Responsible use of antibiotics

Transcription

1 Responsible use of antibiotics Uga Dumpis MD, PhD Department of Infectious Diseases and Infection Control Pauls Stradiņs Clinical University Hospital

2 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

3 Indications for antibiotic use Empirical therapy Confirmed bacterial infection Surgical prophylaxis

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

5 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

6 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

7 Epidemiological considerations Consider most common pathogens causing the infectious syndrome Local pattern of resistance Risk factors for resistance

8 Most common infectious agent Respiratory (Streptococcus pneumoniae) Skin and soft issue (Staphylococcus aureus) Urinary tract (Escherichia Coli)

9 Movement towards confirmed infection Revolutionary diagnostics Multiplex real time PCR Mass spectometry Full genome sequencing Strep A test Nitrite test

10 Pathogen targeted therapy Opportunity to use narrow spectrum drug Different length of treatment for the same disease Optimal dosing Known resistance pattern

11 Pathogen directed therapy Penicillin V Streptococcus pneumonia Streptococcus pyogenes Flucloxacillin Staphylococcus aureus Nitrofurantoin, pivmecillinam Escherichia coli

12 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

13 Favors single dose Favors multiple dose All studies, fixed All studies, random Multi > 24h Multi < 24h Is one dose of antibiotic enough for prohylaxis? McDonald M et al. Aust NZ J Surg. 1998;68: Adapted with permission from Blackwell Synergy 1998.

14 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

15 Additional harm of antibiotics Resistance selection pressure Risk for superinfection Direct toxicity and interractions with other drugs Costs

16 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,

17 Antibiotic R R R. R R

18 Resistance selection pressure Penicillins Aminoglycosides Nitrofurantoin, trimetroprim First generation cephalosporins Second generation cephalosporins Tetracyclines Macrolides Third generation cephalosporins Fluoroquinolones Carbapenems

19 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)

20 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)

21 Marketing and other pressure Penicillin Amoxicillin Oxacillin Gentamycin Metronidazole Nitrofurantoin Trimetroprim III gen cephalosporins Newer Macrolides Fluoroquinolones Penicillins/β- lactamase inhibitors Carbapenems

22 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

23 Drug toxicity and interactions QT prolongation Metronidazole facilitates action of warfarin Loop diurrhetics increase ototoxicity of aminoglycosides Many side effects and interactions unknown

24 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

25 Antagonism Penicillin and tetracyclin (Lepper MH et al, 1951) Ampicillin and chloramphenicol (Mathies AW 1967) Caution needed with unstudied combinations

26 Length of treatment Early ( s) use 3-5 days until fever subsided Later ( s) expansion 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

27 Route of administration Oral therapy prefferable Intravenous administration only for severe disease or specific location Switch to oral treatment works very well

28 No improvement after three days Wrong choice Possible resistance Surgical drainage needed Super infection Non compliance

29 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?

30 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