Target Attainment and Population Pharmacokinetics of Nirmatrelvir/Ritonavir in Critically Ill Adult Patients.

Background: The population pharmacokinetics of nirmatrelvir/ritonavir (NIR/RIT) has not yet been described for critically ill adult patient. Purpose: This was a prospective observational population pharmacokinetic study of nirmatrelvir/ritonavir (NIR/RIT) in critically ill adult patients and identify optimal dosing regimens. Patients and Methods: The prescription of NIR/RIT is determined by the attending physician and ranges from 150mg/100mg to 300mg/100mg twice a day. Two to three serial blood samples were collected for each patient after the second doses. We developed and validated PK model for plasma NIR and plasma RIT. Monte Carlo dosing simulations were performed to assess target attainment. Results: We analyzed 89 plasma samples from 31 adult patients. The data were best described by a one-compartment model. Among the covariates tested on pharmacokinetic parameters, creatinine clearance (CrCL) and area under curve (AUC) of RIT had a significant effect on apparent clearance (CL/F) of NIR. Mean (SD) parameters estimates for the absorption rate constant (Ka), apparent distribution (V/F) and CL/F were 0.42 (0.10) h-1. 36.5 (8.5) L, 3.6 (0.26) L/h, respectively. Dosing simulations showed that the target in vitro 90% effective concentration (EC90) was more likely to be achieved twice a day than once a day at the same daily dose of NIR. High CrCL, low AUC of RIT were associated with a reduced likelihood of NIR reaching the target EC90. Conclusion: Based on our dosing simulations, the initial dosage of NIR/RIT was 300mg/100mg twice a day in critically ill patients with CrCL>45 mL/min; When CrCL in critically ill patients is between 15 and 45 mL/min, NIR/RIT is 150mg/100mg twice a day. The maintenance dose is adjusted according to CrCL and AUC of RIT, with the dosages varying between 75mg/100mg and 300mg/100mg.

Incidence and influencing factors of cephalosporin-induced anaphylaxis: a multicenter cross-sectional study. / é™è„‰æ³¨å°„å¤´å­¢èŒç´ ç±»è¯ç‰©æ‚£è€ è¿‡æ•ååº”å‘ç”ŸçŽ‡åŠå ¶å½±å“å› ç´ çš„å¤šä¸­å¿ƒä¸´åºŠç ”ç©¶.

OBJECTIVES: To investigate the incidence and influencing factors of allergic reactions to cephalosporins. METHODS: A cross-sectional study of 29 medical institutions in Zhejiang Province was conducted from April 2021 to June 2021. The incidence of allergic reactions to cephalosporins was investigated. The influencing factors of cephalosporin-induced allergic reactions were analyzed by Poisson regression. RESULTS: A total of 56 155 patients were included in this study. The total incidence of allergic reactions to cephalosporin was 1.67 ‰, the highest incidences of anaphylaxis occurred in ceftizoxime (4.27‰), followed by ceftriaxone (3.49‰) and cefotaxime (2.40‰). There was no significant difference in the incidence of allergic reactions between patients with negative skin tests and those without skin tests (1.75‰ vs. 1.63‰, RR=1.07, 95%CI:0.70-1.63, P> 0.05). Poisson regression showed that body mass index (BMI) <18.5 kg/cm2 (RR=2.43, 95%CI: 1.23-4.82, P<0.01) and history of ß-lactam antibiotics allergy (RR=33.88, 95%CI: 1.47-781.12, P<0.05) increased cephalosporin-induced anaphylaxis. Compared with cefuroxime, the risk of allergic reactions was increased for ceftriaxone (RR=3.08, 95%CI: 1.70-5.59, P<0.01), ceftazidime (RR=1.89, 95%CI: 1.03-3.47, P<0.05), and ceftriaxone (RR=3.74, 95%CI: 1.64-8.50, P<0.01). CONCLUSIONS: Lower BMI and history of ß-lactam antibiotics allergy increase the risk of cephalosporin allergic reactions, and the routine skin test may not reduce the occurrence of allergic reactions to cephalosporins.

High concentrations of nirmatrelvir/ritonavir in critically ill patients receiving continuous renal replacement therapy.

OBJECTIVES: Nirmatrelvir/ritonavir is a highly efficacious agent against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although dose adjustment is recommended in patients with renal impairment according to the package insert for Paxlovid (Pfizer), there is no dose recommendation for patients with severe renal impairment who require continuous renal replacement therapy (CRRT). METHODS: To characterise the features of nirmatrelvir/ritonavir in critically ill Chinese patients undergoing CRRT, therapeutic drug monitoring of nirmatrelvir/ritonavir was performed by high-performance liquid chromatography tandem mass spectrometry assay in eight patients. RESULTS: Nirmatrelvir trough concentrations ranged from 3325.34 ng/mL to 15 625.46 ng/mL. Concentrations were up to 7-fold higher compared with patients with normal renal function and 2-fold higher compared with patients with end-stage renal disease undergoing haemodialysis. CONCLUSIONS: These results suggest that a dose reduction should be implemented in the treatment of patients with CRRT.

Acute kidney injury associated with colistin sulfate vs. polymyxin B sulfate therapy: A real-world, retrospective cohort study.

OBJECTIVE: To compare the incidence of acute kidney injury (AKI) in patients treated with colistin sulfate (CS) and polymyxin B sulfate (PMB). METHODS: Sociodemographic and laboratory measures of adult patients who received intravenous CS or PMB for at least 72 h for the first time at the study hospital from October 2021 to November 2022 were collected retrospectively. The primary outcome was the incidence of AKI, defined by the Kidney Diseases Improving Global Outcomes criteria. The secondary outcome was 30-day mortality. RESULTS: In total, 109 patients were included in the CS cohort and 176 patients were included in the PMB cohort. The incidence of AKI was significantly higher in the PMB cohort compared with the CS cohort (50.6% vs. 18.3%; P<0.001). On multi-variate analysis, CS therapy [hazard ratio (HR) 0.275; P<0.001] was an independent protective factor for AKI, along with higher estimated glomerular filtration rate. Nevertheless, 30-day mortality was similar in the PMB and CS cohorts (21.6% vs. 13.8%; P=0.099). Multi-variate analyses revealed that CS therapy was not associated with 30-day mortality (HR 0.968; P=0.926), while intensive care unit admission, combination with meropenem, Charlson score and stage 3 AKI were independent risk factors for 30-day mortality. After balancing the baseline characteristics of patients using propensity score matching, the main results were unchanged. CONCLUSION: The incidence of AKI was significantly lower in the CS cohort compared with the PMB cohort. However, 30-day mortality was similar in the two cohorts.

Anti-VEGFR2 F(ab')2 drug conjugate promotes renal accumulation and glomerular repair in diabetic nephropathy.

Poor renal distribution of antibody-based drugs is the key factor contributing to low treatment efficiency for renal diseases and side effects. Here, we prepare F(ab')2 fragmented vascular endothelial growth factor receptor 2 antibody (anti-VEGFR2 (F(ab')2) to block VEGFR2 overactivation in diabetic nephropathy (DN). We find that the anti-VEGFR2 F(ab')2 has a higher accumulation in DN male mice kidneys than the intact VEGFR2 antibody, and simultaneously preserves the binding ability to VEGFR2. Furthermore, we develop an antibody fragment drug conjugate, anti-VEGFR2 F(ab')2-SS31, comprising the anti-VEGFR2 F(ab')2 fragment linked to the mitochondria-targeted antioxidant peptide SS31. We find that introduction of SS31 potentiates the efficacy of anti-VEGFR2 F(ab')2. These findings provide proof of concept for the premise that antibody fragment drug conjugate improves renal distribution and merits drug validation in renal disease therapy.

Expert consensus statement on therapeutic drug monitoring and individualization of linezolid.

Linezolid is an oxazolidinone antibacterial drug, and its therapeutic drug monitoring and individualized treatment have been challenged since its approval. With the in-depth clinical research of linezolid, we have changed our attitude toward its therapeutic drug monitoring and our view of individualized treatment. On the basis of summarizing the existing clinical studies, and based on the practical experience of each expert in their respective professional fields, we have formed this expert consensus. Our team of specialists is a multidisciplinary team that includes pharmacotherapists, clinical pharmacology specialists, critical care medicine specialists, respiratory specialists, infectious disease specialists, emergency medicine specialists and more. We are committed to the safe and effective use of linezolid in patients in need, and the promotion of its therapeutic drug monitoring.

TPGS-based and S-thanatin functionalized nanorods for overcoming drug resistance in Klebsiella pneumonia.

Tigecycline is regarded as the last line of defense to combat multidrug-resistant Klebsiella pneumoniae. However, increasing utilization has led to rising drug resistance and treatment failure. Here, we design a D-alpha tocopheryl polyethylene glycol succinate-modified and S-thanatin peptide-functionalized nanorods based on calcium phosphate nanoparticles for tigecycline delivery and pneumonia therapy caused by tigecycline-resistant Klebsiella pneumoniae. After incubation with bacteria, the fabricated nanorods can enhance tigecycline accumulation in bacteria via the inhibitory effect on efflux pumps exerted by D-alpha tocopheryl polyethylene glycol succinate and the targeting capacity of S-thanatin to bacteria. The synergistic antibacterial capacity between S-thanatin and tigecycline further enhances the antibacterial activity of nanorods, thus overcoming the tigecycline resistance of Klebsiella pneumoniae. After intravenous injection, nanorods significantly reduces the counts of white blood cells and neutrophils, decreases bacterial colonies, and ameliorates neutrophil infiltration events, thereby largely increasing the survival rate of mice with pneumonia. These findings may provide a therapeutic strategy for infections caused by drug-resistant bacteria.

Pharmacokinetic interactions between the potential COVID-19 treatment drugs lopinavir/ritonavir and arbidol in rats.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has occasioned worldwide alarm. Globally, the number of reported confirmed cases has exceeded 84.3 million as of this writing (January 2, 2021). Since there are no targeted therapies for COVID-19, the current focus is the repurposing of drugs approved for other uses. In some clinical trials, antiviral drugs such as remdesivir (Grein et al., 2020), lopinavir/ritonavir (LPV/r) (Cao et al., 2020), chloroquine (Gao et al., 2020), hydroxychloroquine (Gautret et al., 2020), arbidol (Wang et al., 2020), and favipiravir (Cai et al., 2020b) have shown efficacy in COVID-19 patients. LPV/r combined with arbidol, which is the basic regimen in some regional hospitals in China including Zhejiiang Province, has shown antiviral effects in COVID-19 patients (Guo et al., 2020; Xu et al., 2020). A retrospective cohort study also reported that this combination therapy showed better efficacy than LPV/r alone for the treatment of COVID-19 patients (Deng et al., 2020).

On-ward participation of clinical pharmacists in a Chinese intensive care unit for patients with COVID-19: A retrospective, observational study.

BACKGROUND: The practical experiences of active pharmacists involved in managing critically ill patients with coronavirus disease 2019 (COVID-19) have been rarely reported. OBJECTIVE: This work aimed to share professional experiences on medication optimization and provide a feasible reference for the pharmaceutical care of critically ill patients with COVID-19. METHODS: This study was conducted in a COVID-19-designated hospital in China. A group of dedicated clinical pharmacists participated in multidisciplinary rounds to optimize the treatments for critically ill patients with COVID-19. Consensus on medication recommendations was reached by a multidisciplinary team through bi-daily discussion. Related drug, classification, cause, and adjustment content for recommendations were recorded and reviewed. RESULTS: A total of 111 medication recommendations were supplied for 22 out of 33 (56.7%) critically ill patients from 1 February 2020 to 18 March 2020, and 106 (95.5%) of these were accepted. Among these recommendations, 64 (67.7%), 32 (28.8%), and 15 (13.5%) were related to antibiotics and antifungals, antiviral agents, and other drugs, respectively. Recommendation types significantly differed for different anti-infectives (p < 0.05). For antibiotics and antifungals, treatment effectiveness accounted for 60.9% of recommendation types, with 15 (38.5%) cases related to untreated infections. For antiviral agents, adverse drug events were the most common recommendation types (84.4%), with 20 (74.1%) cases related to liver function dysfunction. Discontinuation of suspected antiviral agents (66.7%) was usually recommended after the occurrence of adverse events that may progress and bring poor outcomes. CONCLUSION: Forceful and extensive on-ward participation is recommended for clinical pharmacists in managing critically ill patients. Our experiences highlight the need for special attention toward untreated infections and adverse events related to antiviral agents.

ROS-responsive chitosan-SS31 prodrug for AKI therapy via rapid distribution in the kidney and long-term retention in the renal tubule.

The development of drugs with rapid distribution in the kidney and long-term retention in the renal tubule is a breakthrough for enhanced treatment of acute kidney injury (AKI). Here, l-serine-modified chitosan (SC) was synthesized as a potential AKI kidney-targeting agent due to the native cationic property of chitosan and specific interaction between kidney injury molecule-1 (Kim-1) and serine. Results indicated that SC was rapidly accumulated and long-term retained in ischemia-reperfusion-induced AKI kidneys, especially in renal tubules, which was possibly due to the specific interactions between SC and Kim-1. SC-TK-SS31 was then prepared by conjugating SS31, a mitochondria-targeted antioxidant, to SC via reactive oxygen species (ROS)-sensitive thioketal linker. Because of the effective renal distribution combined with ROS-responsive drug release behavior, the administration of SC-TK-SS31 led to an enhanced therapeutic effect of SS31 by protecting mitochondria from damage and reducing the oxidative stress, inflammation, and cell apoptosis.

Antiviral Agent Therapy Optimization in Special Populations of COVID-19 Patients.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now a global outbreak of disease. The antiviral treatment acts as one of the most important means of SARS-CoV-2 infection. Alteration of physiological characteristics in special populations may lead to the change in drug pharmacokinetics, which may result in treatment failure or increased adverse drug reactions. Some potential drugs have shown antiviral effects on SARS-CoV-2 infections, such as chloroquine, hydroxychloroquine, favipiravir, lopinavir/ritonavir, arbidol, interferon alpha, and remedsivir. Here, we reviewed the literature on clinical effects in COVID-19 patients of these antiviral agents and provided the potential antiviral agent options for pregnant women, elderly patients, liver or renal dysfunction patients, and severe or critically ill patients receiving renal replacement therapy or ECMO after SARS-CoV-2 infection.

Liver Injury in Critically Ill and Non-critically Ill COVID-19 Patients: A Multicenter, Retrospective, Observational Study.

Background: Liver injury commonly occurs in patients with COVID-19. There is limited data describing the course of liver injury occurrence in patients with different disease severity, and the causes and risk factors are unknown. We aim to investigate the incidence, characteristics, risk factors, and clinical outcomes of liver injury in patients with COVID-19. Methods: This retrospective observational study was conducted in three hospitals (Zhejiang, China). From January 19, 2020 to February 20, 2020, patients confirmed with COVID-19 (≥18 years) and without liver injury were enrolled and divided into non-critically ill and critically ill groups. The incidence and characteristics of liver injury were compared between the two groups. Demographics, clinical characteristics, treatments, and treatment outcomes between patients with or without liver injury were compared within each group. The multivariable logistic regression model was used to explore the risk factors for liver injury. Results: The mean age of 131 enrolled patients was 51.2 years (standard deviation [SD]: 16.1 years), and 70 (53.4%) patients were male. A total of 76 patients developed liver injury (mild, 40.5%; moderate, 15.3%; severe, 2.3%) with a median occurrence time of 10.0 days. Critically ill patients had higher and earlier occurrence (81.5 vs. 51.9%, 12.0 vs. 5.0 days; p < 0.001), greater injury severity (p < 0.001), and slower recovery (50.0 vs. 61.1%) of liver function than non-critically ill patients. Multivariable regression showed that the number of concomitant medications (odds ratio [OR]: 1.12, 95% confidence interval [CI]: 1.05-1.21) and the combination treatment of lopinavir/ritonavir and arbidol (OR: 3.58, 95% CI: 1.44-9.52) were risk factors for liver injury in non-critically ill patients. The metabolism of arbidol can be significantly inhibited by lopinavir/ritonavir in vitro (p < 0.005), which may be the underlying cause of drug-related liver injury. Liver injury was related to increased length of hospital stay (mean difference [MD]: 3.2, 95% CI: 1.3-5.2) and viral shedding duration (MD: 3.0, 95% CI: 1.0-4.9). Conclusions: Critically ill patients with COVID-19 suffered earlier occurrence, greater injury severity, and slower recovery from liver injury than non-critically ill patients. Drug factors were related to liver injury in non-critically ill patients. Liver injury was related to prolonged hospital stay and viral shedding duration in patients with COVID-19. Clinical Trial Registration: World Health Organization International Clinical Trials Registry Platform, ChiCTR2000030593. Registered March 8, 2020.

Recommendation of Antimicrobial Dosing Optimization During Continuous Renal Replacement Therapy.

Continuous Renal Replacement Therapy (CRRT) is more and more widely used in patients for various indications recent years. It is still intricate for clinicians to decide a suitable empiric antimicrobial dosing for patients receiving CRRT. Inappropriate doses of antimicrobial agents may lead to treatment failure or drug resistance of pathogens. CRRT factors, patient individual conditions and drug pharmacokinetics/pharmacodynamics are the main elements effecting the antimicrobial dosing adjustment. With the development of CRRT techniques, some antimicrobial dosing recommendations in earlier studies were no longer appropriate for clinical use now. Here, we reviewed the literatures involving in new progresses of antimicrobial dosages, and complied the updated empirical dosing strategies based on CRRT modalities and effluent flow rates. The following antimicrobial agents were included for review: flucloxacillin, piperacillin/tazobactam, ceftriaxone, ceftazidime/avibactam, cefepime, ceftolozane/tazobactam, sulbactam, meropenem, imipenem, panipenem, biapenem, ertapenem, doripenem, amikacin, ciprofloxacin, levofloxacin, moxifloxacin, clindamycin, azithromycin, tigecycline, polymyxin B, colistin, vancomycin, teicoplanin, linezolid, daptomycin, sulfamethoxazole/trimethoprim, fluconazole, voriconazole, posaconzole, caspofungin, micafungin, amphotericin B, acyclovir, ganciclovir, oseltamivir, and peramivir.

[Pharmaceutical care for severe and critically ill patients with COVID-19].

Severe and critically ill patients with coronavirus disease 2019 (COVID-19) were usually with underlying diseases, which led to the problems of complicated drug use, potential drug-drug interactions and medication errors in special patients. Based on Diagnosis and treatment of novel coronavirus pneumonia (trial version 6), and Management of COVID-19: the Zhejiang experience, we summarized the experience in the use of antiviral drugs, corticosteroids, vascular active drugs, antibacterial, probiotics, nutrition support schemes in severe and critically ill COVID-19 patients. It is also suggested to focus on medication management for evaluation of drug efficacy and duration of treatment, prevention and treatment of adverse drug reactions, identification of potential drug-drug interactions, individualized medication monitoring based on biosafety protection, and medication administration for special patients.

Association between the rate of fluoroquinolones-resistant gram-negative bacteria and antibiotic consumption from China based on 145 tertiary hospitals data in 2014.

BACKGROUND: The purpose of the study is to discuss the correlation between the resistance rate of gram negative bacteria to fluoroquinolones (FQ) and antibiotic consumption intensity of 145 China tertiary hospitals in 2014. METHODS: This retrospective study adopted national monitoring data from 2014. Each participating hospital required to report annual consumption of each antibiotic, and the resistance rate of gram negative bacteria to FQ. Then the correlation between antibiotic usage and fluoroquinolones -resistant (FQR) rate was consequently investigated. RESULTS: One hundred forty-five hospitals were included in the study, and the median antibiotic consumption intensity was 46.30 (23.93-115.39) defined daily dosages (DDDs) per 100 patient-days. Cephalosporins ranks first in the antibiotics consumption, followed by fluoroquinolones, penicillins, and carbapenems. Fluoroquinolones resistance rate varied from hospital to hospital. The correlation analysis showed significant relationship between the percentage of FQR Escherichia coli and the consumption of FQs (r = 0.308, p<0.01) and levofloxacin (r = 0.252, p<0.01). For FQR Klebsiella pneumoniae, not only FQs (r = 0.291, p<0.01) and levofloxacin (r = 0.260, p<0.01) use but also carbapenems (r = 0.242, p<0.01) and overall antibiotics (r = 0.247, p<0.01) use showed significant correlation. The resistant proportion of FQR Pseudomonas aeruginosa was observed to be correlated with the consumption of all antibiotics (r = 0.260, p<0.01), FQs (r = 0.319, p<0.01) and levofloxacin (r = 0.377, p<0.01). The percentage of levofloxacin-resistant Acinetobacter baumannii was significantly correlated with the consumption of all antibiotics (r = 0.282, p<0.01), third-generation cephalosporins excluding combinations with beta-lactamase inhibitors (r = 0.246, p<0.01), FQs (r = 0.254, p<0.01) and levofloxacin (r = 0.336, p<0.01). However, the correlation of the ciprofloxacin-resistant A. baumannii and the antibiotics consumption was not found. CONCLUSIONS: A strong correlation was demonstrated between the antibiotic consumption and the rates of FQR gram-negative bacteria. As unreasonable antibiotics usage remains crucial in the proceeding of resistant bacteria selection, our study could greatly promote the avoidance of unnecessary antibiotic usage.

Association between the rate of third generation cephalosporin-resistant Escherichia coli and Klebsiella pneumoniae and antibiotic consumption based on 143 Chinese tertiary hospitals data in 2014.

This study sought to discuss the correlation between the third-generation cephalosporins (3GC)-resistant Escherichia coli and Klebsiella pneumoniae and antibiotic consumption intensity from 143 Chinese tertiary hospitals in 2014. With a retrospective design, the correlation between antibiotic consumption and 3GC-resistant E. coli and K. pneumoniae were performed. 3GC-resistant E. coli was significantly correlated with the consumption of all antibiotics (r = 0.252, p < 0.01), ß-Lactams antibiotics (r = 0.313, p < 0.01), ß-Lactams excluding combinations with ß-lactamase inhibitors (r = 0.365, p < 0.01), cephalosporin (r = 0.398, p < 0.01), cephalosporins excluding combinations with ß-lactamase inhibitors (r = 0.374, p < 0.01), 3GC (r = 0.321, p < 0.01), and 3GC excluding combinations with ß-lactamase inhibitors (r = 0.343, p < 0.01). 3GC-resistant K. pneumoniae was significantly correlated with the consumption of all antibiotics (r = 0.200, p < 0.05), ß-Lactams antibiotics (r = 0.232, p < 0.01), cephalosporin (r = 0.215, p < 0.05), 3GC (r = 0.383, p < 0.01), 3GC excluding combinations with ß-lactamase inhibitors (r = 0.245, p < 0.01), and ß-lactam-ß-lactamase inhibitor combinations (r = 0.218, p < 0.05). There was a significant relationship between the antibiotic consumption and the rates of 3GC-resistant E. coli and K. pneumoniae. Clinicians should grasp the indication of antibiotics use to reduce the production of drug-resistant bacteria.

ROS-responsive nano-drug delivery system combining mitochondria-targeting ceria nanoparticles with atorvastatin for acute kidney injury.

Acute kidney injury (AKI) caused by sepsis is a serious disease which mitochondrial oxidative stress and inflammatory play a key role in its pathophysiology. Ceria nanoparticles hold strong and recyclable reactive oxygen species (ROS)-scavenging activity, have been applied to treat ROS-related diseases. However, ceria nanoparticles can't selectively target mitochondria and the ultra-small ceria nanoparticles are easily agglomerated. To overcome these shortcomings and improve therapeutic efficiency, we designed an ROS-responsive nano-drug delivery system combining mitochondria-targeting ceria nanoparticles with atorvastatin for acute kidney injury. Methods: Ceria nanoparticles were modified with triphenylphosphine (TCeria NPs), followed by coating with ROS-responsive organic polymer (mPEG-TK-PLGA) and loaded atorvastatin (Atv/PTP-TCeria NPs). The physicochemical properties, in vitro drug release profiles, mitochondria-targeting ability, in vitro antioxidant, anti-apoptotic activity and in vivo treatment efficacy of Atv/PTP-TCeria NPs were examined. Results: Atv/PTP-TCeria NPs could accumulate in kidneys and hold a great ability to ROS-responsively release drug and TCeria NPs could target mitochondria to eliminate excessive ROS. In vitro study suggested Atv/PTP-TCeria NPs exhibited superior antioxidant and anti-apoptotic activity. In vivo study showed that Atv/PTP-TCeria NPs effectively decreased oxidative stress and inflammatory, could protect the mitochondrial structure, reduced apoptosis of tubular cell and tubular necrosis in the sepsis-induced AKI mice model. Conclusions: This ROS-responsive nano-drug delivery system combining mitochondria-targeting ceria nanoparticles with atorvastatin has favorable potentials in the sepsis-induced AKI therapy.