Kunz Coyne Ashlan J, El Ghali Amer, Lucas Kristen, Witucki Paige, Rebold Nicholas, Holger Dana J, Veve Michael P, Rybak Michael J
Wayne State University, Detroit, Michigan, USA.
Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.
Open Forum Infect Dis. 2023 Jan 25;10(3):ofad034. doi: 10.1093/ofid/ofad034. eCollection 2023 Mar.
Limited data suggest that serious infections caused by Enterobacterales with a moderate to high risk of clinically significant AmpC production can be successfully treated with cefepime if the cefepime minimum inhibitory concentration (MIC) is ≤2 µg/mL. However, isolates with a cefepime-susceptible dose-dependent (SDD) MIC of 4-8 µg/mL should receive a carbapenem due to target attainment and extended-spectrum β-lactamase (ESBL) concerns.
This was a retrospective cohort study of hospitalized patients with , or bacteremia from January 2015 to March 2022 receiving high-dose cefepime or a carbapenem. Cox regression models were used with incorporation of inverse probability of treatment weighting and time-varying covariates.
Of the 315 patients included, 169 received cefepime and 146 received a carbapenem (ertapenem n = 90, meropenem n = 56). Cefepime was not associated with an increased risk of 30-day mortality compared with carbapenem therapy (adjusted hazard ratio [aHR], 1.45; 95% CI, 0.79-2.14), which was consistent for patients with cefepime SDD isolates (aHR, 1.19; 95% CI, 0.52-1.77). Multivariable weighted Cox models identified Pitt bacteremia score >4 (aHR, 1.41; 95% CI, 1.04-1.92), deep infection (aHR, 2.27; 95% CI, 1.21-4.32), and ceftriaxone-resistant AmpC-E (aHR, 1.32; 95% CI, 1.03-1.59) to be independent predictors associated with increased mortality risk, while receipt of prolonged-infusion β-lactam was protective (aHR, 0.67; 95% CI, 0.40-0.89).
Among patients with bacteremia caused by Enterobacterales with moderate to high risk of clinically significant AmpC production, these data demonstrate similar risk of 30-day mortality for high-dose cefepime or a carbapenem as definitive β-lactam therapy.
有限的数据表明，对于临床上产生具有中度至高风险的AmpC的肠杆菌科细菌引起的严重感染，如果头孢吡肟的最低抑菌浓度（MIC）≤2μg/mL，使用头孢吡肟可成功治疗。然而，由于目标达成情况以及对超广谱β-内酰胺酶（ESBL）的担忧，头孢吡肟敏感剂量依赖性（SDD）MIC为4-8μg/mL的分离株应接受碳青霉烯类药物治疗。
这是一项回顾性队列研究，研究对象为2015年1月至2022年3月期间因 、 或 菌血症住院并接受高剂量头孢吡肟或碳青霉烯类药物治疗的患者。使用Cox回归模型，并纳入治疗权重的逆概率和随时间变化的协变量。
在纳入的315例患者中，169例接受了头孢吡肟治疗，146例接受了碳青霉烯类药物治疗（厄他培南n = 90，美罗培南n = 56）。与碳青霉烯类药物治疗相比，头孢吡肟与30天死亡率增加风险无关（调整后的风险比[aHR]，1.45；95%置信区间[CI]，0.79-2.14），对于头孢吡肟SDD分离株的患者也是如此（aHR，1.19；95%CI，0.52-1.77）。多变量加权Cox模型确定 Pitt菌血症评分>4（aHR，1.41；95%CI，1.04-1.92）、深部感染（aHR，2.27；95%CI，1.21-4.32）和对头孢曲松耐药的AmpC-E（aHR，1.32；95%CI，1.03-1.59）是与死亡风险增加相关的独立预测因素，而接受延长输注的β-内酰胺类药物具有保护作用（aHR，0.67；95%CI，0.40-0.89）。
在临床上产生具有中度至高风险的AmpC的肠杆菌科细菌引起菌血症的患者中，这些数据表明，高剂量头孢吡肟或碳青霉烯类药物作为确定性β-内酰胺类药物治疗的30天死亡率风险相似。
