In hospital Mortality rate

A formal antimicrobial stewardship intervention programme targeting carbapenem-resistant Klebsiella pneumoniae
(CRKP) bacteremia improved mortality, shortened lengths of stay, and reduced costs over a three-year period
C.J.
1Univ.
1
2
Clancy ,
B.A.
1,3
Potoski ,
R.K.
1,3
Shields ,
M.H.
1,3
Nguyen
of Pittsburgh, 2VA Pittsburgh Healthcare System, Pittsburgh, PA, 3Antibiotic Management Program, UPMC Presbyterian
Background
Figure 1. XDR Pathogen Lab: Identifying optimal antimicrobial combinations against UPMC CR-KP strains
Aminoglycoside responses
ompK36 porin genotypes and carbapenem-colistin responses
• Infections caused by carbapenem-resistant Klebsiella pneumoniae
(CRKP) have limited antibiotic treatment options and poor clinical
outcomes.
• Treatment algorithms for multi-drug resistant (MDR)-Gram negative
infections at University of Pittsburgh Medical Center (UPMC) were
created by collaboration between the Antibiotic Stewardship Program
(ASP) and XDR Pathogen lab.
• Beginning June 2013, the ASP began a formal intervention
program using decision support software to allow real-time
recommendations for CRKP infections.
• We assessed clinical and economic parameters of CRKP
bacteremia in the pre- and post-intervention periods.
Table 4. Breakdown of hospital charges
Goals
• To determine the clinical and economic impact of the intervention
Figure 5. Costs by billing categories
Figure 2. Clinical data for treatment regimens among
patients with CR-KP bacteremia
Figure 3. Developing a treatment algorithm
program against CR-KP bacteremia.
KPC- K. pneumoniae
Methods
Gentamicin MIC ≤ 4 µg/ml
Gentamicin MIC > 4 µg/ml
• Analyses
compared pre (6/07-5/13) and post (6/13-4/16)
intervention time periods, and included patients treated with
regimens that did not include the new agent ceftazidime-avibactam.
• Endpoints included 30-day mortality rate, hospital stay after
positive blood culture, mean hospital length of stay (LOS), and 90day readmission rate.
•Financials included mean and median total costs and charges.
Porin ompK36 genotyping
Strains likely to respond to
gentamicin or doripenem +
gentamicin
Wild-type/Other mutants or
doripenem MIC ≤ 8 µg/ml
Ins AA 134-135 GD
or IS5 mutants
Strains likely to respond to
doripenem-colistin
Strains likely not to respond
to currently available
agents
• In-hospital mortality rates comparing pre- to post- groups were
45% (34/75) vs. 19% (8/44), respectively (p=0.003)
• Hospitalization after positive blood culture was 34 vs. 14.5
days, respectively (p=0.006). Median LOS was 60 vs. 25.5 days
• 90-day readmission rate was 39% vs. 36%, respectively
(p=0.001 and NS).
• Estimated median total charges pre vs. post were $1,303,489
vs. $598,805, respectively, with an estimated average cost
saved per CRKP bacteremic patient of $704,684.
• Cost savings in the post period were observed across billing
categories, including antibiotics and pharmacy (Figure 5).
• Results have been consistent across years in the post period.
Conclusions
Results
Figure 4. Overview of the AMP intervention program
Table 1. Timeline for the development of the ASP intervention program
against CR-KP bacteremia
Identify KPC-Kp strains
In vitro synergy testing
and strain typing
Table 2. Impact of ASP intervention
Preintervention
Postintervention
6/2007 to
5/2013
6/2013 to
4/2016
83
44
Average length of stay
76 Days
34.1 Days
Median length of stay
60 Days
25.5 Days
90 day readmission
rate
39%
36%
In hospital Mortality
rate
45%
19%
Date Range
Total Patients
Identify strain-specific
treatment algorithm
Partner with AMP to
implement institutionspecific treatment
recommendations
Disseminate general
treatment
recommendations
through AMP book and
provider education
Liaison with clinical
services to offer advice
on optimal treatment
regimens and dosing
Average Total
Charges/patient
$1,941,879
$1,002,213
Median Total
Charges/patient
$1,303,489
$598,805
•Within 3 days of positive
blood culture, 8 and 4
patients died in the pre
vs.
post
periods,
respectively, and were
excluded from further
analysis.
• The clinical and economic impact of CR-KP bacteremia is
substantial, reflecting propensity for transplant and other
severely-ill patients.
• Differences in strain genetics (e.g., ompK36 genotypes and
patterns of aminoglycoside modifying enzymes), are
associated with differences in antimicrobial responses, even
among ST258 strains considered to be clonal.
•The mortality rate in patients with CRKP was significantly
reduced in the post intervention period, suggesting the benefit
was due to the collaborative ASP and XDR lab intervention.
• Shorter LOS after onset of bacteremia was observed in the
post-intervention period with a significant cost savings.
• Overall, the data suggest that a formal intervention program
directed by ASP improved patient outcomes, shorten hospital
stays, and reduce costs, even prior to the availability of new
agents like ceftazidime-avibactam.
• Our experience highlights the evolving paradigm of
stewardship teams as liaisons between laboratory and
bedside in the management of difficult to treat infections.