-
念珠菌为条件致病真菌,可寄居于人体的不同部位,当人体局部或全身免疫力下降时,其致病性可造成个体浅表或全身感染。白念珠菌(Candidaalbicans)是念珠菌的一种,是引发侵袭性感染的最主要致病菌[1]。近年来,由于抗真菌药物的大量使用,白念珠菌的耐药性逐渐增加。常规抗菌药对白念珠菌的抑制效果明显降低。
相对于单药而言,多种药物联合使用时往往能通过药效互补,起到协同作用,增强抑菌效果[2-3]。联合用药提高了抑菌效果,患者的治疗周期缩短,治疗成本可进一步降低。因此,研究抗白念珠菌药物联合疗法对于治疗白念珠菌感染非常有意义。
一般来说,联合疗法会同时使用抗真菌药和增效剂。目前经典的抗真菌药物有唑类化合物(如氟康唑)、多烯类(如两性霉素B)和棘白菌素类(如卡泊芬净)等,这些药物可直接抑制或杀伤白念珠菌。氯法齐明、法尼醇本身对真菌没有直接抑制作用,但可作为增效剂辅助增强抗真菌药物治疗效果,增强耐药菌的敏感性。近年来,光动力学、声动力学疗法等新兴的技术应用于抗真菌的治疗,同时传统的抗真菌物质在现代技术的改进下也能发挥特有的优势,比如将银制成纳米银颗粒用于抑制白念珠菌增殖。本文将针对白念珠菌尤其是耐药菌的杀伤或抑制作用,聚焦于传统抗真菌药物与声动力学/光动力学疗法、纳米银颗粒这几类抗菌方式,阐述与之相关的联合疗法。
HTML
[1] | ZENG Z R, TIAN G, DING Y H, et al. Surveillance study of the prevalence, species distribution, antifungal susceptibility, risk factors and mortality of invasive candidiasis in a tertiary teaching hospital in Southwest China[J]. BMC Infect Dis,2019,19(1):939. | |
[2] | DE CREMER K, DE BRUCKER K, STAES I, et al. Stimulation of superoxide production increases fungicidal action of miconazole against Candida albicans biofilms[J]. Sci Rep,2016,6:27463. | |
[3] | LOHSE M B, GULATI M, CRAIK C S, et al. Combination of antifungal drugs and protease inhibitors prevent Candida albicans biofilm formation and disrupt mature biofilms[J]. Front Microbiol,2020,11:1027. | |
[4] | ZHANG M, YAN H Y, LU M J, et al. Antifungal activity of ribavirin used alone or in combination with fluconazole against Candida albicans is mediated by reduced virulence[J]. Int J Antimicrob Agents,2020,55(1):105804. | |
[5] | NISHIMOTO A T, SHARMA C, ROGERS P D. Molecular and genetic basis of azole antifungal resistance in the opportunistic pathogenic fungus Candida albicans[J]. J Antimicrob Chemother,2020,75(2):257-270. | |
[6] | DIŽOVÁ S, ČERNÁKOVÁ L, BUJDÁKOVÁ H. The impact of farnesol in combination with fluconazole on Candida albicans biofilm: regulation of ERG20, ERG9, and ERG11 genes[J]. Folia Microbiol (Praha),2018,63(3):363-371. | |
[7] | 周罗成, 王宁, 朱莹莹, 等. 法尼醇在促氟康唑耐药白念珠菌凋亡中的作用机制[J]. 内科理论与实践, 2020, 15(1):49-52. | |
[8] | HUANG X X, ZHENG M Y, YI Y L, et al. Inhibition of berberine hydrochloride on Candida albicans biofilm formation[J]. Biotechnol Lett,2020,42(11):2263-2269. | |
[9] | ZHANG Y, BAI X, YUWEN H S, et al. Alkaloids from Tabernaemontana divaricata combined with fluconazole to overcome fluconazole resistance in Candida albicans[J]. Bioorg Chem,2021,107:104515. | |
[10] | RHIMI W, ANEKE C I, ANNOSCIA G, et al. Effect of chlorogenic and Gallic acids combined with azoles on antifungal susceptibility and virulence of multidrug-resistant Candida spp. and Malassezia furfur isolates[J]. Med Mycol,2020,58(8):1091-1101. | |
[11] | GUO N, LING G H, LIANG X Y, et al. In vitro synergy of pseudolaric acid B and fluconazole against clinical isolates of Candida albicans[J]. Mycoses,2011,54(5):e400-e406. | |
[12] | SHIH P Y, LIAO Y T, TSENG Y K, et al. A potential antifungal effect of chitosan against Candida albicans is mediated via the inhibition of SAGA complex component expression and the subsequent alteration of cell surface integrity[J]. Front Microbiol,2019,10:602. | |
[13] | LO W H, DENG F S, CHANG C J, et al. Synergistic antifungal activity of chitosan with fluconazole against Candida albicans, Candida tropicalis, and fluconazole-resistant strains[J]. Molecules,2020,25(21):5114. | |
[14] | 严园园, 汪天明, 施高翔, 等. 黄连解毒汤联合氟康唑对耐药白念珠菌麦角甾醇的影响[J]. 中国中药杂志, 2015, 40(4):727-732. | |
[15] | SUN W W, WANG D C, YU C X, et al. Strong synergism of dexamethasone in combination with fluconazole against resistant Candida albicans mediated by inhibiting drug efflux and reducing virulence[J]. Int J Antimicrob Agents,2017,50(3):399-405. | |
[16] | LI X Y, YU C X, HUANG X, et al. Synergistic effects and mechanisms of budesonide in combination with fluconazole against resistant Candida albicans[J]. PLoS One,2016,11(12):e0168936. | |
[17] | DELARZE E, BRANDT L, TRACHSEL E, et al. Identification and characterization of mediators of fluconazole tolerance in Candida albicans[J]. Front Microbiol,2020,11:591140. | |
[18] | UPPULURI P, NETT J, HEITMAN J, et al. Synergistic effect of calcineurin inhibitors and fluconazole against Candida albicans biofilms[J]. Antimicrob Agents Chemother,2008,52(3):1127-1132. | |
[19] | O'MEARA T R, ROBBINS N, COWEN L E. The Hsp90 chaperone network modulates Candida virulence traits[J]. Trends Microbiol,2017,25(10):809-819. | |
[20] | YUAN R, TU J, SHENG C Q, et al. Effects of Hsp90 inhibitor ganetespib on inhibition of azole-resistant Candida albicans[J]. Front Microbiol,2021,12:680382. | |
[21] | ZHANG J Q, LIU W, TAN J W, et al. Antifungal activity of geldanamycin alone or in combination with fluconazole against Candida species[J]. Mycopathologia,2013,175(3-4):273-279. | |
[22] | MATTHEWS R C, RIGG G, HODGETTS S, et al. Preclinical assessment of the efficacy of mycograb, a human recombinant antibody against fungal HSP90. [J]. 抗菌试剂及化学方法, 2003, 47(7): 2208-2216. | MATTHEWS R C, RIGG G, HODGETTS S, et al. Preclinical assessment of the efficacy of mycograb, a human recombinant antibody against fungal HSP90.[J]. Antimicrob Agents Chemother, 2003, 47(7):2208-2216. |
[23] | GRELA E, ZDYBICKA-BARABAS A, PAWLIKOWSKA-PAWLEGA B, et al. Modes of the antibiotic activity of amphotericin B against Candida albicans[J]. Sci Rep,2019,9(1):17029. | |
[24] | AVERSA F, BUSCA A, CANDONI A, et al. Liposomal amphotericin B (AmBisome®) at beginning of its third decade of clinical use[J]. J Chemother,2017,29(3):131-143. | |
[25] | KHAN S N, KHAN S, MISBA L, et al. Synergistic fungicidal activity with low doses of eugenol and amphotericin B against Candida albicans[J]. Biochem Biophys Res Commun,2019,518(3):459-464. | |
[26] | CHUDZIK B, BONIO K, DABROWSKI W, et al. Synergistic antifungal interactions of amphotericin B with 4-(5-methyl-1, 3, 4-thiadiazole-2-yl) benzene-1, 3-diol[J]. Sci Rep,2019,9(1):12945. | |
[27] | UCHIDA R, KONDO A, YAGI A, et al. Simpotentin, a new potentiator of amphotericin B activity against Candida albicans, produced by Simplicillium minatense FKI-4981[J]. J Antibiot (Tokyo),2019,72(3):134-140. | |
[28] | FUKUDA T, NAGAI K, YAGI A, et al. Nectriatide, a potentiator of amphotericin B activity from Nectriaceae sp. BF-0114[J]. J Nat Prod,2019,82(10):2673-2681. | |
[29] | YAGI A, UCHIDA R, KOBAYASHI K, et al. Polyketide glycosides phialotides A to H, new potentiators of amphotericin B activity, produced by Pseudophialophora sp. BF-0158[J]. J Antibiot (Tokyo),2020,73(4):211-223. | |
[30] | ALVAREZ C, ANDES D R, KANG J Y, et al. Antifungal efficacy of an intravenous formulation containing monomeric amphotericin B, 5-fluorocytosine, and saline for sodium supplementation[J]. Pharm Res,2017,34(5):1115-1124. | |
[31] | PERLIN D S. Mechanisms of echinocandin antifungal drug resistance[J]. Ann N Y Acad Sci,2015,1354(1):1-11. | |
[32] | LARWOOD D J. Nikkomycin Z—ready to meet the promise? JoF,2020,6(4):261. | |
[33] | KOVÁCS R, NAGY F, TÓTH Z, et al. Synergistic effect of nikkomycin Z with caspofungin and micafungin against Candida albicans and Candida parapsilosis biofilms[J]. Lett Appl Microbiol,2019,69(4):271-278. | |
[34] | CHEN Y L, LEHMAN V N, AVERETTE A F, et al. Posaconazole exhibits in vitro and in vivo synergistic antifungal activity with caspofungin or FK506 against Candida albicans[J]. PLoS One,2013,8(3):e57672. | |
[35] | ROBBINS N, SPITZER M, YU T, et al. An antifungal combination matrix identifies a rich pool of adjuvant molecules that enhance drug activity against diverse fungal pathogens[J]. Cell Rep,2015,13(7):1481-1492. | |
[36] | COOLS T L, STRUYFS C, DRIJFHOUT J W, et al. A linear 19-mer plant defensin-derived peptide acts synergistically with caspofungin against Candida albicans biofilms[J]. Front Microbiol,2017,8:2051. | |
[37] | TROSKIE A M, RAUTENBACH M, DELATTIN N, et al. Synergistic activity of the tyrocidines, antimicrobial cyclodecapeptides from Bacillus aneurinolyticus, with amphotericin B and caspofungin against Candida albicans biofilms[J]. Antimicrob Agents Chemother,2014,58(7):3697-3707. | |
[38] | MASOUDI Y, VAN RENSBURG W, BARNARD-JENKINS B, et al. The influence of cellulose-type formulants on anti- Candida activity of the tyrocidines[J]. Antibiotics (Basel),2021,10(5):597. | |
[39] | SABINO C P, WAINWRIGHT M, RIBEIRO M S, et al. Global priority multidrug-resistant pathogens do not resist photodynamic therapy[J]. J Photochem Photobiol B,2020,208:111893. | |
[40] | HU X Q, HUANG Y Y, WANG Y G, et al. Antimicrobial photodynamic therapy to control clinically relevant biofilm infections[J]. Front Microbiol,2018,9:1299. | |
[41] | PANARIELLO B H D, KLEIN M I, ALVES F, et al. DNase increases the efficacy of antimicrobial photodynamic therapy on Candida albicans biofilms[J]. Photodiagnosis Photodyn Ther,2019,27:124-131. | |
[42] | DAVIES A, GEBREMEDHIN S, YEE M, et al. Cationic porphyrin-mediated photodynamic inactivation of Candida biofilms and the effect of miconazole[J]. J Physiol Pharmacol,2016,67(5):777-783. | |
[43] | LU J J, LI W, ZHENG W A, et al. Successful treatment of kerion with itraconazole and ALA-PDT: a case report[J]. Photodiagnosis Photodyn Ther,2019,27:385-387. | |
[44] | YANG M, DU K Y, HOU Y R, et al. Synergistic antifungal effect of amphotericin B-loaded poly(lactic-co-glycolic acid) nanoparticles and ultrasound against Candida albicans biofilms[J]. Antimicrob Agents Chemother,2019,63(4):e02022-e02018. | |
[45] | Gong-chang YU, Yong ZHANG, Ke NIE. Anti-emetic mechanisms of Xiaobanxia Tang Decoction on the chemotherapy-induced pica model in rats[J]. 中国药理学与毒理学杂志, 2015, 29(S1): 84-85. | Gong-chang YU, Yong ZHANG, Ke NIE. Anti-emetic mechanisms of Xiaobanxia Tang Decoction on the chemotherapy-induced pica model in rats[J]. Chinese Journal of Pharmacology and Toxicology, 2015, 29(S1):84-85. |
[46] | RADHAKRISHNAN V S, REDDY MUDIAM M K, KUMAR M, et al. Silver nanoparticles induced alterations in multiple cellular targets, which are critical for drug susceptibilities and pathogenicity in fungal pathogen (Candida albicans)[J]. Int J Nanomedicine,2018,13:2647-2663. | |
[47] | LARA H H, LOPEZ-RIBOT J L. Inhibition of mixed biofilms of Candida albicans and methicillin-resistant Staphylococcus aureus by positively charged silver nanoparticles and functionalized silicone elastomers[J]. Pathogens,2020,9(10):784. | |
[48] | GUERRERO D J P, BONILLA J J A, LÓPEZ C C O, et al. Encapsulation of silver nanoparticles in polylactic acid or poly(lactic-co-glycolic acid) and their antimicrobial and cytotoxic activities[J]. J Nanosci Nanotechnol,2019,19(11):6933-6941. | |
[49] | LEE B, LEE M J, YUN S J, et al. Silver nanoparticles induce reactive oxygen species-mediated cell cycle delay and synergistic cytotoxicity with 3-bromopyruvate in Candida albicans, but not in Saccharomyces cerevisiae[J]. Int J Nanomedicine,2019,14:4801-4816. |