Responsible use of

antibiotics

Uga Dumpis MD, PhD

Department of Infectious Diseases and

Infection Control

Pauls Stradiņs Clinical University Hospital

Challenges in the hospitals

• Antibiotics are still effective in treatment andprophylaxis

• Most of the antibiotics are prescribed outside the hospitals

• They are prescribed to nearly third of hospitalizedpatients

• Every doctor can prescribe them in most of thecountries

• Most of the antibiotics are generics and arebecoming relatively cheap

• 1/3 to ½ of prescriptions are inappropriate

Indications for antibiotic use

• Empirical therapy

• Confirmed bacterial infection

• Surgical prophylaxis

Hede K. Nature 509, S2–S3 (01 May 2014)

Antibiotic Stewardship

• A program that encourages proper (vs improper) use of antibiotics

• Stewardship goal is to fine tune antibiotic use in regards to

• Efficacy

• Toxicity

• Resistance-induction

• C. difficile-induction

• Iv to po switch

• Cost

• Discontinuation

Empirical therapy

– Clinical signs• Hyperthermia or hypothermia

• Fever

• Tachicardia

• Tachipnoe

• Hypotension

– Laboratory findings• WBC increase, new forms >10%,

• CRP > 100 mg/l

• Procalcitonin > 0.2 ng/ml

– Radiological investigations

Epidemiological considerations

• Consider most common pathogens causing the

infectious syndrome

• Local pattern of resistance

• Risk factors for resistance

• Respiratory (Streptococcus pneumoniae)

• Skin and soft issue (Staphylococcus aureus)

• Urinary tract (Escherichia Coli)

Most common infectious agent

Movement towards confirmedinfection

• Revolutionary diagnostics– Multiplex real time PCR

– Mass spectometry

– Full genome sequencing

• Strep A test

• Nitrite test

• Opportunity to use narrow spectrum drug

• Different length of treatment for the same

disease

• Optimal dosing

• Known resistance pattern

Pathogen targeted therapy

Penicillin V

• Streptococcus pneumonia

• Streptococcus pyogenes

Flucloxacillin

• Staphylococcus aureus

Nitrofurantoin, pivmecillinam

• Escherichia coli

Pathogen directed therapy

• One dose 30 minutes before incision

– Extra dose if large blood loss

• Treatment is something different

• Prophylactic drug should not be used for

treatment

Surgical prophylaxis

Is one dose of antibiotic enough for

prohylaxis?

McDonald M et al. Aust NZ J Surg. 1998;68:388–396. Adapted with permission from Blackwell Synergy © 1998.

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Quality Assurance

Indicator No. 1

% of patients, who received AB within 1 hr prior to incision

Indicator No. 2

% of patients, who received AB based on the Guidelines

Indicator No. 3

% of patients, who received no AB after 24 hr

Additional harm of antibiotics

• Resistance selection pressure

• Risk for superinfection

• Direct toxicity and interractions with other drugs

• Costs

Figure 2 Temporal changes in the proportion of macrolide-resistant streptococci after azithromycin and clarithromycin use Data

shown are for all 204 volunteers followed through to day 42, and for 99 volunteers followed through to day 180. Error bars are 9...Surbhi Malhotra-Kumar , Christine Lammens , Samuel Coenen , Koen Van Herck , Herman Goossens

Effect of azithromycin and clarithromycin therapy on pharyngeal carriage of macrolide-resistant streptococci in healthy

volunteers: a randomised, double-blind, placebo-controlled study

The Lancet, Volume 369, Issue 9560, 2007, 482 - 490

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Resistance selection pressure

• Penicillins

• Aminoglycosides

• Nitrofurantoin, trimetroprim

• First generation cephalosporins

• Second generation cephalosporins

• Tetracyclines

• Macrolides

• Third generation cephalosporins

• Fluoroquinolones

• Carbapenems

Antibiotic use and superinfection

• Clostridium Difficile infection

– III generation cephalosporins, Amoxicillin/Clavulanate,

Clindamycin

• MRSA (Monnet DL et al, 2004)

– Macrolides (Goosens et al, 2004)

– Cephalosporins (Meyer En et al, 2006, Harbath S et al, 2006)

– Fluoroquinolones (Dziekan et al, 2000, , Ernst L et al 2005, Harbath S, 2000,

Charbonneau P et al, 2006)

Antibiotic use and superinfection

• Multidrug-resistant Pseudomonas aeruginosa

– Cephalosporins

Carbapenems (Lopez-Lozano JM, et al 2000)(Leroy O et al, 2005)

• Carbapenem resistant Acinetobacter Baumanii

– Cephalosporins

– Carbapenems (Corbella X et al 2000) (Lee SO et al, 2004)

• Stenotrophomonas maltophila

– Carbapenems, Cephalosporins (Carmeli Y, 1997) (Hanes SD et al,

2002)

Marketing and other pressure

• Penicillin

• Amoxicillin

• Oxacillin

• Gentamycin

• Metronidazole

• Nitrofurantoin

• Trimetroprim

• III gen cephalosporins

• Newer Macrolides

• Fluoroquinolones

• Penicillins/β- lactamaseinhibitors

• Carbapenems

History of alergy

• Up to 20% of hospitalized patients report an allergy to

penicillin

• Anaphylaxis only in 0.01% of penicillin users with 9%

mortality

• Urticaria only in 5%

• Allergy against penicillins does not mean allergy

against cephalosporins

Drug toxicity and interactions

• QT prolongation

• Metronidazole facilitates action of warfarin

• Loop diurrhetics increase ototoxicity of

aminoglycosides

• Many side effects and interactions unknown

Drug combinations

• To cover multiple pathogens

– ß- lactam + glikopeptide

– ß- lactam +aminoglycoside

– ß- lactam+ macrolide

• To prevent development of resistance

– Gonnorhea

– Tuberculosis

• Sinergy

– ß- lactam+ aminoglycoside

– ß- lactam + fluoroquinolone

Antagonism

– Penicillin and tetracyclin (Lepper MH et al, 1951)

– Ampicillin and chloramphenicol (Mathies AW 1967)

• Caution needed with unstudied combinations

Length of treatment

• Early (1940-50s) use 3-5 days until feversubsided

• Later (1960-1990s) expansion 10-14 days forregistration purposes

• Often suggested length of treatment may be toolong

• Lack of randomized control trials

• Shorter treatment for certain conditions might beas safe as longer

Route of administration

• Oral therapy prefferable

• Intravenous administration only for severe disease or

specific location

• Switch to oral treatment works very well

No improvement after three days

• Wrong choice

• Possible resistance

• Surgical drainage needed

• Super infection

• Non – compliance

Questions to answer every time

• Is an antibiotic really needed?

• What is the most common pathogen?

• What is the local resistance pattern?

• Will the chosen drug select for resistance?

• What dose, route, frequency and duration areneeded?

• Is the treatment working?

We are running out of antibiotics

Every extra dose of an antibiotic can be

harmful

Antibiotic stewardship programmes

should address all aspects of

antibiotics use

Use antibiotics responsibly

Conclusions