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 and prophylaxis Most of the antibiotics are prescribed outside the hospitals They are prescribed to nearly third of hospitalized patients Every doctor can prescribe them in most of the countries Most of the antibiotics are generics and are becoming 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
Most common infectious agent Respiratory (Streptococcus pneumoniae) Skin and soft issue (Staphylococcus aureus) Urinary tract (Escherichia Coli)
Movement towards confirmed infection Revolutionary diagnostics Multiplex real time PCR Mass spectometry Full genome sequencing Strep A test Nitrite test
Pathogen targeted therapy Opportunity to use narrow spectrum drug Different length of treatment for the same disease Optimal dosing Known resistance pattern
Pathogen directed therapy Penicillin V Streptococcus pneumonia Streptococcus pyogenes Flucloxacillin Staphylococcus aureus Nitrofurantoin, pivmecillinam Escherichia coli
Surgical prophylaxis One dose 30 minutes before incision Extra dose if large blood loss Treatment is something different Prophylactic drug should not be used for treatment
Favors single dose Favors multiple dose All studies, fixed All studies, random Multi > 24h Multi < 24h Is one dose of antibiotic enough for prohylaxis? 100 10 1 0.1 0.01 McDonald M et al. Aust NZ J Surg. 1998;68:388 396. Adapted with permission from Blackwell Synergy 1998.
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
Antibiotic R R R. R R
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- lactamase inhibitors 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 fever subsided Later (1960-1990s) expansion 10-14 days for registration purposes Often suggested length of treatment may be too long Lack of randomized control trials Shorter treatment for certain conditions might be as 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 are needed? Is the treatment working?
Conclusions 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