1. CHOICE OF ANTIBIOTICS IN THE VIEW OF DEVELOPING ANTIBIOTIC RESISTANCE Dr. Jolanta Miciulevičienė Vilnius City Clinical Hospital National Public Health Surveillance Laboratory BARN 3 rd Workshop ʺ Prevention of Surgical Site Infections ʺ Visby, 2012

2. In 1928 Sir Alexander Fleming, a Scottish bacteriologist, left a Petri dish with staphylococci uncovered. When he returned, he noticed that there was mold growing on it. Upon further examination, he saw that the area around the mold had no bacteria growing. Fleming concluded that the mold was releasing a substance that was inhibiting bacterial growth. He grew a pure culture of the mold and discovered that it was a Penicillium, now known to be Penicillium notatum. Discovery of Penicillin Changes the History of Medicine

4. Antimicrobial resistance Soon after the introduction of the penicillin into clinical practice, the fact that the development of antibiotic resistance would be a problem became apparent. Resistance to penicillin in some strains of Staphylococcus was recognized almost immediately after introduction of the drugs. Resistance to penicillin today occurs in as many as 90% of all strains of Staphylococcus aureus

5. Most commonly, this refers to infectious microbes that have acquired the ability to survive exposures to clinically relevant concentrations of antimicrobial drugs that would kill otherwise sensitive organisms of the same strain. Antimicrobial resistance

6. S.aureus (MRSA, GISA), Enterococcus spp. (VRE), E.coli (ESBL), Klebsiella pneumoniae (ESBL, KPC), Enterobacteriaceae (MDR), Pseudomonas aeruginosa (MDR), Acinobacter baumannii (MDR). Resistant Nosocomial Pathogens

7. Streptococcus pneumoniae, Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa. European Antimicrobial Resistance Surveillance Network ( EARS – Net)

8. EARS – Net participants in Lithuania: 10 laboratories of microbiology 37 hospitals

9. Number of blood-stream infections, Lithuania, 2007 – 2011

10. Staphylococcus aureus: trends of invasive isolates resistant to meticillin (MRSA),Lithuania, 2007-2011 2007m. - 241/22, 2008m. - 280/31, 2009m. - 255/29, 2010m. – 257/36, 2011m. – 263/16

11. Staphylococcus aureus: proportion (%) of invasive isolates resistant to methicillin (MRSA), 2010

12. Klebsiella pneumoniae: trends of invasive isolates resistance to third-generation cephalosporins, fluoroquinolones and aminoglycosides, Lithuania, 2007-2011

13. Klebsiella pneumoniae: proportion (%) of invasive isolates with resistance to third-generation cephalosporins, 2010

14. Klebsiella pneumoniae: proportion (%) of invasive isolates with resistance to carbapenems, 2010

15. Number of K.pneumoniae blood stream infections, Lithuania, 2007-2011.

16. Risk factors of developing bacterial resistance Inappropriate prescribing (overprescribing); Inappropriate selection of antimicrobial (broad spectrum cephalosporins, fluoroquinolones, carbapenems, glycopeptides); Prolonged administration of antimicrobial.

17. Evidence Based “Evidence-based medicine is the process of systematically finding, appraising, and using research findings as the basis for clinical decisions.” BMJ 1995;310:1122-1126 (29 April) William Rosenberg, Anna Donald Evidence-based Medicine: An Approach to Clinical Problem-solving

18. Evidence-based medicine Reference: Cook PP, Catrou P, Gooch M, Holbert D. Effect of reduction in ciprofloxacin use on prevalence of methicillin-resistant Staphylococcus aureus rates within individual units of a tertiary care hospital. Journal of Hospital Infection. 2006; 64: 348-351 Setting: 731-bed tertiary care teaching hospital, Greenville, NC, USA.

19. Evidence based medicine Intervention Reduction - Active monitoring of oral and IV ciprofloxacin use. Impact: Ciprofloxacin use decreased by 31.2% (p<0.0001). MRSA rates decreased from 59.6% to 54.2% (p=0.112). Correlation between ciprofloxacin use and MRSA rates (r=0.70; 95% CI -0.01-0.94 p=0.053).

20. Evidence based medicine Reference: Rahal JJ, Urban C, Horn D, Freeman K, Segal-Maurer S, Maurer J, Mariano N, Marks S, Burns JM, Dominick D, Lim M. Class restriction of cephalosporin use to control total cephalosporin resistance in nosocomial Klebsiella. JAMA, 1998;280(14): 1233-1237 Setting: 500-bed university affiliated community hospital, Queens, NY, USA

21. Evidence based medicine Intervention Restriction - Hospital adopted antibiotic guidelines restricting routine cephalosporin use. Impact: 80.1% reduction in hospital-wide cephalosporin use in 1996 compared to 1995. 44% reduction in incidence of ceftazidime- resistant Klebsiella infection and colonization throughout medical center (p<0.01) and 70.9% reduction in all intensive care units (p<0.001).

22. Evidence based medicine Intervention Restriction - Hospital adopted antibiotic guidelines restricting routine cephalosporin use. Impact: 80.1% reduction in hospital-wide cephalosporin use in 1996 compared to 1995. 44% reduction in incidence of ceftazidime- resistant Klebsiella infection and colonization throughout medical center (p<0.01) and 70.9% reduction in all intensive care units (p<0.001).

23. Take home message: Inappropriate selection and prolonged administration of antimicrobials Fluoroquinolones; Cephalosporins; Carbapenems; Glycopeptides. S.aureus (MRSA, GISA), Enterococcus spp. (VRE), E.coli (ESBL), Klebsiella pneumoniae (ESBL, KPC), Enterobacteriaceae (MDR), Pseudomonas aeruginosa (MDR), Acinobacter baumannii (MDR). THANK YOU !