Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, National Infection Service, Public Health England, London NW9 5EQ, UK.
Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK.
J Antimicrob Chemother. 2021 Jan 1;76(1):160-170. doi: 10.1093/jac/dkaa391.
Boronates are of growing interest as β-lactamase inhibitors. The only marketed analogue, vaborbactam, principally targets KPC carbapenemases, but taniborbactam (VNRX-5133, Venatorx) has a broader spectrum.
MICs of cefepime and meropenem were determined combined with taniborbactam or avibactam for carbapenem-resistant UK isolates. β-Lactamase genes and porin alterations were sought by PCR or sequencing.
Taniborbactam potentiated partner β-lactams against: (i) Enterobacterales with KPC, other class A, OXA-48-like, VIM and NDM (not IMP) carbapenemases; and (ii) Enterobacterales inferred to have combinations of ESBL or AmpC activity and impermeability. Potentiation of cefepime (the partner for clinical development) by taniborbactam was slightly weaker than by avibactam for Enterobacterales with KPC or OXA-48-like carbapenemases, but MICs of cefepime/taniborbactam were similar to those of ceftazidime/avibactam, and the spectrum was wider. MICs of cefepime/taniborbactam nonetheless remained >8 + 4 mg/L for 22%-32% of NDM-producing Enterobacterales. Correlates of raised cefepime/taniborbactam MICs among these NDM Enterobacterales were a cefepime MIC >128 mg/L, particular STs and, for Escherichia coli only: (i) the particular blaNDM variant (even though published data suggest all variants are inhibited similarly); (ii) inserts in PBP3; and (iii) raised aztreonam/avibactam MICs. Little or no potentiation of cefepime or meropenem was seen for Pseudomonas aeruginosa and Acinetobacter baumannii with MBLs, probably reflecting slower uptake or stronger efflux. Potentiation of cefepime was seen for Stenotrophomonas maltophilia and Elizabethkingia meningoseptica, which have both chromosomal ESBLs and MBLs.
Taniborbactam broadly reversed cefepime or meropenem non-susceptibility in Enterobacterales and, less reliably, in non-fermenters.
硼酸盐作为β-内酰胺酶抑制剂越来越受到关注。唯一上市的类似物瓦博巴坦主要针对 KPC 碳青霉烯酶，但坦尼硼（VNRX-5133，Venatorx）具有更广泛的谱。
测定头孢吡肟和美罗培南与坦尼硼或阿维巴坦联合对英国耐碳青霉烯类分离株的 MIC。通过 PCR 或测序寻找β-内酰胺酶基因和孔蛋白改变。
坦尼硼增强了头孢吡肟和美罗培南对以下病原体的活性：（i）产 KPC、其他 A 类、OXA-48 样、VIM 和 NDM（非 IMP）碳青霉烯酶的肠杆菌科；（ii）推测同时具有 ESBL 或 AmpC 活性和通透性降低的肠杆菌科。与阿维巴坦相比，坦尼硼对产 KPC 或 OXA-48 样碳青霉烯酶的肠杆菌科的头孢吡肟的增效作用稍弱，但头孢吡肟/坦尼硼的 MIC 与头孢他啶/阿维巴坦相似，且谱更宽。然而，头孢吡肟/坦尼硼的 MIC 仍>8+4mg/L，占产 NDM 肠杆菌科的 22%-32%。这些产 NDM 肠杆菌科中头孢吡肟/坦尼硼 MIC 升高的相关因素包括：（i）头孢吡肟 MIC>128mg/L；（ii）特定的 ST；（iii）仅对大肠杆菌：1）特定的 blaNDM 变体（尽管发表的数据表明所有变体都被相似地抑制）；2）PBP3 插入；3）升高的氨曲南/阿维巴坦 MIC。产 MBL 的铜绿假单胞菌和鲍曼不动杆菌对头孢吡肟或美罗培南的增效作用很小或没有，这可能反映了较慢的摄取或更强的外排。头孢吡肟对同时具有染色体 ESBL 和 MBL 的嗜麦芽窄食单胞菌和脑膜败血伊丽莎白菌有增效作用。
坦尼硼广泛逆转了肠杆菌科对头孢吡肟或美罗培南的非敏感性，在非发酵菌中则不太可靠。
