抗氧化/抗炎疗法
大肠杆菌的一些因子(例如:黏附素、铁载体、毒素、多糖包膜)在未来可能成为抗尿路感染治疗的有效靶点。[18]Johnson JR. Microbial virulence determinants and the pathogenesis of urinary tract infection. Infect Dis Clin North Am. 2003 Jun;17(2):261-78.http://www.ncbi.nlm.nih.gov/pubmed/12848470?tool=bestpractice.com 在肾盂肾炎的动物模型中,用自由基清除剂过氧化氢酶和二甲基亚砜治疗可以防止肾瘢痕。[62]Gupta R, Verma I, Sharma S, et al. Prevention of tissue injury in an ascending mouse model of chronic pyelonephritis--role of free radical scavengers. Comp Immunol Microbiol Infect Dis. 2004 Jul;27(4):225-34.http://www.ncbi.nlm.nih.gov/pubmed/15177997?tool=bestpractice.com 类似地,对于肾脏接种大肠杆菌的小鼠,如果给予其 cox-2 抑制剂,则接种 6 周后脂蛋白糖显示出较少的肾脏疤痕。[63]Kucuk HF, Bigul SM, Kurt N, et al. Effect of a selective cyclooxygenase-2 inhibitor on renal scarring. Eur Surg Res. 2006;38(5):451-7.http://www.ncbi.nlm.nih.gov/pubmed/16912484?tool=bestpractice.com
疫苗疗法
由于蛋白质纯化和基因重组技术的发展,目前正在研究针对特异性抗原的疫苗。[64]O'Brien VP, Hannan TJ, Nielsen HV, et al. Drug and vaccine development for the treatment and prevention of urinary tract infections. Microbiol Spectr. 2016 Feb;4(1).https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4887100/http://www.ncbi.nlm.nih.gov/pubmed/26999391?tool=bestpractice.com 研究表明,用偶联了白喉类毒素的大肠杆菌荚膜抗原免疫小鼠,可改善疫苗的免疫原性,提高小鼠对后续大肠杆菌暴露的细胞介导免疫活性。[65]Kumar V, Ganguly N, Joshi K, et al. Protective efficacy and immunogenicity of escheria coli K13 diphtheria toxoid conjugate against experimental ascending pyelonephritis. Med Microbiol Immunol. 2005 Aug;194(4):211-7.http://www.ncbi.nlm.nih.gov/pubmed/15909203?tool=bestpractice.com
美罗培南/vaborbactam
Vaborbactam 是一种新型 β-内酰胺酶抑制剂。这种药物正在以与美罗培南联合用药的形式进行开发,作为用于治疗重度革兰氏阴性菌感染(如复杂性尿路感染)的一种新药,包括因细菌对当前可用碳青霉烯类药物产生耐药性而导致的感染。[66]Castanheira M, Huband MD, Mendes RE, et al. Meropenem-vaborbactam tested against contemporary Gram-negative isolates collected worldwide during 2014, including carbapenem-resistant, KPC-producing, multidrug-resistant, and extensively drug-resistant Enterobacteriaceae. Antimicrob Agents Chemother. 2017 Aug 24;61(9):e00567-17.http://www.ncbi.nlm.nih.gov/pubmed/28652234?tool=bestpractice.com[67]Kaye KS, Bhowmick T, Metallidis S, et al. Effect of meropenem-vaborbactam vs piperacillin-tazobactam on clinical cure or improvement and microbial eradication in complicated urinary tract infection: the TANGO I randomized clinical trial. JAMA. 2018 Feb 27;319(8):788-99.https://jamanetwork.com/journals/jama/fullarticle/2673552http://www.ncbi.nlm.nih.gov/pubmed/29486041?tool=bestpractice.com美国食品药品监督管理局 (Food and Drug Administration, FDA) 已批准美罗培南/vaborbactam 用于治疗特定敏感肠杆菌(大肠杆菌、肺炎克雷伯菌以及阴沟肠杆菌复合菌种)引起的成人复杂性尿路感染(包括肾盂肾炎)。
Plazomicin
Plazomicin 是新一代氨基糖苷类抗生素,旨在避免所有临床相关的氨基糖苷类修饰酶,该酶也是氨基糖苷类抗生素耐药的主要机制。[68]Cox G, Ejim L, Stogios PJ, et al. Plazomicin retains antibiotic activity against most aminoglycoside modifying enzymes. ACS Infect Dis. 2018 Jun 8;4(6):980-7.http://www.ncbi.nlm.nih.gov/pubmed/29634241?tool=bestpractice.com Plazomicin 已被 FDA 批准用于治疗 18 岁及以上仅有有限的或没有替代治疗选择患者的复杂性尿路感染,包括肾盂肾炎和某些肠杆菌所致血流感染。