Intensivmedizin up2date 2008; 4(1): 61-84
DOI: 10.1055/s-2007-995381
Operative Intensivmedizin

© Georg Thieme Verlag KG Stuttgart · New York

Infektionen unter medikamentöser Immunsuppression bei transplantierten Intensivpatienten

Christoph  Lichtenstern, Jan  Schmidt, Jens  Encke, Markus  A.  Weigand
Further Information

Publication History

Publication Date:
19 February 2008 (online)

Kernaussagen

Eine strenge Expositionskontrolle gegenüber der Vielzahl potenzieller Erreger ist vor allen anderen Maßnahmen entscheidend bei der intensivmedizinischen Betreuung immunsupprimierter Patienten. Dazu gehören z. B. eine besondere Aufmerksamkeit beim Patientenkontakt, restriktive Indikationen zu invasiven Techniken oder Applikationen und die Beachtung entsprechender baulicher Voraussetzungen.

Eine medikamentöse Prophylaxe sollte bei erwiesener Evidenz durchgeführt werden.

Milde, unspezifische Symptome sind häufig die einzigen primären Anzeichen einer Infektion, die vor einer Aggravierung frühzeitig präemptiv therapiert werden müssen. Dabei muss man an die besondere Bedeutung von Viren, Pilzen und atypischen Bakterien denken, sodass bereits zu Beginn breit wirksame Kombinationstherapien eingesetzt werden sollten.

Bei Sepsis muss auch die Reduktion der Immunsuppression, begleitet von einer engmaschigen Abstoßungsdiagnostik, erwogen werden.

Immunsuppressiva interagieren besonders mit einer Reihe von Antiinfektiva. Dies muss man vor dem Hintergrund der erheblichen Komorbidität von Intensivpatienten beachten.

Literatur

  • 1 Stille W, Brodt H R, Groll A H, Just-Nübling G. Antimikrobielle Therapie nach Transplantation solider Organe (SOT). Antibiotika-Therapie, Klinik und Praxis der antiinfektiösen Behandlung. Stuttgart; Schattauer 2005
  • 2 Ciesek S, Manns M P, Strassburg C P. Folgeerkrankungen nach Organtransplantation.  Internist (Berl). 2006;  47 252-265
  • 3 Xu J, Lucas R, Wendel A. The potential of GM-CSF to improve resistance against infections in organ transplantation.  Trends Pharmacol Sci. 2004;  25 254-258
  • 4 Steinman T I, Becker B N, Frost A E. et al . Guidelines for the referral and management of patients eligible for solid organ transplantation.  Transplantation. 2001;  71 1189-1204
  • 5 Screening of donor and recipient prior to solid organ transplantation.  Am J Transplant. 2004;  4 Suppl 10 10-20
  • 6 Boeken U, Feindt P, Micek M. et al . Procalcitonin (PCT) in cardiac surgery: diagnostic value in systemic inflammatory response syndrome (SIRS), sepsis and after heart transplantation (HTX).  Cardiovasc Surg. 2000;  8 550-554
  • 7 Kornberg A, Grube T, Wagner T. et al . Differentiated therapy with prostaglandin E1 (alprostadil) after orthotopic liver transplantation: the usefulness of procalcitonin (PCT) and hepatic artery resistive index (RI) for the evaluation of early graft function and clinical course.  Clin Chem Lab Med. 2000;  38 1177-1180
  • 8 Qedra N, Wagner F, Jonitz B. et al . Procalcitonin (PCT) is a new biological marker for the diagnosis of non-viral infections after transplantation of intrathoracic organs.  J Heart Lung Transplant. 2001;  20 239
  • 9 Schnitzler M A, Woodward R S, Brennan D C. et al . The effects of cytomegalovirus serology on graft and recipient survival in cadaveric renal transplantation: implications for organ allocation.  Am J Kidney Dis. 1997;  29 428-434
  • 10 Rowshani A T, Bemelman F J, van Leeuwen E M, van Lier R A, ten Berge I J. Clinical and immunologic aspects of cytomegalovirus infection in solid organ transplant recipients.  Transplantation. 2005;  79 381-386
  • 11 Humar A, Michaels M. American Society of Transplantation recommendations for screening, monitoring and reporting of infectious complications in immunosuppression trials in recipients of organ transplantation.  Am J Transplant. 2006;  6 262-274
  • 12 Anglicheau D, Lautrette A, Scieux C. et al . Lowering immunosuppression is safe and effective to treat altered pattern of CMV infection in renal transplant recipients on valaciclovir prophylaxis.  Transplant Proc. 2002;  34 2826-2827
  • 13 Chou N K, Ko W J, Chi N H. et al . Sparing immunosuppression in heart transplant recipients with severe sepsis.  Transplant Proc. 2006;  38 2145-2146
  • 14 Roback J D. CMV and blood transfusions.  Rev Med Virol. 2002;  12 211-219
  • 15 Pescovitz M D, Rabkin J, Merion R M. et al . Valganciclovir results in improved oral absorption of ganciclovir in liver transplant recipients.  Antimicrob Agents Chemother. 2000;  44 2811-2815
  • 16 The C ARI. CMV disease and kidney transplant: prophylaxis for cytomegalovirus infection in patients following renal transplantation.  Nephrology (Carlton). 2004;  9 S27-31
  • 17 European Best Practice Guidelines for Renal Transplantation (part 1).  Nephrol Dial Transplant. 2000;  15 1-85
  • 18 Razonable R R, Emery V C. Management of CMV infection and disease in transplant patients. 27 - 29 February 2004.  Herpes. 2004;  11 77-86
  • 19 Cytomegalovirus.  Am J Transplant. 2004;  4 51-58
  • 20 Epstein-Barr virus and lymphoproliferative disorders after transplantation.  Am J Transplant. 2004;  4 Suppl 10 59-65
  • 21 Other herpesviruses: HHV-6, HHV-7, HHV-8, HSV-1 and -2, VZV.  Am J Transplant. 2004;  4 66-71
  • 22 Gnann J Jr. W, Whitley R J. Clinical practice. Herpes zoster.  N Engl J Med. 2002;  347 340-346
  • 23 Human parvovirus B19.  Am J Transplant. 2004;  4 Suppl 10 92-94
  • 24 Pankuweit S, Moll R, Baandrup U. et al . Prevalence of the parvovirus B19 genome in endomyocardial biopsy specimens.  Hum Pathol. 2003;  34 497-503
  • 25 Jonetzko P, Graziadei I, Nachbaur K. et al . Fatal course of parvovirus B19-associated myocarditis in a female liver transplant recipient.  Liver Transpl. 2005;  11 463-466
  • 26 Maisch B, Richter A, Koelsch S. et al . Management of patients with suspected (peri-) myocarditis and inflammatory dilated cardiomyopathy.  Herz. 2006;  31 881-890
  • 27 Lichtenstern C, Geiss H K, Böttiger B W, Weigand M A. Antimykotische Therapie in der Intensivmedizin.  Intensivmedup2date. 2007;  3 21-40
  • 28 Singh N, Heitman J. Antifungal attributes of immunosuppressive agents: new paradigms in management and elucidating the pathophysiologic basis of opportunistic mycoses in organ transplant recipients.  Transplantation. 2004;  77 795-800
  • 29 Fungal infections.  Am J Transplant. 2004;  4 Suppl 10 110-134
  • 30 Ullmann A J, Cornely O A. Antifungal prophylaxis for invasive mycoses in high risk patients.  Curr Opin Infect Dis. 2006;  19 571-576
  • 31 Shorr A F, Chung K, Jackson W L, Waterman P E, Kollef M H. Fluconazole prophylaxis in critically ill surgical patients: A meta-analysis.  Crit Care Med. 2005;  33 1928-1935
  • 32 Playford E G, Webster A C, Sorrell T C, Craig J C. Antifungal agents for preventing fungal infections in non-neutropenic critically ill and surgical patients: systematic review and meta-analysis of randomized clinical trials.  J Antimicrob Chemother. 2006;  57 628-638
  • 33 Singh N. Antifungal prophylaxis for solid organ transplant recipients: seeking clarity amidst controversy.  Clin Infect Dis. 2000;  31 545-553
  • 34 Walsh T J, Pappas P, Winston D J. et al . Voriconazole compared with liposomal Amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever.  N Engl J Med. 2002;  346 225-234
  • 35 Herbrecht R, Denning D W, Patterson T F. et al . Voriconazole versus Amphotericin B for primary therapy of invasive aspergillosis.  N Engl J Med. 2002;  347 408-415
  • 36 Cornely O A, Maertens J, Winston D J. et al . Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia.  N Engl J Med. 2007;  356 348-359
  • 37 Ullmann A J, Lipton J H, Vesole D H. et al . Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease.  N Engl J Med. 2007;  356 335-347
  • 38 Morrell M, Fraser V J, Kollef M H. Delaying the empiric treatment of candida bloodstream infection until positive blood culture results are obtained: a potential risk factor for hospital mortality.  Antimicrob Agents Chemother. 2005;  49 3640-3645
  • 39 Pappas P G, Rex J H, Sobel J D. et al . Guidelines for treatment of candidiasis.  ClinInfectDis. 2004;  38 161-189
  • 40 Walsh T J, Teppler H, Donowitz G R. et al . Caspofungin versus liposomal Amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia.  N Engl J Med. 2004;  351 1391-1402
  • 41 Charlier C, Hart E, Lefort A. et al . Fluconazole for the management of invasive candidiasis: where do we stand after 15 years?.  J Antimicrob Chemother. 2006;  57 384-410
  • 42 Kuse E R, Chetchotisakd P, da Cunha C A. et al . Micafungin versus liposomal Amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial.  Lancet. 2007;  369 1519-1527
  • 43 Kullberg B J, Sobel J D, Ruhnke M. et al . Voriconazole versus a regimen of Amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: a randomised non-inferiority trial.  Lancet. 2005;  366 1435-1442
  • 44 Reboli A C, Rotstein C, Pappas P G. et al . Anidulafungin versus fluconazole for invasive candidiasis.  N Engl J Med. 2007;  356 2472-2482
  • 45 Arathoon E G, Gotuzzo E, Noriega L M. et al . Randomized, double-blind, multicenter study of caspofungin versus Amphotericin B for treatment of oropharyngeal and esophageal candidiases.  Antimicrob Agents Chemother. 2002;  46 451-457
  • 46 Villanueva A, Gotuzzo E, Arathoon E G. et al . A randomized double-blind study of caspofungin versus fluconazole for the treatment of esophageal candidiasis.  Am J Med. 2002;  113 294-299
  • 47 Ally R, Schurmann D, Kreisel W. et al . A randomized, double-blind, double-dummy, multicenter trial of voriconazole and fluconazole in the treatment of esophageal candidiasis in immunocompromised patients.  Clin Infect Dis. 2001;  33 1447-1454
  • 48 Vazquez J A, Skiest D J, Nieto L. et al . A multicenter randomized trial evaluating posaconazole versus fluconazole for the treatment of oropharyngeal candidiasis in subjects with HIV/AIDS.  Clin Infect Dis. 2006;  42 1179-1186
  • 49 Sandven P, Qvist H, Skovlund E, Giercksky K E. Significance of Candida recovered from intraoperative specimens in patients with intra-abdominal perforations.  Crit Care Med. 2002;  30 541-547
  • 50 Solomkin J S, Mazuski J E, Baron E J. et al . Guidelines for the selection of anti-infective agents for complicated intra-abdominal infections.  Clin Infect Dis. 2003;  37 997-1005
  • 51 Cornely O A, Lasso M, Betts R. et al . Caspofungin for the treatment of less common forms of invasive candidiasis.  J Antimicrob Chemother. 2007;  60 363-369
  • 52 Stevens D A, Kan V L, Judson M A. et al . Practice guidelines for diseases caused by Aspergillus. Infectious Diseases Society of America.  Clin Infect Dis. 2000;  30 696-709
  • 53 Perfect J R, Marr K A, Walsh T J. et al . Voriconazole treatment for less-common, emerging, or refractory fungal infections.  Clin Infect Dis. 2003;  36 1122-1131
  • 54 Singh N, Limaye A P, Forrest G. et al . Combination of voriconazole and caspofungin as primary therapy for invasive aspergillosis in solid organ transplant recipients: a prospective, multicenter, observational study.  Transplantation. 2006;  81 320-326
  • 55 Husain S, Alexander B D, Munoz P. et al . Opportunistic mycelial fungal infections in organ transplant recipients: emerging importance of non-Aspergillus mycelial fungi.  Clin Infect Dis. 2003;  37 221-229
  • 56 Marr K A, Carter R A, Crippa F, Wald A, Corey L. Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients.  ClinInfectDis. 2002;  34 909-917
  • 57 Singh N, Lortholary O, Alexander B D. et al . Antifungal management practices and evolution of infection in organ transplant recipients with cryptococcus neoformans infection.  Transplantation. 2005;  80 1033-1039
  • 58 Stille W, Brodt H R, Groll A H, Just-Nübling G. HIV-Infektion und AIDS. Antibiotika-Therapie, Klinik und Praxis der antiinfektiösen Behandlung. Stuttgart; Schattauer 2005
  • 59 Singh N, Alexander B D, Lortholary O. et al . Cryptococcus neoformans in Organ Transplant Recipients: Impact of Calcineurin-Inhibitor Agents on Mortality.  J Infect Dis. 2007;  195 756-764
  • 60 Pfaller M A, Messer S A, Boyken L. et al . Global trends in the antifungal susceptibility of Cryptococcus neoformans (1990 to 2004).  J Clin Microbiol. 2005;  43 2163-2167
  • 61 Sabbatani S, Manfredi R, Pavoni M, Consales A, Chiodo F. Voriconazole proves effective in long-term treatment of a cerebral cryptococcoma in a chronic nephropathic HIV-negative patient, after fluconazole failure.  Mycopathologia. 2004;  158 165-171
  • 62 Pitisuttithum P, Negroni R, Graybill J R. et al . Activity of posaconazole in the treatment of central nervous system fungal infections.  J Antimicrob Chemother. 2005;  56 745-755
  • 63 Barchiesi F, Spreghini E, Schimizzi A M. et al . Posaconazole and Amphotericin B combination therapy against Cryptococcus neoformans infection.  Antimicrob Agents Chemother. 2004;  48 3312-3316
  • 64 Pneumocystis jiroveci (formerly Pneumocystis carinii).  Am J Transplant. 2004;  4 Suppl 10 135-141
  • 65 Torre D, Speranza F, Martegani R. et al . A retrospective study of treatment of cerebral toxoplasmosis in AIDS patients with trimethoprim-sulphamethoxazole.  J Infect. 1998;  37 15-18
  • 66 Soheilian M, Sadoughi M M, Ghajarnia M. et al . Prospective randomized trial of trimethoprim/sulfamethoxazole versus pyrimethamine and sulfadiazine in the treatment of ocular toxoplasmosis.  Ophthalmology. 2005;  112 1876-1882
  • 67 Nocardia infections.  Am J Transplant. 2004;  4 Suppl 10 47-50
  • 68 Solid organ transplantation in the HIV-infected patient.  Am J Transplant. 2004;  4 83-88
  • 69 Barnard D L. Current status of anti-picornavirus therapies.  Curr Pharm Des. 2006;  12 1379-1390
  • 70 Slifkin M, Doron S, Snydman D R. Viral prophylaxis in organ transplant patients.  Drugs. 2004;  64 2763-2792
  • 71 Salzberger B. [Antiviral therapy: from influenza to Pfeiffer’s disease].  Internist (Berl). 2006;  47 1245-1250
  • 72 Balfour H H Jr. Antiviral drugs.  N Engl J Med. 1999;  340 1255-1268
  • 73 Wutzler P, De Clercq E, Wutke K, Farber I. Oral brivudin vs. intravenous acyclovir in the treatment of herpes zoster in immunocompromised patients: a randomized double-blind trial.  J Med Virol. 1995;  46 252-257
  • 74 Fishman J A, Rubin R H. Infection in organ-transplant recipients.  N Engl J Med. 1998;  338 1741-1751

Dr. med. Christoph Lichtenstern

Klinik für Anaesthesiologie
Universität Heidelberg

Im Neuenheimer Feld 110
69120 Heidelberg

Phone: 06221/56-39432

Fax: 06221/56-5345

Email: christoph.lichtenstern@med.uni-heidelberg.de