Case Western Reserve University, Cleveland, Ohio, USA.
University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.
Antimicrob Agents Chemother. 2024 Sep 4;68(9):e0075124. doi: 10.1128/aac.00751-24. Epub 2024 Aug 12.
Taniborbactam, a bicyclic boronate β-lactamase inhibitor with activity against carbapenemase (KPC), Verona integron-encoded metallo-β-lactamase (VIM), New Delhi metallo-β-lactamase (NDM), extended-spectrum beta-lactamases (ESBLs), OXA-48, and AmpC β-lactamases, is under clinical development in combination with cefepime. Susceptibility of 200 previously characterized carbapenem-resistant and 197 multidrug-resistant (MDR) to cefepime-taniborbactam and comparators was determined by broth microdilution. For (192 KPC; 7 OXA-48-related), MIC values of β-lactam components for cefepime-taniborbactam, ceftazidime-avibactam, and meropenem-vaborbactam were 2, 2, and 1 mg/L, respectively. For cefepime-taniborbactam, 100% and 99.5% of isolates of were inhibited at ≤16 mg/L and ≤8 mg/L, respectively, while 98.0% and 95.5% of isolates were susceptible to ceftazidime-avibactam and meropenem-vaborbactam, respectively. For , MIC values of β-lactam components of cefepime-taniborbactam, ceftazidime-avibactam, ceftolozane-tazobactam, and meropenem-vaborbactam were 16, >8, >8, and >4 mg/L, respectively. Of 89 carbapenem-susceptible isolates, 100% were susceptible to ceftolozane-tazobactam, ceftazidime-avibactam, and cefepime-taniborbactam at ≤8 mg/L. Of 73 carbapenem-intermediate/resistant isolates without carbapenemases, 87.7% were susceptible to ceftolozane-tazobactam, 79.5% to ceftazidime-avibactam, and 95.9% and 83.6% to cefepime-taniborbactam at ≤16 mg/L and ≤8 mg/L, respectively. Cefepime-taniborbactam at ≤16 mg/L and ≤8 mg/L, respectively, was active against 73.3% and 46.7% of 15 VIM- and 60.0% and 35.0% of 20 KPC-producing isolates. Of all 108 carbapenem-intermediate/resistant isolates, cefepime-taniborbactam was active against 86.1% and 69.4% at ≤16 mg/L and ≤8 mg/L, respectively, compared to 59.3% for ceftolozane-tazobactam and 63.0% for ceftazidime-avibactam. Cefepime-taniborbactam had activity comparable to ceftazidime-avibactam and greater than meropenem-vaborbactam against carbapenem-resistant and carbapenem-intermediate/resistant MDR .
他唑巴坦是一种具有针对碳青霉烯酶（KPC）、 Verona 整合子编码的金属β-内酰胺酶（VIM）、新德里金属β-内酰胺酶（NDM）、广谱β-内酰胺酶（ESBLs）、OXA-48 和 AmpCβ-内酰胺酶的活性的双环硼酸β-内酰胺酶抑制剂，目前正在与头孢吡肟联合进行临床开发。通过肉汤微量稀释法测定了 200 株先前特征明确的碳青霉烯类耐药菌和 197 株多药耐药（MDR）对头孢吡肟-他唑巴坦和对照药物的敏感性。对于（192 株 KPC；7 株 OXA-48 相关），头孢吡肟-他唑巴坦、头孢他啶-阿维巴坦和美罗培南-沃巴坦的β-内酰胺成分的 MIC 值分别为 2、2 和 1mg/L。对于头孢吡肟-他唑巴坦，100%和 99.5%的碳青霉烯类耐药菌在≤16mg/L 和≤8mg/L 时被抑制，而 98.0%和 95.5%的分离株对头孢他啶-阿维巴坦和美罗培南-沃巴坦分别敏感。对于，头孢吡肟-他唑巴坦、头孢他啶-阿维巴坦、头孢唑肟-他唑巴坦和美罗培南-沃巴坦的β-内酰胺成分的 MIC 值分别为 16、>8、>8 和>4mg/L。在 89 株碳青霉烯类敏感分离株中，100%的分离株对头孢唑肟-他唑巴坦、头孢他啶-阿维巴坦和头孢吡肟-他唑巴坦在≤8mg/L 时敏感。在 73 株无碳青霉烯酶的碳青霉烯类中介/耐药株中，87.7%对头孢唑肟-他唑巴坦、79.5%对头孢他啶-阿维巴坦敏感，95.9%和 83.6%对头孢吡肟-他唑巴坦在≤16mg/L 和≤8mg/L 时敏感。头孢吡肟-他唑巴坦在≤16mg/L 和≤8mg/L 时，对 73.3%和 46.7%的 15 株 VIM 和 60.0%和 35.0%的 20 株 KPC 产酶株有活性。在所有 108 株碳青霉烯类中介/耐药株中，头孢吡肟-他唑巴坦在≤16mg/L 和≤8mg/L 时的活性分别为 86.1%和 69.4%，而头孢唑肟-他唑巴坦为 59.3%，头孢他啶-阿维巴坦为 63.0%。头孢吡肟-他唑巴坦对碳青霉烯类耐药菌和碳青霉烯类中介/耐药 MDR 的活性与头孢他啶-阿维巴坦相当，优于美罗培南-沃巴坦。
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