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研究生:郭律成
研究生(外文):Lu-Cheng Kuo
論文名稱:泛抗藥性不動桿菌菌血症之研究
論文名稱(外文):Bacteremia of Pan-Drug-Resistant Acinetobacter baumannii
指導教授:楊泮池楊泮池引用關係余忠仁余忠仁引用關係
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:臨床醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:中文
論文頁數:38
中文關鍵詞:泛抗藥性不動桿菌院內感染菌血症
外文關鍵詞:pan-drug-resistant acinetobacter baumanniinosocomial infectionbacteremia
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感染症在內科醫學中佔有重要的角色,院內感染更是一個重要的課題。治療並預防這些感染症,將可以有效地降低病患之死亡率。近年來各種多重抗藥性細菌的出現,如methicillin-resistant Staphylococcus aureus (MRSA)、vancomycin- resistant enterococcus (VRE)、Stenotrophomonas maltophilia及Acinetobacter baumannii等,對於感染症的治療帶來很大的衝擊:原本敏感有效的藥物,逐漸失去了效用,必須使用更加昂貴的後線藥品,更有甚者,對於現有所有抗生素都有抗藥性,臨床診治陷入無藥可用的情況。近三年來在本院逐漸出現不動桿菌(Acinetobacter baumannii)之臨床檢體培養,不論是否確實感染或只是移生(colonization),皆對臨床醫護人員,甚至醫院感染管制政策,都有重大的影響。尤其是多重抗藥(multi-drug-resistant)及泛抗藥性(pan-drug-resistant)菌種的出現,在選擇使用抗生素治療方面,更是臨床醫師的挑戰。
不動桿菌為格蘭氏陰性菌,廣泛存在自然界之生物及非生物,在25%正常人表皮有移生,7%有短暫性咽喉移生。院內感染此菌種之危險因子包括住院日數、手術、傷口、廣效性抗生素、留置導管、人工呼吸器等。不動桿菌之菌血症,即使在使用有效的抗生素之下,死亡率約為52%~61%。但是過去並未有針對泛抗藥性不動桿菌(pan-drug-resistant Acinetobacter baumannii, PDRAB)的任何臨床觀察及研究,因此本研究乃針對本院之泛抗藥性菌種進行回顧性分析研究。
本研究由台大醫院細菌室自1999年1月至2002年4月之所有培養株,包括所有臨床培養檢體之泛抗藥性不動桿菌,並挑出其中血液培養陽性者做案例回顧,分析各項臨床因子、治療方式、出院時存活率、及是否PDRAB為致死原因等。描述此群病患之臨床表現、預後並分析死亡者及存活者之間的相異性。疾病嚴重度則以多重器官衰竭指數(multiple organ dysfunction score, MODS)評估。非菌血症部分,則以泌尿道及傷口感染為研究對象,取其培養陽性且臨床有感染證據的案例,做為菌血症之對照。在院內感染傳播之研究方面,則對於任一部位有培養出泛抗藥性不動桿菌之全部病患,調查其培養出此菌的時間及所在病房,分析其區域(以病房或科別為單位)及時間的叢集性。如果在菌血症病患血液培養陽性發生的前後兩週內,同一病房單位有其他病患有泛抗藥性不動桿菌培養陽性,則有可能此菌之散播。由此判斷是否因為病患之隔離不良、或是醫護人員媒介其院內感染。此外,統計全院所有病房單位出現泛抗藥性不動桿菌培養陽性的次數,找出是否某些單位感染率過高,或是感染率很低,藉此可以對院內感染的政策有所調整。
在研究期間內,共有1,002株泛抗藥性不動桿菌菌株分離。其中有30例菌血症病患,男女比為18:12,年齡分布20至94歲。過去病史,以心臟疾病最多。菌血症平均發生在住院後33天,都是院內感染得到的。臨床表徵方面,發燒有25人(83%)、白血球增加或減少有24人(80%)、休克有16人(53%)、廣泛性凝血異常有9人(30%)。菌血症發生之當時之疾病嚴重度的評估,其MODS平均為7.8,範圍0至19。出院時死亡18人,死亡率60%,其中12例之直接致死因為泛抗藥性不動桿菌,直接致死之死亡率為40%。預測病患死亡之因子,以MODS、休克、廣泛性凝血異常、急性呼吸窘迫症及人工呼吸器等最有顯著關聯。各種治療方法,對死亡率並無影響。對照非菌血症的病患,發現菌血症與否並非影響病患存活的因素,而是以MODS最有統計之顯著性。
院內感染傳播之研究發現幾乎全院各病房皆有此菌之培養報告,且各病例之間有時間及地點之叢集性,因此極有可能是鄰近的病患交互感染所致。但是在小兒血液腫瘤科、骨髓移植、眼科及婦產科病房中,不曾發生任何一次的泛抗藥性不動桿菌感染。
與過去文獻報告之不動桿菌菌血症死亡率52~61%相比,本研究之泛抗藥性不動桿菌菌血症之死亡率60%並沒有較高,直接致死之死亡率也相近。這與吾人原先之預期略有不同。因為泛抗藥性不動桿菌在實驗室中對各種抗生素都是不敏感,臨床上使用抗生素應該也是治療無效,菌血症病患應該都會死亡,何以仍有40%病患得以存活,目前難以解釋。由泛抗藥性不動桿菌的感染源來看,有37%病患只有菌血症,其他63%則可以找到感染源,相較過去的研究11%可知感染源,高出甚多,表示只要仔細尋找感染來源,重複進行培養,常常就可以得到感染途徑的證據。在治療方面,本研究並沒有發現特別有效的治療,有可能因為病例數仍少,顯示不出統計之顯著性,也可能的確沒有抗生素組合可以有效地治療。本研究一項重要的發現是:病患的預後和其發生泛抗藥性不動桿菌感染時的疾病嚴重度有強烈相關,和其是否為菌血症無關。也就是當治療這一類病患的時候,不是去改變各種抗生素的組合,而是要改善病患整體的器官功能,有較好的身體狀況,才是在泛抗藥性不動桿菌感染時,病患得以存活的關鍵。
與過去文獻報告不同的是,本院很少發現在高危險的血液腫瘤病患有泛抗藥性不動桿菌之感染。推測可能是這些病房感染管制措施較為嚴密,護理人力較多,每人照顧之病患較少,較不易引起病患間的散播。由此可知,縱使較為容易得到泛抗藥性不動桿菌院內感染的病患,只要院內感染管制及醫療照護更加嚴謹,也可減少其感染。
Nosocomial infection has a major role in medicine. Proper diagnosis and treatment of nosocomial infections result in decrease of mortality and morbidity. The emergence of multi-drug resistant bacteria, eg. methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococcus (VRE), Stenotrophomonas maltophilia and Acinetobacter baumannii, give a great impact on the antimicrobial therapy. The loss of susceptibility for the first-line antibiotics forces us to use newer antibiotics, which are more expensive. Sometimes, the bacteria developed resistance to all available antimicrobials. In such circumstances, physicians will have no effective antibiotics to treat the patients.
In recent three years, the isolation of Acinetobacter baumannii in various clinical specimens increased in amount in the National Taiwan University Hospital, a tertiary referral center in northern Taiwan. Whether it is a true pathogen or only a colonization, it has great impact on the clinical medicine, even on the policy of hospital infection control. It is a great challenge for physicians to face the patients infected with multi-drug-resistant or pan-drug resistant species.
Acinetobacter baumannii is widely distributed in the nature. It has colonization on the skin of 25% of healthy adults and transient colonization in the pharynx of 7% adults. The risk factors of nosocomial acinetobacter infection are length of hospital stay, operation, wound, used of broad-spectrum antibiotics, indwelling catheters and mechanical ventilation. In previous studies, the mortality rates of patients with acinetobacter bacteremia, even with adequate antibiotics, were 52% to 61%. There was no report about the clinical course of patients with pan-drug-resistant Acinetobacter baumannii (PDRAB).
We retrospectively collected all cases with positive blood culture for PDRAB from blood from the microbiology lab of National Taiwan University Hospital from January 1999 through April 2002. Clinical data were collected, including length of hospital stay, diagnosis, indwelling catheters, operation, classes and duration of antibiotics use, hospital mortality, and the cause of death. The severity of patients was evaluated by multiple organ dysfunction score (MODS). Non-bacteremic patients with urinary tract infection and wound infection were obtained for the comparison with bacteremic patients. For studying the dissemination of PDRAB between patients, time and place clustering of patients with PDRAB isolates were searched.
During the study period, 1,002 isolates of PDRAB were obtained from all clinical samples. Thirty patients with bacteremia were analyzed. The ratio of male to female was 18:12 and the age ranged from 20 to 94 years. Cardiac diseases were the most frequent premorbid condition. The bacteremia developed in an average of 33 days after hospitalization and were all nosocomially acquired. The clinical manifestation included fever in 25 (83%) patients, leukocytosis or leukopenia in 24 (80%), shock in 16 (53%) and disseminated intravascular coagulopathy (DIC) in 9 (30%). The MODS averaged to 7.8 (ranged 0 to 19) on the day of bacteremia. The hospital death occurred in 18 (60%) patients. Among those who died, 12 (40%) were directed caused by PDRAB infection.
Shock, DIC, ARDS, mechanical ventilation and MODS were significant factors to predict mortality after PDRAB bacteremia. The mortality was not influenced by various antibiotic combinations. After comparing with non-bacteremic patients, MODS is the most significant predictor of mortality. Whether the patient is bacteremic has no influence on the outcome.
The study on the in-hospital dissemination showed that PDRAB has been isolated from patients in nearly all wards, except pediatric hemato-oncological ward, bone marrow transplantation unit, ophthalmological and gynecological wards. Time and place clustering is demonstrated.
In this study on the mortality rate of patients with PDRAB bacteremia was similar to that of bacteremia due to non-drug-resistant Acinetobacter baumannii. This is contrary to our expectation. Since PDRAB is resistant to all antibiotics available, the patients with bacteremia should be fatal. The causes that 40% of patients survived from PDRAB bacteremia remain unsolved.
Among all PDRAB bacteremic patients, 37% have no evidence of PDRAB infection except bacteremia. In the remaining 63% of patients, at least one other site revealed positive culture for PDRAB. In contrary to previous study which concluded that Acinetobacter bacteremia usually has unknown portal of entry, we find that greater proportion of patients could be found the portal of entry in our hospital.
Another important finding is that the mortality of PDRAB infection is dependent on the MODS and independent of bacteremia. Therefore, we should make efforts to improve the general condition and organ dysfunction, and not to try every combinations of antibiotics.
The reason why few PDRAB infections occurred in the hemato-oncological patients may be due to more strict measures for infection control, greater nurse-to-patient ratio in these units. Although the patients are in greater risks for nosocomial infections, less PDRAB infection could be achieved by hospital infection control.
一、中文摘要 1
二、緒論 3
三、研究方法與材料 8
四、結果 10
五、討論 14
六、展望 16
七、論文英文簡述 17
八、參考文獻 19
九、圖表 23
1. Zaleznik DF. Hospital-acquired and intravascular device-related infections. In: Fauci et al. Harrison’s Principle of Internal Medicine. 14th ed McGraw-Hill 1998. Chap 137
2. Reese RE, Betts RF. A Practical Approach to Infectious Disease. 4th ed Little, Brown 1996. p.1090.
3. Karam GH, Heffner JE. Emerging issues in antibiotic resistance in blood-borne infections. Amm J Respir Crit Care Med. 2000;162:1610-6
4. Wang JT, et al. A hospital-acquired outbreak of MRSA infection initiated by a surgeon carrier. J Hosp Infect 2001;47:104-9
5. Segal-Maurer S, Urban C, Rahal Jr, JJ. Current perspectives on multidrug-resistant bacteria. Infect Dis Clin North Am. 1996;10:939-57
6. Wood AJJ. Antimicrobial drug resistance. New Engl J Med 1996;335:1445-53
7. Gartlett JG, Froggatt JW. Antibiotic resistance. Arch Otolaryngol Head Neck Surg. 1995;121:392-6
8. Recommendation for preventing the spread of vancomycin resistance: recommendations of the Hospital Infection Control Practice Advisory Committee (HICPAC). Morb Mortal Wkly Rep 1995;44(RR-12):1-13
9. Leclercq R, Derlot E, Duval J, et al. Plasmid0mediated resistance to vancomycin and teicoplanin in Enterococcus faecium. N Engl J Med. 1988;319:157-61
10. Martone WJ. Spread of vancomycin-resistant enterococci: Why did it happen in the United States?
11. Hsueh PR, Teng LJ, Pan HJ, et al. Emergence of vancomycin-resistant enterococcus at a university hospital in Taiwan: Persistence of multiple species and multiple clones. Infect Control Hosp Epidemiol 1999;20:828-33
12. Linden PK, Moellering RC, Wood CA, et al. Treatment of vancomycin-resistant Enterococcus faecium infections with Quinupristin/dalfoprinstin. Clin Infect Dis 2001;33:1816-23
13. Allen DM, Hartman BJ. Acinetobacter species. In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Disease. 5th ed Churchill Livingstone 2000. Chap 209
14. Henricksen SD. Moraxella, Acinetobacter and the Mimeae. Bacteriol Rev. 1973;37:522-61
15. Snydman DR, Maloy MF, Brock SM, et al. Pseudobacteremia: False-positive blood culture from mist tent contamination. Am J Epidemiol. 1977;106:154-9
16. Lowes JA, Smith J, Tabaqchali S, et al. Outbreak of infection in a urological ward. Br Med J. 1982;280:722
17. Buxton AE, Anderson RL, Werdegar D, et al. Nosocomial respiratory tract infection and colonization with Acinetobacter calcoaceticus. Am J Med. 1978;65:507-13
18. Weernink A, Severin WPJ, Tjernberg I, et al. Pillows, an unexpected source of Acinetobacter. J Hosp Infect. 1995;29:189-99
19. Reyes MP, Ganguly S, Fowler M, et al. Pyrogenic reactions after inadvertent infusion of endotoxin during cardiac catheterizations. Ann Intern Med. 1980;93(Pt I):32-5
20. Cunha BA, Klimek JJ, Gracewski J, et al. A common source outbreak of Acinetobacter pulmonary infections traced to Wright respirometers. Postgrad Med J. 1980;56:169-72
21. Alfa MJ, Sitter DL. In-hospital evaluation of contamination of duodenoscopes: A quantitative assessment of the effect of drying. J Hosp Infect. 1991;19:89-98
22. Harvey K, Schuck S. Acinetobacter septicaemia following prolonged intravenous therapy. Med J Aust. 1977;2:121-4
23. Hirai Y. Survival of bacteria under dry conditions; from a viewpoint of nosocomial infection. J Hosp Infect. 1991;19:191-200
24. Wendt C, Dietze B, Dietz E, et al. Survival of Acinetobacter baumannii on dry surfaces. J Clin Microbiol. 1997;35:1394-7
25. Al-Khoja MS, Darrell JH. The skin as the source of Acinetobacter and Moraxella species occurring in blood culture. J Clin Pathol. 1979;32:497-9
26. Rosenthal S, Tager IB. Prevalence of gram-negative rods in the normal pharyngeal flora. Ann Intern Med. 1975;83:355-7
27. Baltimore RS, Duncan RL, Shapiro ED, et al. Epidemiology of pharyngeal colonization of infants with aerobic gram-negative rod bacteria. J Clin Microbiol. 1989;27:91-5
28. Larson EL. Persistent carriage of gram-negative bacteria on hands. Am J Infect Control. 1981;9:112-9
29. Rosenthal SL. Sources of Psudomonas and Acinetobacter species found in human culture materials. Am J Clin Pathol. 1974;62:807-11
30. National Nosocomial Infections Surveillance (NNIS) report: Data summary from October 1986 — April 1996, issued May 1996. Am J Infect Control. 1996;24:380-8
31. Department of Pathology, Singapore General Hospital: Annual Report. 1991;66.
32. Seifert , Strate A, Pulverer G. Nosocomial bacteremia due to Acinetobacter baumannii: Clinical feature, epidemiology, and predictors of mortality. Medicine (Baltimore). 1995;74:340-9
33. Bergogne-Berezin E. The increasing significance of outbreaks of Acinetobacter spp.: The need for control and new agents. J Hosp Infect. 1995;30(Suppl):441-52
34. Bergogne-Berezin E. The increasing role of Acinetobacter species as nosocomial pathogens. Curr Infect Dis Rep. 2001;3:440-4
35. Anstey NM, Currie BJ, Withnall KM. Community-acquired Acinetobacter pneumonia in the northern territory of Australia. Clin Infect Dis. 1992;14:83-91
36. Lortholary O, Fagon J-Y, Hoi AB, et al. Nosocomial acquisition of multi-resistant Acinetobacter baumannii: Risk factors and prognosis. Clin Infect Dis. 1995;20:790-6
37. Carbella X, Piyol M, Ayats J, et al. Relevance of digestive tract colonization in the epidemiology of nosocomial infections due to multiresistant Acinetobacter baumannii. Clin Infect Dis. 1996;23:329-34
38. Koeleman JGM, Parlevliet GA, Dijkshoorn L, et al. Nosocomial outbreak of multiresistant Acinetobacter baumannii on a surgical ward: Epidemiology and risk factors for acquisition. J Hosp Infect. 1997;37:113-23
39. Leibovici L, Konisberger H, Pitlik SD, et al. Patients at risk for inappropriate antibiotic treatment of bacteraemia. J Intern Med. 1992;231:371-4
40. Scepella EG, Wanger AR, Armitige L, et al. Nosocomial outbreak caused by a multiresistant clone of Acinetobacter baumannii: Results of the case-control and molecular epidemiologic investigations. Infect Control Hosp Epidemiol. 1995;16:92-7
41. Ang SW, Lee ST. Emergence of a multiply-resistant strain of Acinetobacter in a burn unit. Ann Acad Med Singapore. 1992;21:660-3
42. Kaul R, Burt J-A, Cork L, et al. Investigation of a multiyear multiple critical care unit outbreak due to relatively drug-sensitive Acinetobacter baumannii: Risk factors and attributable mortality. J Infect Dis. 1996;174:1279-87
43. Glew RH, Moellering RC Jr, Kunz LJ. Infections with Acinetobacter calcoaceticus: Clinical and latoratory studies. Medicine (Baltimore). 1977;56:79-97
44. Traub WH, Spohr M. Antimicrobial drug susceptibility of clinical isolates of Acinetobacter species. Antimicrob Agents Chemother. 1989;33:1617-9
45. Jellison TK, McKinnon PS, Rybak MJ. Epidemiology, resistance, and outcomes of Acinetobacter baumannii bacteremia treated with imipenem-cilastatin or ampicillin-sulbactam. Pharmacotherapy 2001;21:142-8
46. Tilley PAG, Roberts FJ. Bacteremia with Acinetobacter species: Risk factors and prognosis in different clinical settings. Clin Infect Dis 1994;18:896-900
47. Cisneros JM, Reyes MJ, Pachón J, et al. Bacteremia due to Acinetobacter baumannii: Epidemiology, clinical findings, and prognostic features. Clin Infect Dis 1996;22:1026-32
48. Wisplinghoff H, Edmond MB, Pfaller MA, et al. Nosocomial blood stream infections caused by Acinetobacter species in United States hospitals: Clinical features, molecular Epidemiology, and antimicrobial susceptibility. Clin Infect Dis 2000;31:690-7
49. Lai SW, Ng KC, Yu WL, et al. Acinetobacter baumannii bloodstream infection: Clinical features and antimicrobial susceptibilities of isolates. Kaohsiung J Med Sci 1999;15:406-13
50. Corbella X, Montero A, Pujol M, et al. Emergence and rapid spread of carbapenem resistance during a large and sustained hospital outbreak of multiresistant Acinetobacter baumannii. J Clin Microbiol 2000;38:4086-95
51. Chang SC, Chen YC, Luh KT, et al. In vitro activities of antimicrobial agents, alone and in combination, against Acinetobacter baumannii, isolated from blood. Diagn Microbiol Infect Dis 1995;23:105-10
52. Manikal VM, Landman D, Saurina G, et al. Endemic carbapenem-resistant Acinetobacter species in Brooklyn, New York: Citywide prevalence, interinstitutional spread, and relation to antibiotic usage. Clin Infect Dis 2000;31:101-6
53. Tankovic J, Legrand P, Gatines GD, et al. Characterization of a hospital outbreak of imipenem-resistant Acinetobacter baumannii by phenotypic and genotypic typing methods. J Clin Microbiol 1994;32:2677-81
54. Goncalves CR, Vaz TM, Araujo E, et al. Biotyping, serotyping and ribotyping as epidemiological tools in the evaluation of Acinetobacter baumannii dissemination in hospital units. J Med Microbiol 2000,49;773-8
55. D’Agata EMC, Thayer V, Schaffner W. An outbreak of Acinetobacter baumannii: The importance of cross-transmission. Infect Control Hosp Epidemiol 2000;21:588-91
56. Ling ML, Ang A, Wee M, et al. A nosocomial outbreak of multiresistant Acinetobacter baumannii originating from an intensive care unit. Infect Control Hosp Epidemiol 2001;22:48-9
57. Fierobe L, Lucet JC, Decré D, et al. An outbreak of imipenem-resistant Acinetobacter baumannii in critically ill surgical patients. Infect Cont Hosp Epidemiol 2001;22:35-40
58. Marshall JC, Cook DJ, Christou NV, et al. Multiple organ dysfunction score: A reliable descriptor of a complex clinical outcome. Crit Care Med 1995;23:1638-52
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