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High risk of streptococcal septicemia after high dose cytosine arabinoside treatment for acute myelogenous leukemia

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Summary

Twenty-nine adult patients with acute myelogenous leukemia AML who received 40 treatment courses with high dose cytosine arabinoside (HD-A), alone or combined with other cytotoxic drugs, for remission induction (RI) or postremission intensive consolidation (IC) were retrospectively analysed for types and severity of infectious complications. In this paper, we report the unusually high rate of streptococcal septicemia in our patients. Of 13 bacteremic infections in a total of 45 infectious episodes, 10 were caused by streptococci (9 viridans streptococci, 1 group B hemolytic streptococcus). Three of them were lethal. After reviewing all documented cases of streptococcal septicemia in the same study period, four additional cases among adult patients with AML were identified. Three of them have had antileukemic chemotherapy without HD-A, while one have had HD-A as a conditioning regimen for bone marrow transplantation. Only three cases were documented to occur in adult patients with AML. Patients treated with HD-A for RI or IC had a significantly lower risk of streptococcal septicemia during previous chemotherapy-associated febrile neutropenic episodes (1/55 vs 10/45;P=0.01). Neither prophylactic regimens including trimethoprim-sulfamethoxazole nor those without it were effective in preventing streptococcal septicemia. Further studies are needed to confirm these data before the value of additional or alternative prophylactic antibiotics is proven necessary.

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Abbreviations

AML:

Acute myelogenous leukemia

HD-A:

High dose cytosine arabinoside

IC:

Postremission intensive consolidation

RI:

Remission induction

References

  1. Amadori S, Papa G, Avvisati G, Fenu S, Monacra B, Petti MC, Pulsoni A, Mandelli F (1984) Sequential combination of high dose Ara-C (HiDAC) and asparaginase (ASP) for the treatment of advanced acute leukemia and lymphoma. Leuk Res 8:729

    Google Scholar 

  2. Appelbaum PC, Beckwith DG, Dipersio JR, Dyke JW, Salventi JF, Stone LL (1983) Enhanced detection of bacteremia with a new BACTEC resin blood culture medium. J Clin Microbiol 17:48

    Google Scholar 

  3. Barnett MJ, Waxman JH (1985) High-dose cytosine arabinoside in the initial treatment of acute leukemia. Semin Oncol 12 [Suppl 3]:133

    Google Scholar 

  4. Bodey GP, Rodriguez V, Chang H, Narboni G (1978) Fever and infection in leukemic patients. Cancer 41:1610

    Google Scholar 

  5. Bodey GP, Bolivar R, Fainstein V (1982) Infectious complications in leukemic patients. Semin Hematol 19:13

    Google Scholar 

  6. Brown AE (1984) Neutropenia, fever and infection. Am J Med 76:421

    Google Scholar 

  7. Brudler O, Heil G, Kurrle E (1985) Hochdosis-Cytosinarabinosid in der Behandlung rezidivierter oder refraktärer akuter myeloischer Leukämien. Onkologie 8:39

    Google Scholar 

  8. Calvo F, DeCastro H, Brice H (1986) Traitement des épisodes infectieux chez les malades neutropéniques par l'association pipéracilline et amikacine. Presse Méd 15:2353

    Google Scholar 

  9. Cantin G, Brennan JK (1984) High-dose cytosine arabinoside for acute nonlymphocytic leukemia. Am J Haematol 16:59

    Google Scholar 

  10. Carney DN, Fossieck BE Jr, Parker RH, Minna JD (1983) Bacteremia due toStaphylococcus aureus in patients with cancer: report of 45 cases in adults and review of the literature. Rev Infect Dis 4:1

    Google Scholar 

  11. Champlin R, Jacobs A, Gale RP, Ho W, Selch M, Lenarsky C, Feig SA (1985) High-dose cytarabine in consolidation chemotherapy or with bone marrow transplantation for patients with acute leukemia: preliminary results. Semin in Oncol 12 [Suppl 3]:190

    Google Scholar 

  12. Cohen J, Donnelly JP, Worsley AM, Catovsky D, Goldman JM, Galton DAG (1983) Septicemia caused by viridans streptococci in neutropenic patients with leukemia. Lancet II:1452

    Google Scholar 

  13. Dekker AW, Rozenberg-Arska M, Sixma JJ, Verhoef J (1981) Prevention of infection by trimethoprim-sulfamethoxazole plus amphotericin B in patients with acute nonlymphocytic leukemia. Ann Int Med 95:555

    Google Scholar 

  14. Early AP, Preisler HD, Slocum H, Rustum YM (1982) A pilot study of high-dose 1-β-D-Arabino-furanosylcytosine for acute leukemia and refractory lymphoma: clinical response and pharmacology. Canc Res 42:1587

    Google Scholar 

  15. Eortc International Antimicrobial Therapy Project Group (1978) Three antibiotic regimens in the treatment of infection in febrile granulocytopenic patients with cancer. J Infect Dis 137:14

    Google Scholar 

  16. Eortc International Antimicrobial Therapy Project Group (1983) Combination of amikacin and carbenicillin with or without cefazolin as empirical treatment of febrile neutropenic patients. J Clin Oncol 1:597

    Google Scholar 

  17. Ettinger LJ, Biener R, Finklestein JZ, Kamalakar P, Jones GR, Avramis VI, Holcenberg JS (1985) Sequential high-dose cytosine arabinoside and L-asparaginase in childhood leukemia in relapse. Semin Oncol 12 [Suppl 3]:155

    Google Scholar 

  18. Everett ED, Hirschmann JV (1977) Transient bacteremia and endocarditis prophylaxis: a review. Medicine 56:61

    Google Scholar 

  19. Gassmann W, Schmitz N, Kayser W, Löffler H (1987) Ultrahochdosierte Zytostatika — Einsatzmöglichkeiten bei akuten Leukämien? Dtsch Med Wochenschr 112:65

    Google Scholar 

  20. Göbel V, Jürgens H, Rosin H, Göbel U (1985) Keimspektrum aus Blutkulturen von krebskranken Kindern unter zytostatischer Therapie. Internationales Symposium Infektionen bei Problemaptienten, Frankfurt/Main, 17 May 1985 (Abstract)

  21. Granowetter L, Wells H, Lange B (1985) Ceftazidime versus cephalothin, carbenicillin and gentamicin as the initial therapy of the febrile neutropenic cancer patient. Internationales Symposium Infektionen bei Problempatienten, Frankfurt/Main, 17 May 1985 (Abstract)

  22. Guiot HFL, Helmig-Schurter AV, van der Meer JW, van Furth R (1986) Selective antimicrobial modulation of the intestinal microbial flora for infection prophylaxis in patients with hematologic malignancies. Scand J Infect Dis 18:153

    Google Scholar 

  23. Hennemann HH (1985) Septikämien bei Leukämien und malignen Lymphomen. Häufigkeit, Erreger, Ursachen. Klin Wochenschr 63:821

    Google Scholar 

  24. Heinrich S (1984) Vergleichende Untersuchungen mit Norfloxacin. Fortschr Antimikr Antineopl Chemother 3–5:597

    Google Scholar 

  25. Henry SA (1984) Chemoprophylaxis of bacterial infections in granulocytopenic patients. Am J Med 76:645

    Google Scholar 

  26. Hensele J, Bostrom B, Weisdorf D, Ramsay N, McGlave P, Kersey J (1984) Streptococcal sepsis in bone marrow transplant recipients. Lancet I:393

    Google Scholar 

  27. Herzig RH, Wolff SN, Lazarus HM, Philipps GL, Karanes C, Herzig GP (1983) High-dose cytosine arabinoside therapy for refractory leukemia. Blood 62:361

    Google Scholar 

  28. Hines JD, Oken MM, Mazza JJ, Keller AM, Streeter RR, Glick JH (1984) High-dose cytosine arabinoside and m-AMSA is effective therapy in relapsed acute nonlymphocytic leukemia. J Clin Oncol 2:545

    Google Scholar 

  29. Hoogkamp-Korstanje JAA (1984) Comparative in vitro activity of five quinoline derivatives and five other antimicrobial agents used in oral therapy. Eur J Clin Microbiol 3:333

    Google Scholar 

  30. Kantarjian H, Dreiker R, Barlogie B, Plunkett W, Alexanian R (1984) High-dose cytosine arabinoside in multiple myeloma. Eur J Canc Clin Oncol 20:227

    Google Scholar 

  31. Kurrle E, Bhaduri S, Krieger D, Gaus W, Heimpel H, Pflieger H, Arnold R, Vanek E (1981) Risk factors for infections of the oropharynx and the respiratory tract in patients with acute leukemia. J Infect Dis 144:128

    Google Scholar 

  32. Kurrle E, Ehninger G, Freund M, Heil G, Hoelzer D, Link H, Mitrou PS (1986) Age adapted induction and intensified consolidation therapy in acute myelogenous leukemia. Onkologie 9:11

    Google Scholar 

  33. Neu HC, Labthavikul P (1982) In vitro activity of norfloxacin, a quinoline carboxylic acid, compared with that of betalactam, aminoglycosides, and trimethoprim. Antimicrob Agents Chemother 22:23

    Google Scholar 

  34. Newman KA, Schimpff SC, Young VM, Wiernik PH (1981) Lessons learned from surveillance cultures in patients with acute nonlymphocytic leukemia. Usefulness for epidemiologic, preventive and therapeutic research. Am J Med 70:423

    Google Scholar 

  35. Nowrousian MR, Seeber S, Müller AA, Anders C, Öhl S, Schmidt CG (1985) Hochdosierte Cytarabin-Behandlung bei akuten Leukämien und Meningiosis leucaemica: Klinik und Pharmakokinetik. Onkologie 8:26

    Google Scholar 

  36. Ognibene FP, Martin SE, Parker MM, Schlesinhger T, Roach P, Burch C, Shelhamer JH, Parillo JE (1986) Adult respiratory distress syndrome in patients with severe neutropenia. N Engl J Med 315:547

    Google Scholar 

  37. Peterson FB, Buckner CD, Clift RA, Lee S, Nelson N, Counts GW, Meyers JD, Sanders JE, Stewart PS, Bensinger WI, Navari R, Thomas ED (1986) Laminar air flow isolation and decontamination: a prospective randomized study of the effects of prophylactic systemic antibiotics in bone marrow transplant patients. Infection 14:115

    Google Scholar 

  38. Pizzo PA, Hathorn JW, Hiemenz J, Browne M, Commers J, Cotton D, Gress J, Longo D, Marshall D, McKnight J, Rubin M, Skelion J, Thaler M (1986) A randomized trial comparing ceftazidim alone with combination antibiotic therapy in cancer patients with fever and neutropenia. N Engl J Med 315:552

    Google Scholar 

  39. Rozenberg-Arska M, Dekker AW, Verhoef J (1985) Ciprofloxacin for selective decontamination of the alimentary tract in patients with acute leukemia during remission induction treatment: the effect on fecal flora. J Infect Dis 152:104

    Google Scholar 

  40. Rudnick SA, Cadman EC, Capizzi RL, Skeel RT, Bertino JR, McIntosh S (1979) High dose cytosine arabinoside (HDARAC) in refractory acute leukemia. Cancer 44:1189

    Google Scholar 

  41. Sanz MA, Such M, Rafecas FJ, Martin G, Santos M (1983)Staphylococcus epidermidis infections in acute myeloblastic leukemia in patients fitted with Hickman catheters. Lancet II:1191

    Google Scholar 

  42. Singer C, Kaplan MH, Armstrong D (1977) Bacteremia and fungemia complicating neoplastic disease: a study of 364 cases. Am J Med 62:731

    Google Scholar 

  43. Van Der Auwera P (1986) In vitro susceptibility of aerobic gram-negative blood culture isolates to oxolinic acid, norfloxacin, ciprofloxacin, enoxacin, pefloxacin, ofloxacin and oxo-enoxacin. Infection 14:142

    Google Scholar 

  44. Verbist L (1986) Comparative in vitro activity of RO 23-6240, a new quinolone, against gram-positive and gram-negative microorganisms. IXth International Congress of Infectious and Parasitic Diseases, Munich, 20–26 July, 1986 (Abstract No 878)

  45. Wade JC, Schimpff SC, Newman KA, Wiernik PH (1982)Staphylococcus epidermidis: an increasing cause of infection in patients with granulocytopenia. Ann Int Med 97:503

    Google Scholar 

  46. Wade JC, DeJongh CA, Newman KA (1983) Selective antimicrobial modulation as prophylaxis against infection during granulocytopenia: trimethoprim-sulfamethoxazole vs nalidixic acid. J Infect Dis 147:624

    Google Scholar 

  47. Willemze R, Zwaan FE, Colpin G, Keuning JJ (1982) High dose cytosine arabinoside in the management of refractory acute leukemia. Scand J Haematol 29:141

    Google Scholar 

  48. Willemze R, Peters WG, van Hennik MB, Fibbe WE, Kootte MM, van Berkel M, Lie R, Rodenburg CJ, Veltkamp JJ (1985) Intermediate and high-dose ARA-C and m-AMSA (or daunorubicin) as remission and consolidation treatment for patients with relapsed acute leukemia and lymphoblastic non-Hodgkin lymphoma. Scand J Haematol 34:83

    Google Scholar 

  49. Winston DJ, Ho WG, Nakao SL, Gale RP, Champlin RE (1986) Norfloxacin versus vancomycin/polymyxin for prevention of infections in granulocytopenic patients. Am J Med 80:884

    Google Scholar 

  50. Wolff SN, Marion J, Stein RS, Fleaner JM, Lazarus HM, Spitzer TR, Philipps GL, Herzig RH, Herzig GP (1985) High-dose cytosine arabinoside and daunorubicin as consolidation therapy for acute nonlymphocytic leukemia in first remission: a pilot study. Blood 65:1407

    Google Scholar 

  51. Zeiler HJ, Grohe K (1984) The in vitro and in vivo activity of ciprofloxacin. Eur J Clin Microbiol 3:339

    Google Scholar 

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  1. Sektion Infektionskrankheiten und Abteilung Innere Medizin III (Hämatologie und Onkologie) Klinikum, Universität Ulm, Germany

    W. Kern, E. Kurrle & E. Vanek

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  1. W. Kern
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  2. E. Kurrle
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  3. E. Vanek
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Kern, W., Kurrle, E. & Vanek, E. High risk of streptococcal septicemia after high dose cytosine arabinoside treatment for acute myelogenous leukemia. Klin Wochenschr 65, 773–780 (1987). https://doi.org/10.1007/BF01743253

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  • DOI: https://doi.org/10.1007/BF01743253

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