Lin Zhang,1 Juan Zeng,1 Wenying Zhu,1 Jing Sha,1 Yue Tang,1 Bing Leng,2 Nan Guo,2 Jinjiao Jiang1 

1Department of Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 2Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China

Correspondence: Jinjiao Jiang, Department of Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324 Jingwu Roud, Jinan, People’s Republic of China, Email jjjsch@163.com

Purpose: To investigate the impact of varying renal function on serum sulbactam concentrations and antibiotic efficacy in critically ill patients with hospital-acquired pneumonia (HAP) who exhibit no elevation in serum creatinine levels.
Patients and Methods: A prospective observational study was conducted on 23 adult HAP patients in the ICU of Shandong Provincial Hospital who received intravenous cefoperazone/sulbactam, from January 2021 to January 2023. Renal function was estimated using serum creatinine (eGFRcreat) and cystatin C (eGFRcys). An eGFRcreat > 130 mL/min or eGFRcys > 80 mL/min indicated augmented renal clearance. Serum sulbactam levels were measured at 0 min (pre-dose) and 15, 30, 60, 120, 180, 360, and 480 min after the > 6th dose using HPLC-MS/MS.
Results: Among all the 23 patients, 10 had an eGFRcreat above 130 mL/min and 9 had an eGFRcys above 80 mL/min. Additionally, 13 patients exhibited an eGFRcreat ranging from 47 to 123 mL/min, and 14 patients had an eGFRcys in the range of 22 to 75 mL/min. In patients with higher estimated glomerular filtration rate (eGFR), regardless of whether it was based on creatinine or cystatin C, the serum sulbactam concentration tend to decrease more rapidly after the end of administration. Patients with higher eGFR also tend to have a shorter half time and lower drug exposure (AUC). Five patients experienced antibiotic treatment failure. The median eGFRcreat and eGFRcys of these 5 patients were both higher than those patients who responded positively to antibiotic therapy, although not statistically significant.
Conclusion: Patients with higher eGFR demonstrated decreased levels of sulbactam. Despite the discrepancy in GFR estimated by creatinine and cystatin C, both the two biomarkers yielded similar predictions of variability in serum sulbactam concentration. Currently, there is no evidence in this study indicating that differences in renal function affect treatment outcomes in critically ill patients without elevated creatinine levels. Further research is warranted to explore the influence of varying renal function-related pharmacokinetic fluctuations on antibiotic efficacy.

Keywords: sulbactam, HAP, critically ill, pharmacokinetic, renal clearance, Cystatin C