Campbell Patrick O, Chin Paul K L, Dalton Simon C, Metcalf Sarah C L, Douglas Nicholas M, Chambers Stephen T
Department of Infectious Diseases, Christchurch Hospital, Canterbury District Health Board, Christchurch, New Zealand.
Department of Clinical Pharmacology, Christchurch Hospital, Christchurch, New Zealand.
Int J Antimicrob Agents. 2023 Jan;61(1):106695. doi: 10.1016/j.ijantimicag.2022.106695. Epub 2022 Dec 2.
The proportion of patients with invasive methicillin-susceptible Staphylococcus aureus (MSSA) infection who achieve target concentrations of flucloxacillin or cefazolin with standard dosing regimens is uncertain. This study measured drug concentrations in a prospective cohort of patients with invasive S. aureus infections to determine the frequency of target concentration attainment, and risk factors for failure to achieve target concentrations.
Unbound flucloxacillin and cefazolin plasma concentrations were measured at the midpoint between intravenous doses. Adequate and optimal targets were defined as an unbound plasma concentration of ≥1 and ≥2 times the minimum inhibitory concentration (MIC) (flucloxacillin 0.5 mg/L, cefazolin 2 mg/L), respectively (50%fT, 50%fT).
There were 50 patients in each of the flucloxacillin and cefazolin groups. Eighty-five (85%) patients met the target of 50%fT and 95 (95%) patients met the target of 50%fT. The median unbound flucloxacillin concentration was 2.6 mg/L [interquartile range (IQR) 1.0-8.1]. The median unbound cefazolin concentration was 15.4 mg/L (IQR 8.8-28.2). A higher proportion of patients in the flucloxacillin group failed to achieve the optimal target compared with the cefazolin group [13 (26%) vs 2 (4%); P=0.002]. Younger age and higher creatinine clearance were associated with lower plasma concentrations.
Standard dosing of flucloxacillin and cefazolin in the treatment of invasive MSSA infections may not achieve target plasma concentrations for a subgroup of patients. Measuring drug concentrations identifies this subgroup and facilitates dose individualization.
采用标准给药方案治疗侵袭性甲氧西林敏感金黄色葡萄球菌（MSSA）感染患者时，能达到氟氯西林或头孢唑林目标浓度的患者比例尚不确定。本研究对侵袭性金黄色葡萄球菌感染患者的前瞻性队列进行了药物浓度测定，以确定达到目标浓度的频率以及未达到目标浓度的危险因素。
在静脉给药的中点测量未结合的氟氯西林和头孢唑林血浆浓度。将充足和最佳目标分别定义为未结合血浆浓度≥最低抑菌浓度（MIC）的1倍和≥2倍（氟氯西林0.5 mg/L，头孢唑林2 mg/L），即50%fT、50%fT。
氟氯西林组和头孢唑林组各有50例患者。85例（85%）患者达到了50%fT的目标，95例（95%）患者达到了50%fT的目标。未结合氟氯西林浓度的中位数为2.6 mg/L[四分位间距（IQR）1.0 - 8.1]。未结合头孢唑林浓度的中位数为15.4 mg/L（IQR 8.8 - 28.2）。与头孢唑林组相比，氟氯西林组未达到最佳目标的患者比例更高[13例（26%）对2例（4%）；P = 0.002]。年龄较小和肌酐清除率较高与血浆浓度较低相关。
在治疗侵袭性MSSA感染时，氟氯西林和头孢唑林的标准给药可能无法使部分患者达到目标血浆浓度。测量药物浓度可识别出这部分患者并有助于实现个体化给药。
