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Clinical Outcomes and Adverse Effects in Septic Patients with Impaired Renal Function Who Received Different Dosages of Cefoperazone-Sulbactam.

ABSTRACT: This study aimed to compare clinical outcomes and adverse effects in septic patients with impaired renal function who received different dosages of cefoperazone-sulbactam (CFP-SUL 1 g/1 g or 2 g/2 g every 12 h). The retrospective study was conducted using the Chang Gung Research Database to include adult patients who had renal insufficiency presented with septicemia caused by Gram-negative organisms and had received CFP-SUL for more than 1 week. A total of 265 patients (44 in the CFP-SUL 1 g/1 g group and 221 in the CFP-SUL 2 g/2 g group) were eligible to be included in this study. After 1:3 propensity score matching, 41 and 123 patients in the CFP-SUL 1 g/1 g and CFP-SUL 2 g/2 g groups, respectively, were included for analyses. There were no significant between-group differences in all-cause mortality rates and adverse effects, including prolonged prothrombin time. A logistic regression model showed that the Pitt bacteremia score was related to all-cause mortality rate and prolonged prothrombin time was associated with renal replacement therapy. The adverse effects of CFP-SUL did not increase in septic patients with impaired renal function receiving CFP-SUL 2 g/2 g Q12H. However, this study may be underpowered to reveal a difference in all-cause mortality.

SUBMITTER: Tai CH

PROVIDER: S-EPMC9026488 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Clinical Outcomes and Adverse Effects in Septic Patients with Impaired Renal Function Who Received Different Dosages of Cefoperazone-Sulbactam.

Tai Chien-Hsiang CH Tang Hung-Jen HJ Lee Chen-Hsiang CH

Antibiotics (Basel, Switzerland) 20220329 4

This study aimed to compare clinical outcomes and adverse effects in septic patients with impaired renal function who received different dosages of cefoperazone-sulbactam (CFP-SUL 1 g/1 g or 2 g/2 g every 12 h). The retrospective study was conducted using the Chang Gung Research Database to include adult patients who had renal insufficiency presented with septicemia caused by Gram-negative organisms and had received CFP-SUL for more than 1 week. A total of 265 patients (44 in the CFP-SUL 1 g/1 g ...[more]

PMID: 35453212

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Project description:Metabolic state-reprogramming approach was extended from Gram-negative bacteria to Gram-positive bacterium methicillin-resistant Staphylococcus aureus (MRSA) for identifying desired reprogramming metabolites to synergize existing antibiotic killing to MRSA. Metabolomics comparison between MRSA and methicillin-sensitive Staphylococcus aureus showed a depressed metabolic state in MRSA. Valine was identified as the most depressed metabolite/biomarker, and valine, leucine and isoleucine biosynthesis as the most enriched metabolic pathway. Thus, valine was used as a reprogramming metabolite to potentiate existing antibiotic killing to MRSA. Among the tested antibiotics, valine synergized cefoperazone-sulbactam (SCF) to produce the greatest killing effect. The combined effect of SCF and valine was demonstrated in clinical MRSA isolates and in mouse systemic and thigh infection models. Underlying mechanisms were attributed to valine-induced the activation of the pyruvate cycle/the TCA cycle and fatty acid biosynthesis. The activated pyruvate cycle/the TCA cycle elevated proton motive force by NADH and the activated fatty acid biosynthesis promoted membrane permeability by lauric acid. Both together increased cefoperazone uptake, which outpaces efflux action and thereby intracellular drug is elevated to effectively kill MRSA. These results provide the combination of valine and SCF to produce a new drug candidate effective against MRSA.ImportanceMethicillin-resistant Staphylococcus aureus (MRSA) is possibly the most infamous example of antibiotic resistance and new antibiotics are urgently needed to control it. The present study used metabolic state-reprogramming approach to identify an ideal biomarker as an antibiotic adjuvant for reversing the metabolic state of MRSA. The most repressed valine was identified as the adjuvant. Exogenous valine most effectively potentiated cefoperazone-sulbactam (SCF) to kill MRSA in vitro and in vivo. Viability of 18 clinical MRSA isolates was reduced by the top 276.64-fold in the presence of valine and SCF. In mouse models, lower bacterial load in liver, spleen, kidney, thigh, and higher survival were determined in the SCF + valine than valine or SCF alone. Valine promoted MRSA to increase SCF uptake that overcomes the efflux and enzymatic hydrolysis. It also extended the PAE of SCF. These occur because valine activates the pyruvate cycle to elevate proton motive force by NADH and increases membrane permeability by lauric acid. Therefore, the combination of valine and SCF is a new drug candidate effective against MRSA.

Project description:Background:We retrospectively analyzed the effect of tigecycline and cefoperazone/sulbactam therapies on the prognosis of patients with carbapenem-resistant Acinetobacter baumannii bloodstream infection (CRAB-BSI). Methods:CRAB-BSI patients receiving tigecycline therapy or cefoperazone/sulbactam therapy between January 2012 and December 2017 was enrolled, and strict exclusion criteria were followed. The 28-day mortality of patients was analyzed. The impact of cefoperazone/sulbactam therapy on prognosis was evaluated using Cox multivariate regression analysis. The 28-day mortality of patients receiving cefoperazone/sulbactam monotherapy and cefoperazone/sulbactam-based combination therapy was also compared. Results:Three hundred forty eight patients with CRAB-BSI were enrolled in the study. Two hundred ten patients were included after applying the exclusion criteria. Of these, 135 patients received tigecycline therapy and 75 patients received cefoperazone/sulbactam therapy. The 28-day mortality of patients in the latter group was, significantly lower than that of the tigecycline group [29.3% vs. 51.9%; P = 0.001]. Cox multivariate regression analysis revealed that cefoperazone/sulbactam therapy exerted a protective effect on the prognosis of patients [hazard ratio 0.566, 95% confidence interval (0.342-0.940); P = 0.028]. Kaplan-Meier survival curve analysis indicated that the 28-day mortality of patients receiving cefoperazone/sulbactam therapy was lower than that of patients receiving cefoperazone/sulbactam monotherapy, but the difference was not significant (22.2% vs. 40%; P = 0.074). However, the mortality of patients receiving cefoperazone/sulbactam with imipenem/cilastatin was significantly lower than that of patients receiving cefoperazone/sulbactam monotherapy (P = 0.048). Conclusions:Patients treated with cefoperazone/sulbactam therapy had a better clinical outcome. The mortality of patients receiving cefoperazone/sulbactam with imipenem/cilastatin seems to be the lowest.

Project description:Objective: Acute kidney injury (AKI) is a common adverse reaction observed with the clinical use of cefoperazone-sulbactam sodium and mezlocillin-sulbactam sodium. Based upon real-world data, we will herein determine the risk factors associated with AKI in inpatients after receipt of these antimicrobial drugs, and we will develop predictive models to assess the risk of AKI. Methods: Data from all adult inpatients who used cefoperazone-sulbactam sodium and mezlocillin-sulbactam sodium at the First Affiliated Hospital of Shandong First Medical University between January 2018 and December 2020 were analyzed retrospectively. The data were collected through the inpatient electronic medical record (EMR) system and included general information, clinical diagnosis, and underlying diseases, and logistic regression was exploited to develop predictive models for the risk of AKI. The training of the model strictly adopted 10-fold cross-validation to validate its accuracy, and model performance was evaluated employing receiver operating characteristic (ROC) curves and the areas under the curve (AUCs). Results: This retrospective study comprised a total of 8767 patients using cefoperazone-sulbactam sodium, of whom 1116 developed AKI after using the drug, for an incidence of 12.73%. A total of 2887 individuals used mezlocillin-sulbactam sodium, of whom 265 developed AKI after receiving the drug, for an incidence of 9.18%. In the cohort administered cefoperazone-sulbactam sodium, 20 predictive factors (p < 0.05) were applied in constructing our logistic predictive model, and the AUC of the predictive model was 0.83 (95% CI, 0.82-0.84). In the cohort comprising mezlocillin-sulbactam sodium use, nine predictive factors were determined by multivariate analysis (p < 0.05), and the AUC of the predictive model was 0.74 (95% CI, 0.71-0.77). Conclusion: The incidence of AKI induced by cefoperazone-sulbactam sodium and mezlocillin-sulbactam sodium in hospitalized patients may be related to the combined treatment of multiple nephrotoxic drugs and a past history of chronic kidney disease. The AKI-predictive model based on logistic regression showed favorable performance in predicting the AKI of adult in patients who received cefoperazone-sulbactam sodium or mezlocillin-sulbactam sodium.

Dataset Information

Clinical Outcomes and Adverse Effects in Septic Patients with Impaired Renal Function Who Received Different Dosages of Cefoperazone-Sulbactam.

Publications

Clinical Outcomes and Adverse Effects in Septic Patients with Impaired Renal Function Who Received Different Dosages of Cefoperazone-Sulbactam.

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