Antibiotic policy to prevent resistance development

Antibiotic policy to prevent resistance development

Inga Odenholt

Associate professor

Department of Infectious Diseases, Malmö

Lund University, Sweden

Antibiotic Resistance--THE RESULT OF A GLOBALTHE RESULT OF A GLOBAL

FAILURE FAILURE

Antibiotic Resistance--THE RESULT OF A GLOBALTHE RESULT OF A GLOBAL

FAILURE FAILURE

Antibiotic Antibiotic resistanceresistance New treatment New treatment

optionsoptions

Sulphonamides

Tetracyclines

PenicillinsAminoglycosides

Macrolides

Glycopeptides

Streptogramins

Chloramphenicol

Quinolones

Trimetoprim

Lincosamides

1930´s 1940´s 1950´s 1960´s 1970’s 1980´s 1990´s 2000´s

Oxazolidinones

Introduction of New Antibiotic Classes

Cephalosporins

How to combat the increasing resistance?

How to combat the increasing resistance?

STRAMASTRAMASwedish Strategic programme for The Rational use of Antimicrobial Agents and Surveillance of Resistance

www.strama.org

How it all startedHow it all started

• Increasing incidence of Pc-resistant pneumococci (PRP) in Southern Sweden from ~2% to 8-15% in early 1990s

• Deterring international experiences

• Who is responsible for action?

• Discussion between competent authorities and professional organizations resulted in the formation of a national network for the combat of antibiotic resistance (1994)

STRAMA National GroupSTRAMA National Group Swedish Medical Association

Swedish Institute for Infectious Disease Control

National Board of Health and Welfare

Medical Products Agency

National Corporation of Swedish Pharmacies

Swedish Society for Hospital Hygiene and Infection Control

The Swedish Federation of County Councils

Corporation of County Medical Officers

Swedish Association of Local Authorities

The Swedish Network of Pharmacoepidemiology

National Veterinary Institute

The Swedish Board of Agriculture

STRAMASTRAMA Primary objectivesPrimary objectives

1.To create a cross-sectorial national forum to

- share information

- formulate national strategies

- support an initiate research activities

- collaborate with media

2. To stimulate the formation of regional STRAMA - groups in every county

STRAMASTRAMA

1995-1999 Voluntary basis

2000-2002 Supported by the Swedish Government with 320.000 EUR yearly

2003 Funding increased to 800.000 EUR

Examples of Goals for Examples of Goals for STRAMA (out-patients)STRAMA (out-patients)

1. To follow the usage of antibiotics and thepattern of resistance at the national/regional levels

2. To implement therapeutic guidelines andintervention programmes

3. To give feed-back to prescribers

4. Cooperation with media

In order to reduce inappropriate antibiotic use

Antibiotic consumption on a Antibiotic consumption on a national levelnational level

Swedish Diagnosis-Swedish Diagnosis-Antibiotic Prescribing study Antibiotic Prescribing study

2000 and 20022000 and 2002

• Five counties, 1.3 mil inhabitants– chosen to reflect the country’s antibiotic

utilisation

• 140 primary care centres, 600 GPs• One week in November• Recruitment through local STRAMA

groups• Anonymous

Antibiotics for urinary tract infections in the 2000 and 2002 STRAMA Diagnosis-

antibiotic prescribing study

0%

20%

40%

60%

80%

100% No treatmentReferralOn treatmentOthersQuinolonesTrim+sulfaTrimetoprimCefalosporinesTetracyclinesFosfomycinNitrofurantoinPivmecillinam

Antibiotics in the county of Skåne

År

1999 2000 2001 2002 2003 2004 2005

DD

D / 1

00

0 in

v o d

ag

0

1

2

3

4

5

6

TetracyclinsAmoxicillin Penicillin V Cephalosporins Macrolids

Antibiotic consumption on a regional level

0

200

400

600

800

1000

1200

Antibiotics age group 0-6 years, municipalities in Sweden with the highest and lowest consumption, 2002.

The resistance of E. coli in Sweden

0

5

10

15

20

25

1995 1996 1997 1998 1999 2000 2001 2002 2003 2004

År

% r

esis

ten

s

Ampicillin

Trimethoprim

Quinolones

Cefadroxil

Mecillinam

Nitrofurantoin

Resistance pattern

Consumption of fluoroquinolones in 4 districts Uppsala County The effect of prescriber feed-back and educational outreach (DDD/1000 inhabitants/day)

00,20,40,60,8

11,21,41,61,8

1995

1996

Feed-back to the prescribers

Consumption of fluoroquinolones in 4 districts Uppsala County The effect of prescriber feed-back and educational outreach (DDD/1000 inhabitants/day)

00,20,40,60,8

11,21,41,61,8

199519961997

ConclusionsConclusions

• Knowing the national and regional use of antibiotics and the national and regional resistance pattern Interventions e.g. Therapeutic guidelines, education on a local level

• Continuous efforts have led to changes in prescribing patterns (e. g. reduced use of quinolones in uncomplicated UTI, decreased use of of antibiotics in total; 20% in 8 years)

Treatment guidelines

STRAMA in hospitals The point-prevalence study

STRAMA in hospitals The point-prevalence study

• During 2 weeks in November 2003 and 2004 all patients in appr. 80% of the hospitals in Sweden were registered

• 54 hospitals were included• 434 departments• 13536/11 348 patients• 30.9/31.8 % of the patients were treated

with antibiotics

• The aims of the study were to describe the use of antibiotics in Swedish hospitals– Indications/Diagnoses– Choice of antibiotics. Correct or not?– Dose– Community-acquired or nosocomial infections– Infections related to foreign-body devices

The point-prevalence studyThe point-prevalence study

Diagnoses Central nervous systemOphthalmic infectionsMouth and throatUpper respiratory tractBronchitisPulmonary infectionsCardiovascular systemGastrointestinal upperGastrointestinal lowerGastrointestinal transmissible diseasesLiver/bile duct/pancreas/spleenSkin and soft tissueBone and jointUrinary bladder, cystitisKidney, pyelonephritis, febrile urinary tract infectionGenitaliaSepsisIndication not specifiedIndication unclear

• Of all patients in the hospitals, antibiotic treatment was initiated– In 17% due to community-acquired infections– In 9% due to nosocomial infections– In 6% as prophylaxis

The point-prevalence studyThe point-prevalence study

Percentage of antibiotic treated patients per speciality; PPS 2003 och 2004. 2003: tot 4178 treated of 13 536 patients2004: tot 3622 treated, of 11 348 ipatients

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

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PPS 2004

What antibiotics were used?What antibiotics were used?

Antibiotic used for treatment and prophylaxis

0

100

200

300

400

500

600

700

800

900

1000

Cephalosporins Isoxazolyl-pc Quinolones Ampicillin Penicillins Tetracyclins

No o

f ter

apie

s Treatment

Prophylaxis

PPS 2003 Urology, spectrum of used antimicrobials

0

2

4

6

8

10

12

Num

ber o

f DDD

Community aquired Hospital aquired

PPS 2003 Urology

Treatment diagnoses

0

5

10

15

20

25

30

Cystitis Fever Cl difficilecolitis

Genital Lower GI-tract Upper GI-tract Skin / softtissue

Pneumonia Pyelitis Septicemia Others

Num

ber o

f the

rapi

es

Therapy, 62 Prophylaxis, 37

Too much quinolones and cephalosporins!

Too much quinolones and cephalosporins!

CID, 2004;38 (suppl 4): 341-345

SANT-study

Swedish Antibiotic Nursing home Trial

Aims of the studyAims of the study

•To describe and evaluate the treatment of infections in elderly patients in nursing homes

Results of the registrationResults of the registration

• 58 nursing homes with 2752 patients

• 890 infection registrations

• Mean age of 86 years.

• Appr. 2/3 were women

ResultsResults• 43% of the patients had received antibiotics the past

3 months

• 33% had had the same infection the past 3 month

• Urinary tract infections was the most common diagnosis (60 %). Thereafter skin- and soft tissue infections (15 %), pneumonia (15 %) and others

(10 %).

• In 86 % of all registered infections antibiotics were initiated

Treatment of UTIsTreatment of UTIs

• 89 % of the patients received antibiotics

• >50% of the patients had got a UTI diagnosis the past 3 month and > 50% had received antibiotics the past 3 month

0

5

10

15

20

25

30

35

%

• Earlier studies have shown that appr. 50% of patients in nursing homes have asymptomatic bacteriuria

• A majority of these patients receive antibiotics, which is not recommended

What did we learn?What did we learn?

Hospital-acquired infectionsHospital-acquired infections

Percent hospital-acquired infections in relation to all admitted patients in some Swedish counties

0,0

2,0

4,0

6,0

8,0

10,0

12,0

Jönköpings län, 808 Skåne län, 2116 Sweden, 11348

%

Postoperative infections

Device-related HAI

C. difficile enterocolitis

Other HAI

HAI from other hospitals

All

PPS 2003 Hospital acquired infections, foreign devices, 299 st

0

20

40

60

80

100

120

CNS Hart /vascular

Cystitis Upper GI-tr Skin / softtissue

Liver / bile Bone / joint Pneunonia Pyelonefritis Septicemia Others

Num

ber o

f tre

atm

ents

Asymptomatic patients with or without indwelling catheters should not be treated with

antibiotics

Asymptomatic patients with or without indwelling catheters should not be treated with

antibiotics

Antibiotic prophylaxisAntibiotic prophylaxis

PPS 2003All peri-operative prophylaxis in surgical departments

0

20

40

60

80

100

120

Urology 40 Orthopaedics212

Ear surgery 15 General surgery202

Gynaecology 48 Other surgery 65

Nu

mb

er

of

the

rap

ies

Prophylaxis single dose Prophylaxis 24 hours Prophylaxis >24 hours

PPS 2003 Urology, length of peri-operative prophylaxis, 37 therapies

0

5

10

15

20

25

30

Prophylaxis one dose Prophylaxis one day Prophylaxis >1 day

Num

ber o

f the

rapi

es

PPS 2003 Urology, spectrum of substances in peri-operative prophylaxis in DDD

0

2

4

6

8

10

12

14

16

18

Penicillinbroadspectrum

Cephalosporins Trimetoprim Co-trimoxazole Aminoglycosides Fluoroquinolones Imidazoles

Num

ber

of D

DD

Prophylaxis one dose, 3,5

Prophylax one day, 7

Prophylaxis >1 day, 27,4

Too long prophylaxis!Too long prophylaxis!

• One dose before– Transurethral prostate resection– Transrectal prostate core biopsy– Surgery with bowel substitute– Opening of the urinary tract, i.e. radical– prostatectomy

Conclusions

• Too much quinolones and cephalosporins in the hospitals

• Too much quinolones on not recommended indications (e.g. lower UTIs in women)

• Too much antibiotic treatment for urinary tract infections in asymptomatic patients

• Too much antibiotic treatment for urinary tract infections in patients with catheters

• Too long prophylaxis in surgery

If we stop using one antibiotic, can the resistance trend be

reversed?

If we stop using one antibiotic, can the resistance trend be

reversed?

The resistance of E. coli in Sweden

0

5

10

15

20

25

1995 1996 1997 1998 1999 2000 2001 2002 2003 2004

År

% r

esis

ten

s

Ampicillin

Trimetoprim

Nalidixinsyra

Cefadroxil

Mecillinam

Nitrofurantoin

Consumption of Trimethoprim in Kronoberg 1998-Jan 2005

A difficult balance

The best interests

of the individual

The global need for

effective antibacterial

treatment

Appropriate antibacterial Appropriate antibacterial prescribingprescribing

Butler C et al. JAC 2001; 48:435–440