Antimicrobial Therapy for Life-threatening Infections: Speed is Life Duane J. Funk, MD, FRCP(C), Anand Kumar, MD  Critical Care Clinics  Volume 27, Issue 1, Pages 53-76 (January 2011) DOI: 10.1016/j.ccc.2010.09.008 Copyright © 2011 Elsevier Inc. Terms and Conditions

Fig. 1 Cumulative initiation of effective antimicrobial therapy and survival in septic shock. In a large retrospective study of septic shock, Kumar and colleagues demonstrated that median time to effective/appropriate antimicrobial therapy was 6 hours and that for every hour delay more than the first 6 hours, the projected mortality increased by 7.6%/h. X axis represents time (hours) after first documentation of septic shock–associated hypotension. Black bars represent the fraction of patients surviving to hospital discharge and the gray bars represent the cumulative fraction of patients having received effective antimicrobials at any given time point. (From Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006;34:1589–96; with permission.) Critical Care Clinics 2011 27, 53-76DOI: (10.1016/j.ccc.2010.09.008) Copyright © 2011 Elsevier Inc. Terms and Conditions

Fig. 2 Mortality risk (expressed as adjusted odds ratio of death) with increasing delays in initiation of effective antimicrobial therapy. Bars represent 95% CI. An increased risk of death is already present by the second hour after hypotension onset (compared with the first hour after hypotension onset). The risk of death continues to increase up to more than 36 hours after hypotension onset. (From Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006;34:1589–96; with permission.) Critical Care Clinics 2011 27, 53-76DOI: (10.1016/j.ccc.2010.09.008) Copyright © 2011 Elsevier Inc. Terms and Conditions

Fig. 3 The running average of the fraction of 250 patients with septic shock surviving to hospital discharge from fast to slowest antimicrobial initiation time after documentation of hypotension (n = 5715). Decay of survival probability seems to represent a logarithmic function. Approximately 90% of survivors of septic shock received appropriate antimicrobial therapy within 12 hours of documentation of hypotension. Critical Care Clinics 2011 27, 53-76DOI: (10.1016/j.ccc.2010.09.008) Copyright © 2011 Elsevier Inc. Terms and Conditions

Fig. 4 Hospital mortality of candidemic patients in relation to delay in initiating antifungal therapy after index positive blood culture. Mortality risk climbs with increasing delays. (From Morrell M, Fraser VJ, Kollef MH. Delaying the empiric treatment of Candida bloodstream infection until positive blood culture results are obtained: a potential risk factor for hospital mortality. Antimicrob Agents Chemother 2005;49:3640–5; with permission.) Critical Care Clinics 2011 27, 53-76DOI: (10.1016/j.ccc.2010.09.008) Copyright © 2011 Elsevier Inc. Terms and Conditions

Fig. 5 Distribution of antimicrobial delays (A) and odds ratios of 30-day survival (B) in patients more than age 65 years presenting to the ER with community-acquired pneumonia. Approximately 25% of patients did not receive antimicrobial therapy after 8 hours in the ER; mortality in this group was significantly increased. (From Meehan TP, Fine MJ, Krumholz HM, et al. Quality of care, process, and outcomes in elderly patients with pneumonia. JAMA 1997;278:2080–4; with permission.) Critical Care Clinics 2011 27, 53-76DOI: (10.1016/j.ccc.2010.09.008) Copyright © 2011 Elsevier Inc. Terms and Conditions

Fig. 6 Rate of hospital mortality and unfavorable outcome according to the treatment delay in time interval in acute bacterial meningitis. (Data from Koster-Rasmussen R, Korshin A, Meyer CN. Antibiotic treatment delay and outcome in acute bacterial meningitis. J Infect 2008;57:449–54.) Critical Care Clinics 2011 27, 53-76DOI: (10.1016/j.ccc.2010.09.008) Copyright © 2011 Elsevier Inc. Terms and Conditions