1. Mohammed Adel, B.Sc., PharmD
Clinical Pharmacy Department
Al-Ahrar General Hospital
Antibiotics:
Optimization of use & excellence of
outcome
1

2. • Principles of antibiotic use
• Time dependent activity
• Conc. Dependent activity
• Dual activity
• Indications for prophylaxis
Content
2

3. • Vancomycin:
• Mechanism of action
• Indications
• Dosing
• ADR
Content
3

4. Principles of antibiotic use
4
Drug
Dose
Delivery
Duration
De-escalation

5. Principles of antibiotic use
• Prevent infectionProphylactic
• Abort infectionPreemptive
• Initial control of infectionEmpiric
• Cure infection of know
etiology
Definitive
5

6. Principles of antibiotic use
• Prevent endocarditis
• Surgical prophylaxis
Prophylactic
• Against cytomegalovirus in
immune suppressed Pts
Preemptive
• CAP / HAP / VAPEmpiric
• Known etiologic organism &
susceptibility
Definitive
6
Pt= Patient CAP= Community Acquired pneumonia HAP= Hospital Acquired pneumonia VAP=Ventilator Acquired pneumonia

7. Principles of antibiotic use
7
• Initiate appropriate Abx therapy ASAP
Every 1 Hr delay = 8% increase in mortality
• Be aware of the site of infection
Local control
Treating most likely organism
ABX= antibiotics ASAP= as soon as possible

8. Principles of antibiotic use
8
• Possibility of resistance
Abx exposure
Known resistant colonization
Exposure to heath care facilities
Local Abx resistance pattern
• Host factor:
Allergy
Organ function status
ABX= antibiotics

9. Principles of antibiotic use
9
• Severity of illness
Using IV vs PO
Choosing upper end of the dosing range
Consider loading dose
Consider combination therapy
ABX= antibiotics IV= Intravenous
PO= Oral route

10. Principles of antibiotic use
10
• Treat infection… not colonization
• Cultures before Abx
Without delay
• Administer the 1st dose ASAP
• Monitor response to your Abx therapy
After 48-72 Hrs
Take routine Abx time out
ABX= antibiotics ASAP= as soon as possible

11. Principles of antibiotic use
11
• What is time out??
– Time out is the check point at which the
physician should answer these questions:
Does this patient have an infection that will respond
to antibiotics?
Is the patient on the right antibiotic(s), dose, and
route of administration?

12. Principles of antibiotic use
12
• What is time out??
– Time out is the check point at which the
physician should answer these questions:
Can a more targeted antibiotic be used to treat the
infection?
How long should the patient receive the
antibiotic(s)?

13. Principles of antibiotic use
13
• Re-evaluation of therapy depends on:
– Clinical response
– Microbiologic data
Organism ID
Local anti-biogram
Isolate susceptibility

14. Principles of antibiotic use
14
Chk your Pt
-ve Culture
No change Worse Improved
+ve Culture
Optimize

15. Principles of antibiotic use
15
Improving pt
Re-evaluate
the dose
Evaluate
Adverse
effects
1- If culture +ve: refine
your regimen
2- If culture –ve:
decide the duration

16. Principles of antibiotic use
16
Refining / de-
escalating
regimen
• Resolve bug drug mismatch
• Plan the likely duration
• De-escalation:
• Narrowing spectrum
• Eliminate redundancies
• Consider PO route

17. Time dependent activity
17
• Antibiotic needs more time to achieve 99.9% kill
target
• Serum conc. Is not important
• Observed in:
– β-lactams
– Macrolides
– Clindamycin
– Glycopeptides
• How to optimize time dependent effect?

18. 18
Time dependent activity

19. Concentration dependent activity
19
• Antibiotic needs higher concentration to
achieve 99.9% kill target
• Time of exposure Is not important
• Observed in:
– Aminoglycosides
– Fluoroquinolones
– Daptomycin
– Metronidazole
• How to optimize conc. dependent effect?

20. Concentration dependent activity
20
This is Genta !
:D

21. Concentration dependent activity
21
Which kill
better?

22. Mixed pattern activity
22
• Fluoroquinolones differs in it’s pattern
• It uses AUC24:MIC ratio
– For gm -ve ---< 125 for Cipro/Levo
– For gm +ve ---< 30 for Levo

23. 23
Mixed pattern activity
Also:
Daptomycin
Tigecycline
vancomycin

24. Indications for antibiotic prophylaxis
24
• Before dental procedures against IE
• Before surgical procedures
• Before GI endoscopy
• For SBP
• For recurrent UTI
IE= infective endocarditis GI= Gastro-intestinal SBP=
Spontaneous Bacterial Pretonitis UTI= Urinary tract infection

25. Vancomycin
25
• Glycopeptide antibiotic
• Mostly effective against Gm+ve Bacteria
• Always reserved for complicated or multidrug
resistant infections
• Characterized with mixed time/concentration killing
pattern

26. Vancomycin
26

27. Vancomycin
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• Against MRSA in HAP/VAP
• For bacterial IE
• GI chemosterlization (PO)
• Prosthetic joint infection
• CDAD
HAP= Hospital Acquired Pneumonia VAP= Ventilator Acquired Pneumonia IE=Infective
Endocarditis GI=Gastrointestinal
CDAD=C.difficile-Associated Diarrhea

28. Vancomycin
28
• Manufacturer’s labeling:
Usual dose: 500 mg every 6 hours or 1,000 mg
every 12 hours
• Alternate recommendations*:
15 to 20 mg/kg/dose every 8 to 12 hours
*(ASHP/IDSA/SIDP [Rybak, 2009]);

29. Vancomycin
29
• *Complicated infections in seriously ill
patients:
A loading dose of 25 to 30 mg/kg (based on
actual body weight)
*(ASHP/IDSA/SIDP [Rybak, 2009]);

30. Vancomycin
30
• Injection:
– More than10%:
Cardiovascular: Hypotension accompanied by flushing
Dermatologic: Erythematous rash on face and upper
body (red neck or red man syndrome - infusion rate
related)

31. Vancomycin
31
• Injection:
– From 1% to 10%:
Central nervous system: Chills, drug fever
Dermatologic: Rash
Hematologic: Eosinophilia, reversible neutropenia
Local: Phlebitis

32. Vancomycin
32
• Oral:
– More than10%:
Gastrointestinal: Abdominal pain, bad taste (with
oral solution), nausea

33. 33