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)

http://www.cdc.gov/

http://www.who.int/en/

http://www.idsociety.org/

“Antibiotics” - “Societal drugs”

MRSA (1980s)

Evolution of antimicrobial resistance

(抗菌素耐藥性的演變)

VRE (1990s)

ESBL

(1990s)

Carbapenemase:

Class A: KPC

Class D: Oxa

Class B (metallo-b-lactamase): IMP, VIM, NDM

(2000s) 耐甲氧西林 金黃色葡萄球菌

耐萬古黴素腸球菌

廣譜β內酰胺酶腸桿菌科細菌

碳青黴烯酶

Inverse trajectory of declining antibiotic development

Selective pressure for

more MDROs

Use of broad

spectrum antibiotics

Emergence of MDROs

Antimicrobial stewardship & optimization program: patient safety vs public health concern

S. aureus

Penicillin

[1950s] Penicillin-resistant

S. aureus

Evolution of Drug Resistance in S. aureus Methicillin

[1970s] Methicillin-resistant S. aureus (MRSA)

Vancomycin-resistant enterococci (VRE)

Vancomycin

[1990s]

[1997]

Vancomycin intermediate-

resistant S. aureus (VISA)

2002 Vancomycin

resistant S. aureus

Know when to say “no” to vanco

Glycopeptide (vancomycin, teicoplanin) usage in Queen Mary Hospital before and after antibiotic auditing

Department of Medicine except BMT/ICU

Other departments

Immediate concurrent Feedback (ICF)

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

‘Big Gun’ Antibiotic

Appropriate Reason for Preference

Invasive Infection Rx (Known /Suspected

Pathogen) Empirical Rx

Imipenem Atypical Mycobacteria* e.g. M. chelonae

1. Neutropenic fever (Quant’ & Qual’)

2. Fever in Transplant recipient on immuno-supression + +

3. Severe sepsis 4. Deteriorating or fever

persisting ≥72h

ESBL (or AmpC β-lactamase) producing organisms

Meropenem Cefepime

Ceftazidime 1. P.aeruginosa†

2. Melioidosis

Tazocin P.aeruginosa†

Preferably with:- other drugs* ; an aminoglycoside†; a macrolide or doxycyline ‡

0

20

40

60

80

100

120

140

160

CeftazidimeCefepimeTienamMeropenemTazocinSulperazon

Ceftazidime 8.7 7.6

Cefepime 22 51

Tienam 5.9 6.5

Meropenem 4.1 8

Tazocin 17.9 56.1

Sulperazon 7.1 6.2

2002 2003

Use of broad-spectrum antibiotics in ALL Specialties (exclude BMT) in QMH

DD

D p

er 1

000

patie

nt b

ed d

ays

Data from Clinical Pharmacy, QMH

Tazocin

F / 67 AML (diagnosed 4/08)

Chemo (4/08) Fever

Admit: 4 Jul 08

WBC

HGB

PLT

Neu

Lym

Mon

Eso

Baso

4 Jul 08

9.80

10.9

44

6.80

1.30

4.60

0.10

0

Range

4.4 – 10.10

11.7 – 14.8

170 - 380

2.2 – 6.7

1.2 – 3.4

0.2 – 0.7

0.0 – 0.5

0.0 – 0.1

Units

10^9/L

10^12/L

10^9/L

10^9/L

10^9/L

10^9/L

10^9/L

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

Augmentin Tazocin

Antibiotic stewardship program

Augmentin Tazocin

Physician Immediate Concurrent Feedback

Baseline period

Percentage of conformance &

compliance

Usa

ge d

ensi

ty o

f ant

ibio

tics

(per

1,0

00 b

ed-d

ay-

occu

panc

y) &

cru

de m

orta

lity

(per

100

adm

issi

on)

0

10

20

30

40

50

60

70

80

1Q2004

2Q2004

3Q2004

4Q2004

1Q2005

2Q2005

3Q 2005

4Q 2005

1Q2006

2Q2006

3Q2006

4Q2006

1Q2007

2Q2007

3Q2007

4Q2007

0

10

20

30

40

50

60

70

80

90

100

Piperacillin-tazobactam Cefoperazone-sulbactam CeftazidimeCefepime Imipenem-cilastatin MeropenemConformace to guideline Compliance to memo ICF Compliance to phyisician ICFCrude mortality rate (per 100 admission)

Overview of the ASP in a 3-year study period (2005 – 2007)

Eur J Clin Microbiol Infect Dis. 2009 Dec;28(12):1447-56.

Ming Pao 18 Feb 2006

The Antibiotic Stewardship Program Hospital Authority

The Implementation Committee on Antibiotic Stewardship Program

HAHO

Crud

e ep

isode

of E

. col

i bac

tere

mia

(ESB

L +

/ -)

Annual rate / incidence per 10,000 hospital admission

J Antimicrob Chemother. 2012 Mar;67(3):778-80.

ESBL-positive E. coli bacteraemia in Hong Kong, 2000-2010

0

2

4

6

8

10

12

14

16

1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 20080

5

10

15

20

25

30

35

MDR rate Cumulative incidence Incidence density

Int J Antimicrob Agents. 2010 Nov;36(5):469-71.

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

Cumulative incidence as defined by the annual number of MDR-AB isolates per 10,000 hospital admissions

Incidence density as defined by the annual number of MDR-AB isolates per 100,000 patient-days

MD

R rate

Cum

ulat

ive

inci

denc

e &

inci

denc

e de

nsity

Antibiotic stewardship program in Queen Mary Hospital

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®)

Observation:

↑ consumption of meropenem & piperacillin / tazobactam in QMH > HA hospitals

Data from CDARS, HAHO

65.52 (in 2010) ↓ 18% 67.99 (2011)

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)

Data from CDARS, HAHO

59.73 (in 2010) ↓ 18%

60.9 (2011)

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)

Antibiotic Stewardship Program (AT&T in 2010-2011)

Drugs with similar pharmacodynamic / kinetic profile / susceptibility profile

Daily cost: $ 222.6

Daily cost: $ 163.5

Daily cost: $ 318

Daily cost: $ 222

Antibiotic Stewardship Program vs Cost-Effective Usage

Drugs with similar pharmacodynamic / kinetic profile / susceptibility profile

Daily cost: $ 66.6

Daily cost: $ 163.5

Daily cost: $ 90

Daily cost: $ 189

???????

???????

Consumption of Big Gun Antibiotics in All Specialties at 7 Hospitals of HA (2012) U

sage

den

sity

(div

ided

dai

ly d

ose

per 1

000

bed-

day-

occu

panc

y)

[Cefepime, Ceftazidime, Linezolid (oral & intravenous), Meropenem, Piperacillin/tazobactam, Cefoperazone/sulbactam, Impenem/cilastatin, Vancomycin]

A B C D E F QMH HA overall Data from CDARS

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)

Usa

ge d

ensit

y (d

ivid

ed d

aily

dos

e pe

r 100

0 be

d-da

y-oc

cupa

ncy)

[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]

Data from CDARS

A B C D E F HA consumption QMH

Inappropriate Appropriate use of “Big Gun” antibiotics

87% (1208/1383) 46%

(1383/3001)

On “Big Gun” antibiotics N=3001

Microbiology & Infectious Disease Consultation between 1 Jan and 31 Jul 2014 (Queen Mary Hospital)

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 ~99% Bioavailability ~90% Bioavailability ~70-80%

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…

Ongoing ICF Unjustified Antibiotic

Combination

Rectified ?

Not Rectified ?

Trust and collaboration