P1252428409mGwfc

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Improving antibiotic policies and infection
control to decrease antimicrobial resistance in
hospital settings S. Harbarth (Geneva
University Hospitals, CH)
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OUTLINE

• Antibiotic control policies
• Quality of evidence
• Strategic priorities
• The example of perioperative prophylaxis
• Infection control interventions
• Priorities for low-income countries
• Agenda research and policy

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Ongoing flood of reports by expert policy groups
and surveillance networks
Public
WHO/Antimicrobial Resistance Monitoring WHO/GASP
WHO-IUATLD/Global Project on Anti-TB Drug Res.
Surv.
Private
Public
Public
Private
EU/Antibiotic resistance in bacteria from
animals
SENTRY Paul Ehrlich Soc. Alexander
Project CEM/NET Artemis MYSTIC
EU/Enterococci in the food chain EU/Risk
assessment of potential transfer...
FEFANA / E. faecium from animals
s
EU/EARSS EU/ESAR CDC/INSPEAR EU/ENTER-Net EU/EuroT
B
s
Legend
s
CDC/INSPEAR EU/HARMONY ESGARS
TSN
Surveillance
SARISA
EU/ENARE
Research
Courtesy Monnet DL.
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Antibiotic control and reduction of AMRWhat is
the evidence?
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Systematic Review of Interventions to Improve
Antibiotic Prescribing in Hospitals
306 Papers Since 1980
Ramsay et al, J Antimicrob Chemother, 2003 52
764-71 Courtesy Peter Davey, Dundee (UK)
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Belliveau et al Am J Health Syst Pharm. 53
1570-1575, 1996.
Change (in Vancomycin doses) P
t test -31 per 1000 pd lt0.001
Slope 6 per month lt0.001
Ramsay et al, J Antimicrob Chemother 2003 52
764-71
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Change DDD/100 bdm P
t test 0.54 0.2
Slope -0.266 lt0.001
Ansari F et al, J Antimicrob Chemother 2003 52
842-848
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High-quality studies with drug bug data
Effect Drug Bug Drug Only No effect
MDR Gram-negative 5 0 0
C difficile 2 0 0
Vanco-Renterococci 1 1 1
MDR Staph aureus 0 1 0
Courtesy Peter Davey, Dundee (UK)
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Strategies to contain the emergence of
antimicrobial resistance systematic review of
effectiveness

1. Most studies from the developed world only 2/43
   from developing countries (strongly biased)
2. Absence of good evidence which interventions are
   cost-effective in reducing AMR
3. Areas of further investigation- Economic
   evaluation of interventions- Development of
   macro-level strategies- Research in developing
   countries

Wilton et al. J Health Serv Res Pol 2002 7
111-17
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Strategic priorities to optimize antibiotic use
Goldmann et al. JAMA 1996 275 234-240
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Improve antibiotic use

• Monitor and provide feedback on occurrence of AMR

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Patient X, transferred from North Africa
(1)x1 (2)x1 (3)x1
(4)x1 ANTIBIOGRAMMES
Acinetobacter E.coli MRSA
baumanii
-----------------------------------------
------------------------ Penicilline G
RESIST
Flucloxacilline
RESIST Amoxicilline RESIST
RESIST RESIST Co-amoxiclav
INTERM RESIST RESIST
Piperacilline RESIST RESIST
RESIST Piperac.tazob RESIST
RESIST INTERM
------------------------------------------------
----------------- Cefalotine RESIST
RESIST RESIST RESIST Cefoxitine
RESIST RESIST S RESIST
Cefuroxime RESIST RESIST
RESIST RESIST Ceftazidime INTERM
RESIST RESIST RESIST Ceftriaxone
RESIST RESIST RESIST
RESIST Cefepime INTERM RESIST
RESIST RESIST Imipenem S
INTERM S RESIST
Aztreonam
RESIST --------------------------------
-------------------------------- Amikacine
RESIST S RESIST INTERM
Gentamicine RESIST RESIST S
S Tobramycine
RESIST S
------------------------------------------------
---------------- Norfloxacine RESIST
RESIST S RESIST Ciprofloxacine
RESIST S S
------------------------------------------------
---------------- Clindamycine
S Erythromycine
RESIST
------------------------------------------------
---------------- Acide fusidique
RESIST Co-trimoxazole
RESIST RESIST S S
Fosfomycine
S Rifampicine
S Vancomycine
S
Teicoplanine
S --------------------------------
--------------------------------
Is this patient in your ICU? Can you treat his
infection? Can you prevent cross-infection?
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The important role of sentinel hospitals

• Centralization of available laboratory resources
  in a few selected centers
• Monitoring and reporting of AB susceptibility
  data (WHOnet)
• Adapt empiric treatment regimens

Archibald LK Reller LB. Clinical Microbiology
in Developing Countries. Emerg Infect Dis 2001
7 302-305
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Improve antibiotic use

• Monitor and provide feedback on occurrence and
  impact of AMR
• Optimize choice and duration of empiric
  antimicrobial therapy

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Survival Among 401 Patients with Nosocomial
Pneumonia Assigned to Short (8 d) or Long (15 d)
Antimicrobial Treatment
1.0
8-day
0.8
15-day
0.6
Probability of Survival
0.4
0.2
0.0
0
10
20
30
40
50
60
Days after Bronchoscopy
Courtesy J. Chastre, Paris
JAMA 2003 290 2588-98
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Emergence of multiresistant pathogens for
patients who had pulmonary infection recurrence
80
P 0.04
60
62.3
40
42.1
20
0
8-day (n197)
15-day (n204)
Courtesy J. Chastre, Paris
JAMA 2003 290 2588-98
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Improve antibiotic use

• Monitor and provide feedback on occurrence of AMR
• Optimize choice and duration of empiric
  antimicrobial therapy
• Optimize perioperative antimicrobial prophylaxis

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Timing of Perioperative Antibiotic Prophylaxis
and Risk of Infection
incision
Infection rate ()
before incision
Hours after incision
D.C. Classen et al. N Engl J Med. 1992 326
283-285
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Common Misconceptions in Surgical Prophylaxis

• Broad-spectrum is better
• Longer antibiotic prophylaxis is better
• Prophylaxis should be continued until all tubes
  are out

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Misuse of prophylactic antibiotics in a
university hospital, China
80 of prophylactic antibiotics (191/239) were
started after the end of the operation

Suping Hu et al. J Infect 2003 46161-63
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Overuse of prophylactic antibiotics in a
community hospital, Saudi Arabia --
representative cases --
Procedure Delivery Urinary cath C-section Appendec
tomy Cystoscopy Cholecystectomy Incision Episiotom
y Delivery
Prophylactic antibiotics administered Ampicillin,
amikacin, cefotaxime Amoxycillin,
metronidazole Cephradine, ceftriaxone,
gentamicin, metronidazole Cephradine, cefoxitin,
amikacin, metronidazole, TMP-SMX Amikacin,
tetracycline, ceftazidime, amoxycillin-clav Cephra
dine, cefuroxime, gentamicin Ampicillin,
amikacin, amoxycillin-clav, cephradine Amoxycillin
, gentamicin, cephradine, metronidazole Amoxycilli
n, gentamicin, cephradine, metronidazole
Al-Ghamdi S et al. J Hosp Infect 2002 50115-21
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Antibiotic resistance and extended prophylaxis in
2,641 cardiac surgery patients

• Long AB prophylaxis (gt48 h 43) was associated
  with acquired resistance (Gram-negative bacteria
  VRE)
• ? Adjusted OR 1.7 95 CI, 1.1-2.7
• - Conditional logistic regression, matched by
  type of agent and calendar time
• - Adjusted for gender, age, transfer, ICU
  stay, comorbidities, ASA score, type of surgery,
  other AB exposure

Harbarth et al, Circulation 2000 101 2916-21
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Improve perioperative antibiotic prophylaxis (ABP)
Process Problem area System changes
ABP choice appropriate Suboptimal Coverage too large - Guidelines - Adequate supply
Huskins et al, Infect Control Hosp Epidemiol
199819125-35
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Improve perioperative antibiotic prophylaxis (ABP)
Process Problem area System changes
ABP choice appropriate Suboptimal Coverage too large - Guidelines - Adequate supply
Duration adequate Too long (gt1 dose) - Standard order form
Huskins et al, Infect Control Hosp Epidemiol
199819125-35
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Improve perioperative antibiotic prophylaxis (ABP)
Process Problem area System changes
ABP choice appropriate Suboptimal Coverage too large - Guidelines - Adequate supply
Duration adequate Too long (gt1 dose) - Standard order form
Timing correct Too early or too late - Administer in preoperative area - Designate responsible person
Huskins et al, Infect Control Hosp Epidemiol
199819125-35
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Prophylactic Antibiotics and Infections after
Cesarean Section in Colombia
Antibiotic prophylaxis in C-section - Appropriate
indication - Agent, dose, of doses - Timing of
first dose
Weinberg et al. Arch Intern Med 2001 1612357-65
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Use and timing of perioperative antibiotics and
surgical site infection rates
Correct ABP
SSI rate
Weinberg et al. Arch Intern Med 2001 1612357-65
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Improve antibiotic use (2)

• Decrease diagnostic uncertainty
• Improve diagnostic tools
• Promote use of clinical algorithms

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Antibiotic treatment without microbiologic culture
s in China (Hospital) and Nepal (ICU)

Chinan466
Nepaln149
Suping Hu et al. J Infect 2003 46161-63 Shankar
et al. Am J Infect Control 2003 31 410-14
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Use of clinical algorithms

• Prediction of bacteremia mortality in
  hospitalized Malawian children
• Association with lethargy, oral thrush, chronic
  cough and malnutrition
• The WHO Young Infants Study Group
• Clinical prediction rule to identify and treat
  serious bacterial infection

Norton EB et al. Pediatr Infect Dis J 2004 23
145-51 WHO study group. Pediatr Infect Dis J
1999 18 S23-31
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Lancet 2004 363 600-607
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Antibiotic prescriptions in lower respiratory
tract infection comparing standard group and
PCT-guided group
p 0.03
p 0.003
p lt 0.001
p lt 0.001
p 0.003
Antibiotic prescriptions ()
Christ-Crain M et al , Lancet 2004
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Improve antibiotic use (2)

• Decrease diagnostic uncertainty
• Implement formulary restrictions for important
  types of antimicrobial use

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Variable Pre-intervention period Intervention
period (1995/96) (1997/98)
Vials () 199,427 132,496 Total costs
() 699,543 347,261
-- Stable or decreasing resistance rates --
Saez-Llorens et al. Ped Infect Dis J 2000 19
200-6
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Does restriction always work ?

• Formulary restriction at Mass Gen Hosp, Boston
  (USA)
• Imipenem, tic/clav, aztreonam, cefta, cipro,
  pip/tazo require prior approval by infectious
  diseases

• The reality at the same hospital .35-y old
  woman with severe sepsis Ampicillin-sulb,
  clindamycin, penicillin, gentamicin, vancomycin
  were infused intravenously

Gilbert et al. Am J Med 1998 104 17-27
Case report 28-2002 of the MGH, NEJM Sept 12,
2002, p.831-37
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Improve antibiotic use (2)

• Improve diagnostic tools
• Implement formulary restrictions for important
  types of antimicrobial use
• Improve antimicrobial prescribing
• Education (pre- and postgraduate)
• Practice guidelines
• Administrative means (antibiotic order forms)

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Impact of an educational program on antibiotic
use in a tertiary care hospital in Thailand
Prevalence of antibiotic use (in-patients, )
Pre-intervention Post-intervention
OB-GYN 64 35
PEDS 59 50
OPHTHALM 57 28
MEDICINE 46 37
ENT 44 28
SURGERY 41 37
ORTHOPEDICS 36 26
Thamlikitkul V et al. J Clin Epidemiol 1998 51
773-78
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Implementing practice guidelines for appropriate
AB use Systematic review

• 40 studies (in- and outpatient areas)
• Multifaceted implementation methods were most
  successful
• Most useful implementation methods
• Locally adapted guidelines (drug committee)
• Small-group interactive sessions
• Academic detailing
• Participation of opinion leaders
• Feedback to prescribers

Gross PA et al. Med Care 2001 39 Suppl 55-69
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Infection control interventions
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Improve infection control

• Surveillance of AMR infection rates

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Control programs for multiresistant
Staphylococcus aureus (MRSA)
Richet et al. Infect Control Hospital Epi 2003
24 334-341
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Improve infection control

• Surveillance
• Promote and improve hand hygiene

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Compliance is less than 50
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Time constraint major obstacle for hand hygiene
handwashing hand antisepsis
alcohol-based hand rub
1 to 1.5 min
10 to 20 sec
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Average duration of hand hygiene by HCW
Hand washing
(HW)
(HR)
Hand rub
Pittet and Boyce, Lancet Infectious Diseases 2001
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Handwashing an action of the past (except when
hands are soiled)
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www.hopisafe.ch. Pittet D et al, Lancet 2000
356 1307-1312
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Trends in prevalence of nosocomial infections and
MRSA cross-transmission, HUG 1993-1998


www.hopisafe.ch. Pittet D et al, Lancet 2000
356 1307-1312
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Effect of education and performance feedback

• Observation of 15,531 patient contacts in 3
  hospitals in Argentina
• Compliance with hand hygiene increased from
• 17 (no intervention)
• 44 (education)
• 58 (education performance feedback)
• In hospitals with administrative support,
  compliance was significantly higher

Rosenthal et al. Am J Infect Control 2003 31
85-92
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Improve infection control

• Surveillance
• Promote and improve hand hygiene
• Use cohorting and isolation precautions (gowns,
  gloves, signs) not only for SARS.

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ISOLATION COHORTING FOR MRSASystematic review
with 6 high-quality studies

• Isolation wards
• 1 effective, 1 ineffective, 1 transient
• Single room isolation
• 1 transient hospital wide
• Cohorting
• 1 effective hospital wide
• Cohorting Single Room
• 1 effective in paediatric ICU

Cooper BS, Stone SP, Kibbler CC, et al.
Systematic review of isolation policies in the
management of MRSA. Health Technol Assess
200371-194
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Improve infection control

• Surveillance
• Promote and improve hand hygiene
• Use isolation precautions
• Reduce exogenous risk factors
• prevent exposure to contaminated material
• use sterile techniques for invasive procedures
• improve handling of IV fluids and lines

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Some thoughts about the future...
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Research Priorities

• Burden of AMR
• Ecologic studies evaluating impact of inadequate
  antibiotic treatment
• Antibiotic use and infection control
• Prospective comparisons with adequate control of
  confounding (cluster RCT)
• Interventions with clinical outcomes
• Full cost evaluations
• Input from behavioural sciences

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Policy priorities infection control

• Improve systems to recognize AMR and communicate
  clinical impact
• Promote adherence to alcohol-based hand hygiene,
  barrier precautions and basic infection control
• Improve injection safety
• Increase institutional and political commitment

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Policy priorities AB use

• Improve perioperative prophylaxis
• Promote short-course, high-dose AB therapy
• Decrease diagnostic uncertainty by any type of
  diagnostic tools or decision support
• Promote local guidelines and drug committees

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Summary of Measures
C
Ressources
High
B
Middle
Measures

• Surveillance
• Microbiologic support
• Reduce empiric AB use
• Restriction education

• Early detection (screening)
• Decision support systems
• New diagnostic markers
• Academic detailing

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Sweet home