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From Penicillin to Naphthalene. End of antibiotic era?. Prof. Raul Raz Infectious Diseases Unit Ha’Emek Medical Center Afula. Resistance to antimicrobial drugs – A worldwide calamity. Kunin C, 1993.

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From penicillin to naphthalene

From Penicillin to Naphthalene

End of antibiotic era?

Prof. Raul Raz

Infectious Diseases Unit

Ha’Emek Medical Center

Afula




  • 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.


The use of antibiotics
The use of antibiotics misuse, not only by the costs involved, but also by the effects on bacterial resistance.

Hospital

Community Veterinary medicine


Use of antibiotics
Use of antibiotics misuse, not only by the costs involved, but also by the effects on bacterial resistance.

Therapeutic

20%

Agricultural use

50%

Growth promotion

80%

Highly questionable

40-80%

Hospital

20%

Human use

50%

Community

80%

Unnecessary

30-50%


U s a
U.S.A. misuse, not only by the costs involved, but also by the effects on bacterial resistance.

11.2 million Kg. - growth promotion

900 Kg. - animal therapy

1.3 million Kg. - humans


  • Salmonella multiresistant misuse, not only by the costs involved, but also by the effects on bacterial resistance.

  • E.coli

  • Campylobacter jejuni

  • Enterococcus faecium

    Over 80% of infections with salmonella and campylobacter in humans are acquired from animals’ food.


There are today: misuse, not only by the costs involved, but also by the effects on bacterial resistance.

50 penicillins

75 cephalosporins

12 tetracyclines

9 aminoglycocides

3 carbapenemes

1 monobactams

9 macrolides

20 quinolones


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)


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.


Emerging resistant pathogens

Hospital health issue in the last 10-15 years.

MRSA

VRE

VISA

MRSE

ESBL producing by Enterobacteraceae

Acinetobacter

Community

Pneumococci

Salmonella

Shigella

Gonococci

Emerging resistant pathogens


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.


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


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.


Factors contributing to increased antimicrobial resistance
Factors contributing to increased antimicrobial resistance resistant bacteria is much higher than those with antibiotic – sensitive organisms. In the USA it is estimated between $100 million and $30 billion annually.

  • Sicker in-patients populations

  • Large immunocompromised pts.

  • New procedures and instrumentation.

  • Emerging pathogens.

  • Ineffective infection control.

  • Increased antibiotic use.


Mechanisms related to the appearance and spread of antimicrobial resistance
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.


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


  • “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).






Effect of antibiotic resistance on patient management
Effect of antibiotic resistance on patient management become resistant to others.

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.


What can be done to reduce use of antibiotics
What can be done to reduce use of antibiotics? become resistant to others.

Antibiotics Are Not Antipyretics Or…

… Doctor’s tranquilizers...


Is antibiotic resistance reversible
Is antibiotic resistance reversible? become resistant to others.

Several studies show that antibiotic resistance can be reversed by stop using the drug.


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


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)


Sulfonamides and 1981 – 1997 by average DDD/1000 inhabitants/day (%)

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




High antibiotic consumption in danish icu total supply to 30 major icus in denmark in 1995
High antibiotic consumption in Danish ICU? determinant of outcome for patients in 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


Antimicrobial use in long term care facilities
Antimicrobial use in long-term-care facilities determinant of outcome for patients in ICU.

  • 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.


Susceptibility of uropathogens determinant of outcome for patients in ICU.

E.coli


Susceptibility of uropathogens determinant of outcome for patients in ICU.

E.coli


Susceptibility of uropathogens determinant of outcome for patients in ICU.

E.coli


Susceptibility of uropathogens determinant of outcome for patients in ICU.

E.coli


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.



New Strategies the use of antibiotics, at least as a temporary basis.


Structure of a hospital wide quality improvement program to address antimicrobial resistance

Medical the use of antibiotics, at least as a temporary basis.

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


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.


ת ו ד ה באנטיביוטיקה


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