1. PHARMACOECONOMIC ASPECTS FOR ANALYSIS OF TREATMENT ON INFECTION FROM METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS (MRSA) M Sc Stevce Acevski Macedonia

2.  Pharmacoeconomic researches are identifying, measuring and comparing costs and outcomes from therapy in healthcare systems and in society  They are common criteria`s for making decision in health policies  Nowadays all developed countries base their decision making on various pharmacoeconomic analyses, in order to make wise and fruitful decisions, regarding costs and outcomes in the healthcare system PHARMACOECONOMIC ASPECTS FOR ANALYSIS OF TREATMENT ON INFECTION FROM METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS (MRSA) Introduction

3.  Bacterial infections from Methicillin resistant Staphylococcus aureus (MRSA) are serious epidemiological problem, as for hospital patients, and for patients treated in ambulatory *  The Agency for Healthcare Research & Quality (AHRQ) shows that MRSA is connected with 375 000 patients annually, of whom 23 000 died **  MRSA is one of the tree most common intra hospital infections PHARMACOECONOMIC ASPECTS FOR ANALYSIS OF TREATMENT ON INFECTION FROM METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS (MRSA) Introduction - MRSA challenge * Hornberg C, Knoop D, Kipp F., The importance of MRSA in patient care. Epidemiology, prevention and therapy. Orthopade 2006 Nov; 35(11):1159 - 60, 1162 - 4, 1166 - 7. ** Kavanagh K, Calderon L, Saman D and Abusalem S, The use of surveillance and preventative measures for methicillin- resistant Staphylococcus aureus infections in surgical patients, Antimicrobial Resistance and Infection Control 2014, 3:18

4.  Pharmacoeconomic evaluation of therapy of MRSA infections is difficult to make, but of excellence meaning for proper decision  According to fact that antibiotic resistance is growing, multi resistant species are identified on everyday basis, dealing with infections from MRSA is challenge  If we want to make analysis of the key factors in process for dealing with MRSA, then we should examine more perspectives, but precise clinical outcome of every individual should be made PHARMACOECONOMIC ASPECTS FOR ANALYSIS OF TREATMENT ON INFECTION FROM METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS (MRSA) Introduction - MRSA challenge

5. PHARMACOECONOMIC ASPECTS FOR ANALYSIS OF TREATMENT ON INFECTION FROM METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS (MRSA) Perspectives

6.  Positive Staphylococcus aureus culture  Not all positive culture  Eg. 1/3 of all tested health workers with positive Staphylococcus aureus, of which 2.58% MRSA – without symptoms *  Identify and diverse infected, from patients that have positive bacterial identification  Microbiology testing - time frame 24 - 48 h  Genom Era MRSA/SA test – homogenous PCR test – results in 50 min * Mainous G et all. Nasal carriage of Staphylococcus aureus and Methicillin Resistant S. aureus infections in surgical patients, Antimicrobial resistance and infection control 2014, 3:18 PHARMACOECONOMIC ASPECTS FOR ANALYSIS OF TREATMENT ON INFECTION FROM METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS (MRSA) When antibiotic?

7.  When deciding which antibiotic treatment to start, antibiotic`s choice is one way to reduce total financial cost for the treatment  Protocols for specific infections, can give directions which antibiotic to choose Cost of the treatment PHARMACOECONOMIC ASPECTS FOR ANALYSIS OF TREATMENT ON INFECTION FROM METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS (MRSA)

8.  Basic infection  Efficacy of the drug  Adverse reactions of the treatment  Compliance  Availability of health resources  Health insurance of the patient  Possibility of the patient to take care of himself  Costs connected with intravenous administration  Availability of/for PO therapy  Cost of therapeutic failure Cost of the treatment Other factors: PHARMACOECONOMIC ASPECTS FOR ANALYSIS OF TREATMENT ON INFECTION FROM METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS (MRSA)

9. Cost factors in hospitalized patients Direct costs Cost of the treatment (cost pro doses or daily therapy costs) Indirect costs Cost for I.V. administration Cost for follow up and evaluation of the patient Cost for emerged antibiotic resistance and failure of the treatment connected with antimicrobial resistance Cost for adverse reactions from the therapy Cost for therapeutic failure (e.g. prolonged treatment or retreatment with other antibiotic) Cost for hospitalized patients

10.  Use of antibiotics with longer shelf life (once or twice day dosing)  Implementing “switch” principles  Empirically use of P.O. administered antibiotics for hospitalized and ambulatory patients  Limited use of drugs that require plasmatic levels  Familiar with antimicrobial resistance  Tolerability of the drugs, low level of adverse reactions  Antimicrobial spectrum of the drug is essential for limiting drug failures  Bioavailability of the drug, helps to prevent drug usage without adequate tissue penetration Cost reduction strategies PHARMACOECONOMIC ASPECTS FOR ANALYSIS OF TREATMENT ON INFECTION FROM METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS (MRSA)

11. “Switch” therapy PHARMACOECONOMIC ASPECTS FOR ANALYSIS OF TREATMENT ON INFECTION FROM METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS (MRSA) Antimicrobial resistance

12. “Switch” principles PHARMACOECONOMIC ASPECTS FOR ANALYSIS OF TREATMENT ON INFECTION FROM METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS (MRSA)  “Switch” therapy – change from intravenous (IV) to per oral (PO) rout of administration  “Switch” therapy - cuts the costs of the therapy without influence on efficacy of the treatment * ** * Luna C., Vujacich P., Niederman M., Vay C., Gherardi C. Matera J., Jolly E., Impact of BAL data on the therapy and outcome of Ventilator Associated Pneumonia., Chest March 1997, Vol 111. No. 3 **Cyriac JM., James E., Switch over from intravenous to oral therapy: A concise overview., J Pharmacol Pharmacother 2014 Apr; 5(2):83-7

13. “Switch” principles PHARMACOECONOMIC ASPECTS FOR ANALYSIS OF TREATMENT ON INFECTION FROM METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS (MRSA)  Short course of intravenous treatment 2-3 days followed with per oral treatment for the rest of the treatment, has a multiple advantages for a lot of patients  Switch therapy is commonly used practice in the developed countries

14. “Switch” principles When Factors when switch from IV to PO administration: Afebrile for 8 to 12 hours Stabilization of general condition and leading clinical symptoms Normalizing white blood cells Adequate oral intake and gastrointestinal absorption Individual assessment of the patient PHARMACOECONOMIC ASPECTS FOR ANALYSIS OF TREATMENT ON INFECTION FROM METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS (MRSA)

15. “Switch” principles Why Benefits from switch: Reduced risk of hospital infections Reduced risk of complications Shorter hospital stay Reductions on hospital staff Comfort and compliance PHARMACOECONOMIC ASPECTS FOR ANALYSIS OF TREATMENT ON INFECTION FROM METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS (MRSA)

16. Antimicrobial resistance PHARMACOECONOMIC ASPECTS FOR ANALYSIS OF TREATMENT ON INFECTION FROM METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS (MRSA)  Development of resistance - natural phenomenon  Increased use of antimicrobials - increased resistance  Reduction of use does not necessarily reduce resistance!!!

17. Cost of antimicrobial resistance PHARMACOECONOMIC ASPECTS FOR ANALYSIS OF TREATMENT ON INFECTION FROM METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS (MRSA)  All healthcare systems try to evaluate economic cost of antimicrobial resistance, but treatment with antimicrobials can lead from less than £5 to more than £20,000 *  Factors that currently estimate the cost of resistance are modest, they are based loosely on the ‘incremental’ cost related to the extra treatment of resistant over susceptible primary infection * * Smith RD; Coast, J., The economic burden of antimicrobial resistance: Why it is more serious than current studies suggest. Technical Report. London School of Hygiene Tropical Medicine, London 2012

18. Antimicrobial resistance factor in deciding PHARMACOECONOMIC ASPECTS FOR ANALYSIS OF TREATMENT ON INFECTION FROM METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS (MRSA)  When deciding which antibiotic treatment should be used for treating MRSA infection, antimicrobial resistance should be one of the factors in deciding  Knowledge of antimicrobial resistance can help make proper antibiotic choice and lower risk of failure and antibiotic misuse

19. Table 3. Differences in antimicrobial resistance at MRSA isolates in Hungary, Austria and Macedonia HungaryAustriaMacedonia MRSA isolates 1584072 Antibiotic Vancomycin SSS Amikacin SS> 70,8% R Gentamycin 73,7 % R> 90% R Clindamycin RRR Clarithromycin > 90% R Ciprofloxacin > 90% R Levofloxacin > 90% R Moxifloxacin > 90% R Shortcuts: S = Susceptible, I = Intermediate, R = Resistant Horváth A., Malmos G., Pesti N., Kristóf K., Nagy K., Cekovska Z., Kotolácsi G., Gattringer R., Graninger W., Rozgonyi F., Differences in antibiotic resistance between MRSA and MSSA strains isolated in Hungary, Austria and Macedonia, Abstract number: 1733_207, ESCMID 17 th European congress of clinical microbiology an infectious diseases, ICC, Munich, Germany, 2007 Antimicrobial resistance - situation PHARMACOECONOMIC ASPECTS FOR ANALYSIS OF TREATMENT ON INFECTION FROM METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS (MRSA)

20. Evaluate also PHARMACOECONOMIC ASPECTS FOR ANALYSIS OF TREATMENT ON INFECTION FROM METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS (MRSA)  Death rate (%)  Usual days of hospital stay  Hospitalization in ICU  Use of additional medical procedures  Prolonged hospital stay

21. Cost – efficacy of the therapy PHARMACOECONOMIC ASPECTS FOR ANALYSIS OF TREATMENT ON INFECTION FROM METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS (MRSA)

22. Cost – efficacy of the therapy PHARMACOECONOMIC ASPECTS FOR ANALYSIS OF TREATMENT ON INFECTION FROM METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS (MRSA)  Cost efficacy of the antimicrobial treatment starts with the initial therapy, after clinical evaluation of the patient and start of antibiotic treatment  When treating there are possible interventions as: wound cleaning, incision, drainage, antimicrobial testing, parenteral therapy and hospitalization

23. Cost – efficacy of the therapy PHARMACOECONOMIC ASPECTS FOR ANALYSIS OF TREATMENT ON INFECTION FROM METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS (MRSA)  Every day clinical evaluation, results from microbiological testing, can lead to additional treatment change of antibiotic or switch to administration to per oral routes  Everyday evaluation, adverse effects and comorbidities have influence in better cost efficacy ratio

24. PHARMACOECONOMIC ASPECTS FOR ANALYSIS OF TREATMENT ON INFECTION FROM METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS (MRSA)

25. Conclusion 1/3  Main factor in evaluation of antimicrobial agents used in treatment of MRSA infection is patient  Evaluation of economic factors is main step when deciding and use of antimicrobial therapy  Factors that are evaluated are multiple, complex, interconnected and changeable with time PHARMACOECONOMIC ASPECTS FOR ANALYSIS OF TREATMENT ON INFECTION FROM METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS (MRSA)

26. Conclusion 2/3  Make evaluation of the patient with possible infection  Start aggressive antibiotic treatment, in time adjust it as you get clinical and laboratory data  Observe data for antimicrobial resistance, so you could make proper antibiotic use PHARMACOECONOMIC ASPECTS FOR ANALYSIS OF TREATMENT ON INFECTION FROM METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS (MRSA)

27. Conclusion 3/3  Make continuously cost effectiveness evaluations so you could follow costs for MRSA treatment PHARMACOECONOMIC ASPECTS FOR ANALYSIS OF TREATMENT ON INFECTION FROM METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS (MRSA)

29. Thank you for kind your attention