Επιμελητεία αντιβιοτικών(Antimicrobial Stewardship)

Διαμαντής Π Κοφτερίδης

Αναπληρωτής Καθηγητής Παθολογίας –Λοιμώξεων

Πανεπιστήμιο Κρήτης

Antimicrobial prescribing is a complex process determined by many factors

• Guidelines

• Individual health

professional factors

• Patients factors

• Professional interactions

• Incentives and resources

• Άλλα

The problemMisuse and over-use of antibiotics

The problem

• Approximately 40% of all hospitalised inpatients at any given

time receive antibiotics

• ~ 50% are inappropriate

• Antimicrobials account for 30% of hospital pharmacy budgets.

• Inappropriate and excessive use leads to resistance, C.

difficile, increased morbidity, mortality, increased cost, and

reduce quality of life.

• Insufficient knowledge of prescribing professionals

• Between 2000 and 2010, consumption of antibiotic drugs

increased by 36%.

• Brazil, Russia, India, China, and South Africa accounted for

76% of this increase.

• There was increased consumption of carbapenems (45%) and

polymixins (13%), two last-resort classes of antibiotic drugs.

NO ACTION TODAY

NO CURE TOMORROW

International crisis: Less antibiotics/more resistance

• Antimicrobial resistance has been identified as

a major threat by the World Health

Organisation due to the lack of new antibiotics

in the development pipeline and infections

caused by multi-drug resistant pathogens

becoming untreatable

Goossens et al., 2011; Carlet et al., 2011

https://ecdc.europa.eu/..........antimicrobial-resistance-europe-2015.pdf

E. faecium-VRE

E. faecalis-

high level

‘R’ to

gentamycin

MRSA in Europe(As percentage of S. aureus bacteriemia)

2001 2017

Data EARS-Net Atlas

Blood cultures carbapenem I and R

E. coli K. pneumoniae

EARS-NET interactive atlas, data 2017

ITALY 29,7%, GREECE 64.7%, BULGARIA 12.4%, ROMANIA 22.4

Pseudomonas aeruginosa(percentage of blood cultures)

Ceftazidime R Aminoglycosides R

EARS-Net Atlas, data 2017

Carbapenem R

The global pattern of resistance is high.In most European countries >10% of the P. aeruginosa isolates present a combined resistance to 3 or more antimicrobial groups tested (aminoglycosides, carbapenems, ceftazidime, fluoroquinolones, piperacilline tazobactam)

Acinetobacter baumannii

Carbapenem RAminoglycosides R

EARS-NET interactive atlas, data 2017

Acinetobacter represents a public health threat. Limited treatment options in countries of southern and south-eastern EuropeRates of carbapenem resistance: Croatia 96.2%, Greece 94.8%, Italy 78.7%

Lancet Infect Dis 2019; 19: 56–66

New antimicrobial agents(with a novel mechanism of action,research, development)

Actions to prevent and control antimicrobial resistance and nosocomial infections

Infection prevention and control(hand hygiene, screening, isolation)

Prudent use of antimicrobial agents(only when needed, correct dose, correct dose intervals, correct duration)

The solution

Very few new antibioticsSince 1998 only 10 new antibiotics have been approved. Only 2 (linezolid and daptomycin) have new targets of action.

Clin Infect Dis 2011;52(S5):S397–S428

New drugs

IDSAs 10 x ′20

initiative:

“Ten new

antibiotics

released before

2020”

Very few new antibiotics

What is Antimicrobial Stewardship?

The IDSA describes antimicrobial stewardship

• Interventions designed to improve and measure the appropriate

use of antimicrobials by promoting the selection of the optimal

antimicrobial drug regimen, dose, duration of therapy, and route of

administration.

• Antimicrobial stewardships seek to achieve optimal clinical

outcomes related to antimicrobial use, minimize toxicity and other

adverse events, reduce the costs of health care for infections, and

limit the selection for antimicrobial resistant strains.

Dellit et al. Clin Infect Dis 2007;44:159–77

AMS

✓The right antibiotic

✓For the right patient

✓At the right time

✓With the right dose and

✓The right route

✓Causing the least harm to the patient and

future patients

www/cdc.gov/getsmart/healthcare/inpatient-stewardship

Why is AMS important?

• Decreased use of antimicrobials

• Improve clinical outcomes

• Prevent-reduce resistance

Impact on clinical outcomesAntibiotic Stewardship Improves Clinical Outcomes

Ohl et al. Clin Infect Dis 2011;53(S1):S23–S28

RR 2.8 (2.1-3.8) RR 1.7 (1.3-2.1)

RR 0.2 (0.1-0.4)

AMP = Antibiotic Management ProgramUP = Usual Practice

Effective ASPs are

associated with

• Increased clinical and

microbiologic therapeutic

successes

• Reduced incidence of

bacteremia

• Gram-negative

infection

• Antimicrobial drug–

related advers events

• CDI

Impact of Stewardship on Safety? (critical care)

• The reductions in antimicrobial utilization

– Have not been associated with any worsening in nosocomial

infection rates, length of stay or mortality.”

– Stewardship interventions were associated with … fewer

antibiotic adverse events.

Kaki R, et al. J Antimicrob Chemother 2011; 66: 1223-1230

Rates of C. difficile AADRates of Resistant

Enterobacteriaceae

Carling P et al. Infect Control Hosp Epidemiol. 2003;24:699-706

Impact on C. difficile and Resistance

Antibiotic Stewardship Reduces C. difficile Infection and Gram Negative Resistance

• Restriction of

carbapenems is

associated with both

• lower use and

• lower incidence of

carbapenem resistance

P. aeruginosa.

Ohl et al. Clin Infect Dis 2011;53(S1):S23–S28

Projected cost savings if antimicrobial-resistant infection (ARI) rates were reduced from 13.5% to 10%.

Roberts et al. Clin Infect Dis. 2009;49:1175-84

The goals of AMS

Goals of Antimicrobial Stewardship Programs

The 6 Ds: Operational Goals of Antimicrobial Therapy and Stewardship

• Right Diagnosis What infection syndrome is being treated? – Is it responsive to antibiotics?

– Have appropriate diagnostic tests been collected?

• Right Drug(s) – Demonstrated effective Safest Narrowest spectrum

• Right Dose

• Right De-escalation: right Drug(s) redefined when: – Justified by culture results (positive or negative)

– Clinical improvement (e.g., IV to PO switch)

• Right Duration: – Minimum necessary

– Defined infections requiring prolonged therapy

• Right Debridement or source control

How to implement antimicrobial Stewardship Program?

ASP DIRECTORS

ID Physician

ID Pharm D

Microbiology Laboratory

Hospital Epidemiologist

Infection Control Practitioner

Clinical Pharmacy Specialist

Infectious Diseases Division

Specialist with interest in

antimicrobials

Hospital Administrator

Director, Outcomes Research

Medical Information

Systems

Assess the motivations

• Analyse your situation and what problems you want to address.

• Define where you are and where you want to go.

• For example, easier or less costly approaches can include:

– Simple clinical algorithms

– Prescribing guidance for treatment, surgical prophylaxis

– Intravenous (IV) to oral conversion

– Restricting availability of certain antibiotics (formulary restriction)

– Promoting education

Dellit et al. Clin Infect Dis 2007;44:159–77

Antimicrobial stewardship strategies

Περιορισμός συνταγολογίου και

προέγκριση

Προοπτικό audit με παρέμβαση και

feedback

Two core antimicrobial stewardship strategies

Chung GW et al. Virulence 2013; 4:1-7

Identify effective interventionsfor your setting

• When establishing a new stewardship program, it is

best to start with the core strategies and focus on

achieving and maintaining them before adding some

of the supplemental strategies

Front end strategiesPreauthorization and restriction

• Local guidelines

• List of restricted antimicrobial agents and criteria for their use

combined with

Approval system

– It is essential that all aspects of prescribing are supported

by expert advice 24 hours a day.

Back end strategyProspective audit and feedback

Johannsson B. et al. Inf. Control. Hosp. Epidemiol. 2011; 32:367-374

Antimicrobial

review methods

are employed

post-

prescription

Antibiotic “Time outs”All physicians should review of antibiotics 48 hours after antibiotics are

initiated to answer these key questions

• Does this patient have an infection that will respond to antibiotics?

• If so, is the patient on the right antibiotic(s), dose, and route of administration?

• Can a more targeted antibiotic be used to treat the infection (de-escalate)?

• How long should the patient receive the antibiotic(s)?

http://www.cdc.gov/getsmart/healthcare/ implementation/core-elements.html.

ASP Elements Potential Advantages and Disadvantages

Supplemental strategiesEducation

• Effective and useful component when combined with an active

intervention

• It should include health care professionals as well as patients and public

and convince them that is important.

• May include

– General principles of antimicrobial therapy

– Interpretation of antibiotic sudceptibility and antibiograms

– Diagnostic and treatment guidelines

– Discussion of penicillin allergy

Pulcini et al. Virulence. 2013;4:192-202.Dellit et al. Clin Infect Dis 2007;44:159–77

Combination therapy

• There are insufficient data to recommend the routine use of

combination therapy to prevent the emergence of resistance.

• Combination therapy does have a role

– for empirical therapy for critically ill patients at risk of

infection with multidrug- resistant pathogens.

Dellit et al. Clin Infect Dis 2007;44:159–77

Don’t expect too much from combination therapy

• Indications:– Prevent resistance in long-term treatment (tuberculosis)

– Additional killing in endocarditis

– Additional killing in biofilms / prosthetic joint infections

• P. aeruginosa infections– Generally beta-lactam + aminoglycoside

– To increase efficacy, broaden spectrum, limit resistance development

• Carbapenem-R enterobacterales (recommended)

Adequate evidence

Limited (if any) evidence

• There is insufficient evidence to recommend any combination therapy for

serious MRSA infections in actual patient care.

Guidelines and clinical pathways

• Development of evidence-based practice guidelines

incorporating local microbiology and resistance patterns can

improve antimicrobial utilization (A-I).

• Guideline implementation can be facilitated through provider

education and feedback on antimicrobial use and patient

outcomes (A-III)

Dellit et al. Clin Infect Dis 2007;44:159–77

Microbiology laboratory

• The microbiology laboratory plays a critical role in AMS by

1. Providing patient-specific culture and susceptibility data to

optimize individual antimicrobial management

2. Resistance surveillance

– Local antibiograms with pathogen-specific susceptibility data should

be updated at least annually

3. Assisting infection control efforts in molecular epidemiologic

investigation of outbreaks

Dellit et al. Clin Infect Dis 2007;44:159–77

Use of diagnostic tools

• The role of rapid diagnostics and biomarkers is recognized as a key

recommendation by the IDSA.

• Benefits of PCT among patients with RTI and sepsis

• Near-patient rapid tests, e.g. influenza, Strep A, can be useful to identify

patients with bacterial versus viral infections.

• Molecular diagnostics can improve antibiotic stewardship and clinical

outcomes.

Dellit et al. Clin Infect Dis 2007;44:159–77

De-Escalating therapy

• Empiric antimicrobial regimens are often broad spectrum

• Narrowing the spectrum based on

– Culture results

– Discontinue empiric therapy if no evidence of infection

Dellit et al. Clin Infect Dis 2007;44:159–77

Dose optimization

• Include strategies to improve rates of cure and minimize

toxicity

• Such strategies are

– Prolonged or continue dosing of beta-lactams

– Once daily dosing of aminoglycosides

– Appropriate dosing of vancomysin

– Weight based dosing of certain antimicrobials

– Dose adjustments for patients with renal dysfunction

Dellit et al. Clin Infect Dis 2007;44:159–77

Parenteral – oral conversion

• Changing from iv to oral

• Is commonly used for antimicrobial agents with similar oral

concentration achieved (fluroquinolones etc)

• May reduce length of hospital stay and costs and potentially

eliminate risks associated with vascular access.

Antimicrobial order forms

• Antimicrobial order forms decrease antimicrobial

consumption through the use of automatic stop orders and

the requirement of physician justification

Dellit et al. Clin Infect Dis 2007;44:159–77

Literature evaluating the impact of EHRs and CDSSs on patient outcomes is

lacking, although EHRs with integrated CDSSs have demonstrated

improvements in clinical and economic outcomes

Forrest et al. Clin Infect Dis 2014;59(S3):S122–33

Identify key measurementsfor improvement

• Outcome measurements

– Improved clinical outcome

– Reduced antimicrobial resistance

– Adverse drug events

– Cost

– Unintended consequences, such as rates of C. difficile infection

Dellit et al. Clin Infect Dis 2007;44:159–77

Dodds Ashley et al. Clin Infect Dis 2014;59(S3):S112–21

Conclusions

• ASPs, in all types and sizes of hospitals

– Reduce antimicrobial use

– Improve patient outcomes

– Prevent and/or control the emergence of antimicrobial-

resistant organisms

• With careful strategic planning and commitment from all

involved parties, ASPs can become a reality for all hospitals.

Ευχαριστώ