Department of Medical Microbiology, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa; Universitas Academic Laboratory Complex, National Health Laboratory Service, Pretoria, South Africa.
Department of Critical Care, School of Medicine, Faculty of Health Sciences, University of Pretoria, South Africa; Department of Critical Care, Steve Biko Academic Hospital, Pretoria, South Africa.
S Afr Med J. 2022 Aug 30;112(9). doi: 10.7196/SAMJ.2022.v112i9.16371.
Antibiotic dosing in critically ill patients is complicated by variations in the pharmacokinetics of antibiotics in this group. The dosing of imipenem/cilastatin is usually determined by severity of illness and renal function.
To determine the correlation between estimated glomerular filtration rates (eGFRs) calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and imipenem trough levels in critically ill patients.
This prospective observational study was done in the surgical intensive care unit (ICU) at Steve Biko Academic Hospital, Pretoria, South Africa. Imipenem trough levels were measured by high-performance liquid chromatography and compared with eGFRs calculated with the CKD-EPI equation. Correlation was evaluated by the Pearson product-moment correlation coefficient.
The study population consisted of 68 critically ill patients aged between 18 and 81 years; 43 (63%) were male, and the mean weight was 78 kg (range 40 - 140). On admission, 30 patients (44%) had sepsis, 16 (24%) were admitted for trauma, and 22 (32%) were admitted for miscellaneous surgical conditions. Acute Physiology and Chronic Health Evaluation II (APACHE II) scores ranged from 4 to 39 (mean 18). The 28-day mortality rate was 29%. The mean albumin level was 16 g/L (range 7 - 25), the mean creatinine level 142 μmol/L (range 33 - 840), and the mean eGFR 91 mL/min/1.73 m2 (range 6 - 180). Imipenem trough levels ranged between 3.6 and 92.2 mg/L (mean 11.5). The unadjusted Pearson product-moment correlation coefficient between eGFR and imipenem trough level was -0.04 (p=0.761).
Considering the high mortality rate of sepsis in ICUs and the rapid global increase in antimicrobial resistance, it is crucial to dose antibiotics appropriately. Owing to the variability of antibiotic pharmacokinetics in critically ill patients, this task becomes almost impossible when relying on conventional dosing guidelines. This study found that eGFRs do not correlate with imipenem blood levels in critically ill patients and should not be used to determine the dose of imipenem/cilastatin. Instead, the dose should be individualised for patients through routine therapeutic drug monitoring.
由于此类患者的抗生素药代动力学存在差异，因此重症患者的抗生素给药较为复杂。亚胺培南/西司他丁的给药通常根据疾病严重程度和肾功能来确定。
确定应用慢性肾脏病流行病学合作（CKD-EPI）方程计算的估计肾小球滤过率（eGFR）与重症患者的亚胺培南谷浓度之间的相关性。
这是一项在南非比勒陀利亚史蒂夫·比科学术医院外科重症监护病房（ICU）进行的前瞻性观察性研究。采用高效液相色谱法测定亚胺培南谷浓度，并与 CKD-EPI 方程计算的 eGFR 进行比较。通过皮尔逊积矩相关系数评估相关性。
研究人群包括 68 名年龄在 18 至 81 岁之间的重症患者；其中 43 名（63%）为男性，平均体重为 78 公斤（范围为 40 至 140 公斤）。入院时，30 名患者（44%）患有败血症，16 名（24%）因创伤入院，22 名（32%）因各种外科疾病入院。急性生理学和慢性健康评估 II（APACHE II）评分范围为 4 至 39 分（平均 18 分）。28 天死亡率为 29%。白蛋白平均水平为 16 g/L（范围为 7 至 25 g/L），肌酐平均水平为 142 μmol/L（范围为 33 至 840 μmol/L），eGFR 平均水平为 91 mL/min/1.73 m2（范围为 6 至 180 mL/min/1.73 m2）。亚胺培南谷浓度范围为 3.6 至 92.2 mg/L（平均 11.5 mg/L）。未校正的 Pearson 积矩相关系数为-0.04（p=0.761）。
鉴于 ICU 中败血症的高死亡率以及全球范围内抗菌药物耐药性的迅速增加，适当给予抗生素至关重要。由于重症患者的抗生素药代动力学存在差异，因此仅依靠传统的给药指南几乎不可能确定抗生素的剂量。本研究发现，重症患者的 eGFR 与亚胺培南血药浓度无关，不应用于确定亚胺培南/西司他丁的剂量。相反，应通过常规治疗药物监测为患者个体化确定剂量。
