REMI 1925E. Antibiotic de-escalation is associated with lower mortality in patients with severe sepsis and septic shock

Original article: De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock. Garnacho-Montero J, Gutiérrez-Pizarraya A, Escoresca-Ortega A, Corcia-Palomo Y, Fernández-Delgado E, Herrera-Melero I, Ortiz-Leyba C, Márquez-Vácaro JA. Intensive Care Med 2014; 40(1): 32-40. [Summary] [Related Articles]
Introduction: Numerous studies highlight the importance of appropriate antibiotic therapy in patients with severe sepsis and septic shock (SS/SS) to reduce mortality [1], which often lead to start broad-spectrum antibiotics. Then, it makes advisable to reduce the spectrum ("de-escalate") when the microbiological test results become available, although a recent review found no definitive evidence to generalize this strategy [2].
Summary: In a prospective observational study, 626 patients admitted to a general ICU by SS/SS were included to evaluate the impact of antibiotic de-escalation on hospital and 90 days mortality. Positive cultures were obtained in 76.7%, and 38.4% had bacteremia. De-escalation was made in 219 cases (34.9%). By logistic regression analysis, independent factors associated with hospital mortality were: septic shock, SOFA score and inappropriate empirical therapy. De-escalation was a protective factor (OR 0.58; 95% CI 0.36 to 0.93). Because baseline characteristics and clinical status differed among patients receiving and not-receiving de-escalation, propensity score analysis was performed, which also identified de-escalation as a protective factor for mortality. Comparing the subgroup of patients in whom the results of the cultures allowed de-escalate but it was not made (180) with those that were de-escalated (179), APACHE admission score and SOFA score in the day of receiving the culture results were not different, but in patients with de-escalation both hospital (24.5 vs. 32.8 %; P = 0.08) and 90 days mortality (25.1 vs. 36.1 %, P = 0.024) were lower. Authors conclude that de-escalation is safe and is associated with lower mortality in patients with SS/SS.
Comment: This observational study in a heterogeneous population of patients with SS/SS shows how reducing antibiotic spectrum when culture results are known is associated with lower mortality. Despite this study has the limitation of not being randomized, its results are in line with other observational studies where de-escalation was also associated with lower mortality [3]. It should be noted that prevalence of multi-resistant microorganisms ("ESKAPE") in these patients in which infection is the reason for ICU admission is low, and therefore this strategy may not be extrapolated to nosocomial or recurrent infections. Also, it was not explored whether measures directed to source control (surgery, drainage) differed between groups. Nevertheless, this study shows that it is not advisable to prolong unnecessary antibiotic coverage once culture results are received. Of note, in an observational study on 101 neutropenic patients published in the same issue [4], antibiotic de-escalation shows no evidence of any prognostic impact of antibiotic de-escalation on 30 days and one year mortality.
Fernando Martínez-Sagasti
Hospital Clínico San Carlos, Madrid
© REMI, January 2014.
  1. Systematic review and meta-analysis of the efficacy of appropriate empiric antibiotic therapy for sepsis. Paul M, Shani V, Muchtar E, Kariv G, Robenshtok E, Leibovici L. Antimicrob Agents Chemother 2010; 54: 4851-4863. [PubMed]
  2. De-escalation of antimicrobial treatment for adults with sepsis, severe sepsis or septic shock. Silva BN, Andriolo RB, Atallah AN, Salomao R. Cochrane Database Syst Rev 2013; 3: CD007934. [PubMed]
  3. Carbapenem de-escalation therapy in a resource-limited setting. Apisarnthanarak A, Bhooanusas N, Yaprasert A, Mundy LM. Infect Control Hosp Epidemiol 2013; 34: 1310-1313. [PubMed]
  4. De-escalation of antimicrobial treatment in neutropenic patients with severe sepsis: results from an observational study. Mokart D, Slehofer G, Lambert J, Sannini A, Chow-Chine L, Brun JP, Berger P, Duran S, Faucher M, Blache JL, Saillard C, Vey N, Leone M. Intensive Care Med 2014. [PubMed]
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