Plasma Concentration of Posaconazole in Septic Shock Patients with Continuous Renal Replacement Therapy: A Case Report.

Objective: This study aims to evaluate the impact of continuous renal replacement therapy (CRRT) on the plasma concentrations of Posaconazole in critically ill patients. Case presentation: In this study, we reported a patient with septic shock, cardiac arrest, and Multiple Organ Dysfunction Syndrome showed improvement following anti-infective treatment with Posaconazole. The patient's condition improved after Posaconazole was administered for anti-infective treatment. The concentration of Posaconazole was measured during CRRT. The results showed that the trough concentrations of Posaconazole were 1.9mg/L and 0.8mg/L on the 7th and 11th days of CRRT, respectively. The peak concentrations of Posaconazole were 6.6 mg/L and 4.3 mg/L on the 7th and 11th days of CRRT. On the first and second day after the discontinuation of CRRT, the trough concentrations of Posaconazole were 0.7 mg/L and 0.8 mg/L, and the peak concentrations were 2.6 mg/L and 2.2 mg/L. These results indicated that the trough and peak concentrations of Posaconazole were not significantly different before and after CRRT. No adverse reactions occurred during the follow-up. Conclusion: Posaconazole plasma concentrations remained stable during and after CRRT, suggesting that dose adjustments are not necessary in these clinical settings.

Efficacy and safety of colistin sulfate in the treatment of infections caused by carbapenem-resistant organisms: a multicenter retrospective cohort study.

Background: Polymyxins have become an important treatment option for carbapenem-resistant organisms (CRO) infections. However, there is a rare of clinical studies on colistin sulfate. This study sought to investigate the rate of clinical improvement and adverse reactions of colistin sulfate in the treatment of severe infections caused by CRO in critically ill patients and assess the factors associated with 28-day all-cause mortality. Methods: This multicenter retrospective cohort study included intensive care unit (ICU) patients who received colistin sulfate due to CRO infections during July 2021 and May 2022. The primary endpoint was clinical improvement at end of therapy. Secondary endpoints included adverse reactions bacterial clearance rate and 28-day all-cause mortality. Results: A total of 122 patients, who were included between July 2021 and May 2022, were included in this study, of whom 86 (70.5%) showed clinical improvement and 36 (29.5%) showed clinical failure. The comparison of the clinical data of the patients showed that the median sequential organ failure assessment (SOFA) score was higher in the failure group than the improvement group {9.5 [7, 11] vs. 7 [4, 9], P=0.002}, the proportion of patients receiving extracorporeal membrane oxygenation (ECMO) was higher in the failure group than the improvement group (27.8% vs. 12.8%, P=0.046), and the median duration of treatment was longer in the improvement group than the failure group {12 [8, 15] vs. 5.5 [4, 9.75], P<0.001}. A total of 5 (4.1%) patients suffered from acute kidney injury due to increases in creatinine during colistin sulfate treatment. The Cox regression survival analysis showed that the SOFA score [hazards ratio (HR) =1.198, P=0.001], ECMO treatment (HR =2.373, P=0.029), and duration of treatment (HR =0.736, P<0.001) were independently associated with 28-day all-cause mortality. Conclusions: Colistin sulfate is a reasonable choice for the treatment of CRO infections in the current treatment options are limited. The possible kidney injury caused by the colistin sulfate requires intensive monitoring.

[Effect of continuous renal replacement therapy on plasma concentration, clinical efficacy and safety of colistin sulfate].

OBJECTIVE: To investigate the effects of continuous renal replacement therapy (CRRT) on plasma concentration, clinical efficacy and safety of colistin sulfate. METHODS: Clinical data of patients received with colistin sulfate were retrospectively analyzed from our group's previous clinical registration study, which was a prospective, multicenter observation study on the efficacy and pharmacokinetic characteristics of colistin sulfate in patients with severe infection in intensive care unit (ICU). According to whether patients received blood purification treatment, they were divided into CRRT group and non-CRRT group. Baseline data (gender, age, whether complicated with diabetes, chronic nervous system disease, etc), general data (infection of pathogens and sites, steady-state trough concentration, steady-state peak concentration, clinical efficacy, 28-day all-cause mortality, etc) and adverse event (renal injury, nervous system, skin pigmentation, etc) were collected from the two groups. RESULTS: A total of 90 patients were enrolled, including 22 patients in the CRRT group and 68 patients in the non-CRRT group. (1) There was no significant difference in gender, age, basic diseases, liver function, infection of pathogens and sites, colistin sulfate dose between the two groups. Compared with the non-CRRT group, the acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) were higher in the CRRT group [APACHE II: 21.77±8.26 vs. 18.01±6.34, P < 0.05; SOFA: 8.5 (7.8, 11.0) vs. 6.0 (4.0, 9.0), P < 0.01], serum creatinine level was higher [µmol/L: 162.0 (119.5, 210.5) vs. 72.0 (52.0, 117.0), P < 0.01]. (2) Plasma concentration: there was no significant difference in steady-state trough concentration between CRRT group and non-CRRT group (mg/L: 0.58±0.30 vs. 0.64±0.25, P = 0.328), nor was there significant difference in steady-state peak concentration (mg/L: 1.02±0.37 vs. 1.18±0.45, P = 0.133). (3) Clinical efficacy: there was no significant difference in clinical response rate between CRRT group and non-CRRT group [68.2% (15/22) vs. 80.9% (55/68), P = 0.213]. (4) Safety: acute kidney injury occurred in 2 patients (2.9%) in the non-CRRT group. No obvious neurological symptoms and skin pigmentation were found in the two groups. CONCLUSIONS: CRRT had little effect on the elimination of colistin sulfate. Routine blood concentration monitoring (TDM) is warranted in patients received with CRRT.

Plasma concentrations of Colistin sulfate in a patient with septic shock on extracorporeal membrane oxygenation and continuous renal replacement therapy: a case report.

Background: Polymyxins antibiotics have become the first-line clinical drugs in the treatment of refractory gram-negative bacterial infections. Currently, there is a lack of clinical studies on the effect of extracorporeal membrane oxygenation (ECMO) combined with continuous renal replacement therapy (CRRT) on polymyxin concentrations. The purpose of this report was to investigate the changes in the plasma concentrations of Colistin sulfate during ECMO and CRRT and to provide drug administration programs for critically ill patients receiving ECMO and CRRT. Case Description: In this case report, a patient with septic shock caused by severe acute pancreatitis, with abdominal pain and dyspnea as the main manifestations, was treated with ECMO combined with CRRT for life support and multiple anti-infective drugs. However, the symptoms of infection had not got improved, the inflammatory indicators remain high and the body temperature fluctuates repeatedly 36.7-38.5 ℃, was considered as carbapenem-resistant organisms (CROs) infection, and was empirically given Colistin sulfate for anti-infection treatment. Finally, the patient's condition improved and ECMO and CRRT were gradually withdrawn. At the same time, the plasma concentrations of Colistin sulfate before and after ECMO combined with CRRT, was monitored to determine the changes in the plasma concentrations of Colistin sulfate during ECMO and CRRT. Trough and peak concentrations on the 4th day of venovenous ECMO (VV-ECMO) combined with CRRT were 0.36 and 0.98 mg/L, respectively. After withdrawal of ECMO and CRRT, the concentrations were, respectively, 0.27 and 0.34 mg/L for trough concentrations, and 0.82 and 0.98 mg/L for peak concentrations. The data showed that there were no significant differences in the trough and peak concentrations of Colistin sulfate before and after ECMO and CRRT. No adverse effects occurred during follow-up. Conclusions: There were no significant differences in the trough and peak concentrations of Colistin sulfate before and after ECMO and CRRT. Therefore, no dose modification is required for Colistin sulfate in patients receiving ECMO with CRRT.