Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
Microbiol Spectr. 2023 Jun 15;11(3):e0056923. doi: 10.1128/spectrum.00569-23. Epub 2023 May 8.
Cefiderocol and aztreonam-avibactam (ATM-AVI) both had activity against carbapenem-resistant Gram-negative bacilli, including those that produce metallo-β-lactamases (MBLs). We compared the activities and inoculum effects of these antibiotics against carbapenemase-producing (CPE), especially MBL-producing isolates. The MICs of cefiderocol and ATM-AVI were determined using broth microdilution method for a 2016 to 2021 collection of isolates which produced MBL, KPC, or OXA-48-like carbapenemases. MICs with high bacteria inoculum were also evaluated for susceptible isolates. A total of 195 CPE were tested, including 143 MBL- (74 NDM, 42 IMP, and 27 VIM), 38 KPC-, and 14 OXA-48-like-producing isolates. The susceptible rates of MBL-, KPC-, and OXA-48-like producers to cefiderocol were 86.0%, 92.1%, and 92.9%, respectively, and that to ATM-AVI were 95.8%, 100%, and 100%, respectively. NDM producers displayed lower susceptibility and higher MICs/MICs of cefiderocol (78.4%, 2/16 mg/L) than IMP (92.9%, 0.375/4 mg/L) and VIM (96.3%, 1/4 mg/L) producers. NDM- and VIM-producing Escherichia coli showed lower susceptibility to ATM-AVI (77.3% and 75.0%, respectively) compared to MBL-CPE of other species (100% susceptible). Inoculum effects for cefiderocol and ATM-AVI were observed among 95.9% and 95.2% of susceptible CPE, respectively. A switch from susceptible to resistant category was observed in 83.6% (143/171) of isolates for cefiderocol and 94.7% (179/189) for ATM-AVI. Our results revealed that NDM-producing had lower susceptibility to cefiderocol and ATM-AVI. Prominent inoculum effects on both antibiotics were observed for CPE, which suggested a risk of microbiological failure when they were used for CPE infections with high bacteria burden. The prevalence of infections caused by carbapenem-resistant is increasing worldwide. Currently, therapeutic options for metallo-β-lactamase (MBL)-producing remain limited. We demonstrated that clinical metallo-β-lactamase (MBL)-producing isolates were highly susceptible to cefiderocol (86.0%) and aztreonam-avibactam (ATM-AVI) (95.8%). However, inoculum effects on cefiderocol and ATM-AVI were observed for over 90% of susceptible carbapenemase-producing (CPE) isolates. Our findings highlight a potential risk of microbiological failure when using monotherapy with cefiderocol or ATM-AVI to treat severe CPE infection.
头孢地尔和阿维巴坦-美罗培南（ATM-AVI）对碳青霉烯类耐药革兰氏阴性杆菌均具有活性，包括产生金属β-内酰胺酶（MBL）的菌株。我们比较了这些抗生素对产碳青霉烯酶（CPE），尤其是产 MBL 分离株的活性和接种物效应。使用肉汤微量稀释法测定了头孢地尔和 ATM-AVI 对 2016 年至 2021 年收集的产 MBL、KPC 或 OXA-48 样碳青霉烯酶的分离株的 MIC。还评估了高细菌接种物的 MIC 对敏感分离株的影响。共检测了 195 株 CPE，包括 143 株 MBL-（74 株 NDM、42 株 IMP 和 27 株 VIM）、38 株 KPC-和 14 株 OXA-48 样产酶株。MBL-、KPC-和 OXA-48 样产酶株对头孢地尔的敏感率分别为 86.0%、92.1%和 92.9%，对 ATM-AVI 的敏感率分别为 95.8%、100%和 100%。NDM 产酶株的敏感性和头孢地尔的 MIC/MICs（78.4%，2/16 mg/L）均低于 IMP（92.9%，0.375/4 mg/L）和 VIM（96.3%，1/4 mg/L）产酶株。与其他种属的 MBL-CPE（100%敏感）相比，NDM 和 VIM 产大肠埃希菌对 ATM-AVI 的敏感性较低（分别为 77.3%和 75.0%）。头孢地尔和 ATM-AVI 的敏感 CPE 中分别观察到 95.9%和 95.2%的接种物效应。头孢地尔对 171 株敏感分离株中的 83.6%（143/171）和 ATM-AVI 对 189 株敏感分离株中的 94.7%（179/189）从敏感转为耐药。我们的结果表明，NDM 产酶株对头孢地尔和 ATM-AVI 的敏感性较低。两种抗生素对 CPE 均观察到明显的接种物效应，这提示在高细菌负荷的 CPE 感染中使用这些抗生素时存在微生物学失败的风险。目前，对产金属β-内酰胺酶（MBL）的耐药株的治疗选择仍然有限。我们证明了临床产金属β-内酰胺酶（MBL）的耐药株对头孢地尔（86.0%）和阿维巴坦-美罗培南（ATM-AVI）（95.8%）高度敏感。然而，超过 90%的敏感产碳青霉烯酶的耐药株（CPE）对头孢地尔和 ATM-AVI 观察到接种物效应。我们的研究结果强调了在治疗严重 CPE 感染时，单独使用头孢地尔或 ATM-AVI 进行单药治疗可能存在微生物学失败的风险。
