Empfehlungen zur Prävention der Pneumocystis-carinii-Pneumonie bei Kindern und Jugendlichen mit neoplastischen Erkrankungen

Zusammenfassung.

Die Pneumocystis-carinii-Pneumonie (PCP) ist eine der wichtigsten opportunistischen Infektionen bei Kindern und Jugendlichen mit bösartigen Erkrankungen. Hohes Erkrankungsrisiko und eine beträchtliche Mortalität haben zur Chemoprophylaxe bei Patienten mit hämatologischen Neoplasien und nach allogener hämatopoetischer Stammzelltransplantation geführt. Bei autolog transplantierten Patienten und Patienten mit soliden Tumoren und dosisintensiver Chemotherapie kann aufgrund der ausgeprägten T-Zell-Depletion von einem ähnlich hohen Infektionsrisiko ausgegangen werden. Seit mehr als zwei Jahrzehnten steht mit der Gabe von Trimethoprim/Sulfamethoxazol (TMP/SMX) eine bei krebskranken Kindern und Jugendlichen evaluierte, im Allgemeinen gut verträgliche und nahezu 100 % effektive Chemoprophylaxe der PCP zur Verfügung. Sekundäre, nachgewiesenermaßen weniger wirksame und vorwiegend bei HIV-infizierten Patienten evaluierte Verfahren umfassen die Gabe von Dapson bzw. Atovaquone und die Inhalation von aerosolisiertem Pentamidin-Isethionat. Die vorliegende Arbeit gibt eine Übersicht über die Epidemiologie der PCP bei Kindern und Jugendlichen mit bösartigen Erkrankungen bzw. hämatopoetischer Stammzelltransplantation sowie die verfügbaren Verfahren der Chemoprophylaxe und enthält Empfehlungen zu Indikationen und Modalitäten der Chemoprophylaxe der PCP auf der Basis der Literatur.

Pneumocystis carinii pneumonitis (PCP) is one of the most important opportunistic infections in children and adolescents with cancer. Its high frequency and a considerable mortality have led to primary chemoprophylaxis in patients with hematological malignancies and following allogeneic hematopoietic stem cell transplantation. Although less well characterized, patients with autologous stem cell transplantation and patients with dose-intensive chemotherapy for pediatric solid tumors may have a similarly high risk for PCP based on their profound T-cell depletion. For more than two decades, effective chemoprophylaxis for PCP has been available. Trimethoprim and sulfamethoxazole (TMP/SMX) is the prophylactic modality of first choice. The combination has been shown to be almost 100 % efficacious in pediatric cancer patients at highest risk, and it is usually well tolerated in this setting. Secondary alternatives to TMP/SMX include oral dapsone, oral atovaquone, and aerosolized pentamidine-isethionate. These modalities are less effective than TMP/SMX, and have been evaluated predominantly in HIV-infected patients. This article reviews epidemiology and current approaches to chemoprophylaxis for PCP in children and adolescents with cancer and/or hematopoietic stem cell transplantation, and provides evidence-based guidelines for indications and modalities of PCP prophylaxis in this population.

Krebserkrankung - Empfehlungen - Kinder - Jugendliche - Mykosen - Pneumocystis carinii - Pentamidin - Dapson - Trimethoprim/Sulfamethoxazol - Atovaquone

Cancer - children - mycoses - recommendations - Pneumocystis carinii - trimethoprim/sulfamethoxazole - pentamidine - dapsone - atovaquone

Literatur

• 001 Anderson  J A. Antibiotic drug allergy in children.  Curr Opin Pediatr. 1994;;  6 656-660
• 002 Antinori  A, Murri  R, Ammassari  A, De Luca  A, Linzalone  A, Cingolani  A et al. Aerosolized pentamidine, cotrimoxazole and dapsone-pyrimethamine for primary prophylaxis of Pneumocystis carinii pneumonia and toxoplasmic encephalitis.  AIDS. 1995;;  9 1343-1350
• 003 Allegra  C J, Kovacs  J A, Drake  J C, Swan  J C, Chabner  B A, Masur  H. Activity of antifols against Pneumocystis carinii dihydrofolate reductase and identification of a potent new agent.  J Exp Med. 1987;;  165 926-931
• 004 Barber  B A, Pegram  P S, High  K P. Clindamycin/primaquine as prophylaxis for Pneumocystis carinii pneumonia.  Clin Infect Dis. 1996;;  23 718-722
• 005 Beck  J M, Harmsen  A G. Lymphocytes in host defense against Pneumocystis carinii.  Semin Respir Infect. 1998;;  13 330-338
• 006 Bensousan  T, Garo  B, Islam  S, Bourbigot  B, Cledes  J, Garre  M. Possible transfer of Pneumocystis carinii between kidney transplant recipients.  Lancet. 1990;;  336 1066-1067
• 007 Bozzette  S A, Finkelstein  D M, Spector  S A, Frame  P, Powderly  W G, He  W et al. A randomized trial of three antipneumocystis agents in patients with advanced human immunodeficiency virus infection. NIAID AIDS Clinical Trials Group.  N Engl J Med. 1995;;  332 693-699
• 008 Brazinsky  J H, Phillips  J E. Pneumocystis pneumonia transmission between patients with lymphoma.  JAMA. 1969;;  209 1527
• 009 Browne  M J, Hubbard  S M, Longo  D L, Fisher  R, Wesley  R, Ihde  D C et al. Excess prevalence of Pneumocystis carinii pneumonia in patients treated for lymphoma with combination chemotherapy.  Ann Intern Med. 1986;;  104 338-344
• 010 Byrd  J C, Hargis  J B, Kester  K E, Hospenthal  D R, Knutson  S W, Diehl  L F. Opportunistic pulmonary infections with fludarabine in previously treated patients with low-grade lymphoid malignancies: a role for Pneumocystis carinii pneumonia prophylaxis.  Am J Hematol. 1995;;  49 135-142
• 011 Carr  A, Tindall  B, Brew  B J, Marriott  D J, Harkness  J L, Penny  R, Cooper  D A. Low-dose trimethoprim-sulfamethoxazole prophylaxis for toxoplasmic encephalitis in patients with AIDS.  Ann Intern Med. 1992;;  11 106-111
• 012 Centers for Disease Control .Guidelines for prophylaxis against Pneumocystis carinii pneumonia for persons infected with human immunodeficiency virus. MMWR 1989; 38 Suppl 5: 1-9
• 013 Centers for Disease Control .1995 revised guidelines for prophylaxis against Pneumocystis carinii pneumonia for children infected with or perinatally exposed to human immunodeficiency virus. MMWR 1995; 44 (RR-4): 1-11
• 014 Centers for Disease Control .Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients. MMWR 2000; 49 (RR-10): 1-95
• 015 Chan  C, Montaner  J, Lefebvre  E A, Morey  G, Dohn  M, McIvor  R A et al. Atovaquone suspension compared with aerosolized pentamidine for prevention of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected subjects intolerant of trimethoprim or sulfonamides.  J Infect Dis. 1999;;  180 369-376
• 016 Chanock  S J, Luginbuhl  L M, McIntosh  K, Lipshultz  S E. Life-threatening reaction to trimethoprim/sulfamethoxazole in pediatric human immunodeficiency virus infection.  Pediatrics. 1994;;  93 519-521
• 017 Chave  J P, David  S, Wauters  J P, Van Melle  G, Francioli  P. Transmission of Pneumocystis carinii from AIDS patients to other immunosuppressed patients: a cluster of Pneumocystis carinii pneumonia in renal transplant recipients.  AIDS. 1991;;  5 927-932
• 018 Colby  C, McAfee  S, Sackstein  R, Finkelstein  D, Fishman  J, Spitzer  T. A prospective randomized trial comparing the toxicity and safety of atovaquone with trimethoprim/sulfamethoxazole as Pneumocystis carinii pneumonia prophylaxis following autologous peripheral blood stem cell transplantation.  Bone Marrow Transplant. 1999;;  24 897-902
• 019 Committee on Infectious Diseases .1999 Red Book. 24th edition. American Academy of Pediatrics, Elk Grove Village, Ill; 1999:
• 020 Conte  J E Jr, Golden  J A. Concentrations of aerosolized pentamidine in bronchoalveolar lavage, systemic absorption, and excretion.  Antimicrob Agents Chemother. 1988;;  32 1490-1493
• 021 Cyklis  R, Zielinska  A. Pneumocystis carinii infection in children with acute leukemia and non-Hodgkin malignant lymphoma.  Pediatr Pol. 1983;;  58 337-340
• 022 Dei-Cas  E, Brun-Pascaud  M, Bille-Hansen  V, Allaert  A, Aliouat  E M. Animal models of pneumocystosis.  FEMS Immunol Med Microbiol. 1998;;  22 163-168
• 023 DeVita  V T Jr, Goodell  B, Hubbard  S, Geelhoed  G W, Young  R C. Pneumocystis pneumonia in patients with cancer: clinical setting.  Natl Cancer Inst Monogr. 1976;;  43 41-47
• 024 Edelstein  H, McCabe  R E. Atypical presentations of Pneumocystis carinii pneumonia in patients receiving inhaled pentamidine prophylaxis.  Chest. 1990;;  98 1366-1369
• 025 Edman  J C, Kovacs  J A, Masur  H, Santi  D V, Elwood  H J, Sogin  M L. Ribosomal RNA sequence shows Pneumocystis carinii to be a member of the fungi.  Nature. 1988;;  334 519-522
• 026 El-Sadr  W M, Murphy  R L, Yurik  T M, Luskin-Hawk  R, Cheung  T W, Balfour  H H Jr et al. Atovaquone compared with dapsone for the prevention of Pneumocystis carinii pneumonia in patients with HIV infection who cannot tolerate trimethoprim, sulfonamides, or both. Community Program for Clinical Research on AIDS and the AIDS Clinical Trials Group.  N Engl J Med. 1998;;  339 1889-1895
• 027 Ena  J, Amador  C, Pasquau  F, Carbonell  C, Benito  C, Gutierrez  F, Vilar  A. Once-a-month administration of intravenous pentamidine to patients infected with human immunodeficiency virus as prophylaxis for Pneumocystis carinii pneumonia.  Clin Infect Dis. 1994;;  18 901-904
• 028 Ferrazzini  G, Klein  J, Sulh  H, Chung  D, Griesbrecht  E, Koren  G. Interaction between trimethoprim-sulfamethoxazole and methotrexate in children with leukemia.  J Pediatr. 1990;;  117 823-826
• 029 Fischl  M A, Dickinson  G M. Fansidar prophylaxis of Pneumocystis pneumonia in the acquired immunodeficiency syndrome.  Ann Intern Med. 1986;;  105 629
• 030 Fishman  J A. Prevention of infection due to Pneumocystis carinii.  Antimicrob Agents Chemother. 1998;;  42 995-1004
• 031 Garner  J S. Guideline for isolation precautions in hospitals. The Hospital Infection Control Practices Advisory Committee.  Infect Control Hosp Epidemiol. 1996;;  17 53-80
• 032 Girard  P M, Landman  R, Gaudebout  C, Olivares  R, Saimot  A G, Jelazko  P et al. Dapsone-pyrimethamine compared with aerosolized pentamidine as primary prophylaxis against Pneumocystis carinii pneumonia and toxoplasmosis in HIV infection. The PRIO Study Group.  N Engl J Med. 1993;;  328 1514-1520
• 033 Gluckstein  D, Ruskin  J. Rapid oral desensitization to trimethoprim-sulfamethoxazole (TMP-SMZ): use in prophylaxis for Pneumocystis carinii pneumonia in patients with AIDS who were previously intolerant to TMP-SMZ.  Clin Infect Dis. 1995;;  20 849-853
• 034 Goesch  T R, Gotz  G, Stellbrinck  K H, Albrecht  H, Weh  H J, Hossfeld  D K. Possible transfer of Pneumocystis carinii between immunodeficient patients.  Lancet. 1990;;  336 627
• 035 Groll  A H, Beeg  T, Ehrenberg  A, Kreuz  W D, Kornhuber  B. Pneumocystis-carinii Pneumonie unter inhalativer Pentamidinprophylaxe.  Monatsschr Kinderheilkd. 1994;;  142 491-494
• 036 Groll  A H, Keul  H G, Brodt  R, Schneider  M. AIDS-associated atypical Pneumocystis carinii pneumonia revisited.  Clin Infect Dis. 1998;;  26 1005-1006
• 037 Groll  A H, Müller  F MC. Fortschritte in Prävention und Therapie infektiöser Komplikationen bei Kindern und Jugendlichen mit neoplastischen Erkrankungen.  Klin Pädiatr. 1998;;  210 106-114
• 038 Hardy  W D, Feinberg  J, Finkelstein  D M, Power  M E, He  W, Kaczka  C et al. A controlled trial of trimethoprim-sulfamethoxazole or aerosolized pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. AIDS Clinical Trials Group Protocol 021.  N Engl J Med. 1992;;  327 1842-1848
• 039 Hirschel  B, Lazzarin  A, Chopard  P, Opravil  M, Furrer  H J, Ruttimann  S et al. A controlled study of inhaled pentamidine for primary prevention of Pneumocystis carinii pneumonia.  N Engl J Med. 1991;;  324 1079-1083
• 040 Hughes  W, Dorenbaum  A, Yogev  R, Beauchamp  B, Xu  J, McNamara  J et al. Phase I safety and pharmacokinetics study of micronized atovaquone in human immunodeficiency virus-infected infants and children. Pediatric AIDS Clinical Trials Group.  Antimicrob Agents Chemother. 1998;;  42 1315-1318
• 041 Hughes  W T, Feldman  S, Aur  R J, Verzosa  M S, Hustu  H O, Simone  J V. Intensity of immunosuppressive therapy and the incidence of Pneumocystis carinii pneumonitis.  Cancer. 1975;;  36 2004-2009
• 042 Hughes  W T, Kuhn  S, Chaudhary  S, Feldman  S, Verzosa  M, Aur  R J, Pratt  C, George  S L. Successful chemoprophylaxis for Pneumocystis carinii pneumonitis.  N Engl J Med. 1978;;  297 1419-1426
• 043 Hughes  W T, Price  R A, Kim  H K, Coburn  T P, Grigsby  D, Feldman  S. Pneumocystis carinii pneumonitis in children with malignancies.  J Pediatr. 1973;;  82 404-415
• 044 Hughes  W T, Rivera  G K, Schell  M J, Thornton  D, Lott  L. Successful intermittent chemoprophylaxis for Pneumocystis carinii pneumonitis.  N Engl J Med. 1987;;  316 1627-1632
• 045 Hughes  W T. Current issues in the epidemiology, transmission, and reactivation of Pneumocystis carinii.  Semin Respir Infect. 1998;;  13 283-288
• 046 Hughes  W T. Pneumocystis carinii pneumonia: new approaches to diagnosis, treatment and prevention.  Pediatr Infect Dis J. 1991;;  10 391-399
• 047 Hughes  W T. Use of dapsone in the prevention and treatment of Pneumocystis carinii pneumonia: a review.  Clin Infect Dis. 1998;;  27 191-204
• 048 Ioannidis  J P, Cappelleri  J C, Skolnik  P R, Lau  J, Sacks  H S. A meta-analysis of the relative efficacy and toxicity of Pneumocystis carinii prophylactic regimens.  Arch Intern Med. 1996;;  156 177-188
• 049 Johnson  M P, Goodwin  S D, Shands  J W Jr. Trimethoprim-sulfamethoxazole anaphylactoid reactions in patients with AIDS: case reports and literature review.  Pharmacotherapy. 1990;;  10 413-416
• 050 Jules-Elysee  K M, Stover  D E, Zaman  M B, Bernard  E M, White  D A. Aerosolized pentamidine: effect on diagnosis and presentation of Pneumocystis carinii pneumonia.  Ann Intern Med. 1990;;  112 750-757
• 051 Kashuba  A DM, Bertino  J S. Mechanisms of drug interactions. In Piscitelli SC, Rotvold KA. Drug interactions in infectious diseases (1st ed). Humana Press, Totowa, NJ; 2001;: pp 13-38
• 052 Kay  R, DuBois  R E. Clindamycin/primaquine therapy and secondary prophylaxis against Pneumocystis carinii pneumonia in patients with AIDS.  South Med J. 1990;;  83 403-404
• 053 Kazanjian  P, Locke  A B, Hossler  P A, Lane  B R, Bartlett  M S, Smith  J W et al. Pneumocystis carinii mutations associated with sulfa and sulfone prophylaxis failures in AIDS patients.  AIDS. 1998;;  12 873-878
• 054 Kovacs  J A, Hiemenz  J W, Macher  A M, Stover  D, Murray  H W, Shelhamer  J et al. Pneumocystis carinii pneumonia: a comparison between patients with the acquired immunodeficiency syndrome and patients with other immunodeficiencies.  Ann Intern Med. 1984;;  100 663-671
• 055 Kreuz  W, Gungor  T, Funk  M, Linde  R, Ehrenforth  S, Lotz  C, Kornhuber  B. First experience with pentamidine inhalation in human immunodeficiency virus-infected children.  Eur J Pediatr. 1991;;  150 687-688
• 056 Kunz  S, Junker  U, Blaser  J, Joos  B, Meyer  B, Zak  O et al. The scid mouse as an experimental model for the evaluation of anti-Pneumocystis carinii therapy.  J Antimicrob Chemother. 1995;;  36 137-155
• 057 Lehrnbecher  T, Foster  C, Vazquez  N, Mackall  C L, Chanock  S J. Therapy-induced alterations in host defense in children receiving therapy for cancer.  J Pediatr Hematol Oncol. 1997;;  19 399-417
• 058 Leoung  G S, Feigal  D W Jr, Montgomery  A B, Corkery  K, Wardlaw  L, Adams  M et al. Aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia. The San Francisco community prophylaxis trial.  N Engl J Med. 1990;;  323 769-775
• 059 Limper  A H, Hoyte  J S, Standing  J E. The role of alveolar macrophages in Pneumocystis carinii degradation and clearance from the lung.  J Clin Invest. 1997;;  99 2110-2117
• 060 Link  H, Vohringer  H F, Wingen  F, Bragas  B, Schwardt  A, Ehninger  G. Pentamidine aerosol for prophylaxis of Pneumocystis carinii pneumonia after BMT.  Bone Marrow Transplant. 1993;;  11 403-406
• 061 Lyytikainen  O, Ruutu  T, Volin  L, Lautenschlager  I, Jokipii  L, Tiittanen  L, Ruutu  P. Late onset Pneumocystis carinii pneumonia following allogeneic bone marrow transplantation.  Bone Marrow Transplant. 1996;;  17 1057-1059
• 062 Ma  L, Borio  L, Masur  H, Kovacs  J A. Pneumocystis carinii dihydropteroate synthase but not dihydrofolate reductase gene mutations correlate with prior trimethoprim-sulfamethoxazole or dapsone use.  J Infect Dis. 1999;;  180 1969-1978
• 063 Ma  L, Kovacs  J A. Expression and characterization of recombinant human-derived Pneumocystis carinii dihydrofolate reductase.  Antimicrob Agents Chemother. 2000;;  44 3092-3096
• 064 Mackall  C L, Fleisher  T A, Brown  M R, Andrich  M P, Chen  C C, Feuerstein  I M et al. Age, thymopoiesis, and CD4 + T-lymphocyte regeneration after intensive chemotherapy.  N Engl J Med. 1995;;  332 143-149
• 065 Mackall  C L, Fleisher  T A, Brown  M R, Magrath  I T, Shad  A T, Horowitz  M E et al. Lymphocyte depletion during treatment with intensive chemotherapy for cancer.  Blood. 1994;;  84 2221-2228
• 066 Mackall  C L, Stein  D, Fleisher  T A, Brown  M R, Hakim  F T, Bare  C V et al. Prolonged CD4 depletion after sequential autologous peripheral blood progenitor cell infusions in children and young adults.  Blood. 2000;;  96 754-762
• 067 Mackall  C L. T-cell immunodeficiency following cytotoxic antineoplastic therapy: a review.  Oncologist. 1999;;  4 370-378
• 068 Maltezou  H C, Petropoulos  D, Choroszy  M, Gardner  M, Mantzouranis  E C, Rolston  K V, Chan  K W. Dapsone for Pneumocystis carinii prophylaxis in children undergoing bone marrow transplantation.  Bone Marrow Transplant. 1997;;  20 879-881
• 069 Mandell  G L, Petri  W A Jr. Antimicrobial Agents: Sulfonamides, Trimethoprim-Sulfamethoxazole, Quinolones and agents for urinary tract infections. In: Hardman JG, Limbird LE (eds). Goodman & Gilman's The Pharmacological Basis of Therapeutics (9th ed). McGraw-Hill, New York; 1995;: pp 1057-1072
• 070 Mann  R, Badesch  D, Zamora  M, Dreskin  S C. Desensitization to trimethoprim-sulfamethoxazole following lung transplantation.  Chest. 1997;;  111 1147
• 071 Masur  H, Ognibene  F P, Yarchoan  R, Shelhamer  J H, Baird  B F, Travis  W et al. CD4 counts as predictors of opportunistic pneumonias in human immunodeficiency virus (HIV) infection.  Ann Intern Med. 1989;;  111 223-231
• 072 Masur  H. Pneumocystis carinii Pneumonia. In: Shelhamer J, Pizzo PA, Paillo JE, Masur H (eds). Respiratory disease in the immunocompromised host. Lippincott, Philadelphia; 1991;: pp 409-427
• 073 McIntosh  K, Cooper  E, Xu  J, Mirochnick  M, Lindsey  J, Jacobus  D et al. Toxicity and efficacy of daily vs. weekly dapsone for prevention of Pneumocystis carinii pneumonia in children infected with human immunodeficiency virus. ACTG 179 Study Team. AIDS Clinical Trials Group.  Pediatr Infect Dis J. 1999;;  18 432-439
• 074 Mei  Q, Gurunathan  S, Masur  H, Kovacs  J A. Failure of co-trimoxazole in Pneumocystis carinii infection and mutations in dihydropteroate synthase gene.  Lancet. 1998;;  351 1631-1632
• 075 Metroka  C E, Lewis  N J, Jacobus  D P. Desensitization to dapsone in HIV-positive patients.  JAMA. 1992;;  267 512
• 076 Meyers  J D, Pifer  L L, Sale  G E, Thomas  E D. The value of Pneumocystis carinii antibody and antigen detection for diagnosis of Pneumocystis carinii pneumonia after marrow transplantation.  Am Rev Respir Dis. 1979;;  120 1283-1287
• 077 Mirochnick  M, Cooper  E, McIntosh  K, Xu  J, Lindsey  J, Jacobus  D et al. Pharmacokinetics of dapsone administered daily and weekly in human immunodeficiency virus-infected children.  Antimicrob Agents Chemother. 1999;;  43 2586-2591
• 078 Müller  F M, Groll  A H, Walsh  T J. Current approaches to diagnosis and treatment of fungal infections in HIV-infected children.  Eur J Pediatr. 1999;;  158 187-199
• 079 Mustafa  M M, Pappo  A, Cash  J, Winick  N J, Buchanan  G R. Aerosolized pentamidine for the prevention of Pneumocystis carinii pneumonia in children with cancer intolerant or allergic to trimethoprim/sulfamethoxazole.  J Clin Oncol. 1994;;  12 258-261
• 080 Nachman  S A, Müller  B U, Mirochnick  M, Pizzo  P A. High failure rate of dapsone and pentamidine as Pneumocystis carinii pneumonia prophylaxis in human immunodeficiency virus-infected children.  Pediatr Infect Dis J. 1994;;  13 1004-1006
• 081 Ng  V L, Yajko  D M, Hadley  W K. Extrapulmonary pneumocystosis.  Clin Microbiol Rev. 1997;;  10 401-418
• 082 Notheis  G, Belohradsky  B H, Bialek  R, Rieske  K, Wintergerst  U. Pneumocystis-carinii-Pneumonie. In: DGPI Handbuch Infektionen bei Kindern und Jugendlichen. 3. Aufl. Futuramed Verlag, München; 2000;: pp 486-491
• 083 Opravil  M, Hirschel  B, Lazzarin  A, Heald  A, Pechere  M, Ruttimann  S et al. Once-weekly administration of dapsone/pyrimethamine vs. aerosolized pentamidine as combined prophylaxis for Pneumocystis carinii pneumonia and toxoplasmic encephalitis in human immunodeficiency virus-infected patients.  Clin Infect Dis. 1995;;  20 531-541
• 084 Orcutt  T A, Godwin  C R, Pizzo  P A, Ognibene  F P. Aerosolized pentamidine: a well-tolerated mode of prophylaxis against Pneumocystis carinii pneumonia in older children with human immunodeficiency virus infection.  Pediatr Infect Dis J. 1992;;  11 290-294
• 085 Para  M F, Finkelstein  D, Becker  S, Dohn  M, Walawander  A, Black  J R. Reduced toxicity with gradual initiation of trimethoprim-sulfamethoxazole as primary prophylaxis for Pneumocystis carinii pneumonia: AIDS Clinical Trials Group 268.  J Acquir Immune Defic Syndr. 2000;;  24 337-343
• 086 Pifer  L L, Hughes  W T, Stagno  S, Woods  D. Pneumocystis carinii infection: evidence for high prevalence in normal and immunosuppressed children.  Pediatrics. 1978;;  61 35-41
• 087 Podzamczer  D, Salazar  A, Jimenez  J, Consiglio  E, Santin  M, Casanova  A et al. Intermittent trimethoprim-sulfamethoxazole compared with dapsone-pyrimethamine for the simultaneous primary prophylaxis of Pneumocystis pneumonia and toxoplasmosis in patients infected with HIV.  Ann Intern Med. 1995;;  122 755-761
• 088 Podzamczer  D, Santin  M, Jimenez  J, Casanova  A, Bolao  F, Gudiol  G R. Thrice-weekly cotrimoxazole is better than weekly dapsone-pyrimethamine for the primary prevention of Pneumocystis carinii pneumonia in HIV-infected patients.  AIDS. 1993;;  7 501-506
• 089 Pottratz  S T. Pneumocystis carinii interactions with respiratory epithelium.  Semin Respir Infect. 1998;;  13 323-329
• 090 Rees  C A, Lennard  L, Lilleyman  J S, Maddocks  J L. Disturbance of 6 - mercaptopurine metabolism by cotrimoxazole in childhood lymphoblastic leukaemia.  Cancer Chemother Pharmacol. 1984;;  12 87-89
• 091 Sable  C A, Donowitz  G R. Infections in bone marrow transplant recipients.  Clin Infect Dis. 1994;;  18 273-281
• 092 Safrin  S, Lee  B L, Sande  M A. Adjunctive folinic acid with trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia in AIDS patients is associated with an increased risk of therapeutic failure and death.  J Infect Dis. 1994;;  170 912-917
• 093 Schneider  M M, Hoepelman  A I, Eeftinck Schattenkerk  J K, Nielsen  T L, van der Graaf  Y et al. A controlled trial of aerosolized pentamidine or trimethoprim-sulfamethoxazole as primary prophylaxis against Pneumocystis carinii pneumonia in patients with human immunodeficiency virus infection. The Dutch AIDS Treatment Group.  N Engl J Med. 1992;;  327 1836-1841
• 094 Sepkowitz  K A. Effect of prophylaxis on the clinical manifestations of AIDS-related opportunistic infections.  Clin Infect Dis. 1998;;  26 806-810
• 095 Sepkowitz  K A. Pneumocystis carinii pneumonia in patients without AIDS.  Clin Infect Dis. 1993;;  17 Suppl 2 S416-422
• 096 Silvestri  R C, Jensen  W A, Zibrak  J D, Alexander  R C, Rose  R M. Pulmonary infiltrates and hypoxemia in patients with the acquired immunodeficiency syndrome re-exposed to trimethoprim-sulfamethoxazole.  Am Rev Respir Dis. 1987;;  136 1003-1004
• 097 Simonds  R J, Hughes  W T, Feinberg  J, Navin  T R. Preventing Pneumocystis carinii pneumonia in persons infected with human immunodeficiency virus.  Clin Infect Dis. 1995;;  21 Suppl 1 S44-48
• 098 Simone  J V, Holland  E, Johnson  W. Fatalities during remission of childhood leukemia.  Blood. 1972;;  39 759-770
• 099 Slivka  A, Wen  P Y, Shea  W M, Loeffler  J S. Pneumocystis carinii pneumonia during steroid taper in patients with primary brain tumors.  Am J Med. 1993;;  94 216-219
• 100 Souza  J P, Boeckh  M, Gooley  T A, Flowers  M E, Crawford  S W. High rates of Pneumocystis carinii pneumonia in allogeneic blood and marrow transplant recipients receiving dapsone prophylaxis.  Clin Infect Dis. 1999;;  29 1467-1471
• 101 Spencer  C M, Goa  K L. Atovaquone. A review of its pharmacological properties and therapeutic efficacy in opportunistic infections.  Drugs. 1995;;  50 176-196
• 102 Torres  R A, Barr  M, Thorn  M, Gregory  G, Kiely  S, Chanin  E et al. Randomized trial of dapsone and aerosolized pentamidine for the prophylaxis of Pneumocystis carinii pneumonia and toxoplasmic encephalitis.  Am J Med. 1993;;  95 573-583
• 103 Tracy  J W, Webster  L T Jr. Drugs used in the chemotherapy of protozoal infections. In: Hardman JG, Limbird LE (eds). Goodman & Gilman's The Pharmacological Basis of Therapeutics (9th ed). McGraw-Hill, New York; 1995;: pp 987-1008
• 104 Tseng  A. AIDS/HIV. Drugs for opportunistic infections. In: Piscitelli SC, Rotvold KA. Drug interactions in infectious diseases (1st ed). Humana Press, Totowa, NJ; 2001;: pp 61-108
• 105 Tuan  I Z, Dennison  D, Weisdorf  D J. Pneumocystis carinii pneumonitis following bone marrow transplantation.  Bone Marrow Transplant. 1992;;  10 267-272
• 106 US Public Health Services/Infectious Diseases Society of America .1997 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus: disease-specific recommendations. USPHS/IDSA Prevention of Opportunistic Infections Working Group. Clin Infect Dis 1997; 25 Suppl 3: S313-335
• 107 US Public Health Services/Infectious Diseases Society of America .Prevention of opportunistic Infections Working Group. 1999 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus. Clin Infect Dis 2000; 30: S29-65
• 108 Uzzan  B, Bentata  M, Campos  J, Mosnier  A, Krivitzky  A, Perret  G Y, Modigliani  E. Effects of aerosolized pentamidine on glucose homeostasis and insulin secretion in HIV-positive patients: a controlled study.  AIDS. 1995;;  9 901-907
• 109 Vasconcelles  M J, Bernardo  M V, King  C, Weller  E A, Antin  J H. Aerosolized pentamidine as pneumocystis prophylaxis after bone marrow transplantation is inferior to other regimens and is associated with decreased survival and an increased risk of other infections.  Biol Blood Marrow Transplant. 2000;;  6 35-43
• 110 Wacker  P, Ozsahin  H, Groll  A H, Gervaix  A, Reinhard  L, Humbert  J. Trimethoprim-sulfamethoxazole salvage for refractory listeriosis during maintenance chemotherapy for acute lymphoblastic leukemia.  J Pediatr Hematol Oncol. 2000;;  22 340-343
• 111 Walker  D J, Wakefield  A E, Dohn  M N, Miller  R F, Baughman  R P, Hossler  P A et al. Sequence polymorphisms in the Pneumocystis carinii cytochrome b gene and their association with atovaquone prophylaxis failure.  J Infect Dis. 1998;;  178 1767-1775
• 112 Walzer  P D. Pneumocystis carinii pneumonia in patients without human immunodeficiency virus infection.  Clin Infect Dis. 1997;;  25 219-220
• 113 Walzer  P D. Pneumocystis carinii. In: Mandell GL, Bennet JR, Dolin R (eds). Mandell, Douglas and Bennet's Principles and Practice of Infectious Diseases, 5th edition. Churchill Livingstone, Philadelphia; 2000;: pp 2781-2795
• 114 Walzer  P D, Foy  J, Steele  P, Kim  C K, White  M, Klein  R S et al. Activities of antifolate, antiviral, and other drugs in an immunosuppressed rat model of Pneumocystis carinii pneumonia.  Antimicrob Agents Chemother. 1992;;  36 1935-1942
• 115 Weinthal  J, Frost  J D, Briones  G, Cairo  M S. Successful Pneumocystis carinii pneumonia prophylaxis using aerosolized pentamidine in children with acute leukemia.  J Clin Oncol. 1994;;  12 136-140
• 116 Zuidema  J, Hilbers-Modderman  E S, Merkus  F W. Clinical pharmacokinetics of dapsone.  Clin Pharmacokinet. 1986;;  11 299-315