（二）唑类
1、氟康唑：①适应证：深部念珠菌病、急性隐球菌性脑膜炎、侵袭性念珠菌病的预防和治疗。②药代动力学：口服迅速吸收，进食对药物吸收无影响。蛋白结合率低，肾脏清除，血浆半衰期为20-30小时，血中药物可经透析清除。③用法与用量：侵袭性念珠菌病400-800mg/d.念珠菌病的预防：50-200mg/d,疗程不宜超过2-3周。④注意事项：长期治疗者注意肝功能。
2、伊曲康唑：①适应证：曲霉、念珠菌属、隐球菌属和组织胞浆菌等引起的IFI患者。②药代动力学：蛋白结合率99%，血浆半衰期为20-30小时。经肝P450酶系广泛的代谢，代谢产物经胆汁和尿液排泄。③用法与用量：第1-2天200mg,静脉注射，每天2次；第3-14天200mg,静脉注射每天1次;输注时间不得少于1小时；之后序贯使用口服液，200mg每天2次。④注意事项：长期治疗时应注意对肝功能的监测，不得与其他肝毒性药物合用，静脉给药不得与其他药物采用同一通路。
3、伏立康唑：①适应证：免疫抑制患者的严重真菌感染、急性侵袭性曲霉病、由氟康唑耐药的念珠菌引起的侵袭性感染、镰刀霉菌引起的感染等。②药代动力学：高危患者中呈非线性药代动力学，蛋白结合率为58%，组织分布容积为4.6L/kg.清除半衰期为6-9小时。③用法与用量：负荷剂量：静脉给与6mg/kg,每12小时1次，连用2次。输注速度不得超过每小时3mg/kg，在1-2小时内输完。维持剂量:静脉给予4 mg/kg,每12 h 1次。④注意事项：中度至重度肾功能不全患者慎重经静脉给药。
（三）棘白菌素类
1、卡泊芬净：①适应证：发热性中性粒细胞减少患者疑似真菌感染的经验性治疗，并用于治疗侵袭性念珠菌病、念珠菌血症和其他疗法难控制或不能耐受的侵袭性曲霉菌病。②药代动力学：血药浓度与剂量呈等比例增长，蛋白结合率〉96%，清除半衰期为40-50小时。③用法与用量：首日给予一次70mg负荷剂量,随后50mg/d的剂量维持.输注时间不得少于1小时，疗程依患者病情而定。④注意事项：对肝功能受损的患者慎重用药。
2、米卡芬净：是一类新型水溶性棘白菌素类脂肽，它对念珠菌属和曲霉菌属引起的深部真菌感染有广谱抗菌作用，对耐唑类药物的白念珠菌、光滑念珠菌、克柔念珠菌和其他念珠菌均有良好的抗菌活性，但不能抑制新型隐球菌、毛孢子菌属、镰孢属或结合菌。目前主要用于念珠菌属和曲霉菌属所致的深部真菌感染。本品体内分布广泛，血浆和组织浓度较高，主要在肝进行代谢，经胆汁排泄，与其他药物相互作用少。主要的不良反应是肝功能异常,
- 16 -
但发生率并不高。其用于治疗食管念珠菌病的推荐剂量为150mg/d，预防造血干细胞移植患者的念珠菌感染的推荐剂量为50mg/d。
（四）氟胞嘧啶
氟胞嘧啶：①适应证：很少单一用药，一般联合两性霉素B应用于全身念珠菌病，隐球菌病。②药代动力学：口服迅速，几乎完全吸收，经口和非胃肠道给药均可达到相同血药浓度，蛋白结合率低，组织分布广泛，经肾脏以原形消除，血浆半衰期为2.5-5.0小时。③用法与用量：若肾功正常，初始剂量50-150mg/kg分四次给药，6小时一次；若肾功不全，初始剂量25mg/kg，但随后的用量和间期需调整以使血清峰值浓度达到70-80mg/L。④注意事项：监测血肌酐水平一周两次，调整合适剂量，规律监测血细胞计数和肝功情况，当与两性霉素B联用时，两性霉素B会使氟胞嘧啶清除率减低。
参考文献：
[1] Martin GS, Mannino DM, Eaton S, Moss M. The Epidemiology of Sepsis in the United States from 1979 through 2000. N Engl J Med. 2003; 348:1546-54.
[2] Edmond MB, Wallace SE, McClish DK, et al. Nosocomial bloodstream infections in United States hospitals: a three-year analysis. Clin Infect Dis. 1999; 29: 239-244.
[3] Rentz AM, Halpern MT, Bowden R. The impact of candidemia on length of hospital stay, outcome, and overall cost of illness. Clin Infect Dis. 1998; 27: 781-8.
[4] Slavin MA, Australian Mycology Interest Group. The epidemiology of candidaemia and mould Infectious in Australia. J Antimicrob Chemother. 2002; 49 S1: 3-9. [5] Kauffman CA. Fungal Infections. Proc Am Thorac Soc. 2006;3(1):35-40
[6] Tortorano AM, Peman J, Bernhardt H, et al. Epidemiology of candidaemia in europe: results of 28-month European Confederation of Medical Mycology (ECMM) hospital-based surveillance study. Eur J Clin Microbiol Infect Dis. 2004 Apr; 23(4): 317-22.
[7] Meersseman W, Vandecasteele SJ, Wilmer A, et al. Invasive aspergillosis in critically ill patients without malignancy. Am J Respir Crit Care Med. 2004; 170: 621–625.
- 17 -
[8] Denning DW. Aspergillosis in nonimmunocompromised critically ill patients. Am J Respir Crit Care Med. 2004; 170: 580-581.
[9] Garnacho-Montero J, Amaya-Villar R, Ortiz-Leyba C, et al. Isolation of Aspergillus spp. from the respiratory tract in criticallyill patients: risk factors, clinical presentation and outcome. Crit Care 2005; 9: R191-199.
[10] Lewis M, Kallenbach J, Ruff P, et al. Invasive pulmonary aspergillosis complicating influenza A pneumonia in a previously healthy patient. Chest 1985; 87: 691-693.
[11] Karam GH, Griffin FM. Invasive pulmonary aspergillosis in nonimmunocompromised, nonneutropenic hosts. Rev Infect Dis. 1986;8:357-363.
[12] Valles J, Mesalles E, Mariscal D, et al. A 7-year study of severe hospital-acquired pneumonia requiring ICU admission. Intensive Care Med. 2003; 29: 1981-1988.
[13] Vandewoude KH, Blot SI, Depuydt P, et al. Clinical relevance of Aspergillus isolation from respiratory tract samples in critically ill patients. Critical Care. 2006; 10(1):R31
[14] Vandewoude KH, Vogelaers D, Blot SI. Aspergillosis in the ICU—The new 21st century problem? Med Mycol. 2006 Sep;44 Suppl:71-6.
[15] Hartemink KJ, Paul MA, Spijkstra JJ, et al. Immunoparalysis as a cause for invasive aspergillosis? Intensive Care Med. 2003, 29:2068-2071.
[16] Ascioglu S, Rex JH, de Pauw B, et al. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis. 2002; 34: 7-14.
[17] Mermel LA, Farr BM, Sherertz RJ, et al. Guidelines for the Management of Intravascular Catheter–Related Infections. Clin Infect Dis. 2001; 32: 1249-1272.
[18] Leon C, Ruiz-Santana S, Saavedra P, et al. A bedside scoring system (\early antifungal treatment in nonneutropenic critically ill patients with Candida colonization. Crit Care Med. 2006 Mar;34(3):730-7.
[19] Craven DE, Barber TW, Steget KA, et al. Nosocomial pneumonia in the 1990: Update of epidemiology and risk factors. Seninars in Respiratory Infection. 1990; 5(3): 157.
[20] Perfect JR, Cox GM, Lee JY, et al. The impact of culture isolation of Aspergillus species: a
- 18 -
hospital-based survey of aspergillosis. Clin Infect Dis. 2001; 33:1824-1833.
[21] Rees JR, Pinner RW, Hajjeh RA, et al. The epidemiological features of invasive mycotic infections in the San Francisco Bay area, 1992-1993: results of population-based laboratory active surveillance. Clin Infect Dis. 1998; 27: 1138-1147.
[22] Borzotta AP, Beardsley K. Candida infections in critically ill trauma patients: a retrospective case-control study. Arch Surg. 1999; 134:657-64; discussion 664-5.
[23] Hoerauf A, Hammer S, Muller-Myhsok B, et al. Intra-abdominal Candida infection during acute necretizing pancreatitis has a high prevalence and is associated with increased mortality. Crit Care Med. 1998; 26(12):2010-5.
[24] de Vera F, Martinez JF, Clara Verdu R, et al. Pancreatic abscess caused by Candida following wide-spectrum antibiotic treatment. Gastroenterol Hepatol. 1998 Apr;21(4):188-90.
[25] Vandewoude K, Colardyn F, Verschraegen G, et al. Clinical relevance of positive aspergillus cultures in respiratory tract secretions in ICU patients. Program and abstracts of the 44th Interscience Conference of Antimicrobial Agents and Chemotherapy; October 30-November 2, 2004; Washington, DC. Abstract K-1440.
[26] Blumberg HM, Jarvis WR, Soucie JM, 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: 177-86.
[27] Pittet D, Monod M, Suter PM, et al. Candida colonization and subsequent infections in critically ill surgical patients. Ann Surg. 1994 Dec;220(6):751-8.
[28] Piarroux R, Grenouillet F, Balvay P, et al. Assessment of preemptive treatment to prevent severe candidiasis in critically ill surgical patients.Crit Care Med 2004;32(12):2443-2449. [29] Ostrosky-Zeichner L, Pappas PG. Invasive candidiasis in the intensive care unit. Crit Care Med. 2006; 34(3): 857-863.
[30] Petri MG, Konig J, Moecke HP, 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 Mar;23(3):317-25.
- 19 -
[31] Linda W, Kam, Jason D. Management of systemic candidal infections in the intensive care unit. Am J Health-Syst Pharm. 2002: 59; 33-41.
[32] Wey SB, Motomi M, Pfaller MA. et al. Risk factors for hospital acquired candidemia. Arch Intern Med. 1989; 149:2349-53.
[33] Vandewoude K, Blot S, Benoit D, et al. Invasive aspergillosis in critically ill patients: analysis of risk factors for acquisition and mortality. Acta Clin Belg. 2004; 59:251-257.
[34] Pittet D, Huguenin T, Dharan S, et al. Unusual cause of lethal pulmonary aspergillosis in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1996; 154(2Pt1): 541-544.
[35] Rello J, Esandi ME, Mariscal D, et al. Invasive pulmonaryaspergillosis in patients with chronic obstructive pulmonarydisease: report of eight cases and review. Clin Infect Dis. 1998;26: 1473-1475.
[36] Bulpa PA, Dive AM, Garrino MG, et al. Chronic obstructive pulmonary disease patients with invasive pulmonary aspergillosis:benefits of intensive care? Intensive Care Med. 2001; 27: 59-67. [37] Lionakis MS, Kontoyiannis DP. Glucocorticoids and invasive fungal infections. Lancet. 2003;362:1828-1838.
[38] Crean JM, Niederman MS, Fein AM, Feinsilver SH. Rapidly progressive respiratory failure due to Aspergillus pneumonia: a complication of short-term corticosteroid therapy. Crit Care Med. 1992; 20: 148-150.
[39] Palmer LB, Greenberg HE, Schiff MJ. Corticosteroid treatment as a risk factor for invasive aspergillosis in patients with lung disease. Thorax. 1991; 46:15-20.
[40] Rex JH, Walsh TJ, Sobel JD, et al. Practice guidelines for the treatment of candidiasis. Clin Infect Dis. 2000; 30:662-678.
[41] Vincent JL, Anaissie E, Bruining H, et al. Epidemiology, diagnosis and treatment of systemic Candida infection in surgical patients under intensive care. Intensive Care Med. 1998; 24:206-16. [42] 中华内科杂志编辑委员会. 血液病/恶性肿瘤患者侵袭性真菌感染的诊断标准与治疗原则(草案). 中华内科杂志. 2005; 44: 554-556.
[43] 中华内科杂志编辑委员会. 侵袭性肺部真菌感染的诊断标准与治疗原则(草案). 中华内
- 20 -
百度搜索“77cn”或“免费范文网”即可找到本站免费阅读全部范文。收藏本站方便下次阅读，免费范文网，提供经典小说综合文库icu真菌感染指南手册(2007)(4)在线全文阅读。
相关推荐：