摘要
目的：肺部真菌感染多出现在治疗肺部细菌感染的过程中，临床上不易与肺部细菌感染相鉴别，早期诊断困难。研究肺部真菌感染相对于肺部细菌感染的临床特点，对于早期发现、早期诊治肺部真菌感染，具有重要的临床意义。由于非机械通气患者肺部真菌感染的病情相对较轻，预后相对较好，容易被临床医师所忽视，常常导致漏诊和误诊而延误治疗。因此，本文以非机械通气患者为研究对象，通过对肺部真菌感染与肺部细菌感染临床资料的对照研究，了解肺部真菌感染相对特异的临床特点，探讨可与肺部细菌感染相鉴别的临床特征，进一步指导肺部真菌感染的临床诊断和治疗。
方法：采用病例对照研究设计。30例符合入选标准的肺部真菌感染患者为病例组，均为2001年11月至2002年12月间在我院呼吸科住院的患者。对照组30例，为同期入院的肺部细菌感染的患者，且在性别、年龄、基础疾病、体块指数、吸烟指数上与病例组相匹配。本研究比较了两组患者的临床表现、实验室检查、X线检查结果及可能的诱发因素。
结果：30例肺部真菌感染患者与30例肺部细菌感染患者中，出现排痰费力、痰液粘稠不易咳出表现的患者分别为15例（50％）和4例（13％），肺部真菌感染组显著多于肺部细菌感染组（p<0.05）。肺部真菌感染患者中性粒细胞、淋巴细胞、中间核白细胞百分率分别为0.824±0.081、0.115±
0.069、0.063±0.033，肺部细菌感染患者中性粒细胞、淋巴细胞、中间核白细胞百分率分别为0.895±0.051、0.067±0.042、0.039±0.026，两组之间具有显著性差异(p<0.05)。肺部真菌感染组血清白蛋白/球蛋白(A/G)为1.3±0.4，显著低于肺部细菌感染组1.6±0.5(p<0.05)。可能导致肺部真菌感染的诱发因素包括：长期或大剂量应用糖皮质激素治疗、下呼吸道分泌物细菌培养阴性所造成的菌群失调、未曾接受过抗真菌治疗，与肺部细菌感染组相比有显著性差异（P<0.05）。肺部真菌感染患者病原学检查以念珠菌属感染为主，占87.6%, 其中白色念珠菌最多，占56.7%，占全部念珠菌感染的65.4%，对氟康唑耐药的真菌感染也占有一定的比例（30%）。
结论：肺部真菌感染与肺部细菌感染的临床特点有所差别，注意这些临床特点有助于与肺部细菌感染相鉴别，有助于临床医师在治疗肺部细菌感染的过程中及早发现肺部真菌感染，及时进行真菌学检查和抗真菌治疗。肺部真菌感染仍以白色念珠菌感染为主，对氟康唑耐药的真菌也占有一定的比例，提示临床需要结合真菌学检查和药敏实验进行抗真菌治疗。
Objective: Pulmonary fungal infections often occur during the treatment of pulmonary bacterial infections. The clinicians always feel puzzled to distinguish them from pulmonary bacterial infections. It will be of great clinical significance to know about the clinical characteristics of pulmonary fungal infections, the study of which will be helpful for us to make a rapid diagnosis and treatment of such disease. The clinical features of pulmonary fungal infections are not typical and the prognoses are not very serious especially in patients without mechanical ventilation. As a result, clinicians often neglect them. The patients have to suffer much more pain and economic burden due to the misdiagnosis and the delayed treatment. Therefore, We compared several clinical characteristics of pulmonary fungal infections with pulmonary bacterial infections in patients without mechanical ventilation by a case-control study design. Our research is to find out the clinical features of pulmonary fungal infections in these patients, which could distinguish them from the bacterial ones and help us to make a correct diagnosis of such infections.
Method: A case-control study was used. 30 patients with
pulmonary fungal infections or pulmonary bacterial infections were selected into the case group or the control group respectively if they met the strict selection criteria. All the patients we studied were the inpatients of the department of respiratory medicine in our hospital from Nov. 2001 to Dec. 2002. The matched standard was also taken into consideration. The clinical manifestation, laboratory examination results, X-ray check results and several risk factors were involved in the comparison of the two groups.
Results: There were several significant differences between the case group and the control group. 15(50%) patients with pulmonary fungal infections had the difficulties to spit sputum out, which were more than the patients (13%) of those with pulmonary bacterial infections (p<0.05). The percentage of neutrophils, lymphocytes, middle nuclear cell of the case group was 0.824±0.081、0.115±0.069、0.063±0.033 respectively as compared with 0.895±0.051、0.067±0.042、0.039±0.026 of the control group. The two groups had significant differences (p<0.05). A/G(albumin/globulin)was 1.3±0.4 in the case group, which was lower than that in the control group 1.6±0.5(p<0.05). The risk factors of pulmonary fungal infections included long-term or mass scale therapy with corticosteroid, having never accepted the anti-fungi cures and a negative result of germ culture in lower respiratory secretion (p<0.05). Candida, accounting for 87.6%, was the main pathogen that caused the pulmonary fungal infections. Candida albican was the most
common pathogen, which made up 56.7% of pulmonary fungal infections and 87.6% of Candida. Fungus resistant to Fluconazole was also found in a certain proportion（30%）.
Conclusion: we had found several differences of the clinical characteristics between pulmonary fungal and bacterial infections. These differences may be the distinctly clinical features. It will be helpful to pay attention to these clinical features to make distinguish diagnosis from pulmonary bacterial infections. That could be useful for clinicians to find out pulmonary fungal infections promptly. Candida albican was the main pathogen that caused the pulmonary fungal infections. Fungus resistant to Fluconazole was also found in a certain proportion. It suggested that it’s necessary to inspect the pathogens and test the antibiotics sensitivity in vitro.
引文
1 钱小顺,朱元珏,许文兵等.127例肺部真菌感染的临床分析.中华结核和呼吸杂志，2000, 23:417-419
中华医学会呼吸病学分会.社区获得性肺炎诊断和治疗指南（草案）.院内获得性肺炎诊断和治疗指南（草案）.中华结核和呼吸杂志，1999，22（4）:199-203
叶应妩，王毓三 .中华人民共和国卫生部医政司编.全国临床检验操作规程.南京.东南大学出版社.1997
Roilides E, Holmes A, Blake C, et al Impairment of neutrophil antifungal activity against hyphae of Aspergillus fumigatus in children infected with human immunodeficiency virus. J Infect Dis, 1993, 167(4):905-911
Sohnle PG, Hahn BL. Inhibition of pseudohyphal growth as a neutrophil-mediated host defense mechanism against experimental deep Candida albicans infections in mice. J Lab Clin Med, 1993 121(2):235-43
Sweeney JF, Rosemurgy AS, Wei S,et al.Candida antigen titer is a marker of neutrophil dysfunction after severe injury. J Traum, 1994, 36(6):797-802
Sweeney JF, Rosemurgy AS, Sheng W, et al. Impaired polymorphonuclear leukocyte anticandidal function in injured adults with elevated Candida antigen titers. Arch Surg, 1993, 128:40-60
Nugent KM, Onofrio JM. Pulmonary tissue resistance to Candida albicans in normal and in immunosuppressed mice.
Am Rev Respir Dis, 1983, 128:909-914
Blanchard K, Norris BM, Djeu JY. Production of granulocyte-macrophage colony-stimulating factor by large granular lymphocyte stimulated with Candida albicans: role in activation in human neutrophil function. Blood, 1991, 77(10):pp2259-2265
Roilides E, Holmes A, Blake C, et al. Antifungal activity of elutriated human monocytes against Aspergillus fumigatus hyphae: enhancement by granulocyte-macrophage colony-stimulating factor and interferon-gamma. J Infect Dis, 1994, 170(4):894-899
Roilides E, Sein T, Holmes A, et al. Effects of macrophage colony-stimulating factor on antifungal activity of mononuclear phagocytes against Aspergillus fumigatus. J Infect Dis, 1995, 172(4):1028-1034
Gaviria JM, van Burik JA, Dale DC, et al. Modulation of neutrophil-mediated activity against the pseudohyphal form of Candida albicans by granulocyte colony-stimulating factor (G-CSF) administered in vivo. J Infect Dis, 1999, 179(5):1301-1304
Liles WC, Huang JE, van Burik JA, et al. Granulocyte colony-stimulating factor administered in vivo augments neutrophil-mediated activity against opportunistic fungal pathogens. J Infect Dis, 1997, 175(4):1012-1015
Diamond RD, Lyman CA, Wysong DR. Disparate effects of interferon-gamma and tumor necrosis factor-alpha on early
neutrophil respiratory burst and fungicidal responses to Candida albicans hyphae in vitro. J Clin Invest，1991， 87(2):711-720
Roilides E, Uhlig K, Venzon D,Neutrophil oxidative burst in response to blastoconidia and pseudohyphae of Candida albicans: augmentation by granulocyte colony-stimulating factor and interferon-gamma. J Infect Dis，1992，166(3):668-673
Sweeney JF, Rosemurgy AS, Wei S, et al. Lymphocyte dysfunction in injured adults with elevated Candida antigen titers. Surgery, 1993, 114(4):698-703
Dales R, Miller D, White J,Influence of residential fungal contamination on peripheral blood lymphocyte populations in children. Arch Environ Health, 1998, 53(3):190-195
Levitz SM, Selsted ME, Ganz T, et al. In vitro killing of spores and hyphae of Aspergillus fumigatus and Rhizopus oryzae by rabbit neutrophil cationic peptides and bronchoaleveolar macrophages. J Jnfect Dis, 1986, 154: 483-489
Garviria JM, van Burik JAH, Dale DC, et al. Comparison of interferon-γ, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor for priming leukocyte-mediated hyphal damage of opportunistic fungal pathogens. J Infect Dis, 1999, 179:1038-1041
Diamond RD, Clark RA. Damage to Aspergillus fumigatus and Rhizopus oryzae by oxidative and nonoxidative
microbial products of human nertrophils in vitro. Infect Immun, 1982, 38:487-495
Washburn RG, Gallin JI, Bennett JE. Oxidatibe dilling of Aspergillus fumigatus proceeds by parallel myeloperoxidaxe-dependent and –independent pathways. Infect Immun, 1987, 55:2088-2092
Marodi L, Forehand JR, Johnston RB Jr. Mechanisms of host defense against Candida species. II. Biochemical basis for the killing of Candida by mononuclear phagocytes. J Immunol，1991，146(8):2790-2794
Stuck AE, Minder CE, Frey FJ. Risk of infectious complications in patients taking glucocorticosteroids. Rev Infect Dis. 1989, 11:954-963
Skerrett SJ, Niederman MS, Fein AM. Respiratory infections and acute lung injury in systemic illness. Clin Chest Med, 1989, 10:469-502
刘慕莎,段昌琦.抗生素与真菌感染.中国危重病急救医学，1995，7:97.
Yonezawa M, Sugiyama H, Kizawa K, et al. A new model of pulmonary superinfection with Aspergillus fumigatus and Pseudomonas aeruginosa in mice. J Infect Chemother, 2000 6(3):155-161
Wey SB, Mori M, Pfaller MA. Risk factors for hospital-acquired candidamia. Arch Intern Med, 1989, 149:2349-2353
Bross J, Talbot GH, Maislin G, et al. Risk factors for
hospital candidemia: a case-control study in adults without lerkemia. Am J Med, 1989, 87:614-620
Redmond HP, Leon P, Lieberman MD. Impaired macrophage function in severe protein-energy malnutrition. Arch Surg, 1991, 126:192-196
曾清. 重症监护室的院内肺部真菌感染临床研究. 中华医院感染学杂志，2002，12(7):488-490
Utili R, Zampino R, De Vivo F, et al. Improved outcome of pulmonary aspergillosis in heart transplant recipients with early diagnosis and itraconazole treatment. Clin Transplant 2000 , 14(4 Pt 1):282
Perea S, Patterson TF. Invasive Aspergillus infections in hematologic malignancy patients. Semin Respir Infect, 2002, 17(2):99-105
Libanore M, Prini E, Mazzetti M, et al. Invasive Aspergillosis in Italian AIDS patients. Infection 2002, 30(6):341-345