1. Background Goals Methods Conclusions Results
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. Clancy1,2 B.A. Potoski1,3, R.K. Shields1,3, M.H. Nguyen1,3
1Univ. of Pittsburgh, 2VA Pittsburgh Healthcare System, Pittsburgh, PA, 3Antibiotic Management Program, UPMC Presbyterian
Figure 1. XDR Pathogen Lab: Identifying optimal antimicrobial combinations against UPMC CR-KP strains
Figure 5. Costs by billing categories
Background
ompK36 porin genotypes and carbapenem-colistin responses
Aminoglycoside 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
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 days, respectively (p=0.006). Median LOS was 60 vs 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.
Figure 2. Clinical data for treatment regimens among patients with CR-KP bacteremia
Figure 3. Developing a treatment algorithm
To determine the clinical and economic impact of the intervention program against CR-KP bacteremia.
KPC- K. pneumoniae
Gentamicin MIC ≤ 4 µg/ml
Strains likely to respond to gentamicin or doripenem + gentamicin
Gentamicin MIC > 4 µg/ml
Porin ompK36 genotyping
Wild-type/Other mutants or doripenem MIC ≤ 8 µg/ml
Strains likely to respond to doripenem-colistin
Ins AA GD
or IS5 mutants
Strains likely not to respond to currently available agents
Methods
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 90-day readmission rate.
Financials included mean and median total costs and charges.
Conclusions
Results
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.
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
Identify strain-specific treatment algorithm
Partner with AMP to implement institution-specific 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
Table 2. Impact of ASP intervention
Pre-intervention
Post-intervention
Date Range
6/2007 to 5/2013
6/2013 to 4/2016
Total Patients 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%
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.