1. RATIONAL USE OF ANTIBIOTICS
Prof. Dr. A. Çağrı BÜKE
Yeditepe University Medical Faculty
Department of Infectious Diseases

2. Do we use antibiotics rationally ?
Ç. BÜKE Rational Use of Antibiotics
Do we use antibiotics rationally ? NO
Teaching staff
Student
Reason for antibiotic use
Grup A
(Dentist, Pharm)
Grup B
(Others)
As an antipiretics
%33
%37
%19
For the treatment of cold
%49
%81
%83
Start antibiotics available at home
%31
%18
%38
With pharmacist’s concideration %8
%21
%20
40% of people living in UE countries believe that Antibiotics are given for common cold and flu

3. Do antibiotic consumption rise in EU ?
Ç. BÜKE Rational Use of Antibiotics
Do antibiotic consumption rise in EU ?
Antibiotic consumption has been rising in outpatients in Europe
The most common using antibiotic is Penicillins

4. How is antibiotic consumption in Turkey ?
Ç. BÜKE Rational Use of Antibiotics
How is antibiotic consumption in Turkey ?
Turkey ranks first among 40 European countries who consume the most antibiotics
On average, a Turkish citizen consumes three times more antibiotics than someone from the Netherlands
Lancet Infect Dis. 2014;14:

5. Global picture of antibiotic consumption
Ç. BÜKE Rational Use of Antibiotics
Global picture of antibiotic consumption
Compared to the years of 2000 to 2014, the rate of increase in antibiotic use; South Africa 219%, Brazil 68%, India 66%, China 37%, Turkey > 90%

6. Current epidemiology of antibiotic resistance in Turkey
Ç. BÜKE Rational Use of Antibiotics
Current epidemiology of antibiotic resistance in Turkey
The rate of MRSA accounts for more than 50%
The rate of VRE rises fastly
Years
MRSA
VRE %
2008
58.9
5.4
2009
58.5
6.1
2010
53.4
11.2
2011
55.3
17.1
2012
53.8

7. Current epidemiology of antibiotic resistance in Turkey
Ç. BÜKE Rational Use of Antibiotics
Current epidemiology of antibiotic resistance in Turkey
The rate of ESBL production, carbapenem and colistin resistance in K.pneumoniae have been rising
Klebsiella pneumoniae
Years
ESBL (%)
Carbapenem R (%)
Colistin R (%)
2011
53.8
2012
57.8
2013 56 11
2014 52 28
2015 68 30

8. Current epidemiology of antibiotic resistance in Turkey
Ç. BÜKE Rational Use of Antibiotics
Current epidemiology of antibiotic resistance in Turkey
Resistance to PT, Cef, Car, Col among P.aeruginosa increases every year
Pseudomonas aeruginosa
Years
Pip+tazo R
(%)
Cefepim R
Carbapenem R
Colistin R
2011
22.7
21.2
2012
25.2 22
2013 27 33
2014 21 15 24
2015 30 26 32 2

9. Current epidemiology of antibiotic resistance in Turkey
Ç. BÜKE Rational Use of Antibiotics
Current epidemiology of antibiotic resistance in Turkey
Resistance to PT, Cef, Car, Col among P.aeruginosa increases every year
Pseudomonas aeruginosa
Years
Pip+tazo R
(%)
Cefepim R
Carbapenem R
Colistin R
2011
22.7
21.2
2012
25.2 22
2013 27 33
2014 21 15 24
2015 30 26 32 2

10. What’s the consequences of resistant bacterial infections ?
Ç. BÜKE Rational Use of Antibiotics
What’s the consequences of resistant bacterial infections ?
Antibiotic-resistant infections require
Prolonged and/or costlier treatments
Extend hospital stays
Necessitate additional doctor visits and healthcare use
Result in greater disability and death compared with infections that are easily treatable with antibiotics
Rational use of antibiotics is key issue

11. Q-1) Does antibiotic need ?
Ç. BÜKE Rational Use of Antibiotics
Q-1) Does antibiotic need ?
If YES, Q-2
Fever is not an indication for antibiotic use
In many infectious diseases due to other than bacteria have also fever
Antibiotics use only for bacterial infectious diseases
Antibiotics should be given in case of
High clinical suspicion for bacterial infectious diseases and/or
Definitive diagnosis for bacterial infectious diseases
History, physical examination, biochemistry,
radiology, microbiology

12. Q-2 Has the causative microorganism been identified ?
Ç. BÜKE Rational Use of Antibiotics
Q-2 Has the causative microorganism been identified ?
If YES, Q-3
Sample(s) taken from infection site(s)
(Blood, urine, sputum, pus, CSF, peritoneal fluid e.g.)
Gram stain
Immunological methods for determining antigens and/or antibody of microorganisms (ELISA, latex agglutination, EIA, FA)
Molecular methods (PCR)
Bacteriological culture Susceptibility
New Methods
Mass spectro
Amplification tests
Microarray analys
Nanotechnological

13. Q-3 Antimicrobial susceptibility results of microorganism ?
Ç. BÜKE Rational Use of Antibiotics
Q-3 Antimicrobial susceptibility results of microorganism ?
Disc-diffusion method is commonly used for routine testing E-test (Antimicrobial gradient testing) Broth dilution
The test results should be used to guide antibiotic choice
MIC=16
MBC=32

14. Ç. BÜKE Rational Use of Antibiotics
Q-4 Should AB susceptibility results be waiting before starting antibiotic treatment
261 patients with sepsis and septic shock
Mean ages was 59 ± 16; and 41% were female
Mortality was 25% in patients started appropriate antibiotic therapy ≤ 1 h., whereas it was 38.5% in patients when antibiotic was not appropriate and started antibiotic therapy > 1 h p=.03
Appropriate and early given empirical antimicrobial treatment is life saving

15. What should be considered in selecting ampirical antibiotics ?
Ç. BÜKE Rational Use of Antibiotics
What should be considered in selecting ampirical antibiotics ?
The site of infection should be identified
Possible causative microorganisms should be considered
Prior antibiotic susceptibility results for possible microorganisms should be taken into account
Host factors should be regarded
Antibiotics preferred should penetrate in high concentration in infection site
The necessity of combination antibiotic treatment should be evaluated

16. Factors affecting selection of antibiotics “Host factors”
Ç. BÜKE Rational Use of Antibiotics
Factors affecting selection of antibiotics “Host factors”
Age
Gastric acid decreases with ages
Serum concentration of beta lactams increase
Dose adjustment is required
Renal clearance decreases with ages
Dose adjustment is required for beta lactams, aminoglycosides, glycopeptides
- Myoclonus, convulsion
- Neutropenia
- Ototoxicity

17. Factors affecting selection of antibiotics “Host factors”
Ç. BÜKE Rational Use of Antibiotics
Factors affecting selection of antibiotics “Host factors”
Age
Liver functions
- Some antibiotics increase the risk of liver toxicity with ages; INH
The risk of having “Hypersensitivity reactions” increases with ages
Diabetes
- The risk of getting diabetes increases with age
- The risk of hypoglisemia or hyperglisemia increases with fluoroquinolones

18. Factors affecting selection of antibiotics “Host factors”
Ç. BÜKE Rational Use of Antibiotics
Factors affecting selection of antibiotics “Host factors”
Pregnancy
Many antimicrobial agents are capable of crossing the placenta
Antibiotics that can be safely used during pregnancy
Ampicillin, amoxicliilin
Cephalosporins
Eritromycin
INH, rifampicin, ethambuthol
Nitrofurantoin
Chloramphenicol

19. Factors affecting selection of antibiotics “Host factors”
Ç. BÜKE Rational Use of Antibiotics
Factors affecting selection of antibiotics “Host factors”
Pregnancy
Antibiotics that teratogenic during pregnancy;
TMP-SMX (in the 3th trimester of pregnancy)
Metronidazole (in the firs trimester of pregnancy)
Tetracyclines
Toxic effects during pregnancy
Aminoglycoides (The eighth cranial nerve toxicity for fetus)
Fluoroquinolones (Cartilage tissue destruction)

20. Factors affecting selection of antibiotics “Host factors”
Ç. BÜKE Rational Use of Antibiotics
Factors affecting selection of antibiotics “Host factors”
Renal failure
The serum concentration of aminoglycosides increases
Neurotoxicities can occur
Respiratory arrest and death
The doses of beta lactams, glycopeptides and aminoglycosides should be adjusted
Cockcroft-Gault formula estimates creatinine clearance
Creatinine clearance= (140 – Age) X weight / 72 X serum creat
For female 85% of results

21. Factors affecting selection of antibiotics “Host factors”
Ç. BÜKE Rational Use of Antibiotics
Factors affecting selection of antibiotics “Host factors”
Antibiotics that can be safely used in renal failure
Cephalosporins: Cephopherazon, Ceftriaxone
Macrolides: Erytromycin, claritromycin, azithromycin
Tetracyclines: Doxycycline, tigecycline, minocycline
Fluoroquinolones: Moxifloxacin
Others: Clindamycin, rifampin, chloramphenicol

22. Factors affecting selection of antibiotics “Host factors”
Ç. BÜKE Rational Use of Antibiotics
Factors affecting selection of antibiotics “Host factors”
Antibiotics that require dose adjustment in liver failure
Rifampin
Clindamycin
Chloramphenicol
Metronidazole
Cephalosporins (Cephopherazon, Ceftriaxone)
Sulphametoxazole

23. Do antibiotics reach concentrations in infection sites ?
Ç. BÜKE Rational Use of Antibiotics
Do antibiotics reach concentrations in infection sites ?
The entry of antibiotics into the infection sites depends on the
Compartment studied
Molecular size
Electric charge
Lipophilicity
Plasma protein binding
Affinity to active transport and
Host factors
Antibiotics should penetrate excellently
into the tissue and body fluids
Concentration of antibiotics in infection site should be equal and/or higher than the MIC of microorganisms

24. Does antibiotic combination therapy require ?
Ç. BÜKE Rational Use of Antibiotics
Does antibiotic combination therapy require ?
Rationale for combination antibiotic therapy
Synergy or additivity
Decrease resistance
Broaden spectrum
Synergy; >2 log greater activity for the combination than its most active constituent
Neutropenia and sepsis
MDR infections due to P.aeruginosa and A.baumannii
Tuberculosis and HIV infections
Antagonism; >2log decrease in activity for the combination than its most active constituent

25. What is the most effective and safe way to administer antibiotics ?
Ç. BÜKE Rational Use of Antibiotics
What is the most effective and safe way to administer antibiotics ?
Antibiotics can be given by a number of different routes including by mouth, injection into a vein or a muscle
In patients with mild to moderate infections, well-absorbed oral antimicrobial agents can be used
In patients with severe infections are treated with intravenous antimicrobial therapy
Bioavailability of fluoroquinolones, linezolide and TMP-SMX is 100% when they are given oral route.

26. Duration of antibiotic therapy
Ç. BÜKE Rational Use of Antibiotics
Duration of antibiotic therapy
In view of the deleterious effects of prolonged courses of antimicrobial agents, including;
The potential for adverse reactions
Problems with adherence
Selection of antibiotic-resistant organisms, and
High cost
A number of studies have tried to define the optimal duration of therapy, with an emphasis on shorter courses of therapy

27. Duration of antibiotic therapy
Ç. BÜKE Rational Use of Antibiotics
Duration of antibiotic therapy
Evidence supports limiting treatment of;
Uncomplicated UTI in women to 3 days,
Community-acquired pneumonia to 5 days
Ventilator-associated pneumonia to 8 days
The 8-day course was not sufficient for the treatment of
Infections due to P aeruginosa or
In immunocompromised

28. Duration of antibiotic therapy
Ç. BÜKE Rational Use of Antibiotics
Duration of antibiotic therapy
In other situations, a longer duration of therapy is clearly warranted eg, 4-6 weeks for
Endocarditis
Osteomyelitis
Intra-abdominal abscesses
Weeks to months for invasive fungal infections

29. Summary Appropriate use of antimicrobial agents involves;
Ç. BÜKE Rational Use of Antibiotics
Summary
Appropriate use of antimicrobial agents involves;
Obtaining an accurate diagnosis
Determining the need for and
Timing of antimicrobial therapy
Understanding how dosing affects the antimicrobial activities of different agents
Tailoring treatment to host characteristics, using the narrowest spectrum and
Shortest duration of therapy, and switching to oral agents as soon as possible

30. Ç. BÜKE Rational Use of Antibiotics

31. Thank you for your attention
Ç. BÜKE
Thank you for your attention