Najčešće pogreške u propisivanju antibiotika I dio

Most common mistakes in antibiotic prescribing Ist part

Ljiljana Betica Radić – General Hospital Dubrovnik

23. svibnja 2018.

Najčešće pogreške u propisivanju antibiotika I dio

Most common mistakes in antibiotic prescribing Ist part

Ljiljana Betica Radić – General Hospital Dubrovnik

Vesna Mađarić – General Hospital Koprivnica

IX HRVATSKI SIMPOZIJ O REZISTENCIJI BAKTERIJA NA ANTIBIOTIKE 9th Croatian Symposium on Antibiotic Resistance Zagreb, 2-3.03.2018

AGENDA

• „To err is human”

• Important considerations when prescribing antimicrobial therapy

• The most common errors in antibiotic prescribing

• Making the Correct Diagnosis is the Cornerstone of Antibiotic Stewardship

„to err is human” Institute of medicine, 1999

- but errors can be prevented

More people die as a result of medical errors than from motor vehicle accidents (43,458), breast cancer (42,297), or AIDS (16,516) „Human beings, in all lines of work, make errors. Errors can be prevented by designing systems that make it hard for people to do the wrong thing and easy for people to do the right thing”

Wise et al. BMJ 1999; 317:609-610

Where used Types of use Questionable use

50 % HUMAN

50%

ANIMAL

80% PROPHYLAXIS/

GROWN PROMOTION

80% COMMUNITY

20-50% UNNECESSARY

40-80% HIGHLY

QUESTIONABLE

20% HOSPITAL

20% THERAPEUTIC

• we live in the time of increasing antibiotic resistance and insufficiency of new drug development

Questions to Address

• Does this patient need antibiotics ?

• If yes, how urgent?

• Which antibiotic should be chosen?

• What is the appropriate dose/route for this patient?

• How long should the patient be treated for?

Why Antimicrobial drugs are sometimes not successful ? The success of antimicrobial treatment relies on very complicated system

Antibiotic

Host

In vitro testing

MIC & S R

Pathogen

Site of infection

Species

Factors of virulence

Secretion of toxins

Mechanisms of resistance

CNS

Cardiovascular

Respiratory, GIT, UG, ...

need for surgical intervention

Age

BMI

Immune system

Comorbidities

Foreign bodies

PK PD

Metabolism and elimination

The tissue penetration

Mode of action

Side effects

Medication errors could be preventable

Principles of Prudent Antimicrobial Prescribing

RIGHT antibiotic What organisms could be infecting this patient ? What risk factors for resistance does this patient have? Does this antibiotic penetrate to the site of infection ?

RIGHT patient Does this patient have a true infection vs colonisation ?

RIGHT time Did we obtain culture prior to initiating antibiotics ? Was this patient administered antibiotics within an hour ?

RIGHT dose Is the antibiotic dosing appropriate for the patient’s renal or hepatic function ?

RIGHT route Is this patient a candidate for oral treatment ?

LEAST harm Are we choosing the most narrow spectrum antibiotic ? Are we choosing the minimum duration of treatment ? Are we choosing the antibiotic with the least amount of side effects ?

The 4D of antimicrobial therapy: right drug, dose, duration and de-escalation

Appropriate Use of Antibiotics in the ICU

– Should an antibiotic be prescribed at all?

– What is the initial choice?

– What dose, how urgent and for how long?

should every patient with infection in ICU

be on Van and Pip-Taz or Mer”

DE-ESCALATION THERAPY

Level 1

– application of broad spectrum antibiotics and combination therapy to improve outcomes • reducing mortality and

preventing organ dysfunction

Level 2

application of narrow spectrum according to microbiology result in order to minimize resistance

TIMING of initiation od AT… Duration of hypotension before initiation of effective antimicrobial therapy is the

critical determinant of survival in human septic shock *. Kumar, Anand et al. Critical Care Medicine. 34(6):1589-1596, June 2006. DOI: 10.1097/01.CCM.0000217961.75225.E9

Kumar A et al. Crit Care Med 2006; 34:1589-1596.

Inappropriate Antimicrobial Therapy: Prevalence Among ICU Patients

Source: Kollef M, et al: Chest 1999;115:462-74

17,10%

34,30%

45,20%

0%

10%

20%

30%

40%

50%

Community-acquired infection Hospital-acquired infection Hospital-acquired infection after initial community-acquired infection

Inappropriate Antimicrobial Therapy (n = 655 ICU patients with infection)

Patient Group

Unfortunately, not all patients receive appropriate antimicrobial treatment

Does Inadequate Therapy Result from AR?

Inadequate therapy is more likely if antibiotic resistance (AR) is present, and antibiotic resistant organisms are more commonly associated with inadequate therapy (adapted from Kollef)

0

5

10

15

20

25

30

35

40

Kollef MH. Clin Infect Dis 2000;31(Suppl 4):S131-S138.

% Inadequate

Treatment of VAP

PK & PD Antibiotic Principles What do we need to know?

• the importance of understanding PK/PD properties of the major antibiotic classes

• optimal dosing of antibiotics through the use of PK/PD principles can be utilized to reduce the misuse/overuse of these agents and antibiotic resistance

PK/PD parameter

antibiotic

T > MIC penicillins, cephalosporins, carbapenems, aztreonam, erythromycin, clarithromycin, clindamycin, linezolid

AUC 0-24h / MIC fluoroquinolones, aminoglycosides, azithromycin, tetracycline, vancomycin, guinupristin- dalfopristin

C max / MIC fluoroquinolones, aminoglycosides, metronidazole

Rodvold KA. Pharmacotherapy. 2001; 21: 319-330.

LJBR

PK/PD parameter: antibiotic “time dependent”

T > MIC 50-70% increase dosing interval - continuous infusion

Co

ncentr

ation o

f

antibio

tic

MIC

Time

Forrest A. Antimicrobial Agents Chemother 1993; 37:1073-1081.

LJBR

PK/PD parameter: antibiotic: „dose dependent”/ concentration” concentr

ation o

f

antibio

tic

MIC

Time

Cmax > MIC increase the dose

J Infect Dis 1987 & Antimicrobial Agents Chemother 1991.

10 - 12 x

“How high dose is enough?”

„ 20 years“ Croatian Committee for Antibiotic Resistance Surveillance (CARS) from 1996 founded at the Public Health Collegium of the Croatian Academy of Medical Sciences (CAMS) Founder and the first president: Prim.dr.sc. Tera Tambić Prof.dr.sc. Arjana Tambić Andrašević,

president Prim.dr. Marina Payerl Pal,

scientific secretary

Croatian Chapter of the Aliance for the Prudent Use of Antibiotics (APUA) from 2003.

Intersectoral Coordination Mechanism for the Control of the AR „ISKRA” from 2006

from 2006

for how long ?

• Start antibiotics immediately

• Stop antimicrobial treatment, when infection is cured, if patient is afebrile and well for 48 hours

• This usually means approximately seven days of therapy for most ICU infections

• The longer a patient is exposed to an antimicrobial, the greater the likelihood that colonisation with resistant organisms will occur

Espresso – caffe italiano – „strong/short”

It is, of course, a question of perspective. Debate is to be welcomed – but what if it leads to more confusion than clarity? BSAC’s take on the situation was published in the Guardian soon afterwards. BSAC’s reply, published in the Guardian (July 2017), to ‘The antibiotics course has had its day’ article FOLLOW PROFESSIONAL ADVICE ON ANTIBIOTICS

Important considerations when prescribing antimicrobial therapy

obtaine an accurate DIAGNOSIS

determine the NEED for antimicrobial therapy

determine the TIMING of antimicrobial therapy

understand DOSING affects of the various antimicrobial activities

tailor treatment to HOST characteristics

use the NARROWEST spectrum of therapy

use the SHORTEST duration of therapy

SWITCHING to oral agents as soon as possible

NONANTIMICROBIAL interventions, such as abscess drainage, are equally or more important in some cases

Mayo Clin Proc. 2011;86(2):156-167

Publication published in Issue 5, 2013.

SEARCH METHOD 1980 – 2009 89 STUDIES 95 interventions

Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE from 1980 to December 2006 and the EPOC specialized register in July 2007 and February 2009 and bibliographies of retrieved articles.

RESTRICTIVE interventions

were implemented through restriction of the freedom of prescribers to select some antibiotics

PERSUASIVE interventions

used methods for changing professional behaviour: dissemination of educational resources, reminders, audit and feedback, or educational outreach. Restrictive interventions could contain persuasive elements

Selection criteria randomized clinical trials (RCTs), controlled clinical trials (CCT), controlled before-after (CBA) and interrupted time series studies (ITS). Interventions included any professional or structural interventions as defined by EPOC

INTERVENTIONS AIMED TO:

IMPROVE ANTIBIOTIC PRESCRIBING to hospital inpatients, either by increasing effective treatment or by reducing unnecessary treatment The results: effect of the intervention on antibiotic prescribing or microbial outcomes or relevant clinical outcomes

MAIN COMPARISONE

between interventions that had a RESTRICTIVE element and those that were purely PERSUASIVE

Publication published in Issue 5, 2013.

RESULTS Meta-analysis

AUTHORS’ CONCLUSIONS

PERSUASIVE OR RESTRICTIVE INTERVENTIONS

The meta-analysis supports the use of restrictive interventions when the need is urgent, but suggests that persuasive and restrictive interventions are equally effective after six months

DECREASE EXCESSIVE PRESCRIBING

REDUCE antimicrobial resistance and HAI (CD inf. and colonization or inf. with AG- or CEF-resistant gram-GNB, MRSA and VRE)

CLINICAL OUTCOME

INCREASE EFFECTIVE PRESCRIBING Decrease excessive prescribing

4 interventions intended to INCREASE effective prescribing for pneumonia were associated with significant REDUCTION in mortality (risk ratio 0.89, 95% CI 0.82 to 0.97) 9 interventions intended to decrease excessive prescribing were not associated with significant increase in mortality (risk ratio 0.92, 95% CI 0.81 to 1.06)

reduce excessive antibiotic

prescribing to inpatients

can reduce antimicrobial

resistance and HAI

interventions to increase effective

prescribing

can improve clinical outcome

MISUSES OF ANTIBIOTICS

UNNECESSARY Use for noninfectious syndromes •asymptomatic bacteriuria outside of established indications use for nonbacterial infections • Antibiotics for viral uper RTI days of therapy beyond the indicated • Treating CAP for 14 d instead of 5–7 in the absence of clinical data use of redundant antimicrobial therapy • Double anaerobic coverage continuation of empiric broadspectrum therapy when cultures have revealed the infecting pathogen • Continued use of VAN started empirically after growth of Pseudomonas aer.in blood cultures • Continued use of empiric VAN and cefepime in a patient found to have sterile pancreatic necrosis

INAPROPRIATE Use in the setting of established infection to which the pathogen is resistant or •Patient treated with an antibiotic not treating the bacteria recovered in cultures (bug–drug mismatch) use of antimicrobials not recommended in treatment guidelines • use of PIP/TAZto treat uncomplicated CAP

SUBOPTIMAL Use of antimicrobials in the setting of established infection that can be improved in one of the following categories: (1) drug choice, (2) drug route, and (3) drug dose •Use of an overly broad-spectrum agent to treat a susceptible bacterium (eg, cefepime for ampicillin susceptible E. coli infection) • Use of IV FQ when no contraindication to oral therapy • Failure to adjust doses of renally cleared drugs in the setting of acute renal failure

The most common errors in antibiotic prescribing

Use of a broad-spectrum antibiotic when a narrow-spectrum agent would suffice

Excessive duration of therapy

Intravenous therapy when oral therapy would be equally effective

Combination therapy when a single antibiotic would suffice

Failure to change antibiotics when the antibiograms become available

Failure to adjust the dosage in the case of decreased hepatic or renal function

Outdated knowledge of antibiotic resistance and thus initial prescription of the wrong agent

The most common errors in antibiotic prescribing

Assuming the worst case, i.e. routinely starting with single or combined antibiotics appropriate for pathogens such as Pseudomonas or MRSA

Failing to correctly determine colonisation vs contamination vs pathogen

Prolonged empiric antimicrobial treatment without clear evidence of infection

Treatment of a Positive Clinical Culture in the Absence of Disease

Prolonged Prophylactic Therapy

Excessive Use of Certain Antimicrobial Agents

Assessments of antimicrobial use

Drug vs Diagnosis

• Initial assessments of antimicrobial use focused on drug selection and dose, with some evaluation of the accuracy of the diagnosis ascribed to the patient

• More recent reports focus on assessing appropriateness of diagnostic evaluations and resultant diagnostic accuracy, understanding that inaccurate diagnosis leads to inappropriate antimicrobial use

QUALITY IMPROVEMENT • CID 2016:63 (15 December) • 1639

• A new retrospective study included

a random sample of 500 patients receiving systemic antimicrobial drug treatment during a stay at a Veterans Affairs hospital

• In blinded fashion, a panel of infectious disease physicians rated the accuracy of the initial diagnosis and the appropriateness of treatment

• The study builds on previous

results showing that inappropriate antimicrobial prescribing for hospitalized patients is often related to diagnostic error

95

38

0

10

20

30

40

50

60

70

80

90

100

Incorect orindeterminate DG

Correct DG

Inappropriate Antibiotic

The research team found: • 95% of patients who received

an incorrect or indeterminate diagnosis were prescribed inappropriate antibiotics, compared with 38% of those correctly diagnosed

• only 58% of patients received a correct diagnosis, indicating a higher rate of diagnostic errors in this study than previous research unrelated to antibiotic use

• Factors that may contribute to inaccurate diagnosis and inappropriate antibiotic use:

– reliance on intuitive processes

– fatigue

– previous diagnoses from other providers

– lack of experience

• The most common misdiagnoses in the study were:

– pneumonia

– urinary tract infections

– urosepsis

Making the Correct Diagnosis: The Cornerstone of Antibiotic Stewardship

the process of ensuring that antibiotics are used appropriately

A - TEAM all play important roles in ensuring the success of such programs

The aim:

improve the safe and appropriate use of antimicrobials

reduce patient harm

decrease AR

IMPORTANT: there is a significant influence of cultural determinants, social norms, attitudes and beliefs on antimicrobial prescribing behavior and antibiotic use, which result in variation in practice locally, nationally and internacionally

Proposed members of antimicrobial stewardship groups

• A senior leader who has experience of implementing change

• Infectious disease physician

• Microbiologist

• Antimicrobial pharmacist

• Representatives from clinical specialities

• Infection control representative

• Drug and therapeutic committee representative

• Nurse representative

• Primary care representative

If my life could be extended I would dedicate fifty years of study I CHING - The book of change 易经 and then maybe I would not make great mistakes any more Confucius (551-479 b.c.), 17 yo

BE READY FOR CHANGING PRACTICE as QUALITY IMPROVEMENT