Potent Activity of Ertapenem Plus Cefazolin Within Staphylococcal Biofilms: A Contributing Factor in the Treatment of Methicillin-Susceptible Staphylococcus aureus Endocarditis.
Potent Activity of Ertapenem Plus Cefazolin Within Staphylococcal Biofilms: A Contributing Factor in the Treatment of Methicillin-Susceptible Staphylococcus aureus Endocarditis.
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DOI：
10.1093/ofid/ofac159
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发表时间：
2022-05
影响因子：
4.2
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中科院分区：
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除了抗葡萄球菌β-内酰胺类药物和源控制外，在长期甲氧西林敏感金黄色葡萄球菌（MSSA）菌血症（包括感染性心内膜炎（IE））患者中，经验证的抗菌补救选择有限。将厄他培南（ETP）联合头孢唑啉（CZ）治疗的MSSA IE病例与标准β-内酰胺单药治疗的匹配IE病例进行比较。还使用体外MSSA生物膜模型将ETP加CZ的杀菌活性与萘夫西林（NAF）、CZ和ETP单独进行比较。接受CZ或NAF治疗的患者（n =12）发生菌血症的中位持续时间为4天（范围1-16天），而接受ETP + CZ治疗的患者（n=5）发生菌血症的中位持续时间为1天（范围1-3天）（P= 0.01，Mann-Whitney U检验）。 头孢唑林和NAF单独或联合使用在临床相关浓度下不能实现生物膜根除。然而，在标准剂量下，将ETP添加至CZ导致生物膜内的杀菌根除。厄他培南降低了消除MSSA生物膜所需的CZ浓度，使其达到标准剂量体内可达到的水平，从而缩短了MSSA心内膜炎患者的菌血症持续时间。需要进行更大规模的研究，以调查ETP加CZ治疗生物膜相关MSSA感染，如心内膜炎。厄他培南降低了根除甲氧西林敏感金黄色葡萄球菌（MSSA）生物膜所需的头孢唑林浓度，使其达到标准剂量体内可达到的水平，从而缩短了MSSA心内膜炎患者的菌血症持续时间。
Besides antistaphylococcal beta-lactams and source control, there are limited validated antimicrobial salvage options in patients with prolonged methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, including infective endocarditis (IE). MSSA IE cases treated with ertapenem (ETP) plus cefazolin (CZ) were compared with matched IE cases treated with standard beta-lactam monotherapy. The bactericidal activity of ETP plus CZ was also compared with nafcillin (NAF), CZ, and ETP alone using an in vitro MSSA biofilm model. The median duration of bacteremia experienced by patients (n = 12) while on CZ or NAF was 4 days (range 1–16 days) compared with 1 day (range 1–3 days) for patients (n = 5) treated with ETP + CZ (P = .01, Mann-Whitney U test). Cefazolin and NAF alone or in combination did not achieve biofilm eradication at clinically relevant concentrations. However, the addition of ETP to CZ led to bactericidal eradication within biofilms at standard dosing. Ertapenem reduces CZ concentrations required to eradicate MSSA biofilms to those achievable in vivo by standard dosing, translating into shorter bacteremia duration in patients with MSSA endocarditis. Larger studies are needed to investigate ETP plus CZ therapy in the treatment of biofilm-related MSSA infections such as endocarditis. Ertapenem reduces cefazolin concentrations required to eradicate methicillin-susceptible Staphylococcus aureus(MSSA) biofilms to those achievable in vivo by standard dosing, translating into shorter bacteremia duration in patients with MSSA endocarditis.
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