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抗生素耐药性日趋严重,临床对抗生素药敏检测(Antimicrobial susceptibility testing, AST)的时效性与准确性提出了更高要求。传统基于细菌增殖培养的药敏检测方法虽为金标准,但其检测周期长,难以满足早期精准用药的临床需求。因此,开发能够在短时间内直接检测细菌对药物反应的快速表型药敏检测技术具有重要意义。该综述聚焦于基于细菌代谢活性变化监测的快速药敏检测策略,从代谢响应作为早期药物作用指示信号的角度出发,系统梳理了不同信号转导路径下的技术进展。通过分析细菌在抗生素作用后呼吸耗氧、细胞壁合成、能量代谢、胞外电子传递及代谢产物释放等变化,本文进一步归纳了以发光与荧光信号、拉曼光谱、电化学及比色法为代表的检测方法,并比较了其在检测速度、灵敏度、样本适配性及临床转化方面的特点。总体而言,基于代谢活性的药敏检测方法较依赖细菌生长的传统方法检测速度更快,能够实现对细菌药物响应的早期识别,在提升检测效率和临床用药指导价值方面具有重要潜力。
Abstract:The increasing severity of antibiotic resistance has raised higher demands on the timeliness and accuracy of clinical antimicrobial susceptibility testing (AST). Although traditional culture?based AST methods remain the gold standard, their long turnaround time limits their ability to meet the clinical need for early and precise antimicrobial therapy. Therefore, developing rapid phenotypic AST techniques that can directly detect bacterial responses to antibiotics within a short timeframe is of great significance. This review focuses on rapid AST strategies based on monitoring changes in bacterial metabolic activity. From the perspective of metabolic response as an early indicator of antibiotic action, we systematically review the technological advances across different signal transduction pathways. By analyzing antibiotic?induced changes in bacterial oxygen consumption, cell wall synthesis activity, energy metabolism, extracellular electron transfer, and metabolite release, this article further summarizes the major detection modalities, including luminescence/fluorescence, Raman spectroscopy, electrochemistry, and colorimetry, and compares their characteristics in terms of detection speed, sensitivity, sample compatibility, and clinical translational potential. Overall, metabolic activity?based AST methods offer faster turnaround times compared with traditional growth?dependent approaches, enable early detection of bacterial drug responses, and hold significant promise for improving testing efficiency and guiding clinical antimicrobial therapy.
[1] Kariuki S. Lancet, 2024, 404(10459): 1172-1173.
[2] Khan Z A, Siddiqui M F, Park S. Diagnostics, 2019, 9(2): 49.
[3] Jorgensen J H, Ferraro M J. Clin. Infect. Dis., 2009, 49(11): 1749-1755.
[4] Hattab S, Ma A H, Tariq Z, Vega Prado I, Drobish I, Lee R, Yee R. Antibiotics, 2024, 13(8): 786.
[5] Gajic I, Kabic J, Kekic D, Jovicevic M, Milenkovic M, Mitic Culafic D, Trudic A, Ranin L, Opavski N. Antibiotics, 2022, 11(4): 427.
[6] Abram T J, Cherukury H, Ou C Y, Vu T, Toledano M, Li Y Y, Grunwald J T, Toosky M N, Tifrea D F, Slepenkin A, Chong J, Kong L S, Del Pozo D V, La K T, Labanieh L, Zimak J, Shen B, Huang S S, Gratton E, Peterson E M, Zhao W A. Lab on a Chip, 2020, 20(3): 477-489.
[7] Duan B H, Zeng X J, Peng J P. Sci. China Life Sci., 2025, 68(1): 130-143.
[8] Yee R, Dien Bard J, Simner P J. J. Clin. Microbiol., 2021, 59(6): e00138-e00120.
[9] Hassall J, Coxon C, Patel V C, Goldenberg S D, Sergaki C. npj Antimicrob. Resist., 2024, 2(1): 16.
[10] Belenky P, Ye J D, Porter C B M, Cohen N R, Lobritz M A, Ferrante T, Jain S, Korry B J, Schwarz E G, Walker G C, Collins J J. Cell Rep., 2015, 13(5): 968-980.
[11] Zampieri M, Zimmermann M, Claassen M, Sauer U. Cell Rep., 2017, 19(6): 1214-1228.
[12] Chen C, Hong W L. Antibiotics, 2021, 10(3): 311.
[13] Acierno C, Barletta F, Nevola R, Rinaldi L, Sasso F C, Adinolfi L E, Caturano A. Int. J. Mol. Sci., 2025, 26(12): 5574.
[14] van Belkum A, Burnham C D, Rossen J W A, Mallard F, Rochas O, Dunne W M Jr. Nat. Rev. Microbiol., 2020, 18(5): 299-311.
[15] Braissant O, Astasov-Frauenhoffer M, Waltimo T, Bonkat G. Front. Microbiol., 2020, 11: 547458.
[16] Dwyer D J, Belenky P A, Yang J H, MacDonald I C, Martell J D, Takahashi N, Chan C T Y, Lobritz M A, Braff D, Schwarz E G, Ye J D, Pati M, Vercruysse M, Ralifo P S, Allison K R, Khalil A S, Ting A Y, Walker G C, Collins J J. Proc. Natl. Acad. Sci. U. S. A., 2014, 111(20): E2100-E2109.
[17] Rojas-Andrade M D, Perinbam K, Nguyen Q T, Kim J S, Palomba F, Whiteson K, Digman M A, Siryaporn A, Hochbaum A I. ACS Infect. Dis., 2024, 10(12): 4057-4065.
[18] Lobritz M A, Belenky P, Porter C B M, Gutierrez A, Yang J H, Schwarz E G, Dwyer D J, Khalil A S, Collins J J. Proc. Natl. Acad. Sci. U. S. A., 2015, 112(27): 8173-8180.
[19] Price E E, Román-rodríguez F, Boyd J M. Mol. Microbiol., 2021, 116(4): 1009-1021.
[20] Ratzke C, Gore J. PLoS Biol., 2018, 16(3): e2004248.
[21] Gao J, Guo J N, Chen J X, Ding C L, Wang J M, Huang Q, Jian Y, Zhao X Y, Li M, Gao Y, Yang C Y, Wang W. Adv. Healthc. Mater., 2022, 11(6): 2270030.
[22] Rafiee Z, Choi S. Analyst, 2023, 148(11): 2501-2510.
[23] Dixneuf S, Chareire-Kleiberg A C, Mahé P, El Azami M, Kolytcheff C, Bellais S, Guyard C, Védrine C, Mallard F, Josso Q, Rol F. Front. Microbiol., 2023, 14: 1232250.
[24] O’Mahony F C, Papkovsky D B. Appl. Environ. Microbiol., 2006, 72(2): 1279-1287.
[25] Qiu W T, Nagl S. ACS Sens., 2021, 6(3): 1147-1156.
[26] Jusková P, Schmitt S, Kling A, Rackus D G, Held M, Egli A, Dittrich P S. ACS Sens., 2021, 6(6): 2202-2210.
[27] Liu Y, Lehnert T, Mayr T, Gijs M A M. Lab on a Chip, 2021, 21(18): 3520-3531.
[28] Kuru E, Tekkam S, Hall E, Brun Y V, Van Nieuwenhze M S. Nat. Protoc., 2015, 10(1): 33-52.
[29] Lin L Y, Song J, Du Y H, Wu Q Y, Gao J, Song Y L, Yang C Y, Wang W. Angew. Chem. Int. Ed., 2020, 59(29): 11923-11926.
[30] Gao J, Qin J X, Ding C L, Gao Y, Guo J N, Li M, Yang C Y, Wang W. RSC Chem. Biol., 2022, 3(11): 1314-1319.
[31] Walenkiewicz B, VanNieuwenhze M S. ACS Chem. Biol., 2025, 20(1): 162-171.
[32] Yang W X, Zhang X Y, Liu X, Liu Y. Lab. Med. Clinic, 2024, 21(4): 542-547.
[33] Novelli-Rousseau A, Espagnon I, Filiputti D, Gal O, Douet A, Mallard F, Josso Q. Sci. Rep., 2018, 8(1): 3957.
[34] Schr?der U, Beleites C, Assmann C, Glaser U, Hübner U, Pfister W, Fritzsche W, Popp J, Neugebauer U. Sci. Rep., 2015, 5(1): 8217.
[35] Kirchhoff J, Glaser U, Bohnert J A, Pletz M W, Popp J, Neugebauer U. Anal. Chem., 2018, 90(3): 1811-1818.
[36] Tao Y F, Wang Y, Huang S, Zhu P F, Huang W E, Ling J Q, Xu J. Anal. Chem., 2017, 89(7): 4108-4115.
[37] Wang W, Vikesland P J. Environ. Sci. Technol., 2023, 57(36): 13375-13383.
[38] Dina N E, Ali Tahir M, Bajwa S Z, Amin I, Valev V K, Zhang L W. Biosens. Bioelectron., 2023, 219: 114843.
[39] Fu S J, Wang X W, Wang T, Li Z P, Han D M, Yu C S, Yang C, Qu H, Chi H, Wang Y T, Li S, Tian B H, Li W L, Xia Z P. Braz. J. Microbiol., 2020, 51(3): 875-881.
[40] Premasiri W R, Lee J C, Sauer-Budge A, Théberge R, Costello C E, Ziegler L D. Anal. Bioanal. Chem., 2016, 408(17): 4631-4647.
[41] Chien J Y, Gu Y C, Chien C C, Chang C L, Cheng H W, Chiu S W, Nee Y J, Tsai H M, Chu F Y, Tang H F, Wang Y L, Lin C H. Sci. Rep., 2024, 14(1): 19505.
[42] Han Y Y, Lin Y C, Cheng W C, Lin Y T, Teng L J, Wang J K, Wang Y L. Sci. Rep., 2020, 10(1): 12538.
[43] Hong W L, Karanja C W, Abutaleb N S, Younis W, Zhang X Y, Seleem M N, Cheng J X. Anal. Chem., 2018, 90(6): 3737-3743.
[44] Spencer D C, Paton T F, Mulroney K T, Inglis T J J, Sutton J M, Morgan H. Nat. Commun., 2020, 11(1): 5328.
[45] Gopalakrishnan S, Mall D, Pushpavanam S, Karmakar R. Sci. Rep., 2025, 15(1): 5133.
[46] Ralston H, Butterworth A, Clark B, Katsafadou M, Vezza V, Campbell T, Malecha M, Murphy M E, Poojary A, Winter A, Price D, Marrs E, Longmuir A, Hannah S, Hoskisson P A, Corrigan D K. ACS Sens., 2026, 11(2): 1041-1049.
[47] Rafiee Z, Rezaie M, Choi S. Analyst, 2024, 149(11): 3224-3235.
[48] Rao R P, Sharma S, Mehrotra T, Das R, Kumar R, Singh R, Roy I, Basu T. Anal. Chem., 2020, 92(6): 4266-4274.
[49] Zhao J T, Li F, Cao Y X, Zhang X B, Chen T, Song H, Wang Z W. Biotechnol. Adv., 2021, 53: 107682.
[50] Tibbits G, Mohamed A, Call D R, Beyenal H. Biosens. Bioelectron., 2022, 197: 113754.
[51] Celik Yoldas C, Ildiz N, Sagiroglu P, Atalay M A, Demir N Y, Duman M, Ocsoy I. Anal. Chem., 2025, 97(20): 10619-10627.
[52] Chen F E, Kaushik A, Hsieh K, Chang E, Chen L B, Zhang P F, Wang T H. Anal. Chem., 2021, 93(3): 1260-1265.
[53] Zhou X, Wu H T, Chen X Y, Li W R, Zhang J J, Wang M Q, Zhang J, Wang S, Liu Y Q. Food Chem., 2024, 438: 137983.
[54] Postek W, Pacocha N, Garstecki P. Lab on a Chip, 2022, 22(19): 3637-3662.
[55] Koban I, Matthes R, Hübner N O, Welk A, Sietmann R, Lademann J, Kramer A, Kocher T. GMS. Krankenhhyg Interdiszip, 2012, 7(1): Doc06.
[56] Grela E, Koz?owska J, Grabowiecka A. Acta Histochem., 2018, 120(4): 303-311.
[57] Tsukatani T, Suenaga H, Shiga M, Noguchi K, Ishiyama M, Ezoe T, Matsumoto K. J. Microbiol. Meth., 2012, 90(3): 160-166.
[58] Elshikh M, Ahmed S, Funston S, Dunlop P, McGaw M, Marchant R, Banat I M. Biotechnol. Lett., 2016, 38(6): 1015-1019.
[59] Chang X J, Xu Y C, Liu C. FEMS Microbiol. Lett., 2016, 363(7): fnw037.
[60] Jalali M, AbdElFatah T, del Real Mata C, Hosseini I I, Yedire S G, McKay G A, Corsini R, Siavash Moakhar R, Shieh H, Reszetnik G, Hamidi S V, Yansouni C P, Nguyen D, Mahshid S. Nat. Nanotechnol., 2026, 21(2): 288-299.
[61] Lin X D, Zhai K R, Liu B M, Chen J H. Anal. Chem., 2025, 97(31): 17040-17049.
[62] Zheng L B, Shen Y Q, Dong W J, Zheng C C, Zhou R L, Lou Y L. Front. Bioeng. Biotechnol., 2022, 9: 795415.
[63] MacVane S H, Dwivedi H P. J. Antimicrob. Chemother., 2024, 79(Supplement_1): i13-i25.
[64] Reszetnik G, Hammond K, Mahshid S, AbdElFatah T, Nguyen D, Corsini R, Caya C, Papenburg J, Cheng M P, Yansouni C P. Nat. Commun., 2024, 15(1): 9719.
[65] Zhang M, Seleem M N, Cheng J X. J. Vis. Exp., 2022, (180): 62398.
[66] Crane B, Hughes J P, Rowley Neale S J, Rashid M, Linton P E, Banks C E, Shaw K J. Analyst, 2021, 146(18): 5574-5583.
基本信息:
DOI:10.13822/j.cnki.hxsj.2026.0138
中图分类号:O657;R446.5
引用信息:
[1]陈彦羽,丁陈玲,王茜茜,等.基于细菌代谢活性的抗生素药敏快速检测技术研究进展[J].化学试剂().DOI:10.13822/j.cnki.hxsj.2026.0138.
基金信息:
国家自然科学基金项目(22293031,22307070)
2026-07-24
2026-07-24
2026-07-24