Stewardship in the war of resistance

Suresh

Goals of AMS

“4 D”s of optimal antimicrobial therapy

Right Drug,

Right Dose,

Right De-escalation to pathogen directed therapy

Right Duration of therapy

Cost savings

Prevent antimicrobial overuse, misuse, and abuse

Minimize the development of resistance

Why is it so important?

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Are Hospitals Dangerous again???

Hospitals were originally set up for the sick and dying among the poor

The wealthy had physicians go to their homes to provide care

Hospitals were widely and correctly perceived as dangerous places

Pittet et al http://www.hopisafe.ch

Acinetobacter species resistance by wards (%)

ICU MEDICAL

0

10

20

30

40

50

60

70

80

90

2007 2008 2009 2010 2011 20120

10

20

30

40

50

60

70

80

2007 2008 2009 2010 2011 2012

SURGERY

0

10

20

30

40

50

60

70

2007 2008 2009 2010 2011 2012

Institute for Medical Research

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CID 2015;60(9):1295–303

Suresh

CRESpecimen IMI MERO ERTA DORI POLY B COLISTIN TIGECYC

Swab >32 R >32 R >32 R >32 R 0.5 S 0.125 S 1.5 S

Tissue >32 R >32 R >32 R >32 R 1.0 S 0.38 S 4.0 I

Blood >32 R >32 R >32 R >32 R 0.5 S 0.38 S 1.0 S

Blood >32 R >32 R >32 R >32 R 0.5 S 0.38 S 1.0 S

Urine >32 R >32 R >32 R >32 R 0.5 S 0.38 S 12.0 R

Pus >32 R >32 R >32 R >32 R 0.5 S 0.38 S 2.0 S

Unknown >32 R >32 R >32 R >32 R 1.0 S 0.38 S 0.75 S

Blood >32 R >32 R >32 R >32 R 1.0 S 0.25 S 1.5 S

Urine >32 R >32 R >32 R >32 R 0.38 S 0.25 S 8.0 R

Tracheal aspirate >32 R >32 R >32 R >32 R 0.38 S 0.125 S 1.5 S

Blood >32 R >32 R >32 R >32 R 1.0 S 0.38 S 0.75 S

Swab >32 R >32 R >32 R >32 R 0.5 S 0.25 S 2.0 S

Urine >32 R >32 R >32 R >32 R 0.5 S 0.38 S 2.0 S

unknown >32 R >32 R >32 R >32 R 0.5 S 0.25 S 2.0 S

Wound >32 R >32 R >32 R >32 R 0.38 S 0.125 S 1.5 S

Peritoneal fluid >32 R >32 R >32 R >32 R 0.38 S 0.25 S 1.0 S

Urine >32 R >32 R >32 R >32 R 0.38 S 0.125 S 1.5 S

Peritoneal fluid >32 R >32 R >32 R >32 R 0.5 S 0.19 S 1.5 S

Swab >32 R >32 R >32 R >32 R 0.38 S 0.125 S 1.0 S

Urine >32 R >32 R >32 R >32 R 0.5 S 0.125 S 1.0 S

All NDM; MIC using Etest Dr Norazah, IMR

Suresh

MIC 0.5 µg/ml MIC 2 µg/ml

A Norazah et al. MJM, 2009 64; 166-67

Electron microscopy of cell wall of the MRSA

with MIC 2 µg/ml

MRSA is getting too thick skinned

Suresh

60 yr old male

Liver cirrhosis with decompensated liver disease

Blood culture – NDM -1 producing Klebsiella

Liver abscess

Low platelets, INR prolonged, Ascites

Treated with colistin and Meropenam

Blood culture persistently positive

Suresh

‚Antimicrobial resistance is not a new problem but one that is becoming more dangerous; urgent and consolidated efforts are needed to avoid regressing to the pre-antibiotic era.‛

WHO 2011

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What causes resistance?

Suresh 17

Resistant StrainsRare

Resistant Strains Dominant

Antimicrobial Exposure

Selection for antimicrobial-resistant Strains

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0

10

20

30

40

50

0 1 2 3 4 5

Fluoroquinolone consumption

(Outpatient consumption of fluoroquinolones,

DDD per 1000 inhabitant-days)

Flu

oro

qu

ino

lon

e r

esis

tan

ce

(Pro

port

ion o

f fluoro

quin

olo

ne-r

esis

tant

isola

tes

am

ong E

. coli

from

invasiv

e infe

ctions)

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Increased ab use and resistance

Ciprofloxacin Imipenam

Zhanel GG et l., Can J Infect Dis. 1998; 9(6): 382–386.

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Antibiotic use vs Resistance

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AHR, 4.0; P < .001 AHR, 3.5; P < .001

AHR, 2.3; P=.008 AHR, 5.7; P < .001

Harbarth S et al., CID 2001; 33:1462–8

‘The longer a patient is exposed to an

antimicrobial, the greater the likelihood that colonization

with resistant organisms occur’

Hyatt JM, Schentag JJ: Infect Control Hosp Epidemiol 2000

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Improving antibiotic use reduces resistance

Cipro Standard

Antibiotic

duration

3 days 10 days

LOS ICU 9 days 15 days

Antibiotic

resistance/

superinfection

14% 38%

Study terminated early because attending

physicians began to treat standard care group

with 3 days of therapy

Singh N et al. Am J Respir Crit Care Med. 2000;162:505-11.

Suresh

Short-course versus prolonged-course antibiotic therapy for HAP in critically ill adults.

3 studies; 508 patients;

7-8 days vs 10-15 days

Increased 28 day antibioitc free days

OR 4.02; 95% CI 2.26 to 5.78.

Reduced recurrence of VAP due to multi-resistant organisms

OR 0.44; 95% CI 0.21 to 0.95

In 2 studies (N=176) – greater recurrence for non fermenting gram-negatives; no increased mortality

OR 2.18; 95% CI 1.14 to 4.16

Cochrane Database Syst Rev. 2011 Oct 5;(10)

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Penicillin resistance in pneumococcus isolates taken from children, and β lactam use in

the six months before swab collection.

Nasrin D et al. BMJ 2002;324:28

Prospective cohort study over two years of 461

children < 4 years living in Canberra, Australia

The odds ratio was 4.67 (1.29 to 17.09, P=0.02) in children who had received β lactam in the two months before their nasal

swab

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Observational study; follow up at 2 and 12 weeks

General practices in Oxfordshire.

119 children with RTI, 71 received beta lactam antibiotic

Prescribing amoxicillin, more than triples the mean minimum inhibitory concentration for ampicillin (9.2 µg/ml v 2.7 µg/ml, P=0.005)

Chung A et al. BMJ 2007;335:429

Chung A et al. BMJ 2007;335:429

How many % of URTI encounters were prescribed antibiotic(s)?

• 299 / 970= 30.8%

Public

• 3363/ 5512 = 61.0%

Private

• 3662 / 6482 = 56.5%

Overall

National Medical Care Survey Healthcare Statistics Unit

Clinical Research Centre

Unpublished data from the

2010 National Medical Care Survey

How many % of AGE encounters were prescribed antibiotic(s)?

• 8 / 141= 5.7%

Public

• 263/ 1206= 21.8%

Private

• 271 / 1347= 20.1%

Overall

National Medical Care Survey Healthcare Statistics Unit

Clinical Research Centre

Unpublished data from the

2010 National Medical Care Survey

Suresh

‚Clinicians are used to the antibiotic fix. This means that even when a patient has no infection but is unwell, antibiotics are used to treat them. This is reassuring to the doctor…‛

A Shetty 2010

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Antibiotic resistance: a survey of physician perceptions

Surveyed 490 internal medicine physicians at 4 Chicago-area hospitals

Antibiotic resistance was perceived as a very important national problem by 87%

Only 55% rated the problem as very important at their own hospitals

97% believed that widespread and inappropriate antibiotic use were important causes of resistance

Only 60% favored restricting use of broad-spectrum antibiotics

Wester CW et al., Arch Intern Med. 2002 Oct 28;162(19):2210-6

AMS – How to do it right?

Suresh

‚Victorious warriors win first and then go to war, while defeated warriors go to war first and then seek to win‛

― Sun Tzu, The Art of War

Suresh

‚Although infection control departments have been given primary ‘responsibility’ for controlling and preventing infections, they can only put processes and structures in place—they cannot, on their own, change practice.‛

Suresh

It is likely to be impossible to stem the increasing tide of antibiotic resistance without system-wide, multidisciplinary collaboration and without strong administrative support and commitment,‛

Suresh Valiquette et al., CID 2007; 45:S112–21

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Department level usage

DEPARTMENTCEFTRIAXONE

JAN-MAR APR-JUNE JULY-SEPT OCT-DEC

MEDICAL 130.65

ID 110.46

SURGICAL 5.33

ORTHO 12.78

OBS&GY 7.17

NEURO 95.39

OPHTAL 6.86

ANAES 449.90

CCU 34.40

PLASTICS/BURNS 0.91

DDD/1000 Pt days HSgB 78.12

Average 85.39

SD 137.17

Mean (+SD) 222.56

Pharmacy Dept, Hosp Sg Buloh

Suresh

AMS Techniques - 1

Formulary restrictions – Preprescription authorisation

Usage of Inj. Vancomycin (500 mg/vl)

66 2350 15222

22362498

8221

1411

84

2300

2814

6738

65 106

12861633

0370

10909671517

40254 422

01450

1000

2000

3000

4000

5000

6000

7000

8000

9000

MAIN

BLOCK

NEURO UN MAT RT ORTHO PAEDS IPR DERM

VA

LS

E

2002

2003

2004

Data courtesy of Pharmacy Dept, HKL

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AMS techniques - 2

Post prescription – Review and feedback

Dr. Benedict Sim & Hospital AMS team

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Who is right?

n (354) %

Mutual agreement (both specialists agreed) with prescribing physician 172 48.6

Agreement by at least one specialist with prescribing physician 276 78.0

Mutual disagreement (both specialists disagreed) 78 22.0

Disagreement between specialists 104 29.4

Casaroto et al. BMC Infectious Diseases (2015) 15:248

Suresh

AMS techniques - 2

Post prescription -72 hour review

Courtesy of Pharmacy Dept, HSgB

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AMS techniques - 2

Post prescription -72 hour review

Courtesy of Pharmacy Dept, HSgB

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AMS techniques - 3

Clinical guidelines, treatment algorithms, order sets

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Point Prevalence study

H. Akhloufi et al., Eur J Clin Microbiol Infect Dis (2015) 34:1631–1637

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H. Akhloufi et al., Eur J Clin Microbiol Infect Dis (2015) 34:1631–1637

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AMS techniques - 4

Education

Essential element

Alone only marginally effective

Not demonstrated to have sustained impact

CID 2007;44:159-77

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AMS techniques - 5

IV – PO Switch

Highly bioavailable antibiotics

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Pharmacy driven stewardship

Dosing recommendations

Oral administration for selected highly bioavailable antibiotics

Cessation of perioperative prophylaxis within 24 hrs for clean and clean-contaminated surgery

Streamlining – identifying patients on 2 or more antibiotics

Streamlining - Identifying patients with duplicate cover

Sharing usage data with units with high use

Suresh

Suresh

“I think we can reduce the

use of antibiotics

dramatically. I believe we

can reduce the number of

resistant organisms

dramatically. Yes, it seems

overwhelming at times. But if

each of us does a little, all

of us can do a lot."

S. Michael Marcy, MDKaiser Foundation Hospital Panorama City