SEPSIS, AND SEPTIC SHOCK Megan Dorsey, PGY-1 Pharmacy Practice - PowerPoint PPT Presentation

EVALUATING APPROACHES TO REDUCE DELAY OF FIRST AND SECOND DOSE ANTIBIOTICS FOR PATIENTS ADMITTED FOR SEPSIS, SEVERE SEPSIS, AND SEPTIC SHOCK Megan Dorsey, PGY-1 Pharmacy Practice Resident Providence Alaska Medical Center Anchorage, AK IRB status: Approved

Disclosure Statement • Speaker: Megan Dorsey • Conflict of interest: None • Sponsorship: None • Propriety information or results of ongoing research is subject to different interpretation • Speaker’s presentation is educational in nature and abides by the non - commercial guidelines

Learning Objectives • Discuss rationale and evidence for timely antibiotic administration in patients with sepsis • Examine the effectiveness of preplanned interventions aimed at reducing time to administration for 1 st and 2 nd dose antibiotics

Providence Alaska Medical Center • Tertiary care community medical center in Anchorage, AK • Not for profit • Level II trauma center • Largest hospital in the state of Alaska • 402 Beds • 62 Emergency Department beds • 37 Adult ICU beds http://akfmr.org/wp-content/uploads/2014/04/providence-hospital-in-anchorage_3028.jpg

Pre-Test Assessment Questions • Per the Surviving Sepsis Campaign Guidelines, how soon should antibiotic therapy be initiated on a patient presenting to the ED with suspected sepsis? A. 30 minutes C. 3 hours B. 1 hour D. 6 hours • Lapses in second dose antibiotic administration could potentially cause, which of the following: A. Decreased therapy efficacy C. Risk of developing poor outcomes B. Risk of developing resistance D. All of the above • Preliminary data from this study done at Providence Alaska Medical Center, shows a ____ decrease in late antibiotics following 3 planned interventions: A. 21.6% C. 19.8% B. 5% D. 11.2%

Study Objectives • Examine the timing of first and second doses of antibiotics in patients diagnosed with sepsis, severe sepsis, and septic shock admitted from the ED to an inpatient floor • Evaluate the effectiveness of process changes aimed at reducing delays in 1 st and 2 nd dose antibiotic administration • Identify areas of further improvement to help reduce further antibiotic delays

Importance of Time to First Dose • Linear increase in mortality was associated with each hour delay in initial antibiotic therapy • “Hour - 1 Bundle” o Measure lactate o Obtain cultures o Administer broad spectrum antibiotics o Start fluid resuscitation with 30 ml/kg of fluid (crystalloid preferred) o Begin vasopressors during/after resuscitation, if indicated Ferrer, et al. Crit Care Med. 2014. Kumar, et al. Crit Care Med. 2006. Rhodes, et al. Crit Care Med . 2017

Importance of Time to Second Dose • Limited data exists examining effects of delayed second dose antibiotics • One retrospective study, including 828 patients with sepsis o Major delays were associated with a greater risk of hospital mortality (OR: 1.61, CI 1.01-2.57, p=0.046) o Increased odds of requiring mechanical ventilation in patients not mechanically ventilated at time of second dose (OR 2.44, CI 1.27-4.69, p = 0.007). • Theoretical effects: decreased efficacy of therapy, increased risk of resistance Leisman, et al. Crit Care Med . 2017. Martinez, et al. Antimicrob Agents Chemother. 2012.

Methodology • Retrospective review of electronic health records of patients admitted from the emergency department to an inpatient floor with sepsis, severe sepsis, or septic shock • 1 st and 2 nd dose antibiotic administration times were collected at 3 time periods: Provider Post- Post- Minibag Baseline Meeting Minibag Meeting/ED Start Systems in Group ED RPh Pyxis Group RPh Group Services Pre-Interventions Post-Interventions

Methodology Inclusion Criteria Exclusion Criteria • Admission to an inpatient floor from • Age < 18 years old the emergency department • Transfer from an outside facility • Diagnosis of sepsis, severe sepsis, or • Pregnancy septic shock • Incarceration • Age > 18 years old • Failure to meet inclusion criteria • Administration of at least 2 doses of an antibiotic with a dosing interval < 24 hours

Sepsis Definitions • Sepsis : Evidence or suspicion of infection with two or more of the following: o Temp > 38.3 ˚C or < 36 ˚C o HR > 90 bpm o RR > 20 bpm o WBC > 12,000 or < 4,000 or > 10% immature bands • Severe Sepsis : Sepsis (per above criteria) + one of the following: o Platelets < 100,000 o Coagulopathy (INR > 1.5 or PTT > 60 sec) o PaO2/FiO2 < 250 (or < 200 if pneumonia) o Lactate > 2 mmol/L o SBP < 90 mmHg or MAP < 65 mmHg o SCr > 2 mg/dL or UOP < 0.5 ml/kg/hr for 2 consecutive hours o Total bilirubin > 2 mg/dL • Septic Shock : Severe Sepsis (per above criteria) + hypotension despite fluid resuscitation Levy, et al. Crit Care Med . 2003.

188 patients excluded 437 patients • 77 did not have sepsis screened • 50 transferred from OSF • 42 did not have 2 doses of same antibiotic • 19 did not receive ED antibiotics 249 patients included

188 patients excluded 437 patients • 77 did not have sepsis screened • 50 transferred from OSF • 42 did not have 2 doses of same antibiotic • 19 did not receive ED antibiotics 249 patients included 380 antibiotics included

188 patients excluded 437 patients • 77 did not have sepsis screened • 50 transferred from OSF • 42 did not have 2 doses of same antibiotic • 19 did not receive ED antibiotics 249 patients included 380 antibiotics 500 antibiotic included administrations

188 patients excluded 437 patients • 77 did not have sepsis screened • 50 transferred from OSF • 42 did not have 2 doses of same antibiotic • 19 did not receive ED antibiotics 249 patients included 380 antibiotics 500 antibiotic included administrations Pre-Implementations Post-Implementations N=250 N=250 Post-Minibag Post ED RPh/Meeting N=94 N=156

Pre-Interventions Post-Interventions P-Value N=250 N=250 Gender • Female 126 (50.4%) 130 (52%) 0.72 • Male 124 (49.6%) 120 (48%) Age 61.5 + 13.6 56.7 + 13.5 0.29 Diagnosis • Sepsis 80 (32%) 109 (43.6%) 0.007 • Severe Sepsis 129 (51.6%) 112 (44.8%) 0.13 • Septic Shock 41 (16.4%) 29 (11.6%) 0.12 Inpatient Units • Med/Surg/Ortho 67 (26.8%) 105 (42%) 0.003 • PCU 79 (31.6%) 49 (19.6%) 0.002 • ICU 43 (17.2%) 43 (17.2%) 1 • CTICU/CICU 21 (8.4%) 17 (6.8%) 0.44 • IMCU 24 (9.6%) 18 (7.2%) 0.33 • Other 16 (6.4%) 18 (7.2%) 0.72 Antibiotics • Piperacillin/tazobactam 54 (21.6%) 85 (34%) 0.09 • Ceftriaxone 43(17.2%) 78 (31.2%) 0.06 • Azithromycin 41 (16.4%) 28 (11.2%) 0.002 • Cefepime 27 (10.8%) 11 (4.4%) 0.007 • Cefazolin 6 (2.4%) 4 (1.6%) 0.35 • Clindamycin 1 (0.4%) 17 (6.8%) <0.001

Pre-Interventions Post-Interventions P-Value N=250 N=250 Gender • Female 126 (50.4%) 130 (52%) 0.72 • Male 124 (49.6%) 120 (48%) Age 61.5 + 13.6 56.7 + 13.5 0.29 Diagnosis • Sepsis 80 (32%) 109 (43.6%) 0.007 • Severe Sepsis 129 (51.6%) 112 (44.8%) 0.13 • Septic Shock 41 (16.4%) 29 (11.6%) 0.12 Inpatient Units • Med/Surg/Ortho 67 (26.8%) 105 (42%) 0.003 • PCU 79 (31.6%) 49 (19.6%) 0.002 • ICU 43 (17.2%) 43 (17.2%) 1 • CTICU/CICU 21 (8.4%) 17 (6.8%) 0.44 • IMCU 24 (9.6%) 18 (7.2%) 0.33 • Other 16 (6.4%) 18 (7.2%) 0.72 Antibiotics • Piperacillin/tazobactam 54 (21.6%) 85 (34%) 0.09 • Ceftriaxone 43(17.2%) 78 (31.2%) 0.06 • Azithromycin 41 (16.4%) 28 (11.2%) 0.002 • Cefepime 27 (10.8%) 11 (4.4%) 0.007 • Cefazolin 6 (2.4%) 4 (1.6%) 0.35 • Clindamycin 1 (0.4%) 17 (6.8%) <0.001

Data Analysis • First Dose “Late” : dose administered more than 1 hour from ED admission • Antibiotics were excluded if ordered after another antibiotic was already given • Second Dose “Late” : time between first and second dose was either > 25% of the antibiotic dosing interval OR > 2 hours Primary Endpoint Reduction in number of aggregate late 1 st and 2 nd dose antibiotics between the pre- and post- intervention groups

Aggregate Late 1 st or 2 nd Doses Pre-Interventions Post Interventions p-value N=250 N=250 121 (48%) 97 (39%) 0.03 70% 60% 61% • Excluded vancomycin 52% 50% 48% doses due to variable 40% kinetics 39% 30% • 19.8% decrease in late 20% doses between the groups 10% 0% Pre-Intervention Post-Intervention Late On-time

Secondary Analysis Pre-Interventions Post-Interventions p-value Number of Late 1 st Doses 87 (82.1%) 66 (61.1%) <0.001 Number of Late 2 nd Doses 34 (23.6%) 31 (21.8%) 0.719 90% 80% 78% 82% 76% 80% 70% 70% 60% 61% 60% 50% 50% 40% 40% 39% 30% 30% 24% 22% 20% 20% 18% 10% 10% 0% 0% Pre-Intervention Post-Intervention Pre-Intervention Post-Intervention Late On-time Late On-time

Secondary Analysis Pre-Interventions Post-Intervention Difference p-value (95% CI) Average Delay of 1 st and 2 nd Doses 3.01 + 1.89 1.93 + 1.93 1.09 (0.78-1.38) <0.001 Average Delay to 1 st Dose 2.49 + 1.43 1.43 + 1.95 0.71 (0.25-1.17) 0.003 Average Delay to 2 nd Dose 3.53 + 2.21 2.09 + 1.09 1.44 (1.03-1.84) <0.001

Secondary Analysis Number of Late ( >1 hours from door to dose) and On-time doses over study period based on drug 120% 100% 100% 100% 100% 100% 90% 90% 75% 80% 71% 68% 62% 60% 50% 40% 33% 20% 0%