Predicting multi-drug resistance in Pseudomonas aeruginosa

in the UK and Ireland

Rosy Reynolds, Russell Hope, Kirsty Maheron behalf of

The BSAC Working Party on Resistance Surveillance

O348 22nd ECCMID, London, 31 Mar - 3 Apr 2012 rosy.reynolds@nbt.nhs.uk

BSAC Resistance Surveillance Project

• UK & Ireland

• 40 laboratories(25 up to 2009)

• Bacteraemia (2003 - 2010)

• Hospital-onset lower respiratory infection (2008/09 - 2010/11)

• Target: 280 P.aeruginosa isolates /year in each programme (was 250)

• Excluding duplicate within 14 days and (in RTI) cystic fibrosis

• Central testing - HPA, London; Quotient Bioresearch, Fordham.

• BSAC agar dilution MICs & breakpoints.

www.bsacsurv.org

2012

Central Laboratories

HPA Colindale• Russell Hope• David Livermore• and many others

Quotient Bioresearch• Kirsty Maher• Ian Morrissey• and many others

Collecting Laboratories

Sponsors 2003-2010

• Astellas• AstraZeneca• Cerexa / Forest• Cubist• J&J / Janssen• Merck / MSD • Novartis (Chiron)• Pfizer (Wyeth) • Theravance

Associate sponsor• Basilea

ACKNOWLEDGEMENTS

BSAC Resistance Surveillance Project 2003-11

Single & multiple non-susceptibility

bacteraemia

3.71.6

0.20

5

10

15

20

% n

on

-su

sce

ptib

le

CA

Z >

8

CIP

>0

.5

GE

N >

4

IPM

>4

TZ

P >

16

MD

R3

MD

R4

MD

R5

4/16862 centres4 years

Single & multiple non-susceptibility

bacteraemia respiratory

3.7

1.6

0.2

7.0

2.30.7

0

5

10

15

20

% n

on

-su

sce

ptib

le

CA

Z

CIP

GE

N

IPM

TZ

P

MD

R3

MD

R4

MD

R5

5/6683 centres2 years

1

2

3

4

5P

erc

en

t

0 20 40 60 80 100Age, years

Bacteraemia

Age Distribution of Patients

1686 isolates

1

2

3

4

5P

erc

en

t

0 20 40 60 80 100Age, years

Respiratory Infection

Age Distribution of Patients

668 isolates

0

.005

.01

.015

.02

.025

De

nsi

ty

0 20 40 60 80 100Age, years

Bacteraemia Respiratory

Smoothed distribution

Age Distribution of Patients

1

2

3

4

5

Pe

rce

nt

0 20 40 60 80 100Age, years

Bacteraemia

1

2

3

4

5

Pe

rce

nt

0 20 40 60 80 100Age, years

Respiratory Infection

Other patient characteristics

Detail of focus in bacteraemia

16 84

39 61

Bacteraemia

RespiratoryICU/HDU%

Respiratory

Bacteraemia

60 40

59 41

Bacteraemia

Respiratorymale%

Respiratory

Bacteraemia

20 80

100

Bacteraemia

Respiratoryrespiratory focus %

Respiratory

Bacteraemia

RTI line/SSSI/GI UTI BacteraemiaKnown focus

RT

I

line

SS

SI

GI t

ract

UT

I

oth

er

mis

sin

g

BacteraemiaOriginal data

62 38

100

Bacteraemia

Respiratoryhospital onset %

Respiratory

Bacteraemia

Predictors considered

Predictors alone

P

notes

Age <0.001 Fractional polynomial

Sex NS Male vs female

Hospital onset 0.009 >48 hours vs other

Speciality <0.001 ICU vs non-ICU

Focus of infection

0.001

0.746

UTI or

line/SSI/GI vs RTI

Sample site 0.001 Blood vs Respiratory

Logistic regression models with robust errors for centre clustering;Infants under 1 year excluded.

Predictors considered

Predictors alone

P

together

P

notes

Age <0.001 <0.001 Fractional polynomial

Sex NS - Male vs female

Hospital onset 0.009 - >48 hours vs other

Speciality <0.001 0.001 ICU vs non-ICU

Focus of infection

0.001

0.746

0.020

0.850

UTI or

line/SSI/GI vs RTI

Sample site 0.001 - Blood vs Respiratory

Logistic regression models with robust errors for centre clustering;Infants under 1 year excluded.

Predictors considered

Predictorsalone

P

together

P

notes

Age <0.001 <0.001 Fractional polynomial

Sex NS - Male vs female

Hospital onset 0.009 - >48 hours vs other

Speciality <0.001 0.001 ICU vs non-ICU

Focus of infection

0.001

0.746

0.020

0.850

UTI or

line/SSI/GI vs RTI

Sample site 0.001 - Blood vs Respiratory

Logistic regression models with robust errors for centre clustering;Infants under 1 year excluded.

Age

05

1015

%m

ultir

esi

sta

nt

<1

1-49

50-6

3

64-7

1

72-7

9

80

Respiratory0

510

15%

mul

tire

sist

ant

<1

1-49

50-6

3

64-7

1

72-7

9

80

Bacteraemia

Patient with line-derived infection, not in ICU

Age

0

5

10

15

% M

ulti

resi

sta

nt

20 40 60 80 100Age, years

% Multiresistant by age - model

Estimate & 95% CI

Model shows patient aged 65 with line-derived infection

Intensive Care

KEY other speciality intensive care / high dependency

Bacteraemia Respiratory

0

5

10

15

% M

ultir

esis

tant

non-ICU ICU/HDU non-ICU ICU/HDU

ModelObserved - unadjusted

0

5

10

15

% M

ultir

esis

tant

other speciality ICU/HDU

OR2.45

Focus of infectionModelObserved - unadjusted

KEY RTI line/SSSI/GI UTI unknown/minor

Model shows patient aged 65, not in ICU

0

1

2

3

4

5

6

7

8

9

10

% M

ultir

esis

tant

RTI Line/SSSI/GI UTI

OR0.95

OR0.32Bacteraemia Respiratory

0

1

2

3

4

5

6

7

8

9

10

% M

ultir

esis

tant

RTI line/SSSI/GI UTI unknown/minor RTI

Multiple resistancein Pseudomonas aeruginosafrom bloodstream and hospital-onset respiratory infectionin the UK and Ireland:

• remains fairly uncommon (3-7%)

but is more likely in

• in younger patients (except infants)

• patients in intensive care

and less likely in

• infections from the genitourinary tract

0

20

40

60

80

100%

no

n-s

usc

ep

tible

CA

Z

CIP

GE

N

IPM

TZ

P

Bacteraemia Respiratory

MDR P. aeruginosa

62 bacteraemia, 49 respiratory.

Multiply-resistant P. aeruginosa