| Background:Severe sepsis and septic shock are common causes of mortality in hospital,especially in critically ill patients.Early,adequate antimicrobial therapy targeting at the most likely pathogens before microbiological information is available(broad-spectrum empirical antibiotics therapy)has been shown as extremely important measure to reduce the mortality rates.Empirical antibiotics therapy is also recommended by international guidelines for management of severe sepsis and septic shock in 2012.However,broad-spectrum antibiotics therapy is not without its drawbacks,the risk of leading to overuse of antibiotics and an increase in antimicrobial resistance make it great demand to develop options that are more rational.Antibiotics de-escalation therapy,a strategy in which broad-spectrum empirical antibiotics therapy is started initially but the spectrum is narrowed or an antibiotic is eliminated as soon as microbiological results are available,has been proved to minimize the emergence of drug-resistant organisms and therapy costs during the treatment of patients with severe sepsis and/or septic shock by numerous studies.The strategy termed as "de-escalation therapy" appears theoretically correct.However,a number of crucial elements are unknown and definitely confound de-escalation practice.What was the time period of de-escalation and does it make a difference?Were any algorithms used for broad-spectrum empiric antibiotics choices and were antibiotics correctly chosen as this affects outcomes?What was the source of severe sepsis/septic shock?Correspondingly,de-escalation therapy was realized in approximately 35-45%of the cases.Meanwhile,the current evidence available is not consistent.Some studies concluded that de-escalation was a protective factor for mortality,while others have shown that de-escalation did not affect the mortality,even increased the number of antibiotic days and the risk of superinfection.Because of the lack of sufficiently powered randomized controlled trials(RCTs),the absence of adequate evidence for the efficacy of de-escalation of broad-spectrum empiric antibiotics therapy for patients with severe sepsis and/or septic shock make it hard to draw firm conclusions.Considering the concrete condition of these critically ill patients with severe sepsis and/or septic shock,high-quality randomized controlled trials are hard to come true.A meta-analysis is a feasible way to provide relatively high-grade evidence.Meta-analysis is an important tool of evidence-based medicine,which can provide evidence of higher level and is favored by clinicians,guidelines makers and Health decision-making department.Also,meta-analysis included non-randomized controlled studies plays more and more important role in evidence supports.It is possible to obtain a relatively objective and reliable conclusion by determining the appropriate inclusion and exclusion criteria,properly evaluating quality of the included literature and selecting proper statistical methods.Aim:We performed a meta-analysis of available comparative studies to evaluate the impact of de-escalation therapy on clinical outcomes in adult patients with severe sepsis and/or septic shock.Methods:We performed a systematic literature search in PubMed,EMBASE,Web of Science,and CENTRAL on The Cochrane Library without time or language limitation.The search terms used were "sepsis," "septic shock" and "de-escalation."The inclusion criteria were:(1)Participants:adult patients(age?18 years)which were diagnosed as severe sepsis and/or septic shock and demanded empiric antibiotics therapy.According to current guidelines,severe sepsis was defined as the presence of infection with systemic manifestations and sepsis-induced organ failure or tissue hypoperfusion;septic shock was defined as severe sepsis with hypotension which cannot be reversed by fluid resuscitation".(2)Interventions and comparisons:continuation of broad-spectrum empiric antibiotics therapy and de-escalation therapy.De-escalation was defined as eliminating of an antibiotics or narrowing the spectrum of antibiotic therapy.(3)Outcomes:the mortality when follow-up ends.(4)Study:any comparative studies,including observational studies and randomized clinical trials.The relative risk(RR)with 95%confidence intervals(CI)was used to evaluate the impact of de-escalation therapy on mortality rate.All statistical analyses were performed by using the statistical software Stata 12.0(StataCorp LP,College Station,TX,USA).Results:Our meta-analysis included nine individual studies,comprising a total of 1873 patients.The mortality trended lower in de-escalation group than in the continuation of broad-spectrum antibiotics group,however,there was no significant statistical difference(RR=0.74,95%CI 0.54-1.03,p=0.005,12=63.8%).When picking out four studies with high methodological quality(NOS score ? 7 points),we found no significant statistical difference in mortality between the de-escalation group and the continuation group without significant heterogeneity(RR=0.85,95%CI 0.67-1.08,p=0.373,I2=3.9%).Then we picked out five prospective studies and got a similar conclusion(RR=0.91,95%CI 0.75-1.12,p=0.651,I2=0.0%).The pooled de-escalation rate in observational studies was 39.5%(95%CI 0.293-0.497,p=0.000,I2=95.2%).When we selected the three studies enrolling general patients with severe sepsis and/or septic shock which were performed in Western populations,the pooled de-escalation rate was 37.1%without significant heterogeneity(95%CI 0.330-0.413,p=0.156,I2=46.2%).Conclusion:Our meta-analysis concluded that antibiotic de-escalation therapy has no detrimental impact on mortality in patients with severe sepsis and/or septic shock,as compared to the continuation of broad-spectrum antibiotics.Since de-escalation affords an opportunity to limit overuse of broad-spectrum antibiotics,it should be considered as an advisable option in clinical practice.However,research in this regard has not been accomplished.Well-designed RCTs or better-matched observational studies focusing on other important clinical outcomes are still pressing needs in the near future. |
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