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Klin Padiatr 2005; 217: 120-129
DOI: 10.1055/s-2005-872506
Therapie von Infektionen in der Kinderonkologie

© Georg Thieme Verlag Stuttgart · New York

Diagnostik und Therapie von ZNS-Infektionen bei pädiatrischen onkologischen Patienten

Diagnosis and Management of Central Nervous System Infections in Pediatric Cancer PatientsP. Hernárz Driever1 , S. Reich1
  • 1Klinik für Pädiatrie mit Schwerpunkt Onkologie und Hämatologie, Charité-Universitätsmedizin Berlin
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Publication History

Publication Date:
15 November 2005 (online)

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Zusammenfassung

Infektionen des zentralen Nervensystems (ZNS) sind eine der häufigsten Ursachen für neurologische Defizite bei pädiatrisch-onkologischen Patienten. Nicht immer manifestieren sich die Symptome eindeutig und erlauben daher keine scharfe Trennung von mannigfaltigen Differenzialdiagnosen. Die wiederholte klinisch-neurologische Untersuchung ermöglicht die gezielte Auswahl der notwendigen laborchemischen und neuroradiologischen Maßnahmen sowie der Erregerdiagnostik. Aufgrund der hohen Mortalität sowie Folgemorbidität bei verzögert antiinfektiös behandelten Patienten ist eine empirische Therapie mit adäquaten Dosen notwendig, bis diagnostische Hinweise zur spezifischen Behandlung führen. Die vorliegende Arbeit enthält Empfehlungen der Arbeitsgruppe „Infektionen bei immunsupprimierten Kindern” der Deutschen Gesellschaft für Pädiatrische Infektiologie (DGPI) und der Deutschen Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH) zu Diagnosik und Therapie von ZNS-Infektionen bei immunsupprimierten Kindern.

Abstract

Infections of the central nervous system (CNS) are a common cause of neurological abnormalities in pediatric oncology patients apart from cancer disease of the CNS. Often symptoms do not present unequivocally, impeding a clear distinction from other differential diagnosis. Repeated neurological examinations of the patient allow selecting the necessary laboratory tests and imaging techniques. As delayed antiinfectious treatment is associated with high mortality and severe sequelae of survivors, patients do need empirical therapy using adequate doses until diagnostic results allow a more specific treatment. This article provides the recommendations of the Infectious Diseases Working Party of the German Society for Pediatric Infectious Diseases (DGPI) and the German Society for Pediatric Hematology/Oncology (GPOH) for diagnosis and treatment of infections of the CNS in immunocompromised patients.

Schlüsselwörter

zentrales Nervensystem - Infektionen - Onkologie - Kinder

Key words

central nervous system - infections - oncology - children

Literatur

  • 1 Archer G L, Climo M W. Antimicrobial susceptibility of coagulase-negative staphylococci.  Antimicrob Agents Chemother. 1994;  38 2231-2237
    PubMedGoogle Scholar
  • 2 Ashwal S. Neurologic evaluation of the patient with acute bacterial meningitis.  Neurol Clin. 1995;  13 549-577
    PubMedGoogle Scholar
  • 3 Bayston R. Epidemiology, diagnosis, treatment, and prevention of cerebrospinal fluid shunt infections.  Neurosurg Clin N Am. 2001;  12 703-708
    Google Scholar
  • 4 Beal M F, O'Carroll C P, Kleinman G M. et al . Aspergillosis of the nervous system.  Neurology. 1982;  32 473-479
    PubMedGoogle Scholar
  • 5 Bonsu B K, Harper M B. Fever interval before diagnosis, prior antibiotic treatment, and clinical outcome for young children with bacterial meningitis.  Clin Infect Dis. 2001;  32 566-572
    CrossrefPubMedGoogle Scholar
  • 6 Brook I. Anaerobic infections in children.  Microbes Infect. 2002;  4 1271-1280
    CrossrefPubMedGoogle Scholar
  • 7 Brook I. Meningitis and shunt infection caused by anaerobic bacteria in children.  Pediatr Neurol. 2002;  26 99-105
    CrossrefPubMedGoogle Scholar
  • 8 Brookhouser P E, Auslander M C, Meskan M E. The pattern and stability of postmeningitic hearing loss in children.  Laryngoscope. 1988;  98 940-948
    PubMedGoogle Scholar
  • 9 Buxhofer V, Ruckser R, Kier P. et al . Successful treatment of invasive mould infection affecting lung and brain in an adult suffering from acute leukaemia.  Eur J Haematol. 2001;  67 128-132
    CrossrefPubMedGoogle Scholar
  • 10 Calfee D P, Wispelwey B. Brain abscess.  Semin Neurol. 2000;  20 353-360
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Camarata P J, Dunn D L, Farney A C. et al . Continual intracavitary administration of amphotericin B as an adjunct in the treatment of aspergillus brain abscess: case report and review of the literature.  Neurosurgery. 1992;  31 575-579
    CrossrefPubMedGoogle Scholar
  • 12 Chamberlain M C, Kormanik P A, Barba D. Complications associated with intraventricular chemotherapy in patients with leptomeningeal metastases.  J Neurosurg. 1997;  87 694-699
    CrossrefPubMedGoogle Scholar
  • 13 Chimelli L, Mahler-Araujo M B. Fungal infections.  Brain Pathol. 1997;  7 613-627
    PubMedGoogle Scholar
  • 14 Clemons K V, Sobel R A, Williams P L. et al . Comparative toxicities and pharmacokinetics of intrathecal lipid (amphotericin B colloidal dispersion) and conventional deoxycholate formulations of amphotericin B in rabbits.  Antimicrob Agents Chemother. 2001;  45 612-615
    CrossrefPubMedGoogle Scholar
  • 15 de Montalembert M. [Bacterial meningitis in children: how many lumbar punctures?].  Pediatrie. 1993;  48 17-19
    PubMedGoogle Scholar
  • 16 Denning D W, Stevens D A. Antifungal and surgical treatment of invasive aspergillosis: review of 2 121 published cases.  Rev Infect Dis. 1990;  12 1147-1201
    CrossrefPubMedGoogle Scholar
  • 17 Dooley D P, Carpenter J L, Rademacher S. Adjunctive corticosteroid therapy for tuberculosis: a critical reappraisal of the literature.  Clin Infect Dis. 1997;  25 872-887
    CrossrefPubMedGoogle Scholar
  • 18 Duke T, Mokela D, Frank D. et al . Management of meningitis in children with oral fluid restriction or intravenous fluid at maintenance volumes: a randomised trial.  Ann Trop Paediatr. 2002;  22 145-157
    CrossrefPubMedGoogle Scholar
  • 19 Einsele H, Bertz H, Beyer J. et al . Infectious complications after allogeneic stem cell transplantation: epidemiology and interventional therapy strategies - guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO).  Ann Hematol. 2003;  82 S 175-S 185
    PubMedGoogle Scholar
  • 20 Elgamal E A, Murshid W R. Intracavitary administration of amphotericin B in the treatment of cerebral aspergillosis in a non immune-compromised patient: case report and review of the literature.  Br J Neurosurg. 2000;  14 137-141
    CrossrefPubMedGoogle Scholar
  • 21 Farr B M, Scheld W M. Nosocomial meningitis.  Serious Hospital Inf. 1998;  10 1-7
    PubMedGoogle Scholar
  • 22 Fernandez-Viladrich P, Corbella X, Corral L. et al . Successful treatment of ventriculitis due to carbapenem-resistant Acinetobacter baumannii with intraventricular colistin sulfomethate sodium.  Clin Infect Dis. 1999;  28 916-917
    PubMedGoogle Scholar
  • 23 Guppy K H, Thomas C, Thomas K. et al . Cerebral fungal infections in the immunocompromised host: a literature review and a new pathogen - Chaetomium atrobrunneum: case report.  Neurosurgery. 1998;  43 1463-1469
    CrossrefPubMedGoogle Scholar
  • 24 Hall W A, Martinez A J, Dummer J S. et al . Nocardial brain abscess: diagnostic and therapeutic use of stereotactic aspiration.  Surg Neurol. 1987;  28 114-118
    PubMedGoogle Scholar
  • 25 Hedlund G L, Boyer R S. Neuroimaging of postnatal pediatric central nervous system infections.  Semin Pediatr Neurol. 1999;  6 299-317
    PubMedGoogle Scholar
  • 26 Kanchanapoom T, Koirala J, Goodrich J. et al . Treatment of central nervous system infection by vancomycin-resistant enterococcus faecium.  Diagn Microbiol Infect Dis. 2003;  45 213-215
    CrossrefPubMedGoogle Scholar
  • 27 Kaplan K. Brain abscess.  Med Clin North Am. 1985;  69 345-360
    PubMedGoogle Scholar
  • 28 Kaplan S L. Clinical presentations, diagnosis, and prognostic factors of bacterial meningitis.  Infect Dis Clin North Am. 1999;  13 579-594
    CrossrefPubMedGoogle Scholar
  • 29 Klibanov O M, Filicko J E, DeSimone J A. et al . Sensorineural hearing loss associated with intrathecal vancomycin.  Ann Pharmacother. 2003;  37 61-65
    CrossrefPubMedGoogle Scholar
  • 30 Krupova Y, Sejnova D, Dzatkova J. et al . Prospective study on fungemia in children with cancer: analysis of 35 cases and comparison with 130 fungemias in adults.  Support Care Cancer. 2000;  8 427-430
    CrossrefPubMedGoogle Scholar
  • 31 LePage E. Using a ventricular reservoir to instill amphotericin B.  J Neurosci Nurs. 1993;  25 212-217
    PubMedGoogle Scholar
  • 32 Link H, Bohme A, Cornely O A. et al . Antimicrobial therapy of unexplained fever in neutropenic patients - guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO), Study Group Interventional Therapy of Unexplained Fever, Arbeitsgemeinschaft Supportivmassnahmen in der Onkologie (ASO) of the Deutsche Krebsgesellschaft (DKG-German Cancer Society).  Ann Hematol. 2003;  82 S 105-S 117
    PubMedGoogle Scholar
  • 33 Lipton J D, Schafermeyer R W. Evolving concepts in pediatric bacterial meningitis - Part I: Pathophysiology and diagnosis.  Ann Emerg Med. 1993;  22 1602-1615
    PubMedGoogle Scholar
  • 34 Lukes S A, Posner J B, Nielsen S. et al . Bacterial infections of the CNS in neutropenic patients.  Neurology. 1984;  34 269-275
    PubMedGoogle Scholar
  • 35 Lutsar I, McCracken G H, Friedland I R. Antibiotic pharmacodynamics in cerebrospinal fluid.  Clin Infect Dis. 1998;  27 1117-1127
    PubMedGoogle Scholar
  • 36 Marchiori C, Tonon E, Boscolo Rizzo P. et al . [Brain abscesses after extracranial infections of the head and neck area].  Hno. 2003;  51 813-822
    CrossrefPubMedGoogle Scholar
  • 37 Maschmeyer G. Interventional antimicrobial therapy in febrile neutropenic patients.  Diagn Microbiol Infect Dis. 1999;  34 205-212
    CrossrefPubMedGoogle Scholar
  • 38 Mathisen G E, Johnson J P. Brain abscess.  Clin Infect Dis. 1997;  25 763-779
    PubMedGoogle Scholar
  • 39 Matsubara H, Makimoto A, Higa T. et al . Successful treatment of meningoencephalitis caused by methicillin-resistant Staphylococcus aureus with intrathecal vancomycin in an allogeneic peripheral blood stem cell transplant recipient.  Bone Marrow Transplant. 2003;  31 65-67
    CrossrefPubMedGoogle Scholar
  • 40 Mayhall C G, Archer N H, Lamb V A. et al . Ventriculostomy-related infections. A prospective epidemiologic study.  N Engl J Med. 1984;  310 553-559
    CrossrefPubMedGoogle Scholar
  • 41 Mechleb B, Khater F, Eid A. et al . Late onset Ommaya reservoir infection due to Staphylococcus aureus: case report and review of Ommaya Infections.  J Infect. 2003;  46 196-198
    CrossrefPubMedGoogle Scholar
  • 42 Mikrobiologie DGfHu .Infektionen des Zentralnervensystems. Qualitätsstandards in der mikrobiologisch-infektiologischen Diagnostik. Urban und Fischer, München 2001
    Google Scholar
  • 43 Moller K, Larsen F S, Bie P. et al . The syndrome of inappropriate secretion of antidiuretic hormone and fluid restriction in meningitis - how strong is the evidence?.  Scand J Infect Dis. 2001;  33 13-26
    PubMedGoogle Scholar
  • 44 Nau R, Bruck W. Neuronal injury in bacterial meningitis: mechanisms and implications for therapy.  Trends Neurosci. 2002;  25 38-45
    CrossrefPubMedGoogle Scholar
  • 45 Nau R, Sorgel F, Prange H W. Pharmacokinetic optimisation of the treatment of bacterial central nervous system infections.  Clin Pharmacokinet. 1998;  35 223-246
    PubMedGoogle Scholar
  • 46 Nenoff P, Kellermann S, Schober R. et al . Rhinocerebral zygomycosis following bone marrow transplantation in chronic myelogenous leukaemia. Report of a case and review of the literature.  Mycoses. 1998;  41 365-372
    PubMedGoogle Scholar
  • 47 Neurologie DGf .Leitlinien für Diagnostik und Therapie in der Neurologie. 2. Überarbeitung 2003
    Google Scholar
  • 48 Neuropädiatrie Gf. Deutsche Gesellschaft für Kinderheilkunde und Jugendmedizin .Leitlinien Kinderheilkunde und Jugendmedizin. Urban und Fischer, München 2001
    Google Scholar
  • 49 Paris M M, Hickey S M, Uscher M I. et al . Effect of dexamethasone on therapy of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis.  Antimicrob Agents Chemother. 1994;  38 1320-1324
    CrossrefPubMedGoogle Scholar
  • 50 Pfausler B, Spiss H, Beer R. et al . Treatment of staphylococcal ventriculitis associated with external cerebrospinal fluid drains: a prospective randomized trial of intravenous compared with intraventricular vancomycin therapy.  J Neurosurg. 2003;  98 1040-1044
    CrossrefPubMedGoogle Scholar
  • 51 Pfisterer W, Muhlbauer M, Czech T. et al . Early diagnosis of external ventricular drainage infection: results of a prospective study.  J Neurol Neurosurg Psychiatry. 2003;  74 929-932
    CrossrefPubMedGoogle Scholar
  • 52 Pomeroy S L, Holmes S J, Dodge P R. et al . Seizures and other neurologic sequelae of bacterial meningitis in children.  N Engl J Med. 1990;  323 1651-1657
    PubMedGoogle Scholar
  • 53 Pruitt A A. Nervous system infections in patients with cancer.  Neurol Clin. 2003;  21 193-219
    CrossrefPubMedGoogle Scholar
  • 54 Saez-Llorens X. Brain abscess in children.  Semin Pediatr Infect Dis. 2003;  14 108-114
    CrossrefPubMedGoogle Scholar
  • 55 Saez-Llorens X, McCracken G H. Bacterial meningitis in children.  Lancet. 2003;  361 2139-2148
    CrossrefPubMedGoogle Scholar
  • 56 Scholz H, Behloradsky B H, Heininger U. et al .DGPI Handbuch Infektionen bei Kindern und Jugendlichen. 4. Aufl. Futuramed-Verlag, München 2004
    Google Scholar
  • 57 Schroten H. Diagnostik und Therapie der bakteriellen Meningitis.  Monatsschrift Kinderheilkd. 2004;  152 382-390
    CrossrefPubMedGoogle Scholar
  • 58 Segal-Maurer S, Mariano N, Qavi A. et al . Successful treatment of ceftazidime-resistant Klebsiella pneumoniae ventriculitis with intravenous meropenem and intraventricular polymyxin B: case report and review.  Clin Infect Dis. 1999;  28 1134-1138
    PubMedGoogle Scholar
  • 59 Sell S H. Long term sequelae of bacterial meningitis in children.  Pediatr Infect Dis. 1983;  2 90-93
    PubMedGoogle Scholar
  • 60 Shah S, Ohlsson A, Shah V. Intraventricular antibiotics for bacterial meningitis in neonates. Cochrane Database Syst Rev 2004; CD004496
    Google Scholar
  • 61 Snedeker J D, Kaplan S L, Dodge P R. et al . Subdural effusion and its relationship with neurologic sequelae of bacterial meningitis in infancy: a prospective study.  Pediatrics. 1990;  86 163-170
    PubMedGoogle Scholar
  • 62 Sommers L M, Hawkins D S. Meningitis in pediatric cancer patients: a review of forty cases from a single institution.  Pediatr Infect Dis J. 1999;  18 902-907
    CrossrefPubMedGoogle Scholar
  • 63 Stapleton S R, Bell B A, Uttley D. Stereotactic aspiration of brain abscesses: is this the treatment of choice?.  Acta Neurochir (Wien). 1993;  121 15-19
    CrossrefPubMedGoogle Scholar
  • 64 Steiger H J, Reuelen H J. Manual Neurochirurgie. Ecomed, Landsberg 1999
    Google Scholar
  • 65 Syrogiannopoulos G A, Lourida A N, Theodoridou M C. et al . Dexamethasone therapy for bacterial meningitis in children: 2- versus 4-day regimen.  J Infect Dis. 1994;  169 853-858
    PubMedGoogle Scholar
  • 66 Talan D A, Zibulewsky J. Relationship of clinical presentation to time to antibiotics for the emergency department management of suspected bacterial meningitis.  Ann Emerg Med. 1993;  22 1733-1738
    PubMedGoogle Scholar
  • 67 Tan T Y, Pitman I, Penrose-Stevens A. et al . Treatment of a vancomycin-resistant Enterococcus faecium ventricular drain infection with quinupristin/dalfopristin and review of the literature.  J Infect. 2000;  41 95-97
    PubMedGoogle Scholar
  • 68 Tunkel A R, Scheld W M. Acute bacterial meningitis.  Lancet. 1995;  346 1675-1680
    CrossrefPubMedGoogle Scholar
  • 69 de Beek D van, de Gans J, McIntyre P. et al .Corticosteroids in acute bacterial meningitis. Cochrane Database Syst Rev 2003; CD004305
    Google Scholar
  • 70 den Berg H van, Gerritsen E J, Haraldsson A. et al . Changes in cell and protein content of cerebrospinal fluid in children with acute lymphoblastic leukaemia after allogeneic bone marrow transplantation.  Bone Marrow Transplant. 1993;  12 615-619
    PubMedGoogle Scholar
  • 71 Wald E R, Kaplan S L, Mason E O. et al . Dexamethasone therapy for children with bacterial meningitis. Meningitis Study Group.  Pediatrics. 1995;  95 21-28
    PubMedGoogle Scholar
  • 72 Williamson J C, Glazier S S, Peacock J E. Successful treatment of ventriculostomy-related meningitis caused by vancomycin-resistant Enterococcus with intravenous and intraventricular quinupristin/dalfopristin.  Clin Neurol Neurosurg. 2002;  104 54-56
    CrossrefPubMedGoogle Scholar
  • 73 Yaramis A, Gurkan F, Elevli M. et al . Central nervous system tuberculosis in children: a review of 214 cases.  Pediatrics. 1998;  102 E 49
    PubMedGoogle Scholar
  • 74 Yogev R. Cerebrospinal fluid shunt infections: a personal view.  Pediatr Infect Dis. 1985;  4 113-118
    PubMedGoogle Scholar

Dr. Pablo Hernáiz Driever

Klinik für Pädiatrie mit Schwerpunkt Onkologie und Hämatologie · Charité-Universitätsmedizin Berlin

Augustenburger Platz 1

D-13353 Berlin

Phone: 0 30/4 50 66 61 73

Fax: 0 30/4 50 56 69 06

Email: pablo.hernaiz@charite.de

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