Transcript P-Vialex

Ruolo dell’infettivologo all’interno
dei programmi di stewardship
Pierluigi Viale
Clinica
di Malattie Infettive
Policlinico S. Orsola – Malpighi
Infectious Diseases Society of America and the Society for Healthcare
Epidemiology of America guidelines for developing an institutional program to
enhance antimicrobial stewardship.
Dellit TH, et al. Clin Infect Dis 2007; 44:159–177
Antimicrobial Stewardship: DEFINITIONS
An activity that optimizes antimicrobial management and
includes selection, dosing, route and duration of
antimicrobial therapy.
A marriage of infection control (Epidemiologist), and antimicrobial
management (Infectious Diseases specialist) finalized to share the principles
of the optimized treatment between the bench to bed side point of view
and the hospital-wide vision
Classic AMS interventions
 Restrictive: selective reporting of laboratory susceptibilities, formulary
restriction, requiring prior authorization of prescriptions by infectious diseases
physicians, microbiologists, pharmacists etc, therapeutic substitutions,
automatic stop orders and antibiotic policy change strategies including cycling,
rotation and cross-over studies.
 Persuasive: distribution of educational materials; educational meetings;
local consensus processes; educational outreach visits; local opinion leaders;
reminders provided verbally, on paper or on computer; audit and feedback.
Cochrane Database of Systematic Reviews
30 APR 2013 DOI: 10.1002/14651858.CD003543.pub3
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003543.pub3/full#CD003543-fig-0003
Comparison of Prior Authorization and Prospective Audit
with Feedback for
Antimicrobial Stewardship. Mehta JM et al, Infect Control Hosp Epidemiol 2014;35:1092-1099
Quasi-experimental study. Antimicrobial use during the 24 months before and after
implementation of an ASP strategy change was compared. The ASP used prior
authorization alone during the preintervention period In the post- intervention period
prospective audit was implemented for cefepime, piperacillin/tazob, and vancomycin.
The primary end point was antimicrobial consumption in days of therapy per 1,000
patient-days (DOT/1,000-PD). Secondary end points included length of stay (LOS).
In total, 55,336 patients were included (29,660 pre and 25,676 post).
Audits occurred Monday through
Friday by 3 ID–trained clinical
pharmacists and included all
patients in the hospital with an
active order for any of those
agents. Suggested modifications,
if necessary, were communicated
to the covering provider, and
acceptance of the them was at
their discretion.
Comparison of Prior Authorization and Prospective Audit
with Feedback for
Antimicrobial Stewardship. Mehta JM et al, Infect Control Hosp Epidemiol 2014;35:1092-1099
ANTIMICROBIALS CONSUMPTION – slope DOT per 1000 PD per month
Comparison of Prior Authorization and Prospective Audit
with Feedback for
Antimicrobial Stewardship. Mehta JM et al, Infect Control Hosp Epidemiol 2014;35:1092-1099
LENGHT of HOSPITAL STAY
Assessment of empirical antibiotic therapy optimisation in six hospitals: an
observational cohort study. Braykov NP et al, Lancet Infect Dis 2014; 14: 1220–27
chart review of adult inpatients receiving one or more antimicrobials in six US hospitals on 4 days
Across the six study sites, 4119 (60%) of 6812 inpatients received antimicrobials.
Of 1200 randomly selected patients with active antimicrobials, 730 (61%) met
inclusion criteria.
At the start of therapy, 220 (30%) pts were afebrile and had normal WBC counts.
Appropriate cultures were collected from 432 (59%) patients,
By the 5th day of therapy, 12.5% of empirical antimicrobials were escalated, 21.5%
were narrowed or discontinued, and 66·4% were unchanged.
Assessment of empirical antibiotic therapy optimisation in six hospitals: an
observational cohort study. Braykov NP et al, Lancet Infect Dis 2014; 14: 1220–27
AMS UPDATE OCTOBER 2015
The current state of knowledge is sufficient to make stewardship
implementation a priority in all hospitals, especially given the emerging
threat of resistance, however comparative effectiveness and
sustainability of different approaches are not well known.
Antimicrobial stewardship:
time to revisit the strategy
The PRESENT
COMPULSORY PROGRAMS
vs
POST PRESCRIPTION REVIEWS (semi-compulsory programs)
The NEXT FUTURE
SHARED NEW PARADIGMS for MANAGEMENT
RIGHT USE OF “FAST-MICROBIOLOGY
STRUCTURED CLINICA PATHWAYS
PROBLEM-DRIVEN PROTOCOLS and PROGRAMS
The dream of the
outcome-directed
stewardship
RIGHT USE OF FAST-MICROBIOLOGY
The rapid molecular diagnostics strategy
Especially considering multidrug-resistant (MDR) Gram-negative bacteria, the
rapid and accurate detection of antibiotic resistance determinants offers the
potential to transform clinical practice by:
1) informing early appropriate antibiotic therapy;
2) shortening the duration and narrowing the spectrum of activity of antibiotic
regimens, thus limiting the selection of antibiotic-resistant bacteria;
3) improving clinical outcomes;
4) streamlining development of new antimicrobials by quickly identifying patients
infected with antibiotic-resistant bacteria and enriching participant enrollment
in clinical trials
RIGHT USE OF FAST-MICROBIOLOGY
Study
Organism
Population
s
Perez et al Gram-neg 201 pts with BSI
APLM 2013
(100 pre-intervention,
101 intervention)
Huang et al Aerobic
CID 2013 Gram-pos,
Gram-neg
and yeast
Clerc et al Gram-neg
CID 2013
Wenzler et A.
al. ECCMID baumannii
2014
Perez et al
J Infect
2014
Carreno et
al ICAAC
2014
XDR
Gram-neg
Gram-neg
Gram-pos
501 pts with BSI
(256 pre-intervention,
245 intervention)
MALDI-TOF MS and ASP
Antibiotic use
Patient outcome
Time to antibiotic optimization
LOS (11.9 d vs 9.3 d; P = .01)
46-h reduction (P =.004);
Reduced time to active treatment Hospital costs per pt (P =
(P < .001
.009)
Time to effective therapy of 30.1 2.8-day decrease in mean
vs 20.4 h (P = .021)
LOS (P = .07)
Optimal antibiotic therapy (90.3 Reduced mortality (20.3%
vs 47.3 h; P < .001)
vs 14.5%; P= .02)
202 pts with BSI
Greater percentage of patients NR
with ID consultation compared
with Gram stain results alone
(35.1% vs 20.8%; P = NR)
109 pts with BSI and/or Time to effective therapy (77.7 h Increase in clinical cure
pneumonia
vs 36.6 h; P < .0001)
(15% vs 34%; P = .016)
(66 pre-intervention, 53
intervention)
265 pts with BSI
Time to optimal antibiotic therapy Reduced mortality (21% vs
(112 pre-intervention, (80.9 h vs 23 h; P < .001)
8.9%; P = .01)
153 intervention)
104 pts with BSI
NR
Time to sepsis resolution 4
(78 pre and 26 post
vs. 3 days (P=0.08)
test)
RIGHT USE OF FAST-MICROBIOLOGY
Verigene
Nanoparticle Probe Technology (Nucleic
Acid Extraction and PCR Amplification)
Study Organisms
Population
Sango et Enterococcu 74 pts with BSI
al. JCM s spp.
(46 pre–BC-GP,
2013
28 post–BC-GP)
Crane et Gram-pos
al. ICAAC
2014
Lee et al NS
ICAAC
2014
Hill et al. Gram-neg
JCM 2014
Antibiotic use
Patient outcome
Mean time to appropriate LOS was significantly
therapy was 23.4 h shorter shorter (P = .0484)
in the post intervention
Lower hospital costs (P =
group (P = .0054)
.02)
146 pts with BSI Mean time to optimal
Non significant decreased
(73 pre and 73
therapy was 21 h shorter
hospital and ICU LOS
intervention)
(p=0.01)
Net savings $612,000
81 pts with BSI
Time to antibiotic switch (73 Trend toward in 30-day
(45 pre, 36
vs 16 h, p<0.001)
mortality (11% vs. 5%,
intervention)
p=0.19)
22/54 pts with BSI Organism identification an NR
evaluated
average of 24 h faster than
conventional identifications
Medical management could
have been modified for
31.8% of patients an
average 33 h sooner
Verigene use in the management of patients with
Gram negative bloodstream infections
Tedeschi S et al. ICAAC 2015
Matched case-control study (admission ward, isolated
microorganism)
Adult patients with a Gram-neg BSI and ≤1 of the following
underlying conditions:
 CRE rectal carriage
 ICU stay at the time of drawing positive BCs
 Hematological or solid malignancy
 Liver transplant recipients
Real-time notification and ID specialist intervention
Verigene use in the management of patients with
Gram negative bloodstream infections
Tedeschi S et al. ICAAC 2015
Age (median, IQR)
Male sex
Charlson index
Intensive Care Unit
Surgery
Medical ward
Targeted therapy < 24h
Days of empirical therapy
Empiric antibiotic consumption
(DDD)
In-hospital mortality
Cases
N=27 (%)
65, 53-74
17 (63.0)
5, 3-7
17 (63.0)
3 (11.1)
7 (25.9)
5 (18.5)
2, 1-2
132.4
Controls
N=29 (%)
66, 53.5-76.5
17 (58.0)
6, 4-8
15 (51.7)
7 (24.1)
7 (24.1)
1 (3.4)
3, 3-4
286.5
<0.001
<0.001
<0.01
6 (22.2)
5 (17.2)
0.63
p
0.95
0.74
0.16
1
STRUCTURED CLINICAL PATHWAYS
Impact of an antimicrobial stewardship-led intervention for S. aureus bacteraemia: a
quasi-experimental study Nguyen CT et al, J Antimicrob Ther Advance Access published Sep 3, 2015
Bundle endpoint
1 empirical antibiotics within 24 h of positive Gram’s stain
2 intravenous b-lactam therapy for MSSA bacteraemiaa
3 standardized duration of therapy
4 repeated blood cultures at least every 48 h until clearance is documented
5 therapeutic vancomycin level of at least 10 mg/L for uncomplicated
bacteraemia or at least 15 mg/L for complicated bacteraemia
6 TT echocardiogram for complicated bacteraemia
7 eliminate or debride foci of infection
Impact of an antimicrobial stewardship-led intervention for S. aureus bacteraemia: a
quasi-experimental study Nguyen CT et al, J Antimicrob Ther, advance access published Sep 3, 2015
One hundred and seventy patients with SAB were included: 82 patients in the preintervention group and 88 patients in the ASP-intervention group.
Overall bundle adherence to quality performance measures improved from 56.1% (46/82) in
the pre-intervention group to 84.1% (74/88) in the ASP-intervention group (P,0.001)
Clinical outcomes
Pre-ASP group,
n= 82
ASP group
n =88
P
Mortality within 30 days
of first positive blood culture
19.5%
11%
0.200
Readmission within 30 days
with recurrent SAB 9
11.0%
1.1%
0.008
STRUCTURED CLINICAL PATHWAYS
BATMAN-SAB study
Pol. S. Orsola-Malpighi 2016-2017
Bundle
Bundle endpoint
endpoint
1.
Daily warning
for AMS
team
intervention
1 empirical
antibiotics
within
24and
h ofimmediate
positive Gram’s
stain
2.
2
3.
3
4.
4
5.
5
Real time empirical
forMSSA
positive
Gram’s stain
intravenous
b-lactamantibiotics
therapy for
bacteraemiaa
switch to b-lactam
therapy
for MSSA bacteraemia
standardized
duration
of therapy
microbiologically
and clinically
driven
duration
of therapy
 shortage)
repeated
blood cultures
at least
every
48 h until
clearance (goal
is documented
repeated blood
cultureslevel
every
until10
clearance
is uncomplicated
documented
therapeutic
vancomycin
of48
at hleast
mg/L for
6. therapeutic
of atfor
least
15 mg/L for
every BSI
bacteraemiavancomycin
or at leastlevel
15 mg/L
complicated
bacteraemia
7.
Echocardiographic
for every bacteraemia
BSI
6 TT
echocardiogramstudy
for complicated
8.
Immediate
removing
7 eliminate
orCVC
debride
foci of infection
9. Surgical debridement of extra blood foci of infection
10.PET-scan study for the early detection of metastatic foci
11.Neck Ultrasound study for CVC recipients
STRUCTURED CLINICAL PATHWAYS
Community-acquired
pneumonia:
impact
of
empirical antibiotic therapy without respiratory
fluoroquinolones
nor
third
generation
cephalosporins.
Pradelli J, et al Eur J Clin Microb Infect Dis 2015; 34:511-8
PROBLEM-DRIVEN PROTOCOLS and PROGRAMS
Impact of Antimicrobial Stewardship Intervention on Coagulase- Negative
Staphylococcus Blood Cultures in Conjunction with Rapid Diagnostic Testing.
Nagel JL et al, J. Clin. Microbiol. 2014, 52:2849
single-center, quasi-experimental study.
Adult patients with a CoNS blood culture
identified via MALDI-TOF over a 3-month period were compared to a historical control
group with CoNS identified by conventional methods . Patients were divided into 4
categories:
Pts with CoNS BSI before/after implementation of MADLI-TOF plus AST intervention
Pts with CoNS contamination before/after MADLI-TOF plus AST intervention
During the preintervention study period, prescribers were immediately notified of positive
Gram stain results from blood cultures. The AST did not intervene for positive bacterial
cultures in real time but AST reviewed daily reports from Monday through Friday for all
patients receiving restricted antimicrobials and recommended therapy changes on the basis
of institutional guidelines and clinical judgment. Between the patients for whom changes
were recommended may have included patients with blood cultures positive for CoNS. All
stewardship activities, except for the addition of real-time alerts for positive blood
cultures during the intervention period, remained unchanged during the study time frame.
Impact of Antimicrobial Stewardship Intervention on Coagulase- Negative
Staphylococcus Blood Cultures in Conjunction with Rapid Diagnostic Testing.
Nagel JL et al, J. Clin. Microbiol. 2014, 52:2849
OUTCOMES – CoNS bacteremia
Impact of Antimicrobial Stewardship Intervention on Coagulase- Negative
Staphylococcus Blood Cultures in Conjunction with Rapid Diagnostic Testing.
Nagel JL et al, J. Clin. Microbiol. 2014, 52:2849
OUTCOMES – CoNS contamination