Diagnostik und Therapie von ZNS-Infektionen bei pädiatrischen onkologischen Patienten

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
• 2 Ashwal S. Neurologic evaluation of the patient with acute bacterial meningitis.  Neurol Clin. 1995;  13 549-577
• 3 Bayston R. Epidemiology, diagnosis, treatment, and prevention of cerebrospinal fluid shunt infections.  Neurosurg Clin N Am. 2001;  12 703-708
• 4 Beal M F, O'Carroll C P, Kleinman G M. et al . Aspergillosis of the nervous system.  Neurology. 1982;  32 473-479
• 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
• 6 Brook I. Anaerobic infections in children.  Microbes Infect. 2002;  4 1271-1280
• 7 Brook I. Meningitis and shunt infection caused by anaerobic bacteria in children.  Pediatr Neurol. 2002;  26 99-105
• 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
• 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
• 10 Calfee D P, Wispelwey B. Brain abscess.  Semin Neurol. 2000;  20 353-360
• 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
• 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
• 13 Chimelli L, Mahler-Araujo M B. Fungal infections.  Brain Pathol. 1997;  7 613-627
• 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
• 15 de Montalembert M. [Bacterial meningitis in children: how many lumbar punctures?].  Pediatrie. 1993;  48 17-19
• 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
• 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
• 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
• 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
• 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
• 21 Farr B M, Scheld W M. Nosocomial meningitis.  Serious Hospital Inf. 1998;  10 1-7
• 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
• 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
• 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
• 25 Hedlund G L, Boyer R S. Neuroimaging of postnatal pediatric central nervous system infections.  Semin Pediatr Neurol. 1999;  6 299-317
• 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
• 27 Kaplan K. Brain abscess.  Med Clin North Am. 1985;  69 345-360
• 28 Kaplan S L. Clinical presentations, diagnosis, and prognostic factors of bacterial meningitis.  Infect Dis Clin North Am. 1999;  13 579-594
• 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
• 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
• 31 LePage E. Using a ventricular reservoir to instill amphotericin B.  J Neurosci Nurs. 1993;  25 212-217
• 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
• 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
• 34 Lukes S A, Posner J B, Nielsen S. et al . Bacterial infections of the CNS in neutropenic patients.  Neurology. 1984;  34 269-275
• 35 Lutsar I, McCracken G H, Friedland I R. Antibiotic pharmacodynamics in cerebrospinal fluid.  Clin Infect Dis. 1998;  27 1117-1127
• 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
• 37 Maschmeyer G. Interventional antimicrobial therapy in febrile neutropenic patients.  Diagn Microbiol Infect Dis. 1999;  34 205-212
• 38 Mathisen G E, Johnson J P. Brain abscess.  Clin Infect Dis. 1997;  25 763-779
• 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
• 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
• 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
• 42 Mikrobiologie DGfHu .Infektionen des Zentralnervensystems. Qualitätsstandards in der mikrobiologisch-infektiologischen Diagnostik. Urban und Fischer, München 2001
• 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
• 44 Nau R, Bruck W. Neuronal injury in bacterial meningitis: mechanisms and implications for therapy.  Trends Neurosci. 2002;  25 38-45
• 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
• 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
• 47 Neurologie DGf .Leitlinien für Diagnostik und Therapie in der Neurologie. 2. Überarbeitung 2003
• 48 Neuropädiatrie Gf. Deutsche Gesellschaft für Kinderheilkunde und Jugendmedizin .Leitlinien Kinderheilkunde und Jugendmedizin. Urban und Fischer, München 2001
• 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
• 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
• 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
• 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
• 53 Pruitt A A. Nervous system infections in patients with cancer.  Neurol Clin. 2003;  21 193-219
• 54 Saez-Llorens X. Brain abscess in children.  Semin Pediatr Infect Dis. 2003;  14 108-114
• 55 Saez-Llorens X, McCracken G H. Bacterial meningitis in children.  Lancet. 2003;  361 2139-2148
• 56 Scholz H, Behloradsky B H, Heininger U. et al .DGPI Handbuch Infektionen bei Kindern und Jugendlichen. 4. Aufl. Futuramed-Verlag, München 2004
• 57 Schroten H. Diagnostik und Therapie der bakteriellen Meningitis.  Monatsschrift Kinderheilkd. 2004;  152 382-390
• 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
• 59 Sell S H. Long term sequelae of bacterial meningitis in children.  Pediatr Infect Dis. 1983;  2 90-93
• 60 Shah S, Ohlsson A, Shah V. Intraventricular antibiotics for bacterial meningitis in neonates. Cochrane Database Syst Rev 2004; CD004496
• 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
• 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
• 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
• 64 Steiger H J, Reuelen H J. Manual Neurochirurgie. Ecomed, Landsberg 1999
• 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
• 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
• 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
• 68 Tunkel A R, Scheld W M. Acute bacterial meningitis.  Lancet. 1995;  346 1675-1680
• 69 de Beek D van, de Gans J, McIntyre P. et al .Corticosteroids in acute bacterial meningitis. Cochrane Database Syst Rev 2003; CD004305
• 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
• 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
• 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
• 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
• 74 Yogev R. Cerebrospinal fluid shunt infections: a personal view.  Pediatr Infect Dis. 1985;  4 113-118