From Penicillin to Naphthalene

1. From Penicillin to Naphthalene End of antibiotic era? Prof. Raul Raz Infectious Diseases Unit Ha’Emek Medical Center Afula

2. Resistance to antimicrobial drugs – A worldwide calamity Kunin C, 1993

3. Antibiotics are being recognized as agents that are truly societal drug, since their use in individual patients can also affect the family and the community. • As each patient is treated, there is an influence upon the entire normal bacterial flora shed in his/her surroundings.

4. No other group of drugs has such an effect on society by its misuse, not only by the costs involved, but also by the effects on bacterial resistance. • Therefore, the time has come for the medical profession (administrators, physicians, etc.) to moderate its insistence on clinical freedom to prescribe what it likes when it likes. J.M. Gould, 1985.

5. The use of antibiotics Hospital Community Veterinary medicine

6. Use of antibiotics Therapeutic 20% Agricultural use 50% Growth promotion 80% Highly questionable 40-80% Hospital 20% Human use 50% Community 80% Unnecessary 30-50%

7. U.S.A. 11.2 million Kg. - growth promotion 900 Kg. - animal therapy 1.3 million Kg. - humans

8. Salmonella multiresistant • E.coli • Campylobacter jejuni • Enterococcus faecium Over 80% of infections with salmonella and campylobacter in humans are acquired from animals’ food.

9. There are today: 50 penicillins 75 cephalosporins 12 tetracyclines 9 aminoglycocides 3 carbapenemes 1 monobactams 9 macrolides 20 quinolones

10. Given this huge array of antibiotics, it would seem that an individual could not possibly die of an infection in a hospital. (H. Neu, 1993)

11. Antimicrobial resistance has emerged as a major public health issue in the last 10-15 years. A steady increase in resistance continues despite the introduction of new antibiotics, and resistant bacteria have been associated with increased patients morbidity and mortality as well as with increased cost.

12. Hospital MRSA VRE VISA MRSE ESBL producing by Enterobacteraceae Acinetobacter Community Pneumococci Salmonella Shigella Gonococci Emerging resistant pathogens

13. More than half of hospitalized patients receive antibiotics and those drugs cost up to 50% of hospital budget! In addition, 25-50% of all antibiotics prescription are inappropriate as a result of incorrect choice of drugs, dose and duration.

14. Influence of the appropriateness of antimicrobial treatment upon mortality rates in the management of nosocomial bacteraemia in different specialties (adapted from Jamuitrat et al) Assessment of Mortality rate in specialty (%) Antimicrobial therapy Surgery Medicine Paediatrics Total Appropriate 21.9 32.7 7.7 27.3 Inappropriate 28.1 77.5 25.0 53.9

15. The cost of caring for patients with infections caused by resistant bacteria is much higher than those with antibiotic – sensitive organisms. In the USA it is estimated between $100 million and $30 billion annually.

16. Factors contributing to increased antimicrobial resistance • Sicker in-patients populations • Large immunocompromised pts. • New procedures and instrumentation. • Emerging pathogens. • Ineffective infection control. • Increased antibiotic use.

17. Mechanisms related to the appearance and spread of antimicrobial resistance • Introduction of a resistant organisms to previously susceptible population. • Acquisition of resistance by a susceptible strain (spontaneous mutation or genetic transfer). • Dissemination or spread of a resistant organism.

18. Overuse of antimicrobials and poor compliance with infection-control measures have been identified as the major reason for an increasing trend in antimicrobial resistance.

19. “Patients often pressure physicians for unneeded antibiotics”. • Physicians appear to be trying to maximize patient’s satisfaction by giving antibiotics when patients want. • And..”any intervention to reduce antibiotic prescribing must pay as much attention to the patient as to the physician”. (Journal of Family Practice, 10/2001).

21. Bacteria will develop resistant to virtually every antibiotic given enough time. • Resistance may eventually occur to any antibiotic. The time to resistance, however, can vary considerably.

22. For example: penicillin -resistant pneumococcus took 25 years to emerge as a clinical problem. • Quinolones- resistant Enterobacteracae became a problem after 10 years.

23. With some bacteria, resistance to new drugs has emerged much more rapidly.

24. Organisms resistant to one antimicrobial agent are likely to become resistant to others. • For example: • First gonococci resistant to tetracycline was also resistant to penicillin. • First pneumococci resistant to penicillin showed also resistance to macrolides.

25. Effect of antibiotic resistance on patient management Patient-relatedIncreased length of hospital stay Increased risk of therapy with an inappropriate antimicrobial Increased risk of treatment with more toxic antimicrobials Increased risk of death Hospital-relatedIncreased antimicrobial costs Increased cost of length of patient stay Increased costs during patient stay from additional supportive/supplementary therapies.

26. What can be done to reduce use of antibiotics? Antibiotics Are Not Antipyretics Or… … Doctor’s tranquilizers...

32. Is antibiotic resistance reversible? Several studies show that antibiotic resistance can be reversed by stop using the drug.

33. The effect of changes in the consumption of macrolide antibiotics on erythromycin resistance in group A streptococci in Finland The New England Journal of Medicine 1997; 337:441-6

34. The total amount of antibiotics sold for human use in Norway 1981 – 1997 by average DDD/1000 inhabitants/day (%) Antibiotic 1981 1987 1993 1997 DDD(%) DDD(%) DDD(%) DDD(%) Penicillins 4.5 ( 39) 5.0 ( 37) 7.2 ( 44) 7.4 ( 50) Penicillin V 3.1 ( 27) 3.7 ( 28) 5.3 ( 33) 5.1 ( 34) Amoxicillin 0.3 ( 3) 0.3 ( 2) 0.6 ( 4) 0.9 ( 6) Ampicillin 0.6 ( 5) 0.6 ( 5) 0.4 ( 3) 0.3 ( 2) Macrolides 0.6 ( 5) 1.3 ( 10) 1.6 ( 10) 1.6 ( 11) Tetracyclines 3.0 ( 26) 4.0 ( 30) 4.8 ( 29) 3.5 ( 23) Trimethoprim- co-trimoxazole 3.2 ( 28) 2.5 ( 19) 2.0 ( 12) 1.4 ( 9) Other antibiotics 0.3 ( 3) 0.5 ( 4) 0.6 ( 4) 0.9 ( 6) Sum 11.6 (100) 13.3 (100) 16.2 (100) 14.8 (100)

37. Sulfonamides and trimethoprim J01E Quinolones J01M Macrolides, Lincosam., Streptogramins J01F Tetracyclines J01A Cephalosporins J01D Penicillins J01C Total outpatient antibiotic use in 26 European countries in 2002 + Israel 2002 European Surveillance of Antimicrobial Consumption (ESAC) Others J01B+J01G+J01X

38. The ICU are the main source of the appearance of multidrug resistant bacteria

39. Antimicrobial resistance has emerged as an important determinant of outcome for patients in ICU. • ICU’s are facing increasingly rapid emergence and spread of antibiotic-resistant bacteria.

40. High antibiotic consumption in Danish ICU?Total supply to 30 major ICUs in Denmark in 1995 Antimicrobials Supply of antibiotics (DDD/100 patient days) Median Quartiles Span Aminopenicillins 25.6 14.5-32.3 2.4-94.3 Penicillin G 16.5 9.0-23.0 5.0-53.0 Second-generation cephalosporins 9.5 6.4-17.0 1.8-51.4 Macrolides 11.2 7.6-16.5 0.0-40.8 Metronidazole 12.6 7.1-15.2 0.0-23.4 Aminoglycosides 9.5 5.5-13.1 0.5-35.6 Penicillin-resistant penicillins 6.1 3.7- 9.2 1.0-19.9 Quinolones 3.7 2.0 -6.8 0.4-22.9 Penicillin V 2.2 0.8- 5.3 0.0-21.8 Third-generation cephalosporines 1.7 0.6- 5.0 0.0-14.1 Antifungal agents 1.3 0.7- 3.1 0.0-31.6 Vancomycin 0.6 0.2- 1.4 0.0-20.6 Carbapenems 0.5 0.0- 1.1 0.0-38.2 Rifampicins 0.3 0.0- 2.3 0.0- 6.7 Sulfonamides and trimethoprim 0.2 0.0- 1.0 0.0-11.7 Carboxy-and ureido-penicillins 0.5 0.1- 1.3 0.0- 2.7 Sulfonamides 0.7 0.0- 1.2 0.0- 6.7

41. Antimicrobial use in long-term-care facilities • 40% of all systemic drug prescribed are antibiotics • Point prevalence studies showed that more than 10% of LTCF residents received antibiotics. • A resident will receive al least one course of systemic antibiotics during a 1-year period. • 50-75% of systemic antibiotics are prescribed inappropriately.

42. Susceptibility of uropathogens E.coli

43. Susceptibility of uropathogens E.coli

44. Susceptibility of uropathogens E.coli

45. Susceptibility of uropathogens E.coli

46. Can an educational program improve the diagnosis and treatment of pharyngotonsillitis in the ambulatory care setting?Israel Journal of Medical Sciences 1995;31 (7)432-435.

47. Education programs can have some impact in the reduction of the use of antibiotics, at least as a temporary basis.

48. New Strategies

49. Medical Executive Committee Hospital Administration Hospital Epidemiology (Infection Control) Infectious Diseases Microbiology Outcomes/ Quality Analysis Education Infection-Control Strategies Antibiotic-Control Strategies Structure of a hospital-wide quality-improvement program to address antimicrobial resistance Antimicrobial Resistance Leadership Team (Hospital Committees) Pharmacy

50. עשרת הדברות לשימוש מושכל באנטיביוטיקה 6. להשתמש באנטיביוטיקה מניעתית בצורה מבוקרת. 1. אין לוותר מול דרישות החולים במתן לא מוצדק של אנטיביוטיקה. 7. להזכיר לצוותים רפואיים לפעול בהתאם לנהלים כדי למנוע העברת חיידקים בין חולים (רחצת ידיים). 2. חינוך חולים וקרובי משפחה לשימוש מושכל. 3. ניסיון לזיהוי פתוגן. 8. לעודד חולים ועובדים להתחסן. 4. בחירת קורסים קצרים עם תכשירים בעלי ספקטרום צר. 9. תוכניות לניטור מתמשך של חיידקים ורגישויות. 10. שימוש מושכל באנטיביוטיקה בחקלאות. 5. לדאוג לסיום כל הקורס שניתן.