Efficacy and safety of clarithromycin for patients with sepsis or septic shock:a systematic review and meta-analysis

Background:Clarithromycin exerts an immunomodulatory role in several human diseases.However,whether this effect improves the prognosis in patients with sepsis remains controversial,and higher levels of clinical evidence are urgently needed.To the best of our knowledge,no meta-analysis to date has reported the clinical efficacy and safety of clarithromycin in sepsis.Methods:A comprehensive literature search of PubMed,EMBASE,and the Cochrane Library was conducted up to December 31,2022.Only randomized controlled trials comparing the clinical efficacy and safety of clarithromycin with controls among patients with sepsis or septic shock were included.Data were pooled by applying a fixed-effects model and a relative risk(RR)estimate with 95%confidence intervals(CIs)using Review Manager(version 5.3;Cochrane Collaboration,Copenhagen,Denmark).Results:Three randomized controlled trials involving a total of 910 patients were included.The pooled results confirmed that clarithromycin had no beneficial effect on progression to multiple organ dysfunction syndrome(RR:1.51;95%CI:1.02-2.25;P=0.04;I^(2)=0%),28-day mortality(RR:1.09;95%CI:0.87-1.36;P=0.46;I^(2)=0%),and 90-day mortality(RR:0.86;95%CI:0.71-1.03;P=0.10;I^(2)=81%)in patients with sepsis or septic shock.Moreover,there was no difference in other serious adverse events between patients who received clarithromycin and those in the control group(RR:1.02;95%CI:0.87-1.19;P=0.83;I^(2)=18%).Conclusion:Our meta-analysis did not reveal an improvement to short-term outcomes in patients with sepsis treated with clarithromycin.However,administration of clarithromycin did not increase the risk of adverse events.

Combination therapy of thiamine,vitamin C and hydrocortisone in treating patients with sepsis and septic shock:a meta-analysis and trial sequential analysis

Background:The objective of this study was to evaluate the clinical efficacy of thiamine and vitamin C with or without hydrocortisone coadministration on the treatment of sepsis and septic shock.Methods:MEDLINE,EMBASE and CENTRAL databases were searched for randomized controlled trials(RCTs)that made a comparative study between the combination therapy of vitamin C and thiamine with or without hydrocortisone and the administration of placebo in patients with sepsis or septic shock.Two reviewers independently performed study selection,data extraction and quality assessment.Both short-term mortality and change in the sequential organ failure assessment(SOFA)score from baseline(delta SOFA)were set as the primary outcomes.Secondary endpoints included intensive care unit(ICU)mortality,new onset of acute kidney injury,total adverse events,ICU and hospital length of stay,duration of vasopressor usage and ventilator-free days.Meanwhile,trial sequential analysis was conducted for primary outcomes.Results:Eight RCTs with 1428 patients were included in the current study.The results showed no significant reduction of short-term mortality in sepsis and septic shock patients who received combination therapy of vitamin C and thiamine with or without hydrocortisone compared to those with placebo{risk ratio(RR),1.02[95%confidence interval(CI),0.87 to 1.20],p=0.81,I2=0%;risk difference(RD),0[95%CI,−0.04 to 0.05]}.Nevertheless,the combination therapy was associated with significant reduction in SOFA score[mean difference(MD),−0.63,(95%CI,−0.96 to−0.29,p<0.001,I^(2)=0%]and vasopressors duration(MD,−22.11[95%CI,−30.46 to−13.77],p<0.001,I2=6%).Additionally,there were no statistical differences in the pooled estimate for other outcomes.Conclusions:In the current meta-analysis,the combination therapy of vitamin C and thiamine,with or without hydrocortisone had no impact on short-term mortality when compared with placebo,but was associated with significant reduction in SOFA score among patients with sepsis and septic shock.