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DATE, 2018
Agenda
• Announcements
• Presenter: Title• Case Discussions
• Open Discussion
Gram Negative Blood Stream InfectionsZahra Kassamali Escobar, PharmD, BCIDP
UW Medicine | Valley Medical Center
March 19, 2019
Agenda
Goal: Determine optimal treatment and duration once GNR BSI has been identified
1.) How long to treat2.) What antibiotic agent to treat with 3.) Repeat blood cultures
A 62 yo female presents to your hospital with sepsis. Urine and blood cultures grow E. coli
On Day 3, the patient is stabilized. What duration of therapy would you recommend to complete a course.
a. 5 daysb. 7 daysc. 10 daysd. 14 days
Inpatient adults with GNR bacteremia, afebrile & hemodynamically stable x48h
N = 604
CONTROL GROUP: 14 days of antibiotics
N = 298
TREATMENT GROUP: 7 days of antibiotics
N = 306
PRIMARY OUTCOME (within 90 days):All-cause mortality ▪ Relapse of bacteremia ▪ Local/distant infectious complications ▪
Readmission ▪ Extended hospital stay > 14 days
14-DAY TREATMENT: 48.3%Mortality: 10.7% (n = 32)
Readmitted: 42.6% (n = 127)LOS >14 d: 6.4% (n = 19)Relapse BSI: 2.7% (n = 8)
Complications: 3.7% (n = 11)
7-DAY TREATMENT: 45.8%Mortality: 11.8% (n = 36)
Readmitted: 38.9% (n = 119)LOS >14 d: 4.9% (n = 15)Relapse BSI: 2.6% (n = 8)
Complications: 5.9% (n = 18)
Patient population
PATIENTS SOURCE
BACTERIAL ORGANISM
71 years old
50% female
25%
malignancy60%
independently functional
20-25%
urinary device
Urinary
Primary BSI
Abdominal
RespiratoryCVC
Skin/Soft
tissue
6.7
11.1
65.1
17.1
9.2
15.3
60.8
18.9
0 20 40 60 80 100
Pseudomonas spp
Klebsiella spp
E. coli
MDR
7-DAY
14-DAY
Yahav et al. Clin Infect Dis. 2018 Dec 11.
Does this trial apply to my patients?
Inpatient adults with GNR bacteremia, afebrile & hemodynamically stable x48h
N = 604
Included, 604
Non-eligible, 2638
Excluded, 1565
Unable to
consent, 810
Pt refused, 370
MD refused,
150
Uncontrolled source, 912
Hemodynamically unstable or fever, 653
Polymicrobial, 557
Immunosuppressed,
365
N = 4807Patients with GN bacteremia screened for trialYahav et al. Clin Infect Dis. 2018 Dec 11.
Antibiotic selection, IV
1
5
12
5
21
56
0
8
13
5
24
51
0 20 40 60 80 100
SMX/TMP
Carbapenem
Aminoglycoside
Quinolone
Beta-lactam,
beta-lactamase inhibitor
Cephalosporin
7-day 14-day
Yahav et al. Clin Infect Dis. 2018 Dec 11.
Percent (%)
The patient is ready for discharge but has 4 days on antibiotic therapy remaining.
What oral agent would you recommend?
a. Amoxicillin/clavulanateb. Cefpodoxime c. Levofloxacind. Sulfamethoxazole/trimethoprim
Antibiotic selection, PO
8
21
71
9
14
77
0 20 40 60 80 100
SMX/TMP
Beta-lactam,beta-lactamase inhibitor
Quinolone
7-day 14-day
36% (7-day) and 19%( 14-day) groups received only IV antibiotics
Yahav et al. Clin Infect Dis. 2018 Dec 11.
Percent (%)
Highly BioavailableN = 106
Moderately BioavailableN = 179
Low BioavailableN = 77
Levofloxacin CiprofloxacinSMX/TMP
Beta-lactams
Time to Failure: Faster with low bioavailable abx
HighLevofloxacin
ModerateCiprofloxacinSMX/TMP
LowBeta-lactams
MD is writing a script for the antibiotic you recommended, she calls and asks: Remind me, when was day 1?
Day 1
a. When empiric antibiotic startedb. When targeted antibiotic startedc. When the blood culture first clearedd. Not sure
Culture drawn Empiric Antibiotics
Targeted Antibiotic to culture result
Blood culture clearance
Duration of therapy: When Is Day 1?
Culture drawn Empiric Antibiotics
Targeted Antibiotic to culture result
Blood culture clearance
Time
As long as active antimicrobial agent
Yahav et al. Clin Infect Dis. 2018 Dec 11.
Duration of therapy: Accounting for Blood Culture Clearance
Num
ber o
f cas
es o
f bac
tere
mia
S. aureus
E. coli
Skin co
mmensals
Enterococcu
s spp.
Wiggers et al. 2016 BMC Infect Dis. 16:286
Summary
• Treat Gram negative bacteremia for 7 days
• Patient must show signs of clinical improvement
• Source must be controlled
• Antibiotic selection
• Based on organism susceptibility
• IV: Cephalosporin
• PO: Fluoroquinolones
• No need to repeat blood cultures for clearance
• Unless:
• Uncontrolled source
• Ongoing infection (e.g. endovascular)