Antimykotische Therapie in der Intensivmedizin

Kernaussagen

Obwohl die invasive Candidiasis ein verbreitetes Problem ist, ist eine routinemäßige antimykotische Prophylaxe beim nicht-neutropenen oder immunsupprimierten Patienten bisher noch nicht indiziert, da große multizentrische Studien dazu bislang fehlen. Außerdem ist die epidemiologische Entwicklung hin zu resistenten Candida spp. zu beachten. Darüber hinaus sollte eine empirische bzw. präemptive Therapie nach einer validierten Risikoabschätzung wertvoller sein als die Prophylaxe. Die neu auftretenden komplexen Pilzinfektionen der kritisch kranken Patienten auf Intensivstationen - unabhängig ob durch Hefe- oder Schimmelpilze verursacht - machen evidenzbasierte Therapiestrategien notwendig (Abb. [2] und [3]). Dabei sollte es das Ziel sein, die Überlebensrate der Intensivpatienten deutlich zu verbessern.

Literatur

• 1 Martin G S, Mannino D M, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000.  N Engl J Med. 2003;  348 1546-1554
• 2 Blumberg H M, Jarvis W R, Soucie J M. et al . Risk factors for candidal bloodstream infections in surgical intensive care unit patients: the NEMIS prospective multicenter study. The National Epidemiology of Mycosis Survey.  Clin Infect Dis. 2001;  33 177-186
• 3 Petri M G, Konig J, Moecke H P. et al . Epidemiology of invasive mycosis in ICU patients: a prospective multicenter study in 435 non-neutropenic patients. Paul-Ehrlich Society for Chemotherapy, Divisions of Mycology and Pneumonia Research.  Intensive Care Med. 1997;  23 317-325
• 4 Vincent J L, Anaissie E, Bruining H. et al . Epidemiology, diagnosis and treatment of systemic Candida infection in surgical patients under intensive care.  Intensive Care Med. 1998;  24 206-216
• 5 Vincent J L, Sakr Y, Sprung C L. et al . Sepsis in European intensive care units: results of the SOAP study.  Crit Care Med. 2006;  34 344-353
• 6 Pfaller M A, Jones R N, Doern G V. et al . International surveillance of bloodstream infections due to Candida species: frequency of occurrence and antifungal susceptibilities of isolates collected in 1997 in the United States, Canada, and South America for the SENTRY Program. The SENTRY Participant Group.  J Clin Microbiol. 1998;  36 1886-1889
• 7 Pfaller M, Pappas P, Wingard J. Invasive Fungal Pathogens: Current Epidemiological Trends.  Clin Infect Dis. 2006;  43 S3-S14
• 8 Mora-Duarte J, Betts R, Rotstein C. et al . Comparison of caspofungin and Amphotericin B for invasive candidiasis.  N Engl J Med. 2002;  347 2020-2029
• 9 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
• 10 Ostrosky-Zeichner L, Pappas P. Invasive candidiasis in the intensive care unit.  Crit Care Med. 2006;  34 857-863
• 11 Munoz P, Burillo A, Bouza E. Criteria used when initiating antifungal therapy against Candida spp. in the intensive care unit.  Int J Antimicrob Agents. 2000;  15 83-90
• 12 Kam A P, Xu J. Diversity of commensal yeasts within and among healthy hosts.  Diagn Microbiol Infect Dis. 2002;  43 19-28
• 13 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
• 14 Alexander B, Pfaller M A. Contemporary Tools for the Diagnosis and Management of Invasive Mycoses.  Clin Infect Dis. 2006;  43 S15-S23
• 15 Hope W W, Walsh T J, Denning D W. Laboratory diagnosis of invasive aspergillosis.  Lancet Infect Dis. 2005;  5 609-622
• 16 Odabasi Z, Mattiuzzi G, Estey E. et al . Beta-D-glucan as a diagnostic adjunct for invasive fungal infections: validation, cutoff development, and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome.  Clin Infect Dis. 2004;  39 199-205
• 17 Ostrosky-Zeichner L, Alexander B D, Kett D H. et al . Multicenter clinical evaluation of the (1 → 3) beta-D-glucan assay as an aid to diagnosis of fungal infections in humans.  Clin Infect Dis. 2005;  41 654-659
• 18 Dodds A shley, Lewis R, Lewis J S. et al . Pharmacology of Systemic Antifungal Agents.  Clinical Infectious Diseases. 2006;  43 S28-S39
• 19 Bates D W, Su L, Yu D T. et al . Mortality and costs of acute renal failure associated with Amphotericin B therapy.  Clin Infect Dis. 2001;  32 686-693
• 20 Ostrosky-Zeichner L, Marr K A, Rex J H, Cohen S H. Amphotericin B: time for a new „gold standard”.  Clin Infect Dis. 2003;  37 415-425
• 21 Maschmeyer G, Ruhnke M. Update on antifungal treatment of invasive Candida and Aspergillus infections.  Mycoses. 2004;  47 263-276
• 22 Bates D W, Yu D T. Clinical impact of drug-drug interactions with systemic azole antifungals.  Drugs Today (Barc). 2003;  39 801-813
• 23 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
• 24 Pappas P G, Rex J H, Sobel J D. et al . Guidelines for treatment of candidiasis.  Clin Infect Dis. 2004;  38 161-189
• 25 Boyd A E, Modi S, Howard S J. et al . Adverse reactions to voriconazole.  Clin Infect Dis. 2004;  39 1241-1244
• 26 FDA ADAC .Briefing Document for Voriconazole (Oral and Intravenous Formulations). 2001
• 27 Raad I, Chapman S, Bradsher R. Posaconazole (POS) Salvage Therapy for Invasive Fungal Infections (IFI).  ICAAC. 2004;  Abstract
• 28 Denning D W. Echinocandin antifungal drugs.  Lancet. 2003;  362 1142-1151
• 29 Goodman J L, Winston D J, Greenfield R A. et al . A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation.  N Engl J Med. 1992;  326 845-851
• 30 Shorr A F, Chung K, Jackson W L. et al . Fluconazole prophylaxis in critically ill surgical patients: A meta-analysis.  Crit Care Med. 2005;  33 1928-1935
• 31 Pelz R K, Hendrix C W, Swoboda S M. et al . Double-blind placebo-controlled trial of fluconazole to prevent candidal infections in critically ill surgical patients.  Ann Surg. 2001;  233 542-548
• 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 Winston D J, Pakrasi A, Busuttil R W. Prophylactic fluconazole in liver transplant recipients. A randomized, double-blind, placebo-controlled trial.  Ann Intern Med. 1999;  131 729-737
• 34 Klastersky J. Antifungal therapy in patients with fever and neutropenia-more rational and less empirical?.  N Engl J Med. 2004;  351 1445-1447
• 35 Pittet D, Monod M, Suter P M. et al . Candida colonization and subsequent infections in critically ill surgical patients.  Ann Surg. 1994;  220 751-758
• 36 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
• 37 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
• 38 Ostrosky-Zeichner L, Oude L ashof, Kullberg B J, Rex J H. Voriconazole salvage treatment of invasive candidiasis.  Eur J Clin Microbiol Infect Dis. 2003;  22 651-655
• 39 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
• 40 Rex J H, Pappas P G, Karchmer A W. et al . A randomized and blinded multicenter trial of high-dose fluconazole plus placebo versus fluconazole plus Amphotericin B as therapy for candidemia and its consequences in nonneutropenic subjects.  Clin Infect Dis. 2003;  36 1221-1228
• 41 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
• 42 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
• 43 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
• 44 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
• 45 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
• 46 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
• 47 Maertens J, Raad I, Petrikkos G. et al . Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy.  Clin Infect Dis. 2004;  39 1563-1571
• 48 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
• 49 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
• 50 Pfaller M A, Diekema D J, Jones R N. et al . Trends in antifungal susceptibility of Candida spp. isolated from pediatric and adult patients with bloodstream infections: SENTRY Antimicrobial Surveillance Program, 1997 to 2000.  J Clin Microbiol. 2002;  40 852-856
• 51 Pfaller M A, Messer S A, Hollis R J, Jones R N. Antifungal activities of posaconazole, ravuconazole, and voriconazole compared to those of itraconazole and Amphotericin B against 239 clinical isolates of Aspergillus spp. and other filamentous fungi: report from SENTRY Antimicrobial Surveillance Program, 2000.  Antimicrob Agents Chemother. 2002;  46 1032-1037