Beganovic Maya, Daffinee Kathryn E, Luther Megan K, LaPlante Kerry L
Infectious Diseases Research Program, Providence Veterans Affairs Medical Center, Providence, Rhode Island, USA.
College of Pharmacy, University of Rhode Island, Kingston, Rhode Island, USA.
Antimicrob Agents Chemother. 2021 Feb 17;65(3). doi: 10.1128/AAC.01680-20.
is recognized as an urgent public health threat by the Centers for Disease Control and Prevention (CDC). Current treatment options are scarce, particularly against carbapenem-resistant (CRAB). We simulated the impact of minocycline standard (200 mg load + 100 mg Q12h) and high (700 mg load + 350 mg Q12h) doses, polymyxin B (2.5 mg/kg Q12h), sulbactam (1 g Q6h and 9 g/24 h as continuous infusion), and meropenem (intermittent 1 or 2 g Q8h and 6 g/24 h as continuous infusion) alone or in combination against CRAB and non-CRAB isolates by simulating human therapeutic dosing regimens in a 72-h, pharmacodynamic (IVPD) model. There were no monotherapy regimens that demonstrated bactericidal activity against the tested non-CRAB and CRAB strains. Resistance development was common in monotherapy regimens. Against the CRAB isolate, the triple combination of high-dose minocycline (AUC/MIC 21.2), polymyxin B (AUC/MIC 15.6), and continuous-infusion sulbactam (67% ) was the most consistently active regimen. Against non-CRAB, the triple therapy regimen of high-dose minocycline (AUC/MIC 84.8) with continuous-infusion meropenem (100% ) and continuous-infusion sulbactam (83% ), as well as the double therapy of high-dose minocycline (AUC/MIC 84.8) with continuous-infusion meropenem (100% ), resulted in persistently bactericidal activity. In conclusion, triple therapy with high-dose minocycline, continuous-infusion sulbactam, and polymyxin B produced the most significant kill against the carbapenem-resistant , with no regrowth and minimal resistance development.
被美国疾病控制与预防中心（CDC）认定为紧急公共卫生威胁。目前的治疗选择稀缺，尤其是针对耐碳青霉烯类鲍曼不动杆菌（CRAB）。我们通过在72小时的药效学（IVPD）模型中模拟人体治疗给药方案，模拟了米诺环素标准剂量（负荷剂量200mg + 每12小时100mg）和高剂量（负荷剂量700mg + 每12小时350mg）、多粘菌素B（每12小时2.5mg/kg）、舒巴坦（每6小时1g和每24小时9g持续输注）和美罗培南（每8小时间歇1或2g和每24小时6g持续输注）单独或联合使用对CRAB和非CRAB分离株的影响。没有单一疗法方案对测试的非CRAB和CRAB菌株表现出杀菌活性。在单一疗法方案中耐药性发展很常见。针对CRAB分离株，高剂量米诺环素（AUC/MIC 21.2）、多粘菌素B（AUC/MIC 15.6）和持续输注舒巴坦（67%）的三联组合是最持续有效的方案。针对非CRAB，高剂量米诺环素（AUC/MIC 84.8）与持续输注美罗培南（100%）和持续输注舒巴坦（83%）的三联疗法方案，以及高剂量米诺环素（AUC/MIC 84.8）与持续输注美罗培南（100%）的双联疗法，产生了持续的杀菌活性。总之，高剂量米诺环素、持续输注舒巴坦和多粘菌素B的三联疗法对耐碳青霉烯类鲍曼不动杆菌产生了最显著的杀灭效果，没有再生长且耐药性发展最小。
