南方医科大学学报 ›› 2026, Vol. 46 ›› Issue (7): 1576-1584.doi: 10.12122/j.issn.1673-4254.2026.07.11
• • 上一篇
侯杰1,2(
), 陈维琳2(
), 彭亮2, 乔甫3, 康梅2(
), 马莹2(
)
收稿日期:2025-11-07
出版日期:2026-07-20
发布日期:2026-07-20
通讯作者:
康梅,马莹
E-mail:microbe_houjie@hotmail.com;wl1335058287@163.com;kangmei@sina.com;majiying72@hotmail.com
作者简介:侯 杰,硕士,E-mail: microbe_houjie@hotmail.com基金资助:
Jie HOU1,2(
), Weilin CHEN2(
), Liang PENG2, Fu QIAO3, Mei KANG2(
), Ying MA2(
)
Received:2025-11-07
Online:2026-07-20
Published:2026-07-20
Contact:
Mei KANG, Ying MA
E-mail:microbe_houjie@hotmail.com;wl1335058287@163.com;kangmei@sina.com;majiying72@hotmail.com
摘要:
目的 评估基于基质辅助激光解吸电离飞行时间质谱(MALDI-TOF MS)的抗真菌药物敏感性试验(MS-AFST)快速检测热带念珠菌氟康唑耐药性的临床应用潜能。 方法 回顾性分析2018~2023年四川大学华西医院血流感染热带念珠菌的检出情况,并经念珠菌显色培养与MALDI-TOF MS行菌种鉴定。抗真菌药物敏感性试验以 CLSI 微量肉汤稀释法(BMD)为参考标准,对比评估 Sensititre YeastOne 显色药敏试验、优化前处理后基于最小谱图改变浓度(MPCC)的 MS-AFST 法检测氟康唑耐药性的一致性。 结果 本研究纳入的41分离株均为热带念珠菌,其唑类耐药率和非野生型菌株占比在36.59%~68.29%,且唑类高度交叉耐药。Sensititre YeastOne与CLSI BMD的分类一致性和基本一致性均为100%,二者最小抑菌浓度高度相关。基于MPCC的MS-AFST可以3 h左右快速检测热带念珠菌氟康唑耐药表型,与CLSI BMD参考方法和Sensititre YeastOne的分类一致性均为92.68%,基本一致性均为90.24%,极重大误差2株,小误差1株。 结论 基于 MPCC 的 MS-AFST 可快速检测热带念珠菌氟康唑耐药性,且与参考方法一致性较好,但仍存在分类错误,需进一步优化方法并探究其机制。
侯杰, 陈维琳, 彭亮, 乔甫, 康梅, 马莹. MALDI-TOF MS 可快速检测热带念珠菌的氟康唑耐药性[J]. 南方医科大学学报, 2026, 46(7): 1576-1584.
Jie HOU, Weilin CHEN, Liang PENG, Fu QIAO, Mei KANG, Ying MA. Rapid detection of fluconazole resistance in Candida tropicalis using MALDI-TOF mass spectrometry[J]. Journal of Southern Medical University, 2026, 46(7): 1576-1584.
| Isolates | Sensititre YeastOne | CLSI BMD | MS-AFST | |||
|---|---|---|---|---|---|---|
| MIC (µg/mL) | Phenotype | MIC (µg/mL) | Phenotype | MPCC (µg/mL) | Phenotype | |
| 20200253 | 1 | S | 1 | S | 0.25 | S |
| 19200247 | 1 | S | 1 | S | 1 | S |
| 19200191 | 1 | S | 1 | S | 1 | S |
| 19200153 | 1 | S | 2 | S | 1 | S |
| 19200102 | 1 | S | 1 | S | 1 | S |
| 19200098 | 1 | S | 1 | S | 1 | S |
| 18200156 | 1 | S | 1 | S | 1 | S |
| 18200150 | 1 | S | 1 | S | 1 | S |
| 18200142 | 1 | S | 1 | S | 1 | S |
| 18200115 | 1 | S | 1 | S | 1 | S |
| 18200018 | 1 | S | 1 | S | 1 | S |
| 22200035 | 1 | S | 1 | S | 1 | S |
| 21200152 | 2 | S | 2 | S | 2 | S |
| 20200269 | 2 | S | 2 | S | 1 | S |
| 20200161 | 2 | S | 2 | S | 2 | S |
| 19200195 | 2 | S | 2 | S | 0.5 | S |
| 19200050 | 2 | S | 2 | S | 2 | S |
| 18200200 | 2 | S | 2 | S | 1 | S |
| 18200199 | 2 | S | 2 | S | 1 | S |
| 21200090 | 4 | SDD | 4 | SDD | 2 | S |
| 19200042 | 8 | R | 8 | R | 2 | S |
| 22200070 | 16 | R | 32 | R | 16 | R |
| 21200118 | 32 | R | 32 | R | 16 | R |
| 18200162 | 32 | R | 32 | R | 32 | R |
| 19200145 | 64 | R | 64 | R | 8 | R |
| 21200116 | 128 | R | 128 | R | 256 | R |
| 20200204 | 128 | R | 128 | R | 256 | R |
| 19200169 | 128 | R | 128 | R | 256 | R |
| 18200183 | 128 | R | 128 | R | 32 | R |
| 18200053 | 128 | R | 128 | R | 16 | R |
| 21200146 | 256 | R | 256 | R | 128 | R |
| 20200248 | 256 | R | 256 | R | 4 | S |
| 21200261 | 256 | R | 256 | R | 256 | R |
| 21200282 | 256 | R | 512 | R | 256 | R |
| 22200005 | 256 | R | 512 | R | 256 | R |
| 21200112 | 256 | R | 256 | R | 256 | R |
| 20200186 | 256 | R | 256 | R | 256 | R |
| 20200111 | 256 | R | 256 | R | 256 | R |
| 20200037 | 256 | R | 256 | R | 128 | R |
| 19200199 | 256 | R | 256 | R | 256 | R |
| 18200179 | 256 | R | 256 | R | 16 | R |
表1 热带念珠菌临床分离株氟康唑耐药性检测试验结果
Tab.1 Results for fluconazole resistance testing of clinical isolates of Candida tropicalis
| Isolates | Sensititre YeastOne | CLSI BMD | MS-AFST | |||
|---|---|---|---|---|---|---|
| MIC (µg/mL) | Phenotype | MIC (µg/mL) | Phenotype | MPCC (µg/mL) | Phenotype | |
| 20200253 | 1 | S | 1 | S | 0.25 | S |
| 19200247 | 1 | S | 1 | S | 1 | S |
| 19200191 | 1 | S | 1 | S | 1 | S |
| 19200153 | 1 | S | 2 | S | 1 | S |
| 19200102 | 1 | S | 1 | S | 1 | S |
| 19200098 | 1 | S | 1 | S | 1 | S |
| 18200156 | 1 | S | 1 | S | 1 | S |
| 18200150 | 1 | S | 1 | S | 1 | S |
| 18200142 | 1 | S | 1 | S | 1 | S |
| 18200115 | 1 | S | 1 | S | 1 | S |
| 18200018 | 1 | S | 1 | S | 1 | S |
| 22200035 | 1 | S | 1 | S | 1 | S |
| 21200152 | 2 | S | 2 | S | 2 | S |
| 20200269 | 2 | S | 2 | S | 1 | S |
| 20200161 | 2 | S | 2 | S | 2 | S |
| 19200195 | 2 | S | 2 | S | 0.5 | S |
| 19200050 | 2 | S | 2 | S | 2 | S |
| 18200200 | 2 | S | 2 | S | 1 | S |
| 18200199 | 2 | S | 2 | S | 1 | S |
| 21200090 | 4 | SDD | 4 | SDD | 2 | S |
| 19200042 | 8 | R | 8 | R | 2 | S |
| 22200070 | 16 | R | 32 | R | 16 | R |
| 21200118 | 32 | R | 32 | R | 16 | R |
| 18200162 | 32 | R | 32 | R | 32 | R |
| 19200145 | 64 | R | 64 | R | 8 | R |
| 21200116 | 128 | R | 128 | R | 256 | R |
| 20200204 | 128 | R | 128 | R | 256 | R |
| 19200169 | 128 | R | 128 | R | 256 | R |
| 18200183 | 128 | R | 128 | R | 32 | R |
| 18200053 | 128 | R | 128 | R | 16 | R |
| 21200146 | 256 | R | 256 | R | 128 | R |
| 20200248 | 256 | R | 256 | R | 4 | S |
| 21200261 | 256 | R | 256 | R | 256 | R |
| 21200282 | 256 | R | 512 | R | 256 | R |
| 22200005 | 256 | R | 512 | R | 256 | R |
| 21200112 | 256 | R | 256 | R | 256 | R |
| 20200186 | 256 | R | 256 | R | 256 | R |
| 20200111 | 256 | R | 256 | R | 256 | R |
| 20200037 | 256 | R | 256 | R | 128 | R |
| 19200199 | 256 | R | 256 | R | 256 | R |
| 18200179 | 256 | R | 256 | R | 16 | R |
图1 热带念珠菌临床分离株唑类Sensititre YeastOne显色药敏试验结果
Fig.1 Results of Sensititre YeastOne chromogenic antifungal susceptibility testing of clinical isolates of Candida tropicalis. MIC: Minimum inhibitory concentration; CBP: Clinical breakpoint; ECV: Epidemiological cut-off.
图2 热带念珠菌临床分离株微量肉汤稀释法氟康唑MIC分布图
Fig.2 MIC distribution of fluconazole in clinical isolates of Candida tropicalis by broth microdilution. CLSI BMD: Clinical and laboratory standards institute broth microdilution; MIC: Minimum inhibitory concentration.
图3 热带念珠菌临床分离株两种微量肉汤稀释法检测氟康唑MIC线性回归
Fig.3 Linear regression of fluconazole MIC detected by two broth microdilution methods for Candida tropicalis clinical isolates.
图4 4种不同样本质谱前处理方法的MALDI-TOF MS图
Fig.4 MALDI-TOF MS plots of 4 different sample pretreatment methods. A: First pretreatment protocol. B: Second pretreatment protocol. C: Third pre-treatment protocol. D: Fourth pretreatment protocol.
图5 热带念珠菌氟康唑耐药株与敏感株CCI矩阵热图
Fig.5 CCI matrix heatmap of fluconazole-resistant and fluconazole-susceptible strains of Candida tropicalis. A: Fluconazole resistant Candida tropicalis clinical isolate 22200070; B: Fluconazole susceptible Candida tropicalis clinical isolate 19200050. CCI: Composite correlation index; MPCC: Minimal profile change concentration.
图6 热带念珠菌临床分离株氟康唑MPCC与MIC线性回归
Fig.6 Linear regression between fluconazole MPCC and MIC. A: CLSI BMD MIC compared with MPCC;B: Sensititre YeastOne MIC compared with MPCC.
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