Ulinastatin has been found to have anti-inflammatory effect for patients with sepsis. However, its clinical effects were conflicting. The study aimed to investigate the cost-effectiveness of ulinastatin and to perform mediation analysis to explore the proportion of the total effects that can be explained by inflammatory responses. This is a retrospective study involving critically ill patients with sepsis from January 2014 to July 2017. A total of 263 patients were included in the study, involving 179 patients in the ulinastatin group and 84 in the control group. Ulinastatin group showed significantly lower 28-day mortality rate than that in the control group (31% vs. 55%; p < 0.001). Both total (46330 [26000,83500] vs. 19870 [8747,41140] RMB; p < 0.01) and drug cost (18210 [9492,31920] vs. 7230 [2675,19270] RMB; p < 0.01) were significantly higher in the ulinastatin group than the control group. In multivariable model, the adjusted odds ratio for ulinastatin was 0.304 (95% CI: 0.152 to 0.592; p = 0.001). The mediation analysis showed that the use of ulinastatin was able to reduce the probability of death by 23.5%. The average causal mediation effect of delta C-reactive protein (CRP) was 8%, accounting for 35% of the total effect.
The effectiveness of piperacillin/tazobactam for managing nosocomial pneumonia caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae is unknown. To answer this question, we conducted a retrospective cohort study in two tertiary teaching hospitals of patients admitted between January 2018 and July 2021 with a diagnosis of nosocomial pneumonia caused by ESBL-producing K. pneumoniae receiving either piperacillin/tazobactam or carbapenems within 24 h from the onset of pneumonia for at least 72 h. Clinical outcomes, including 28-day mortality and 14-day clinical and microbiological cure, were analyzed. Of the 136 total patients, 64 received piperacillin/tazobactam and 72 received carbapenems. The overall 28-day mortality was 19.1% (26/136). In the inverse probability of treatment weighted cohort, piperacillin/tazobactam therapy was not associated with worse clinical outcomes, as the 28-day mortality (OR, 0.82, 95% CI, 0.23–2.87, p = 0.748), clinical cure (OR, 0.94, 95% CI, 0.38–2.35, p = 0.894), and microbiological cure (OR, 1.10, 95% CI, 0.53–2.30, p = 0.798) were comparable to those of carbapenems. Subgroup analyses also did not demonstrate any statistical differences. In conclusion, piperacillin/tazobactam could be an effective alternative to carbapenems for treating nosocomial pneumonia due to ESBL-producing K. pneumoniae when the MICs are ≤8 mg/L.
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