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Antibiotic prescription patterns in the empiric therapy of severe sepsis: combination of antimicrobials with different mechanisms of action reduces mortality

Ana Díaz-Martín123*, María Luisa Martínez-González4, Ricard Ferrer56, Carlos Ortiz-Leyba123, Enrique Piacentini5, Maria Jesus Lopez-Pueyo7, Ignacio Martín-Loeches46, Mitchell M Levy8, Antoni Artigas46, José Garnacho-Montero123 and for the Edusepsis Study Group

Author Affiliations

1 Intensive Care Unit, Critical Care and Emergency Department, Virgen del Rocío University Hospital, Avda. Manuel Siurot s/n, Seville 41013, Spain

2 Instituto de Biomedicina de Sevilla (IBIS), Virgen del Rocío University Hospital/CSIC/Seville University, 41013 Seville, Spain

3 Spanish Network for Research in Infectious Disease (REIPI), Virgen del Rocío University Hospital, Avda. Manuel Siurot, s/n. 41013, Seville, Spain

4 Critical Care Center, Sabadell Hospital, Autonomous University of Barcelona, Corporació Sanitaria Universitària Parc Taulí, 08208 Sabadell, Spain

5 Intensive Care Unit, Mútua Terrassa University Hospital, University of Barcelona, Plaça Dr, Robert 5, Terrassa, 08221, Barcelona, Spain

6 CIBER-Enfermedades Respiratorias

7 Intensive Care Unit, General Yagüe Hospital, Avda del Cid Campeador, 96 09005 Burgos, Spain

8 Medical Intensive Care Unit, Rhode Island Hospital/Brown University, 593 Eddy St,, Providence, RI 02903, USA

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Critical Care 2012, 16:R223  doi:10.1186/cc11869

See related commentary by Kumar and Kethireddy,

Published: 18 November 2012



Although early institution of adequate antimicrobial therapy is lifesaving in sepsis patients, optimal antimicrobial strategy has not been established. Moreover, the benefit of combination therapy over monotherapy remains to be determined. Our aims are to describe patterns of empiric antimicrobial therapy in severe sepsis, assessing the impact of combination therapy, including antimicrobials with different mechanisms of action, on mortality.


This is a Spanish national multicenter study, analyzing all patients admitted to ICUs who received antibiotics within the first 6 hours of diagnosis of severe sepsis or septic shock. Antibiotic-prescription patterns in community-acquired infections and nosocomial infections were analyzed separately and compared. We compared the impact on mortality of empiric antibiotic treatment, including antibiotics with different mechanisms of action, termed different-class combination therapy (DCCT), with that of monotherapy and any other combination therapy possibilities (non-DCCT).


We included 1,372 patients, 1,022 (74.5%) of whom had community-acquired sepsis and 350 (25.5%) of whom had nosocomial sepsis. The most frequently prescribed antibiotic agents were β-lactams (902, 65.7%) and carbapenems (345, 25.1%). DCCT was administered to 388 patients (28.3%), whereas non-DCCT was administered to 984 (71.7%). The mortality rate was significantly lower in patients administered DCCTs than in those who were administered non-DCCTs (34% versus 40%; P = 0.042). The variables independently associated with mortality were age, male sex, APACHE II score, and community origin of the infection. DCCT was a protective factor against in-hospital mortality (odds ratio (OR), 0.699; 95% confidence interval (CI), 0.522 to 0.936; P = 0.016), as was urologic focus of infection (OR, 0.241; 95% CI, 0.102 to 0.569; P = 0.001).


β-Lactams, including carbapenems, are the most frequently prescribed antibiotics in empiric therapy in patients with severe sepsis and septic shock. Administering a combination of antimicrobials with different mechanisms of action is associated with decreased mortality.