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Die Kolonisationsresistenz im Verdauungstrakt, ein bedeutsamer Faktor der antimikrobiellen Chemotherapie von Patienten mit schwerer Immundeffizienz

  • D. Van der Waaij
  • H. G. de Vries-Hospers

Zusammenfassung

Im Zeitraum der letzten 10 Jahre konnten in der antimikrobiellen Behandlung von stark immunsupprimierten Patienten bedeutsame Fortschritte erreicht und eine große Anzahl von Antibiotika mit einer ein breites Spektrum abdeckenden Aktivität entwickelt werden. Die Bedeutung der sofortigen empirischen oder kalkulierten Antibiotikatherapie bei Ausbruch fieberhafter Episoden granulozytopenischer Patienten ist seit den 70er Jahren allgemein anerkannt (EORTC 1978 a). Diese häufig kostenwirksame parenterale Behandlung mit Antibiotikakombinationen (Tattersal et al. 1972; Klastersky et al. 1974; Issel et al. 1979; Schimpff 1979; Menichetti et al. 1986) ist bis zum Ende der Knochenmarksuppression fortzuführen, um die Wahrscheinlichkeit einer Infektion zu vermindern. Hierbei ist allerdings die Möglichkeit der Ausbildung und Selektion von Resistenzphänomenen gegen primär wirksame Antibiotika gegeben, da am Standort potentiell pathogener Bakterien unvermeidlich auch subinhibitorisch wirksame Konzentrationen von Antibiotika auftreten können. Im Fall einer erworbenen Resistenz können die resistenten Bakterien die durch Antibiotika gehemmte Standortflora überwuchern und auf andere Patienten der Station übertragen werden (Schimpff et al. 1972). Dies ist insofern von großer klinischer Bedeutung, da auf einer hämatologischonkologischen Station bei praktisch allen Patienten im Laufe der ersten Wochen einer Remissions-Induktionstherapie Fieber auftritt.

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Literatur

  1. Bartels HA (1953) Monilial infection of the mouth following antibiotic therapy. Oral Surg 7:790–795CrossRefGoogle Scholar
  2. Bodey GP, Buckly M, Sathe YS, Freireich EJ (1966) Quantitative relationship between circulating leukocytes and infections in patients with acute leukemia. Ann Intern Med 64:328–340PubMedGoogle Scholar
  3. Bodey GP, Gehan EA, Freireich EJ (1973) Protected environment and prophylactic antibiotics. N Engl J Med 288:477–483Google Scholar
  4. Buck AC, Cooke EM (1969) The fate of ingested Pseudomonas aeruginosa in normal persons. J Med Microbiol 2:521— 525Google Scholar
  5. Cooke EM, Hettiaratchy GT, Buck AC (1972) Fate of ingested Escherichia coli in normal persons. J Med Microbiol 5:361–369PubMedCrossRefGoogle Scholar
  6. De Vries Hospers HG, Van der Waaij D (1978) Amphotericin B concentrations in saliva after application of 2% amphotericin in orabase. Infection 6:16–20PubMedCrossRefGoogle Scholar
  7. De Vries-Hospers HG, Sleijfer DTh, Mulder NH, Van der Waaij D, Nieweg HO, Van Saene HKF (1981) Bacteriologic aspects of selective decontamination of the digestive tract as a method of infection prevention in granulocytopenic patients. Antimicrob Agents Chemother 19:813–820PubMedGoogle Scholar
  8. De Vries-Hospers HG, Mulder NH, Sleijfer DTh, Van Saene HKF (1982) The effect of amphotericin B lozenges on the presence and number of Candida cells in the oropharynx of neutropenic leukemia patients. Infection 10:71–75PubMedCrossRefGoogle Scholar
  9. De Vries-Hospers HG, Welling GW, Swabb EA, Van der Waaij D (1984) Selective decontamination of the digestive tract with aztreonam: a study in ten healthy volunteers. J Infect Dis 150:636–641PubMedCrossRefGoogle Scholar
  10. De Vries-Hospers HG, Welling GW, Van der Waaij D (1987) Influence of quinolones on throat and faecal flora of healthy volunteers. Pharm Weekbl [Sci] Ed 9 Suppl: 41–44Google Scholar
  11. Dekker AW, Rozenberg-Arska M, Sixma JJ, Verhoef J (1981) Prevention of infection by trimethoprim-sulfamethoxazole plus amphotericin B in patients with acute non-lymphocytic leukemia. N Engl J Med 95:555–559Google Scholar
  12. Donhuijsen K, Samandari S (1985) Tiefe Mykosen bei Leukämien und malignen Lymphomen. Dtsch Med Wochenschr 110:903–907PubMedCrossRefGoogle Scholar
  13. EORTC Gnotobiotic Project Group (Dietrich M, Gaus W, Vossen JM, Van der Waaij D, Wendt F, 1977) Protective isolation and antimicrobial decontamination in patients with high susceptibility to infection. A prospective randomized study of gnotobiotic care in acute leukemia patients. 1: Clinical results. Infection 5:107–114CrossRefGoogle Scholar
  14. EORTC International Antimicrobial Chemotherapy Project Group (1978 a) Three antibiotic regimens in the treatment of infection in febrile granulocytopenic patients with cancer. J Infect Dis 137:14–29Google Scholar
  15. EORTC Gnotobiotic Project Group (1978 b) Protective isolation and antimicrobial decontamination in patients with high susceptibility to infection. A prospective cooperative study of gnotobiotic care in acute leukemia patients. III. The quality of isolation and decontamination. Infection 6:175–191Google Scholar
  16. Ford JM, Gulen MH (1977) Prophylactic granulocyte transfusions. Exp Hematol 5:401–419Google Scholar
  17. Gaya H, Tattersall MHN, Hutchinson RM, Spiers ASD (1973) Changing pattern of infection in cancer patients. Eur J Cancer 9:401–419PubMedCrossRefGoogle Scholar
  18. Giuliano M, Pantosti A, Gentile G, Venditti M, Arcese W, Martino P (1989) Effects on oral and intestinal microfloras of norfloxacin and pefloxacin for selective decontamination in bone marrow transplant patients. Antimicrob Agents Chemother 33:1709–1713PubMedGoogle Scholar
  19. Graw RG, Herzig GP, Perry S, Henderson ES (1972) Normal granulocyte transfusion therapy. Treatment of septicemia due to gramnegative bacteria. N Engl J Med 287:367371Google Scholar
  20. Gurwith MJ, Brunton JL, Lank BA, Ronald AR, Harding GKM (1978) Granulocytopenia in hospitalized patients. I. Prognostic factors and etiology of fever. Am J Med 64: 121–132PubMedCrossRefGoogle Scholar
  21. Herzig RH, Herzig GP, Graw RG, Bull MI, Ray KK (1977) Successful granulocyte transfusion therapy for gramnegative septicemia. A prospective randomized controlled study. N Engl J Med 296:701–705PubMedCrossRefGoogle Scholar
  22. Hofstra W, De Vries-Hospers HG, Van der Waaij D (1982) Concentrations of amphotericin B in faeces and blood of healthy volunteers after oral administration of various doses. Infection 10:223–227PubMedCrossRefGoogle Scholar
  23. Issel BF, Keating KJ, Valdivieso M, Bodey GP (1979) Continuous infusion of tobramycin combined with carbenicillin for infections in cancer patients. Am J Med Sci 227: 311–318CrossRefGoogle Scholar
  24. Karp JE, Dick JD, Merz WG (1988) Systemic infection and colonization with and without prophylactic norfloxacin use over time in the granulocytopenic, acute leukemia patient. Eur J Clin Oncol 24 Suppl 1:5–13Google Scholar
  25. Kern W, Kurrle E, Vanek E (1987) Ofloxacin for prevention of bacterial infections in granulocytopenic patients. Infection 15:427–430PubMedCrossRefGoogle Scholar
  26. Klastersky J, Henry A, Hensgens C, Daneau D (1974) Gramnegative infection in cancer. Study of empiric therapy comparing carbenicillin-cephalotin with and without gentamicin. JAMA 227:45–48PubMedCrossRefGoogle Scholar
  27. Kurrle E, Bhaduri S, Heimpel H (1980) The efficiency of strict reverse isolation and antimicrobial decontamination in remission induction therapy of leukemia. Blut 40:187195Google Scholar
  28. Kurrle E, Bhaduri S, Heimpel H (1981) Risk factors for infections of the oropharynx and the respiratory tract in patients with acute leukemia. J Infect Dis 144:128–136PubMedCrossRefGoogle Scholar
  29. Kurrle E, Dekker AW, Gaus W, Haralambie E, Krieger D, Rozenberg-Arska M, De Vries Hospers HG, Van der Waaij D, Wendt F (1986) Prevention of infection in acute leukemia: a prospective randomized study on the efficacy of two different drug regimens for antimicrobial prophylaxis. Infection 14:226–232PubMedCrossRefGoogle Scholar
  30. Levine AS, Siegel SE, Schreiber AD (1971) Protected environment and prophylactic antibiotic program in chemotherapy of acute leukemia. Am J Med Sci 262:138–159CrossRefGoogle Scholar
  31. Leleux A, Snoeck R, Gerain J, Van der Auwera P, Daneau D, Meunier F (1989) Prevention par la pefloxacin des infections chez les malades cancereux granulocytopenues. La Press Medicinale 18:21–25Google Scholar
  32. Lolekha S (1986) Consequences of treatment of gastro-intestinal infections. Scand J Infect Dis 49:154–159Google Scholar
  33. Mangiaracine A (1951) Oral moniliasis following antibiotic therapy — a warning. N Engl J Med 244:655Google Scholar
  34. Maschmayer G, Haralambie E, Gaus W, Kern W, Dekker AW, De Vries-Hospers HG, Sizoo W, Konig W, Gutzler F, Daenen S (1988) Ciprofloxacin and norfloxacin for decontamination in patients with severe granulocytopenia. Infection 16:98–104CrossRefGoogle Scholar
  35. Menichetti F, Del Favero A, Guerciolini R, Tonato M, Aversa F, Roila F, Frongillo RF, Martelli MF, Davis S, Pauluzzi S (1986) Empiric antimicrobial therapy in febrile granulocytopenic patients. Randomized prospective comparison of amikacin plus piperacillin with or without parenteral trimethoprim/sulfamethoxazole. Infection 14:261–267PubMedCrossRefGoogle Scholar
  36. Meunier-Carpentier F (1982) Significance and clinical manifestations of fungemia. In: Klastersky J (ed) Infections in cancer patients, Raven Press, New York, pp 141–155Google Scholar
  37. Midtvedt T (1985) Microflora-associated characteristics (MACs) and germfree animal characteristics (GACs) in man and animal. Microecol Ther 15:295–302Google Scholar
  38. Mulder JG, Wiersma ME, Welling GW, Van der Waaij D (1984) Low dose oral tobramycin treatment for selective decontamination of the digestive tract; a study in human volunteers. J Antimicrob Chemother 13:495–504PubMedCrossRefGoogle Scholar
  39. Muytjens HL, Van Veldhuizen GL, Welling GW, Van der Ros-van de Repe J, Boerema HBJ, Van der Waaij D (1983) Selective decontamination of the digestive tract by pipemidic acid. Antimicrob Agents Chemother 24:902–904Google Scholar
  40. Nord CE, Kager L, Heimdahl A (1974) Impact of antimicrobial agents on the gastrointestinal microflora and the risk of infections. Am J Med 76:99–106CrossRefGoogle Scholar
  41. Pizzo PhA, Commers J, Cotton D, Gress J, Hathorn J, Hiemenz J, Longo D, Marshall D, Robichaud KJ (1984 a) Approaching the controversies in antibacterial management in cancer patients. Am J Med 76:436–449Google Scholar
  42. Pizzo PhA, Young LS (1984b) Limitations of current antimicrobial therapy in the immunosuppressed host: looking at both sides of the coin. Am J Med 75:101–110CrossRefGoogle Scholar
  43. Remmington JS, Schimpff JS (1981) Please don’t eat the salads. N Engl J Med 304: 433–435CrossRefGoogle Scholar
  44. Rozenberg-Arska M, Dekker AW, Verhoef J (1983) Colistin and trimethoprim-sulfamethoxazole for the prevention of infection in patients in acute non-lymphocytic leukemia. Decrease of the emergence of resistant bacteria. Infection 11:167–169PubMedCrossRefGoogle Scholar
  45. Rozenberg-Arska M, Dekker AW (1987) Ciprofloxacin for infection prevention in patients with acute leukemia. Pharm Weekbl [Sci] 9 Supp1:45–47Google Scholar
  46. Selden R, Lee S, Wang WLL, Bennett JV, Eickhoff TC (1971) Nosocomial klebsiella infections: intestinal colonization as a reservoir. Ann Intern Med 74:657–664PubMedGoogle Scholar
  47. Schimpff SC, Young VM, Greene WH, Vermeulen GD, Moody MR, Wiernik PH (1972) Origin of infection in acute nonlymphocytic leukemia. Significance of hospital acquisition of potential pathogens. Ann Intern Med 77:707–714PubMedGoogle Scholar
  48. Schimpf SC, Greene W, Young VM, Wiernik PH (1974) Significance of Pseudomonas aeruginosa in the patient with leukemia or lymphoma. J Infect Dis 130: S 24—S 31Google Scholar
  49. Schimpff SC (1979) Therapy of infections in patients with granulocytopenia. Med Clin North Am 61:1101–1118Google Scholar
  50. Sleijfer DTh, Mulder NH, De Vries-Hospers HG, Nieweg HO, Fidler V, Van der Waaij D, Van Saene HKF (1980) Infection prevention in granulocytopenic patients by selective decontamination of the digestive tract. Eur J Cancer 16:859–869PubMedCrossRefGoogle Scholar
  51. Smiths J, Prior AP, Arblaster PG (1966) Incidence of candida in hospital in-patients and the effects of antibiotic therapy. Br Med J 1:208–210CrossRefGoogle Scholar
  52. Tattersall MHN, Spiers ASD, Darrell JH (1972) Initial therapy with combination of five antibiotics in febrile patients with leukemia and neutropenia. Lancet I:162–65Google Scholar
  53. Thomas FE, Jackson RT, Mell A, Alford RH (1977) Sequential hospitalwide outbreaks of resistant Serratia and Klebsiella infections. Arch Intern Med 137:581–584PubMedCrossRefGoogle Scholar
  54. Van der Waaij D, Berghuis-de Vries JM, Lekkerkerk van der Wees JEC (1971) Colonization resistance of the digestive tract in conventional and antibiotic treated mice. J Hyg 68: 405–411Google Scholar
  55. Van der Waaij D, Berghuis-de Vries JM (1974) Selective elimination of Enterobacteriaceae species from the digestive tract in mice and monkeys. J Hyg 72:205–211CrossRefGoogle Scholar
  56. Van der Waaij D, Vossen JM, Korthals Altes C, Hartgrink C (1977) Reconventionalization following antibiotic decontamination in man and animals. Am J Clin Nutr 30:1887–1895PubMedGoogle Scholar
  57. Van der Waaij D (1979 a) Colonization resistance of the digestive tract as a major lead in the selection of antibiotics for therapy. In: Van der Waaij D, Verhoef J (eds) New criteria for antimicrobial therapy; maintenance of colonization resistance, Excerpta Medica, Amsterdam-Oxford, pp 271–280Google Scholar
  58. Van der Waaij D, Vossen JM, Hartgrink C, Nieweg HO (1979 b) Polyene antibiotics in the prevention of Candida albicans colonization in the digestive tract of patients with severely decreased resistance to infections. In: Van der Waaij D, Verhoef J (eds) New criteria for antimicrobial prophylaxis: maintenance of digestive tract colonization resistance. Excerpta Medica, Amsterdam-Oxford, pp 135–144Google Scholar
  59. Van der Waaij D (1982 a) Colonization resistance of the digestive tract: clinical consequences and implications. J Antimicrob Chemother 10: 263–270CrossRefGoogle Scholar
  60. Van der Waaij D (1982 b) Gut resistance to colonization: Clinical usefulness of selective use of orally administered antimicrobial and antifungal drugs. In: Klastersky J (ed) Infections in cancer patients, Raven Press, New York, pp 73–85Google Scholar
  61. Van der Waaij D, Hofstra W, Wiegersma N (1982 c) Effect of betalactam antibiotics on the resistance of the digestive tract to colonization. J Infect Dis 146: 417–422CrossRefGoogle Scholar
  62. Van der Waaij D, Aberson J, Thijm HA, Welling GW (1982d) The screening of four aminoglycosides in the selective decontamination of the digestive tract in mice. Infection 88:35–40CrossRefGoogle Scholar
  63. Van der Waaij D (1984) Effect of antibiotics on colonization resistance. In: Easman CSF, Jeljaszewicz J (eds) Medical Microbiology, Academic Press, London, pp 342–346Google Scholar
  64. Van der Waaij D, De Vries-Hospers HG, Welling GW (1986) The influence of antibiotics on gut colonization. J Antimicrob Chemother 18 Suppl C:155–158Google Scholar
  65. Van der Waaij D (1987) Colonization resistance of the digestive tract; mechanism and clinical consequences. Nahrung 5–6:507–517Google Scholar
  66. Van der Waaij D (1988) Selective decontamination of the digestive tract: general principles. Eur J Cancer Clin Oncol 24 Suppl 1:1–3Google Scholar
  67. Van der Waaij D (1989) The ecology of the human intestine and its consequences for overgrowth by pathogens such as Clostridium difficile. Ann Rev Microbiol 43:69–87CrossRefGoogle Scholar
  68. Van Saene HKF, Driessen LHHM (1979) Importance of treatment of Staphylococcus aureus carriership in the prevention and therapy of Staphylococcus aureus infections. In: Van der Waaij D, Verhoef J (eds) New criteria for antimicrobial prophylaxis: maintenance of digestive tract colonization resistance. Excerpta Medica, Amsterdam-Oxford, pp 197–207Google Scholar
  69. Wade JC, De Jongh CA, Newman KA, Crowley J, Wiernik PH, Shimpff SC (1983) Selective antimicrobial modulation as prophylaxis against infection during granulocytopenia: trimethoprim-sulfamethoxazole vs nalidixic acid. J Infect Dis 147:624–634PubMedCrossRefGoogle Scholar
  70. Welling GW (1979) Beta-aspartylglycine, an indicator of decreased colonization resistance? In: New criteria for antimicrobial therapy: maintenance of digestive tract colonisation resistance. Excerpta Medica, Amsterdam Oxford, pp 65–71Google Scholar
  71. Welling GW (1982) Comparison of methods for the detection of a-aspartylglycine in fecal supernatants of leukemic patients treated with antimicrobial agents. J Chromatogr 232:55–62PubMedCrossRefGoogle Scholar
  72. Welling GW, Groen G (1989) Inactivation of aztreonam by faecal supernatants of healthy volunteers as determined by HPLC. J Antimicrob Chemother 24:805–809PubMedCrossRefGoogle Scholar
  73. Wiegersma N, Jansen G, Van der Waaij D (1982) The effect of twelve antimicrobial drugs on the colonization resistance of the digestive tract of mice. J Hyg 88:221–230CrossRefGoogle Scholar
  74. Williams Smith H (1975) Survival of orally administered É. coli in the alimentary canal of man. Nature 225:500–502CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

  • D. Van der Waaij
  • H. G. de Vries-Hospers

There are no affiliations available

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