真菌性角膜炎常见菌种分析及体外药物敏感试验
摘要
目的分析真菌性角膜炎的致病菌种分布情况和体外药敏试验结果,为指导临床治疗提供实验依据。
方法统计山东省眼科研究所2000～2006年间真菌性角膜炎病例的培养和菌种鉴定结果,同时选择临床常见的茄病镰刀菌、烟曲霉和黄曲霉三种菌株各15株进行体外药物单独和联合药敏试验,试验药物为二性霉素B、伊曲康唑和氟康唑。
结果①6年间共对898份临床标本进行真菌的分离培养,阳性结果770份,阳性率为85.7%。共分离鉴定出12个菌属的27种真菌,其中镰刀菌属占71.0%(547/770),曲霉菌属占10.9%(84/770),链格孢菌属占9.61%(74/770)。致病菌为镰刀菌属的515例患者包括10个菌种,主要为茄病镰刀菌185例(33.8%)、尖孢镰刀菌154例(28.2%)与串珠镰刀菌150例(27.4%),其余32例(5.9%)未能明确致病菌种。84例曲霉菌性角膜炎患者的致病菌包括6个菌种,主要为黄曲霉45例(53.6%)与烟曲霉菌33例(39.3%)。②体外药敏试验结果显示真菌对二性霉素B的敏感性最高(91.1%),对伊曲康唑的敏感性为71.1%,对氟康唑的敏感性较低(51.1%)。镰刀菌对二性霉素B的敏感率最高(80%),明显高于对伊曲康唑和氟康唑的敏感率(x~2=13.400,P＜0.01;x~2=16.425,P＜0.01);对伊曲康唑的敏感率和对氟康唑的敏感率相比无显著性差异(x~2=0.370,P＞0.05)。曲霉菌对伊曲康唑100%敏感,与对二性霉素B的敏感率(96.7%)相比差异无统计学意义(x~2=1.170,P＞0.05);但明显高于对氟康唑的敏感率(x~2=4.615,P＜0.05);曲霉菌对氟康唑和二性霉素B的敏感率相比差异也有统计学意义(x~2=6.280,P＜0.05)。③联合药物试验结果显示二性霉素B与氟康唑联合应用时57.8%具有协同作用,与伊曲康唑联合时31.1%具有协同作用,伊曲康唑和氟康唑联合时55.6%具有协同作用。前两组的协同作用差异有统计学意义(x~2=6.48,P＜0.05),第二组与第三组的协同作用差异有统计学意义(x~2=5.745,P＜0.05),第一组与第三组的协同作用差异无统计学意义(x~2=0.452,P＞0.05)。④二性霉素B单独药敏时MIC为1.060±2.699μg/ml,与伊曲康唑联合时MIC则为0.492±1.396μg/ml,差异有统计学意义(t=3.801,P＜0.01);与氟康唑联合时为0.421±0.823μg/ml,差异有统计学意义(t=3.639,P＜0.05)。伊曲康唑单独药敏时MIC为0.781±6.367μg/ml,与二性霉素B联合应用时则为0.387±3.739μg/ml,差异有统计学意义(t=3.514,P＜0.01);与氟康唑联合时为0.523±3.468μg/ml,差异有统计学意义(t=4.136,P＜0.01)。氟康唑单独药敏时MIC为47.760±24.427μg/ml,与伊曲康唑联合应用时则为17.549±19.041μg/ml,差异有统计学意义(t=9.852,P＜0.01);与二性霉素B联合时为16.757±15.600μg/ml,差异有统计学意义(t=10.804,P＜0.01)。
结论①镰刀菌、曲霉菌和链隔孢霉是真菌性角膜炎主要的致病菌种。②治疗真菌性角膜炎时首选二性霉素B,曲霉菌感染时也可首选伊曲康唑,但氟康唑作用较差。③联合用药时可选择二性霉素B和氟康唑或伊曲康唑和氟康唑联合,二性霉素B和伊曲康唑联合时效果可能较差。④药物联合使用时参考药敏结果调整剂量。
Objective To analyze the pathogens distribution and in vitro drug sensitivity in fungal keratitis during 2000～2006 in Shandong Province.
Methods Samples by corneal scrapings and corneal buttons from keratoplasties were subjected to fungal cultures and identifications,and 45 isolates were investigated the in vitro drug sensitivity of AMB、FCZ and ICZ alone and interactively.
Results①898 patients were diagnosed as fungal keratitis from 2000 to 2006,of which 770(85.7%) were positive in fungal culture.12 genus and 27 species fungi were identified in 770 cases,of which the common pathogens were 547 Fusarium(71.0%,547/770),84 Aspergillus(10.9%,84/770),and 74 Alternaria(9.6%,74/770) respectively. In the genus Fusarium,10 species were included except for 32 cases with the pathogens unidentified to the species level, and the main species were 185 F.Solani(33.8%),154 F.oxysporum(28.2%) and 150 F.moniliforme(27.4%).6 species were involved in the genus Aspergillus,with A.flavus(53.6%) and A.fumigatus(39.3%) being the common species.②In the drug sensitivity test in vitro,the total susceptibility rate of AMB、ICZ and FCZ was 91.1%、71.1%and 51.1%.AMB was more sensitive than ICZ and FCZ for Fusarium(P＜0.01).As for Aspergi llus,AMB and ICZ were more sensitive than FCZ(P＜0.05).③The combination drug sensitivity test of AMB and FCZ showed that the synergestic was 57.8%,that of AMB and ICZ combination were 31.1%,ICZ and FCZ were 55.6%.The rates of synergestic between the combination AMB & FCZ and combination FCZ&ICZ were higher than that of cmobination AMB & ICZ(P＜0.05).④The geometric mean MICs of the three agents were significantly reduced in the combination drug senitivity test(P＜0.05).
Conclusions①Genus Fusarium,Aspergillus and Alternaria are the main pathogens in fungal keratitis in Shandong Province from 2000 to 2006.②AMB was the first chose for keratitis therapy,ICZ could be thought first when the pathogenic was Aspergillus.FCZ was not good selection for keratitis.③The combination of AMB and FCZ and the combination ICZ and FCZ were better than AMB and ICZ combination in keratitis therapy.④The dose of drug should be adjust in clinical therapy refer to the in vitro drug sensitivity test.
方法统计山东省眼科研究所2000～2006年间真菌性角膜炎病例的培养和菌种鉴定结果,同时选择临床常见的茄病镰刀菌、烟曲霉和黄曲霉三种菌株各15株进行体外药物单独和联合药敏试验,试验药物为二性霉素B、伊曲康唑和氟康唑。
结果①6年间共对898份临床标本进行真菌的分离培养,阳性结果770份,阳性率为85.7%。共分离鉴定出12个菌属的27种真菌,其中镰刀菌属占71.0%(547/770),曲霉菌属占10.9%(84/770),链格孢菌属占9.61%(74/770)。致病菌为镰刀菌属的515例患者包括10个菌种,主要为茄病镰刀菌185例(33.8%)、尖孢镰刀菌154例(28.2%)与串珠镰刀菌150例(27.4%),其余32例(5.9%)未能明确致病菌种。84例曲霉菌性角膜炎患者的致病菌包括6个菌种,主要为黄曲霉45例(53.6%)与烟曲霉菌33例(39.3%)。②体外药敏试验结果显示真菌对二性霉素B的敏感性最高(91.1%),对伊曲康唑的敏感性为71.1%,对氟康唑的敏感性较低(51.1%)。镰刀菌对二性霉素B的敏感率最高(80%),明显高于对伊曲康唑和氟康唑的敏感率(x~2=13.400,P＜0.01;x~2=16.425,P＜0.01);对伊曲康唑的敏感率和对氟康唑的敏感率相比无显著性差异(x~2=0.370,P＞0.05)。曲霉菌对伊曲康唑100%敏感,与对二性霉素B的敏感率(96.7%)相比差异无统计学意义(x~2=1.170,P＞0.05);但明显高于对氟康唑的敏感率(x~2=4.615,P＜0.05);曲霉菌对氟康唑和二性霉素B的敏感率相比差异也有统计学意义(x~2=6.280,P＜0.05)。③联合药物试验结果显示二性霉素B与氟康唑联合应用时57.8%具有协同作用,与伊曲康唑联合时31.1%具有协同作用,伊曲康唑和氟康唑联合时55.6%具有协同作用。前两组的协同作用差异有统计学意义(x~2=6.48,P＜0.05),第二组与第三组的协同作用差异有统计学意义(x~2=5.745,P＜0.05),第一组与第三组的协同作用差异无统计学意义(x~2=0.452,P＞0.05)。④二性霉素B单独药敏时MIC为1.060±2.699μg/ml,与伊曲康唑联合时MIC则为0.492±1.396μg/ml,差异有统计学意义(t=3.801,P＜0.01);与氟康唑联合时为0.421±0.823μg/ml,差异有统计学意义(t=3.639,P＜0.05)。伊曲康唑单独药敏时MIC为0.781±6.367μg/ml,与二性霉素B联合应用时则为0.387±3.739μg/ml,差异有统计学意义(t=3.514,P＜0.01);与氟康唑联合时为0.523±3.468μg/ml,差异有统计学意义(t=4.136,P＜0.01)。氟康唑单独药敏时MIC为47.760±24.427μg/ml,与伊曲康唑联合应用时则为17.549±19.041μg/ml,差异有统计学意义(t=9.852,P＜0.01);与二性霉素B联合时为16.757±15.600μg/ml,差异有统计学意义(t=10.804,P＜0.01)。
结论①镰刀菌、曲霉菌和链隔孢霉是真菌性角膜炎主要的致病菌种。②治疗真菌性角膜炎时首选二性霉素B,曲霉菌感染时也可首选伊曲康唑,但氟康唑作用较差。③联合用药时可选择二性霉素B和氟康唑或伊曲康唑和氟康唑联合,二性霉素B和伊曲康唑联合时效果可能较差。④药物联合使用时参考药敏结果调整剂量。
Objective To analyze the pathogens distribution and in vitro drug sensitivity in fungal keratitis during 2000～2006 in Shandong Province.
Methods Samples by corneal scrapings and corneal buttons from keratoplasties were subjected to fungal cultures and identifications,and 45 isolates were investigated the in vitro drug sensitivity of AMB、FCZ and ICZ alone and interactively.
Results①898 patients were diagnosed as fungal keratitis from 2000 to 2006,of which 770(85.7%) were positive in fungal culture.12 genus and 27 species fungi were identified in 770 cases,of which the common pathogens were 547 Fusarium(71.0%,547/770),84 Aspergillus(10.9%,84/770),and 74 Alternaria(9.6%,74/770) respectively. In the genus Fusarium,10 species were included except for 32 cases with the pathogens unidentified to the species level, and the main species were 185 F.Solani(33.8%),154 F.oxysporum(28.2%) and 150 F.moniliforme(27.4%).6 species were involved in the genus Aspergillus,with A.flavus(53.6%) and A.fumigatus(39.3%) being the common species.②In the drug sensitivity test in vitro,the total susceptibility rate of AMB、ICZ and FCZ was 91.1%、71.1%and 51.1%.AMB was more sensitive than ICZ and FCZ for Fusarium(P＜0.01).As for Aspergi llus,AMB and ICZ were more sensitive than FCZ(P＜0.05).③The combination drug sensitivity test of AMB and FCZ showed that the synergestic was 57.8%,that of AMB and ICZ combination were 31.1%,ICZ and FCZ were 55.6%.The rates of synergestic between the combination AMB & FCZ and combination FCZ&ICZ were higher than that of cmobination AMB & ICZ(P＜0.05).④The geometric mean MICs of the three agents were significantly reduced in the combination drug senitivity test(P＜0.05).
Conclusions①Genus Fusarium,Aspergillus and Alternaria are the main pathogens in fungal keratitis in Shandong Province from 2000 to 2006.②AMB was the first chose for keratitis therapy,ICZ could be thought first when the pathogenic was Aspergillus.FCZ was not good selection for keratitis.③The combination of AMB and FCZ and the combination ICZ and FCZ were better than AMB and ICZ combination in keratitis therapy.④The dose of drug should be adjust in clinical therapy refer to the in vitro drug sensitivity test.
引文
1 谢立信,王富华,史伟云.1997至2002年山东省眼科研究所穿透性角膜移植术的原因分析.中华眼科杂志,2006;42(8):704-708
2 钟文贤,孙士营,赵靖,等.1054例化脓性角膜炎的回顾性分析,中华眼科杂志2007:43(3):245-250
3 Leck AK,Thomas PA,Hagan M,et al.Aetiology of suppurative corneal ulcers in Ghana and South India,and epidemiology of fungal keratitis.Br J Ophthalmol,2002;86:1211-1215
4 王端礼.医学真菌学-实验室检验指南[M].第1版.人民卫生出版社,2005:203,266-275,318-321,421-430
5 Leber TH.Keratomycosis aspergillina als ursache von hypopyonkeratitis.Grafes Arch Ophthalmol,1879;25:285-301
6Sharma S,Srinivasan M,George C.The current status of Fusarium species in mycotic keratitis in south India.indian J Med Microbiol,1993;11:140-7
7 Srinivasan M,Gonzales C,George C,et al.Epidemiology and aetiological diagnosis of corneal ulceration in Madurai,South India.Br J Ophthalmol,1997;81:965-971
8 张文华,潘志强,王智群,等.化脓性角膜溃疡常见致病菌的变迁.中华眼科杂志,2002;38:8-12
9 邓新国,吕雪芳,庞广仁,等.312例化脓性角膜溃疡的病因和病原分析.眼科研究,1995;13:110-113
10 Srinivasan R,Kanungo R.Goyal JL,et al.Spectrum of oculomycosis in South India.Acta Ophthalmol,1991;69:744-9
11 Gopinathan U,Garg P,Femandes M,et al.The epidemiological features and Laboratory results of fungal keratitis.A 10 year review at a referral eye care center.Cornea,2002;21:555-559
12 Kunimoto D,Sharma S,Garg P,et al.Corneal ulceration in the elderly in Hyderabad,South India.BrJ Ophthalmol,2000;84:54-59
13 王丽娅,张月琴,王印其,等.中国三地区真菌性角膜病致病种的调查.中华眼科杂志,2000:36:138-140.
14 Wei-li CHEN,Chun-ying W U,Fung-ring HU,et al.Therapeutic penetrating keratoplasty for microbial keratitis in Taiwan from 1987-2001.Am J Ophthalmol,2004;137:736-743
15 Tanure MAG,Cohen EJ,Sudesh S,et al.Spectrum of fungal keratitis at Wills eye hospital,Philadelphia,Pennsylvania.Cornea,2000;19:307-312
16 Tanure MAG,Cohen E J,Sudesh SF,et al..Spectrum of Fungal Keratitis at Wills Eye Hospital,Philadelphia,Pennsylvania.Cornea,2000;19:307-312
17 Rondeau N,Bourcier T,Chaumeil C,et al.Fungal keratitis at the Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts:retrospective study of 19 cases.J Fr Ophtalmol,2002;25:890-896
18Ritterband,David C,John A,et al.Fungal Keratitis at the New York Eye and Ear Infirmary.Cornea,2006;25:264-267
19 Bhartiya P,Daniell M,Constantinou M,et al.Fungal keratitis in Melbourne.Clin Experiment Ophthalmol,2007;35:124-130
20 Chander J,Sharma A,Prevalence of fungal coneal ulcers in northren India.Infection,1994;22:207-209
21Xie L,Zhong W,Shi W,et al.Spectrum of fungal keratitis in north China.Ophthalmology,2006;113:1943-1948
22孙旭光,王智群,罗时运,等.眼部真菌感染的病原学分析.中华眼科杂志,2002;38:405-407
23 王丽娅,孙声桃,张月琴,等.河南地区真菌性角膜病致病菌种调查.中国实用眼科杂志,2003;21:224-225
24 Liesegang TJ,Forster RK.Spectrum of microbial keratitis in South Florida.Am J Ophthalmol,1980;90:38-47
25 Rosa RH Jr,Miller D,Alfonso EC,et al.The changing spectrum of fungal keratitis in South Florida.Ophthalmology,1994;101:1005-1013
26 Bharathi M,Ramakrishnan R,Vasu S,et al.Epidemiological characteristics and laboratory diagnosis of fungal keratitis.A three-year study.Indian journal of Ophthalmology,2003;51:315-321
27 Bharathi MJ,Ramakrishnan R,Vasu S,et al.Aetiological diagnosis of microbial keratitis in South India - A study of 1618 cases.Indian Journal of Medical Microbiology,2002;20:19-24
28 ChowdharyA,Singh K.Spectrum of Fungal Keratitis in North India.Comea,2005;24(1):8-15
29 卢嘉彪,陈家祺,王丽娅.广州地区真菌性角膜病的病原体及其发病情况的变迁.眼科研究,1998;16:289-290
30 郑玮清,王文莉,李若瑜,等.微量法检测皮肤癣菌对6种抗真菌药物敏感性.中华皮肤科杂志,1999;32:350-352
31 周春英,郑玮清,周东,等.试管法检测氟康唑和特比萘芬对常见致病性真菌的敏感性观察.中国麻风病皮肤杂志,2000;16:85-87
32 佟盼琢,李若瑜,万喆,等.应用M38-P方案测定皮肤癣菌对抗真菌药物的敏感性.中国麻风病皮肤杂志,2001;17:147-149
33 Jessup CJ,Ryder NS,Ghannoum MA.An evalution of the in vitro activity of terbinafine.Medical Mycology,2001;38:155
34 杨秀敏,万哲,李若瑜.抗真菌药对角膜真菌感染病原菌的体外药敏试验研究.中国麻风皮肤病杂志,2005;21:770-773
35 Te Dorsthorst DT,Verweij PE,Meis JF,et al.Comparison of fractional inhibitory concentration index with response surface modeling for characterization of in vitro interaction of antifungals against itraconazole-susceptible and resistant aspergillus fumigatus isolates.Antimicrob Agents Chemother,2002;46:702-707
36 Ryder NS,Leitner L.Synergistic interaction of terbinafine with triazoles or amphotericin B against Aspergillus species.Med Mycol,2001;39:91-95
37Kontoyiannis P,Lewis RE,Sagar N,et al.Itraconazole-amphotericin B antagonism in Aspergillus fumigatus:an E-test-based strategy.Antimicrob Agents Chemother,2000;44:2915-2918
38 Mosquera J,Sharp A,Moore CB,et al.In vitro interaction of terbinafine with itraconazole,fluconazole,mphotericin B and 5-flucytosine against Aspergillus spp.Antimicrob Chemother,2002;50:189-194
39 Nguyen MH,Barchiesi F,McGough DA,et al.In vitro evaluation of combinationof fluconazole and flucytosine against Cryptococcus neoformans var neofomans.Antimicrob Agents Chemother,1995:39:1691-1695
40 董平,万哲,李若瑜.抗真菌药单独及联合应用对曲霉菌的体外药敏试验研究.中华检验医学杂志,2003;26(9):527-529
41 Ryder NS,Leitner L.Synergistic interaction of terbinafine with triazoles or amphotericin B against Aspergillus species.Med Mycol,2001;39:91-95
42 郭秀军,廖万清,任大明,等.伊曲康唑与二性霉素B抗新生隐球菌临床分离株的实验研究.中华皮肤科杂志,2003;12:711-713
1 邓新国,吕雪芳,庞广仁,等.312例化脓性角膜溃疡的病因和病原分析.眼科研究,1995;13:110-113
2 钟文贤,谢立信,史伟云,等.真菌性角膜炎654例感染谱分析.中华医学杂志,2006;86-1681-1685
3 张文华,潘志强,王智群,等.化脓性角膜溃疡常见致病菌的变迁.中华眼科杂志,2002;38:8-12
4 Kaufman HE,Barron BA,Mcdonald MB,et al.Companion handbook to the cornea second edition.Boston:Butterworth,2000.147.
5 Tanure MAG,Cohen EJ,Sudesh S,et al.Spectrum of fungal keratitis at Wills eye hospital,Philadelphia,Pennsylvania.Cornea,2000;19:307-312
6 Leber TH.Keratomycosis aspergillina als ursache von hypopyonkeratitis.Grafes Arch.Ophthalmol,1879;25:285-301
7 Tanure MAG,Cohen EJ,Sudesh S,et al.Spectrum of fungal keratitis at Wills eye hospital,Philadelphia,Pennsylvania.Cornea,2000;19:307-312
8 Tanure,Marco Antonio G,Cohen,et al.Spectrum of Fungal Keratitis at Wills Eye Hospital,Philadelphia,Pennsylvania.Cornea,2000;19:307-312
9 Rondeau N,Bourcier T,Chaumeil C,et al.Fungal keratitis at the Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts:retrospective study of 19 cases.J Fr Ophtalmol,2002;25:890-896
10 Ritterband,David C,John A,et al.Fungal Keratitis at the New York Eye and Ear Infirmary.Cornea,2006;25:264-267
11 Bhartiya P,Daniell M,Constantinou M,et al.Fungal keratitis in Melbourne.Clin Experiment Ophthalmol,2007;35:124-130
12 Leck AK,Thomas PA,Hagan M,et al.Aetiology of suppurative Corneal ulcers in Ghana and South India,and epidemiology of fungal keratitis.Br J Ophthalmol,2002;86:1211-1215
13 Gopinathan U,Garg P,Femandes M,et al.The cpidemiological features and Laboratory results of fungal keratitis.A 10 year review at a referral eye care center.Cornea,2002;21:555-559
14 Bharathi MJ,Ramakrishnan R,Vasu S,et al.Epidemiological characteristics and laboratory diagnosis of fungal keratitis.A threeyearstudy.Indian J Ophthalmol,2003;51(4):315.321
15 Chowdhary A,Singh K.Spectrum of Fnngal Keratitis in North India.Cornea,2005,24(1):8.15
16 Deshpande SD,Koppikar GV.A study of mycotic keratitis inMumbal.Indian J Pathol Microbiol.1999;42:81-87
17 Garg P,Gopinathan U,Choudhary K,et al.Keratomycosis:clinical and microbiologic experience with dematiaceous fungi.Ophthalmology,2000;107:574-580
18 Kunimoto DY,Sharma S,GargP,et al.Comealulceration in the elderly in Hyderabad,south India.Br J Ophihalmol,2000;84:54-59
19 Chander J.Sharma A.Prevalence of fungal coneal ulcers in northren India.Infection,1994;22:207.209
20 Khanal B,Kaini KR,Deb M,et al.Microbial keratitis in eastern Nepa1.Tropical Doctor,2001;31:168-169
21 ChowdharyA,Singh K.Spectrum of Fungal Keratitis in North India.Comea,2005;24(1):8-15
22 SUN Xu-guang,ZHANG Yan,LI Ran,et al.Etiological analysis on ocular fungal infection in the period of 1989-2000.Chinese Medical Journal,2004;117:598-600
23 孙声桃,王丽娅,徐筠,等.互隔交链孢霉菌性角膜炎的临床与病原学研究.中华眼科杂志,2007:43:32-35.
24 王丽娅,张月琴,王印其,等.中国三地区真菌性角膜病致病种的调查.中华眼科杂志,2000:36:138-140
25 Tanure MA,Cohen EL,Sidesh S,et al.Spectrum of fungal keratitis at Wills Eye Hospital Philadelphia,Pennsylvan ia.Cornea,2000;19:307-312
26 M Srinivasan,C.Gonzales,C.George,et al.Epidemiology and aetiological diagnosis of corneal ulceration in Madurai,south India.Br J Ophthalmol,1997;81:965-971
27 Liesegang TJ,Forster RK.Spectrum of microbial keratitis in South Florida.Am J Ophthalmol,1980:90:38-47
28 Rosa RH Jr,Miller D,Alfonso EC,et al.The changing spectrum of fungal keratitis in South Florida.Ophthalmology,1994:101:1005-1013
29 Bharathi MJ,Ramakrishnan R,Vasu S,et al.Aetiological diagnosis of microbial keratitis in South India - A study of 1618 cases.Indian Journal of Medical Microbiology,2002:20:19-24
30 孙旭光,王智群,罗时运,等.眼部真菌感染的病原学分析.中华眼科杂志,2002:38:405-407
31 Ghannoum MA,Rex JH,Galgiani JN.Susceptibility testing of fungi:current status of correlation of in vitro data with clinical outcome.J Clin Microbiol,1996;34:489-495
32 Rex JH,Pfaller MA.Has antifungal susceptibility testing come of age? Clin Infect Dis,2002;35:982-989
33 佟盼琢,李若瑜,万喆,等.应用M38-P方案测定皮肤癣菌对抗真菌药物的敏感性.中国麻风病皮肤杂志, 2001:17:147-149
34 Jessup CJ,Ryder NS,Ghannoum MA.An evalution of the in vitro activity of terbinafine.Medical Mycology,2001:38:155
35 吴伟元,何林,吴劲松,等.E-test法检测3种抗真菌药物对128株酵母菌的体外活性.中国抗感染化疗杂志,2005;5:89-91
36 徐英春,谢秀丽,王澎.Etest法测定伊曲康唑对曲霉和酵母菌的体外抗菌活性.中国新药杂志,2004;2:163-165
37 Pfaller MA,Messer SA,Bolmstrom A,et al.Multisete reproducibility of the Etest MIC method for antifungal susceptibility testing of yeast isolates.J Clin Microbiol,1996;34:1691-1693
38 Espinel-Ingroff A,Pfaller M,Erwin ME,et al.Interlaboratory evaluation of Etest method for testing antifungal susceptibilities of pathogenic yeasts to five antifungal agents by using Casitone agar and solidified RPMI 1640 medium with 2%glucose.J Clin Microbial,1996:34:848-852
39 Colombo AL,Barchiesi F,McGough DA,et al.Comparison of Etest and National Committee for Clinical Laboratory Standards broth macrodilution method for azole antifungal susceptibility testing.J Clin icrobial,1995:33:535-540
40 WangerA,Mils K,Nelson PW,et al.Comparison of Etest and NCCLS broth macrodilution mehod for antifungal susceptibility testing:Enhanced ablity to detect ampnotericin B-resistant Candida isolates.Antimicrbial Agents and Chemotherapy,1995:39:2520-2522
41 van Eldere J,Joosten L,Verhaeghe V,et al.Fluconazole and amphotericin B antifungal susceptibility testing by NCCLS broth macrodilution method compared with Etest and semiautomated broth microdilution test.Jclin Microbiol,1996;34:842-847
42 张晓冬,徐莉.Etest法和NCCLS微量法检测念珠菌对氟康唑的敏感性.中国皮肤性病学杂志,2006;4:
43 徐修礼,杨佩红,孙怡群.真菌药敏纸片扩散法实验与应用研究.临床检验杂志,2006;24:278-279
44 李若瑜,万哲,陈剑.采用葡萄糖消耗法快速测定念珠菌对唑类药物的敏感性.临床皮肤科杂志,2003;9:499-501
45 Riesselman MH,Kazen KC,Culter JE.Petermination of antifungal MICs by a rapid susceptibility assay[J].J Clin Microbiol,2000:38:333-340
46 董平,万哲,李若瑜.抗真菌药单独及联合应用对曲霉菌的体外药敏试验研究.中华检验医学杂志,2003:26(9):527-529
47 郭秀军,廖万清,任大明,等.伊曲康唑与二性霉素B抗新生隐球菌临床分离株的实验研究.中华皮肤科杂 志, 2003; 12: 711-713
48 Barchiesi F, Falconi DiFrancesco L, Scalise G, et al. In vitro activities of terbinafine in combination with fluconazole and itraconazole against isolates of Candida albicans with reduced susceptibility to azoes. Antimicrob Agents Chemother, 1997; 41: 1812-1814
2 钟文贤,孙士营,赵靖,等.1054例化脓性角膜炎的回顾性分析,中华眼科杂志2007:43(3):245-250
3 Leck AK,Thomas PA,Hagan M,et al.Aetiology of suppurative corneal ulcers in Ghana and South India,and epidemiology of fungal keratitis.Br J Ophthalmol,2002;86:1211-1215
4 王端礼.医学真菌学-实验室检验指南[M].第1版.人民卫生出版社,2005:203,266-275,318-321,421-430
5 Leber TH.Keratomycosis aspergillina als ursache von hypopyonkeratitis.Grafes Arch Ophthalmol,1879;25:285-301
6Sharma S,Srinivasan M,George C.The current status of Fusarium species in mycotic keratitis in south India.indian J Med Microbiol,1993;11:140-7
7 Srinivasan M,Gonzales C,George C,et al.Epidemiology and aetiological diagnosis of corneal ulceration in Madurai,South India.Br J Ophthalmol,1997;81:965-971
8 张文华,潘志强,王智群,等.化脓性角膜溃疡常见致病菌的变迁.中华眼科杂志,2002;38:8-12
9 邓新国,吕雪芳,庞广仁,等.312例化脓性角膜溃疡的病因和病原分析.眼科研究,1995;13:110-113
10 Srinivasan R,Kanungo R.Goyal JL,et al.Spectrum of oculomycosis in South India.Acta Ophthalmol,1991;69:744-9
11 Gopinathan U,Garg P,Femandes M,et al.The epidemiological features and Laboratory results of fungal keratitis.A 10 year review at a referral eye care center.Cornea,2002;21:555-559
12 Kunimoto D,Sharma S,Garg P,et al.Corneal ulceration in the elderly in Hyderabad,South India.BrJ Ophthalmol,2000;84:54-59
13 王丽娅,张月琴,王印其,等.中国三地区真菌性角膜病致病种的调查.中华眼科杂志,2000:36:138-140.
14 Wei-li CHEN,Chun-ying W U,Fung-ring HU,et al.Therapeutic penetrating keratoplasty for microbial keratitis in Taiwan from 1987-2001.Am J Ophthalmol,2004;137:736-743
15 Tanure MAG,Cohen EJ,Sudesh S,et al.Spectrum of fungal keratitis at Wills eye hospital,Philadelphia,Pennsylvania.Cornea,2000;19:307-312
16 Tanure MAG,Cohen E J,Sudesh SF,et al..Spectrum of Fungal Keratitis at Wills Eye Hospital,Philadelphia,Pennsylvania.Cornea,2000;19:307-312
17 Rondeau N,Bourcier T,Chaumeil C,et al.Fungal keratitis at the Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts:retrospective study of 19 cases.J Fr Ophtalmol,2002;25:890-896
18Ritterband,David C,John A,et al.Fungal Keratitis at the New York Eye and Ear Infirmary.Cornea,2006;25:264-267
19 Bhartiya P,Daniell M,Constantinou M,et al.Fungal keratitis in Melbourne.Clin Experiment Ophthalmol,2007;35:124-130
20 Chander J,Sharma A,Prevalence of fungal coneal ulcers in northren India.Infection,1994;22:207-209
21Xie L,Zhong W,Shi W,et al.Spectrum of fungal keratitis in north China.Ophthalmology,2006;113:1943-1948
22孙旭光,王智群,罗时运,等.眼部真菌感染的病原学分析.中华眼科杂志,2002;38:405-407
23 王丽娅,孙声桃,张月琴,等.河南地区真菌性角膜病致病菌种调查.中国实用眼科杂志,2003;21:224-225
24 Liesegang TJ,Forster RK.Spectrum of microbial keratitis in South Florida.Am J Ophthalmol,1980;90:38-47
25 Rosa RH Jr,Miller D,Alfonso EC,et al.The changing spectrum of fungal keratitis in South Florida.Ophthalmology,1994;101:1005-1013
26 Bharathi M,Ramakrishnan R,Vasu S,et al.Epidemiological characteristics and laboratory diagnosis of fungal keratitis.A three-year study.Indian journal of Ophthalmology,2003;51:315-321
27 Bharathi MJ,Ramakrishnan R,Vasu S,et al.Aetiological diagnosis of microbial keratitis in South India - A study of 1618 cases.Indian Journal of Medical Microbiology,2002;20:19-24
28 ChowdharyA,Singh K.Spectrum of Fungal Keratitis in North India.Comea,2005;24(1):8-15
29 卢嘉彪,陈家祺,王丽娅.广州地区真菌性角膜病的病原体及其发病情况的变迁.眼科研究,1998;16:289-290
30 郑玮清,王文莉,李若瑜,等.微量法检测皮肤癣菌对6种抗真菌药物敏感性.中华皮肤科杂志,1999;32:350-352
31 周春英,郑玮清,周东,等.试管法检测氟康唑和特比萘芬对常见致病性真菌的敏感性观察.中国麻风病皮肤杂志,2000;16:85-87
32 佟盼琢,李若瑜,万喆,等.应用M38-P方案测定皮肤癣菌对抗真菌药物的敏感性.中国麻风病皮肤杂志,2001;17:147-149
33 Jessup CJ,Ryder NS,Ghannoum MA.An evalution of the in vitro activity of terbinafine.Medical Mycology,2001;38:155
34 杨秀敏,万哲,李若瑜.抗真菌药对角膜真菌感染病原菌的体外药敏试验研究.中国麻风皮肤病杂志,2005;21:770-773
35 Te Dorsthorst DT,Verweij PE,Meis JF,et al.Comparison of fractional inhibitory concentration index with response surface modeling for characterization of in vitro interaction of antifungals against itraconazole-susceptible and resistant aspergillus fumigatus isolates.Antimicrob Agents Chemother,2002;46:702-707
36 Ryder NS,Leitner L.Synergistic interaction of terbinafine with triazoles or amphotericin B against Aspergillus species.Med Mycol,2001;39:91-95
37Kontoyiannis P,Lewis RE,Sagar N,et al.Itraconazole-amphotericin B antagonism in Aspergillus fumigatus:an E-test-based strategy.Antimicrob Agents Chemother,2000;44:2915-2918
38 Mosquera J,Sharp A,Moore CB,et al.In vitro interaction of terbinafine with itraconazole,fluconazole,mphotericin B and 5-flucytosine against Aspergillus spp.Antimicrob Chemother,2002;50:189-194
39 Nguyen MH,Barchiesi F,McGough DA,et al.In vitro evaluation of combinationof fluconazole and flucytosine against Cryptococcus neoformans var neofomans.Antimicrob Agents Chemother,1995:39:1691-1695
40 董平,万哲,李若瑜.抗真菌药单独及联合应用对曲霉菌的体外药敏试验研究.中华检验医学杂志,2003;26(9):527-529
41 Ryder NS,Leitner L.Synergistic interaction of terbinafine with triazoles or amphotericin B against Aspergillus species.Med Mycol,2001;39:91-95
42 郭秀军,廖万清,任大明,等.伊曲康唑与二性霉素B抗新生隐球菌临床分离株的实验研究.中华皮肤科杂志,2003;12:711-713
1 邓新国,吕雪芳,庞广仁,等.312例化脓性角膜溃疡的病因和病原分析.眼科研究,1995;13:110-113
2 钟文贤,谢立信,史伟云,等.真菌性角膜炎654例感染谱分析.中华医学杂志,2006;86-1681-1685
3 张文华,潘志强,王智群,等.化脓性角膜溃疡常见致病菌的变迁.中华眼科杂志,2002;38:8-12
4 Kaufman HE,Barron BA,Mcdonald MB,et al.Companion handbook to the cornea second edition.Boston:Butterworth,2000.147.
5 Tanure MAG,Cohen EJ,Sudesh S,et al.Spectrum of fungal keratitis at Wills eye hospital,Philadelphia,Pennsylvania.Cornea,2000;19:307-312
6 Leber TH.Keratomycosis aspergillina als ursache von hypopyonkeratitis.Grafes Arch.Ophthalmol,1879;25:285-301
7 Tanure MAG,Cohen EJ,Sudesh S,et al.Spectrum of fungal keratitis at Wills eye hospital,Philadelphia,Pennsylvania.Cornea,2000;19:307-312
8 Tanure,Marco Antonio G,Cohen,et al.Spectrum of Fungal Keratitis at Wills Eye Hospital,Philadelphia,Pennsylvania.Cornea,2000;19:307-312
9 Rondeau N,Bourcier T,Chaumeil C,et al.Fungal keratitis at the Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts:retrospective study of 19 cases.J Fr Ophtalmol,2002;25:890-896
10 Ritterband,David C,John A,et al.Fungal Keratitis at the New York Eye and Ear Infirmary.Cornea,2006;25:264-267
11 Bhartiya P,Daniell M,Constantinou M,et al.Fungal keratitis in Melbourne.Clin Experiment Ophthalmol,2007;35:124-130
12 Leck AK,Thomas PA,Hagan M,et al.Aetiology of suppurative Corneal ulcers in Ghana and South India,and epidemiology of fungal keratitis.Br J Ophthalmol,2002;86:1211-1215
13 Gopinathan U,Garg P,Femandes M,et al.The cpidemiological features and Laboratory results of fungal keratitis.A 10 year review at a referral eye care center.Cornea,2002;21:555-559
14 Bharathi MJ,Ramakrishnan R,Vasu S,et al.Epidemiological characteristics and laboratory diagnosis of fungal keratitis.A threeyearstudy.Indian J Ophthalmol,2003;51(4):315.321
15 Chowdhary A,Singh K.Spectrum of Fnngal Keratitis in North India.Cornea,2005,24(1):8.15
16 Deshpande SD,Koppikar GV.A study of mycotic keratitis inMumbal.Indian J Pathol Microbiol.1999;42:81-87
17 Garg P,Gopinathan U,Choudhary K,et al.Keratomycosis:clinical and microbiologic experience with dematiaceous fungi.Ophthalmology,2000;107:574-580
18 Kunimoto DY,Sharma S,GargP,et al.Comealulceration in the elderly in Hyderabad,south India.Br J Ophihalmol,2000;84:54-59
19 Chander J.Sharma A.Prevalence of fungal coneal ulcers in northren India.Infection,1994;22:207.209
20 Khanal B,Kaini KR,Deb M,et al.Microbial keratitis in eastern Nepa1.Tropical Doctor,2001;31:168-169
21 ChowdharyA,Singh K.Spectrum of Fungal Keratitis in North India.Comea,2005;24(1):8-15
22 SUN Xu-guang,ZHANG Yan,LI Ran,et al.Etiological analysis on ocular fungal infection in the period of 1989-2000.Chinese Medical Journal,2004;117:598-600
23 孙声桃,王丽娅,徐筠,等.互隔交链孢霉菌性角膜炎的临床与病原学研究.中华眼科杂志,2007:43:32-35.
24 王丽娅,张月琴,王印其,等.中国三地区真菌性角膜病致病种的调查.中华眼科杂志,2000:36:138-140
25 Tanure MA,Cohen EL,Sidesh S,et al.Spectrum of fungal keratitis at Wills Eye Hospital Philadelphia,Pennsylvan ia.Cornea,2000;19:307-312
26 M Srinivasan,C.Gonzales,C.George,et al.Epidemiology and aetiological diagnosis of corneal ulceration in Madurai,south India.Br J Ophthalmol,1997;81:965-971
27 Liesegang TJ,Forster RK.Spectrum of microbial keratitis in South Florida.Am J Ophthalmol,1980:90:38-47
28 Rosa RH Jr,Miller D,Alfonso EC,et al.The changing spectrum of fungal keratitis in South Florida.Ophthalmology,1994:101:1005-1013
29 Bharathi MJ,Ramakrishnan R,Vasu S,et al.Aetiological diagnosis of microbial keratitis in South India - A study of 1618 cases.Indian Journal of Medical Microbiology,2002:20:19-24
30 孙旭光,王智群,罗时运,等.眼部真菌感染的病原学分析.中华眼科杂志,2002:38:405-407
31 Ghannoum MA,Rex JH,Galgiani JN.Susceptibility testing of fungi:current status of correlation of in vitro data with clinical outcome.J Clin Microbiol,1996;34:489-495
32 Rex JH,Pfaller MA.Has antifungal susceptibility testing come of age? Clin Infect Dis,2002;35:982-989
33 佟盼琢,李若瑜,万喆,等.应用M38-P方案测定皮肤癣菌对抗真菌药物的敏感性.中国麻风病皮肤杂志, 2001:17:147-149
34 Jessup CJ,Ryder NS,Ghannoum MA.An evalution of the in vitro activity of terbinafine.Medical Mycology,2001:38:155
35 吴伟元,何林,吴劲松,等.E-test法检测3种抗真菌药物对128株酵母菌的体外活性.中国抗感染化疗杂志,2005;5:89-91
36 徐英春,谢秀丽,王澎.Etest法测定伊曲康唑对曲霉和酵母菌的体外抗菌活性.中国新药杂志,2004;2:163-165
37 Pfaller MA,Messer SA,Bolmstrom A,et al.Multisete reproducibility of the Etest MIC method for antifungal susceptibility testing of yeast isolates.J Clin Microbiol,1996;34:1691-1693
38 Espinel-Ingroff A,Pfaller M,Erwin ME,et al.Interlaboratory evaluation of Etest method for testing antifungal susceptibilities of pathogenic yeasts to five antifungal agents by using Casitone agar and solidified RPMI 1640 medium with 2%glucose.J Clin Microbial,1996:34:848-852
39 Colombo AL,Barchiesi F,McGough DA,et al.Comparison of Etest and National Committee for Clinical Laboratory Standards broth macrodilution method for azole antifungal susceptibility testing.J Clin icrobial,1995:33:535-540
40 WangerA,Mils K,Nelson PW,et al.Comparison of Etest and NCCLS broth macrodilution mehod for antifungal susceptibility testing:Enhanced ablity to detect ampnotericin B-resistant Candida isolates.Antimicrbial Agents and Chemotherapy,1995:39:2520-2522
41 van Eldere J,Joosten L,Verhaeghe V,et al.Fluconazole and amphotericin B antifungal susceptibility testing by NCCLS broth macrodilution method compared with Etest and semiautomated broth microdilution test.Jclin Microbiol,1996;34:842-847
42 张晓冬,徐莉.Etest法和NCCLS微量法检测念珠菌对氟康唑的敏感性.中国皮肤性病学杂志,2006;4:
43 徐修礼,杨佩红,孙怡群.真菌药敏纸片扩散法实验与应用研究.临床检验杂志,2006;24:278-279
44 李若瑜,万哲,陈剑.采用葡萄糖消耗法快速测定念珠菌对唑类药物的敏感性.临床皮肤科杂志,2003;9:499-501
45 Riesselman MH,Kazen KC,Culter JE.Petermination of antifungal MICs by a rapid susceptibility assay[J].J Clin Microbiol,2000:38:333-340
46 董平,万哲,李若瑜.抗真菌药单独及联合应用对曲霉菌的体外药敏试验研究.中华检验医学杂志,2003:26(9):527-529
47 郭秀军,廖万清,任大明,等.伊曲康唑与二性霉素B抗新生隐球菌临床分离株的实验研究.中华皮肤科杂 志, 2003; 12: 711-713
48 Barchiesi F, Falconi DiFrancesco L, Scalise G, et al. In vitro activities of terbinafine in combination with fluconazole and itraconazole against isolates of Candida albicans with reduced susceptibility to azoes. Antimicrob Agents Chemother, 1997; 41: 1812-1814