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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
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
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?