Antibiotic Prescription Patterns in the Empiric Therapy of Severe Sepsis: Combination of Antimicrobials with Different Mechanisms of Action Reduces Mortality

Overview

Journal Crit Care

Specialty Critical Care

Date 2012 Nov 20

PMID 23158399

Citations 24

Authors

Ana Diaz-Martin

Maria Luisa Martinez-Gonzalez

Ricard Ferrer

Carlos Ortiz-Leyba

Enrique Piacentini

Maria Jesus Lopez-Pueyo

Ignacio Martin-Loeches

Mitchell M Levy

Antoni Artigas

Jose Garnacho-Montero

Affiliations

Soon will be listed here.

Abstract

Introduction: 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.

Methods: 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).

Results: 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).

Conclusions: 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.

Citing Articles

Practical Lessons on Antimicrobial Therapy for Critically Ill Patients.

Cusack R, Little E, Martin-Loeches I Antibiotics (Basel). 2024; 13(2).

PMID: 38391547 PMC: 10886263. DOI: 10.3390/antibiotics13020162.

Mutational Switch-Backs Can Accelerate Evolution of to a Combination of Ciprofloxacin and Doxycycline.

Mehta H, Ibarra D, Marx C, Miller C, Shamoo Y Front Microbiol. 2022; 13:904822.

PMID: 35615518 PMC: 9125183. DOI: 10.3389/fmicb.2022.904822.

Prolonged Infusion of β-Lactams Decreases Mortality in Patients with Septic Shock: A Retrospective before-and-after Study.

Richter D, Dietrich M, Lalev L, Schmitt F, Fiedler M, Bruckner T Antibiotics (Basel). 2021; 10(6).

PMID: 34201244 PMC: 8229114. DOI: 10.3390/antibiotics10060687.

A Comparative Sensitivity Study of "Ceftriaxone-Sulbactam-EDTA" and Various Antibiotics against Gram-negative Bacterial Isolates from Intensive Care Unit.

Singh S, Sahu C, Patel S, Singh A, Yaduvanshi N Indian J Crit Care Med. 2021; 24(12):1213-1217.

PMID: 33446975 PMC: 7775946. DOI: 10.5005/jp-journals-10071-23573.

An approach to antibiotic treatment in patients with sepsis.

Martinez M, Plata-Menchaca E, Ruiz-Rodriguez J, Ferrer R J Thorac Dis. 2020; 12(3):1007-1021.

PMID: 32274170 PMC: 7139065. DOI: 10.21037/jtd.2020.01.47.

References

Damas P, Garweg C, Monchi M, Nys M, Canivet J, Ledoux D . Combination therapy versus monotherapy: a randomised pilot study on the evolution of inflammatory parameters after ventilator associated pneumonia [ISRCTN31976779]. Crit Care. 2006; 10(2):R52. PMC: 1550875. DOI: 10.1186/cc4879. View

Baddour L, Yu V, Klugman K, Feldman C, Ortqvist A, Rello J . Combination antibiotic therapy lowers mortality among severely ill patients with pneumococcal bacteremia. Am J Respir Crit Care Med. 2004; 170(4):440-4. DOI: 10.1164/rccm.200311-1578OC. View

Rotschafer J, Ullman M, Sullivan C . Optimal use of fluoroquinolones in the intensive care unit setting. Crit Care Clin. 2010; 27(1):95-106. DOI: 10.1016/j.ccc.2010.11.005. View

de With K, Meyer E, Steib-Bauert M, Schwab F, Daschner F, Kern W . Antibiotic use in two cohorts of German intensive care units. J Hosp Infect. 2006; 64(3):231-7. DOI: 10.1016/j.jhin.2006.05.018. View

Alberti C, Brun-Buisson C, Burchardi H, Martin C, Goodman S, Artigas A . Epidemiology of sepsis and infection in ICU patients from an international multicentre cohort study. Intensive Care Med. 2002; 28(2):108-21. DOI: 10.1007/s00134-001-1143-z. View

Paul M, Benuri-Silbiger I, Soares-Weiser K, Leibovici L . Beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and meta-analysis of randomised trials. BMJ. 2004; 328(7441):668. PMC: 381218. DOI: 10.1136/bmj.38028.520995.63. View

Dupont H, Carbon C, Carlet J . Monotherapy with a broad-spectrum beta-lactam is as effective as its combination with an aminoglycoside in treatment of severe generalized peritonitis: a multicenter randomized controlled trial. The Severe Generalized Peritonitis Study Group. Antimicrob Agents Chemother. 2000; 44(8):2028-33. PMC: 90009. DOI: 10.1128/AAC.44.8.2028-2033.2000. View

Kumar A . Optimizing antimicrobial therapy in sepsis and septic shock. Crit Care Clin. 2009; 25(4):733-51, viii. DOI: 10.1016/j.ccc.2009.08.004. View

Esteban A, Frutos-Vivar F, Ferguson N, Penuelas O, Lorente J, Gordo F . Sepsis incidence and outcome: contrasting the intensive care unit with the hospital ward. Crit Care Med. 2007; 35(5):1284-9. DOI: 10.1097/01.CCM.0000260960.94300.DE. View

10.

Dellinger R, Levy M, Carlet J, Bion J, Parker M, Jaeschke R . Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med. 2007; 34(1):17-60. PMC: 2249616. DOI: 10.1007/s00134-007-0934-2. View

11.

Tessmer A, Welte T, Martus P, Schnoor M, Marre R, Suttorp N . Impact of intravenous {beta}-lactam/macrolide versus {beta}-lactam monotherapy on mortality in hospitalized patients with community-acquired pneumonia. J Antimicrob Chemother. 2009; 63(5):1025-33. DOI: 10.1093/jac/dkp088. View

12.

Kumar A, Zarychanski R, Light B, Parrillo J, Maki D, Simon D . Early combination antibiotic therapy yields improved survival compared with monotherapy in septic shock: a propensity-matched analysis. Crit Care Med. 2010; 38(9):1773-85. DOI: 10.1097/CCM.0b013e3181eb3ccd. View

13.

Angus D, Lidicker J, Clermont G, Carcillo J, Pinsky M . Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001; 29(7):1303-10. DOI: 10.1097/00003246-200107000-00002. View

14.

Garnacho-Montero J, Sa-Borges M, Sole-Violan J, Barcenilla F, Escoresca-Ortega A, Ochoa M . Optimal management therapy for Pseudomonas aeruginosa ventilator-associated pneumonia: an observational, multicenter study comparing monotherapy with combination antibiotic therapy. Crit Care Med. 2007; 35(8):1888-95. DOI: 10.1097/01.CCM.0000275389.31974.22. View

15.

Al-Hasan M, Wilson J, Lahr B, Thomsen K, Eckel-Passow J, Vetter E . Beta-lactam and fluoroquinolone combination antibiotic therapy for bacteremia caused by gram-negative bacilli. Antimicrob Agents Chemother. 2009; 53(4):1386-94. PMC: 2663102. DOI: 10.1128/AAC.01231-08. View

16.

Knaus W, Wagner D, Draper E, Zimmerman J, Bergner M, Bastos P . The APACHE III prognostic system. Risk prediction of hospital mortality for critically ill hospitalized adults. Chest. 1991; 100(6):1619-36. DOI: 10.1378/chest.100.6.1619. View

17.

Safdar N, Handelsman J, Maki D . Does combination antimicrobial therapy reduce mortality in Gram-negative bacteraemia? A meta-analysis. Lancet Infect Dis. 2004; 4(8):519-27. DOI: 10.1016/S1473-3099(04)01108-9. View

18.

Rodriguez A, Mendia A, Sirvent J, Barcenilla F, De La Torre-Prados M, Sole-Violan J . Combination antibiotic therapy improves survival in patients with community-acquired pneumonia and shock. Crit Care Med. 2007; 35(6):1493-8. DOI: 10.1097/01.CCM.0000266755.75844.05. View

19.

Garnacho-Montero J, Garcia-Garmendia J, Barrero-Almodovar A, Jimenez-Jimenez F, Perez-Paredes C, Ortiz-Leyba C . Impact of adequate empirical antibiotic therapy on the outcome of patients admitted to the intensive care unit with sepsis. Crit Care Med. 2003; 31(12):2742-51. DOI: 10.1097/01.CCM.0000098031.24329.10. View

20.

Kumar A, Safdar N, Kethireddy S, Chateau D . A survival benefit of combination antibiotic therapy for serious infections associated with sepsis and septic shock is contingent only on the risk of death: a meta-analytic/meta-regression study. Crit Care Med. 2010; 38(8):1651-64. DOI: 10.1097/CCM.0b013e3181e96b91. View