and untested patients (n = 58) (median 18 h and 48 h, respectively, p < 0.001), and also in tested compared to untested group patients (median 36 vs 48 h, p < 0.001). Hospital LOS was significantly shortened in EV positive compared to EV negative patients (median 3 days and 4 days respectively, p = 0.013), while an overall reduction was not observed between tested and untested group patients. CONCLUSIONS In this study we demonstrate that antimicrobial treatment duration could be significantly shortened in neonates and young infants < 90 days of age with aseptic meningitis after the introduction of a rapid CSF EV PCR test compared to untested patients before test introduction

Frequency and Clinical Presentation of Mucocutaneous Disease Due to Mycoplasma pneumoniae Infection in Children With Community-Acquired Pneumonia

Importance The diagnosis of Mycoplasma pneumoniae infection as the cause of mucocutaneous disease is challenging because current diagnostic tests are not able to differentiate M pneumoniae infection from carriage. Objective To examine the frequency and clinical presentation of M pneumoniae-induced mucocutaneous disease in children with community-acquired pneumonia (CAP) using improved diagnostics. Design, Setting, and Participants This prospective, longitudinal cohort study included 152 children aged 3 to 18 years with CAP enrolled in a CAP study from May 1, 2016, to April 30, 2017, at the University Children's Hospital Zurich. Children were inpatients or outpatients with clinically defined CAP according to the British Thoracic Society guidelines. Data analysis was performed from July 10, 2017, to June 29, 2018. Main Outcomes and Measures Frequency and clinical presentation of M pneumoniae-induced mucocutaneous disease in childhood CAP. Mycoplasma pneumoniae infection was diagnosed by polymerase chain reaction (PCR) of oropharyngeal samples and confirmed with the measurement of specific peripheral blood IgM antibody-secreting cells by enzyme-linked immunospot assay to differentiate M pneumoniae-infected patients from carriers with CAP caused by other pathogens. Mucocutaneous disease was defined as any eruptive lesion that involved skin and/or mucous membranes occurring during the CAP episode. Results Among 152 enrolled children with CAP (median [interquartile range] age, 5.7 [4.3-8.9] years; 84 [55.3%] male), 44 (28.9%) tested positive for M pneumoniae by PCR; of these, 10 children (22.7%) developed mucocutaneous lesions. All 10 patients with mucocutaneous eruptions tested positive for specific IgM antibody-secreting cells. Skin manifestations were found in 3 cases (2.8%) of M pneumoniae PCR-negative CAP (P < .001). The spectrum of M pneumoniae-induced mucocutaneous disease included M pneumoniae-induced rash and mucositis (3 cases [6.8%]), urticaria (2 cases [4.5%]), and maculopapular skin eruptions (5 cases [11.4%]). Two patients had ocular involvement as the sole mucosal manifestation (bilateral anterior uveitis and nonpurulent conjunctivitis). Patients with M pneumoniae-induced mucocutaneous disease had longer duration of prodromal fever (median [interquartile range], 10.5 [8.3-11.8] vs 7.0 [5.5-9.5] days; P = .02) and higher C-reactive protein levels (median [interquartile range], 31 [22-59] vs 16 [7-23] mg/L; P = .04) than patients with CAP due to M pneumoniae without mucocutaneous manifestations. They were also more likely to require oxygen (5 [50%] vs 1 [5%]; P = .007), to require hospitalization (7 [70%] vs 4 [19%]; P = .01), and to develop long-term sequelae (3 [30%] vs 0; P = .03). Conclusions and Relevance Mucocutaneous disease occurred significantly more frequently in children with CAP due to M pneumoniae than in children with CAP of other origins. Mycoplasma pneumoniae-induced mucocutaneous disease was associated with increased systemic inflammation, morbidity, and a higher risk of long-term sequelae