Sharing of AMR control in local public hospital hurdles and ways to overcome
Vincent CC Cheng
MBBS (HK), MD (HK), MRCP (UK), PDipID (HK), FRCPath,
FHKCPath, FHKAM (Pathology)
Consultant & Infection Control Officer, Queen Mary Hospital
Hon Associate Professor, Department of Microbiology,
The University of Hong Kong
Worldwide Concern on Improving the
containment of Antibiotic Resistance
(2001)
“Antibiotics” - “Societal drugs”
http://www.cdc.gov/
http://www.who.int/en/
http://www.idsociety.org/
Evolution of antimicrobial resistance
(抗菌素耐藥性的演變)
ESBL
VRE
(1990s)
MRSA
(1980s)
(1990s)
廣譜β內酰
胺酶腸桿
耐萬古黴素 菌科細菌
腸球菌
耐甲氧西林
金黃色葡萄球菌
Carbapenemase: 碳青黴烯酶
Class A: KPC
Class D: Oxa
Class B (metallo-b-lactamase):
IMP, VIM, NDM
(2000s)
Inverse trajectory of declining antibiotic development
Antimicrobial stewardship & optimization program:
patient safety vs public health concern
Emergence
of MDROs
Use of
broad
spectrum
antibiotics
Selective
pressure for
more MDROs
Know when to say “no” to vanco
Evolution of Drug Resistance in S. aureus
Methicillin
Penicillin
MethicillinPenicillin-resistant
S. aureus
resistant
[1970s]
[1950s]
S. aureus
S. aureus (MRSA)
[1997]
Vancomycin
[1990s]
Vancomycin
2002
resistant
S. aureus
Vancomycin
intermediateresistant
S. aureus
(VISA)
Vancomycin-resistant
enterococci (VRE)
Glycopeptide (vancomycin, teicoplanin) usage in
Queen Mary Hospital before and after antibiotic auditing
Immediate concurrent
Feedback (ICF)
Department of Medicine
except BMT/ICU
Other departments
Br J Clin Pharmacol. 2001 Oct;52(4):427-32.
Overall prevalence of ESBL for K.pneumoniae and
E. coli among all isolates in Queen Mary Hospital
Data from Dept of Microbiology, QMH
Big-Gun antibiotic audit (2002)
‘Big Gun’ Antibiotics in General Wards
Appropriate Reason for Preference
‘Big Gun’
Antibiotic
Imipenem
Invasive Infection Rx
(Known /Suspected
Pathogen)
Atypical Mycobacteria*
e.g. M. chelonae
Cefepime
ESBL (or AmpC βlactamase) producing
organisms
Ceftazidime
1.
2.
Tazocin
P.aeruginosa†
Meropenem
P.aeruginosa†
Melioidosis
Empirical Rx
1.
2.
3.
4.
Neutropenic fever
(Quant’ & Qual’)
Fever in Transplant
recipient on immunosupression + +
Severe sepsis
Deteriorating or fever
persisting ≥72h
Preferably with:- other drugs* ; an aminoglycoside†; a macrolide or doxycyline ‡
DDD per 1000 patient bed days
Use of broad-spectrum antibiotics in ALL Specialties
160
(exclude BMT) in QMH
140
120
Ceftazidime
100
Cefepime
Tienam
Meropenem
80
Tazocin
Sulperazon
60
40
20
0
2002
2003
Ceftazidime
8.7
7.6
Cefepime
22
51
Tienam
5.9
6.5
Meropenem
4.1
8
17.9
56.1
7.1
6.2
Tazocin
Sulperazon
Data from Clinical Pharmacy, QMH
F / 67
AML (diagnosed 4/08)
Chemo (4/08)
Fever
Admit: 4 Jul 08
Tazocin
4 Jul 08
Range
Units
WBC
9.80
4.4 – 10.10 10^9/L
HGB
10.9
11.7 – 14.8 10^12/L
PLT
44
170 - 380
10^9/L
Neu
6.80
2.2 – 6.7
10^9/L
Lym
1.30
1.2 – 3.4
10^9/L
Mon
4.60
0.2 – 0.7
10^9/L
Eso
0.10
0.0 – 0.5
10^9/L
Baso
0
0.0 – 0.1
10^9/L
M/77
Past health :
IHD
PTB
Bronchiectasis
BPH
fever for 2 days
chills and rigor
dysuria, hematuria
nausea and vomiting
T 38 C, BP 130/80, P 79/min
Chest clear
Abd mild loin tenderness on
L side
WCC 15.4
Cr
123
Septic workup done
Antibiotic stewardship program
Augmentin
Tazocin
Physician Immediate Concurrent Feedback
Augmentin
Tazocin
80
100
Baseline period
90
70
80
60
70
50
60
50
40
40
30
30
20
20
10
10
0
0
1Q
2004
2Q
2004
3Q
2004
4Q
2004
1Q
2005
2Q
2005
Piperacillin-tazobactam
Cefepime
Conformace to guideline
Crude mortality rate (per 100 admission)
3Q
2005
4Q
2005
1Q
2006
Cefoperazone-sulbactam
Imipenem-cilastatin
Compliance to memo ICF
2Q
2006
3Q
2006
4Q
2006
1Q
2007
2Q
2007
3Q
2007
4Q
2007
Ceftazidime
Meropenem
Compliance to phyisician ICF
Eur J Clin Microbiol Infect Dis. 2009 Dec;28(12):1447-56.
Percentage of conformance & compliance
Usage density of antibiotics (per 1,000 bed-dayoccupancy) & crude mortality (per 100 admission)
Overview of the ASP in a 3-year study period (2005 – 2007)
Ming Pao 18 Feb 2006
The Antibiotic Stewardship Program
Hospital Authority
The Implementation Committee on
Antibiotic Stewardship Program
HAHO
Annual rate / incidence per 10,000 hospital admission
Crude episode of E. coli bacteremia (ESBL + / -)
ESBL-positive E. coli bacteraemia in Hong Kong, 2000-2010
J Antimicrob Chemother. 2012 Mar;67(3):778-80.
Changes in the rate, cumulative incidence and incidence density of MDR-AB
according to definition: resistance to carbapenems class (imipenem, meropenem)
MDR rate as defined by the annual MDR-AB rate
among all A. baumannii isolates
35
14
12
10
30
Cumulative incidence as defined by the annual number
of MDR-AB isolates per 10,000 hospital admissions
25
Incidence density as defined by the annual number of
MDR-AB isolates per 100,000 patient-days
20
8
15
MDR rate
Cumulative incidence & incidence density
16
6
10
4
2
5
0
0
1997
1998
1999
2000
MDR rate
2001
2002
2003
Cumulative incidence
2004
2005
2006
2007
2008
Incidence density
Int J Antimicrob Agents. 2010 Nov;36(5):469-71.
Antibiotic stewardship program in Queen Mary Hospital
Observation:
↑ consumption of meropenem & piperacillin / tazobactam in QMH > HA hospitals
Recommendation:
Empirical regimen of “A T & I” or “A T & T”
Stable patients: Amoxicillin / clavulanate (Augmentin®) as first line therapy
Not responding to first line therapy: Ticarcillin / clavulanate (Timentin®)
Critically ill patients: Imipenem / cilastatin (Tienam®)
Big Gun antibiotics consumption (6 Big Gun & Van / Lin) in QMH
(MED / SUR / ORT / ONC / ICU & HDU) (DDD per acute 1000 BDO)
80.32 (in 2009)
65.52 (in 2010) ↓ 18%
67.99 (2011)
Data from CDARS, HAHO
Big Gun antibiotics consumption (6 Big Gun & Van / Lin) in HKWC
(MED / SUR / ORT / ONC / ICU & HDU) (DDD per 1000 BDO)
73.09 (in 2009)
59.73 (in 2010) ↓ 18%
60.9 (2011)
Data from CDARS, HAHO
Antibiotic Stewardship Program (AT&T in 2010-2011)
Daily cost: $ 222.6
Daily cost: $ 163.5
Drugs with similar pharmacodynamic / kinetic profile / susceptibility profile
Daily cost: $ 318
Daily cost: $ 222
Antibiotic Stewardship Program vs Cost-Effective Usage
Daily cost: $ 66.6
???????
Daily cost: $ 163.5
Drugs with similar pharmacodynamic / kinetic profile / susceptibility profile
Daily cost: $ 90
???????
Daily cost: $ 189
Consumption of Big Gun Antibiotics in All Specialties at 7 Hospitals of HA (2012)
Usage density (divided daily dose per 1000 bed-day-occupancy)
[Cefepime, Ceftazidime, Linezolid (oral & intravenous), Meropenem, Piperacillin/tazobactam,
Cefoperazone/sulbactam, Impenem/cilastatin, Vancomycin]
A
B
C
D
QMH
E
F
HA overall
Data from CDARS
Usage density (divided daily dose per 1000 bed-day-occupancy)
Consumption of ALL Broad Spectrum Antibiotics with potential for selecting MDROs in All
Key Specialties (ICU & HDU / MED / ONC / ORT / SUR) at 7 Hospitals of HA (2008 - 2013)
[Cefepime, Ceftazidime, Cefoperazone/sulbactam, Piperacillin/tazobactam, Meropenem,
Impenem/cilastatin, Vancomycin, Linezolid (iv/po), Cefotaxime, Ceftriaxone, Ciprofloxacin (iv/po),
Levofloxacin (iv/po), Moxifloxacin (iv/po), Ofloxacin (iv/po), Piperacillin, Ticarcillin/clavulanate]
A
B
C
D
QMH
E
F
HA consumption
Data from CDARS
Microbiology & Infectious Disease Consultation
between 1 Jan and 31 Jul 2014 (Queen Mary Hospital)
Inappropriate
Appropriate use of “Big Gun”
antibiotics
87% (1208/1383)
On “Big Gun”
antibiotics
46%
(1383/3001)
N=3001
Integration of ASP into daily clinical consultation
IMPACT Guidelines (Third Edition)
Local Key References for
• Antibiotic resistance
• Antibiotic stewardship program
• Selected antimicrobial use
• Empirical Rx of common infections
• Known-pathogen therapy
• Surgical prophylaxis
• Cost & dosage of antimicrobials
Click here to view full guidelines
http://ha.home/ho/ps/impact.pdf
IV to oral switch
Fluoroquinolones
Ciprofloxacin
Levofloxacin
Moxifloxacin
Bioavailability ~70-80%
Bioavailability ~99%
Bioavailability ~90%
IV to PO regimen
200mg IV q12h  250mg PO q12h
400mg IV q12h  500mg PO q12h
400mg IV q8h  750mg PO q12h
IV to PO regimen
The Oral and IV route
of administration is
interchangeable
IV to PO regimen
400mg IV q24h  400mg PO q24h
After IV to oral switch…
Rectified ?
Ongoing ICF
Unjustified
Antibiotic
Combination
Not Rectified ?
Trust and collaboration