PURPOSE: Inappropriate antibiotic therapy is a risk factor for poor outcomes in serious bacterial and fungal infections, including septic shock. In addition, antibiotic resistance is a risk factor for inappropriate therapy, but it is unknown if resistance remains a risk factor for poor outcomes in patients who are treated appropriately. The goal of the current study is to determine if antibiotic resistance is associated with worse survival in patients with septic shock who are treated with initial appropriate antibiotic therapy.
METHODS: A retrospective cohort study was conducted in a 1200 bed academic medical center from January 2002 to September 2006. All patients with culture positive septic shock requiring vasopressors treated with appropriate antibiotic therapy within the first 24 hours were included in the analysis. Antibiotic resistance was defined as: (1) vancomycin-resistant Enterococcus (VRE) or methicillin-resistant Staphylococcus aureus (MRSA) for gram-positive organisms, (2) resistance to cefepime, piperacillin-tazobactam, or a carbapenem for gram-negative organisms, (3) Candida glabrata or Candida krusei species.
RESULTS: A total of 586 patients were included in the analysis, and 296 died in the hospital (50.5% mortality). Of the organisms isolated, 253 (43.2%) were gram-positive, 303 (51.7%) were gram-negative, and 50 (5.1%) were Candida species. In addition, 144 organisms (24.6%) demonstrated antimicrobial resistance. The proportion of resistant organisms varied by organism subtype: 98 (38.7%) resistant gram-positive organisms, 39 (12.9%) resistant gram-negative organisms, and 7 (23.3%) resistant fungal organisms. The in-hospital mortality for susceptible organisms was 228 (50.7%) versus 68 (50.0%) for resistant organisms (p=0.892). When separated by individual organisms, antibiotic resistance was a risk factor for mortality only in those infected with Staphylococcus aureus (10 [22.7%] MSSA vs 33 [42.3%] MRSA, p=0.03).
CONCLUSIONS: In patients with culture positive septic shock who received appropriate therapy, antimicrobial resistance was not a risk factor for mortality, unless the patient was infected with Staphylococcus aureus.
CLINICAL IMPLICATIONS: Selection of initial appropriate antimicrobials in septic shock is crucial as resistance in those treated appropriately is not a risk factor for mortality outside of MRSA.
DISCLOSURE: The following authors have nothing to disclose: Andrew Labelle, Scott Micek, Richard Reichley, Justin Hoffman, Alex Hoban, Paul Juang, Marin Kollef
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