This document discusses principles of antibiotic use and optimization. It covers time dependent and concentration dependent antibiotic activity and mixed patterns. Prophylactic, preemptive, empiric and definitive antibiotic uses are defined. Vancomycin mechanisms of action, indications, dosing and adverse drug reactions are reviewed. Optimization includes appropriate dosing, duration, de-escalation and monitoring treatment response.

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
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• 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
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• 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
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• 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
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• 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
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• 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
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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
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• 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
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• 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
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This is Genta !
:D

21. Concentration dependent activity
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Which kill
better?

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

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Mixed pattern activity
Also:
Daptomycin
Tigecycline
vancomycin

24. Indications for antibiotic prophylaxis
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• 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
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• 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
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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
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• 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
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• *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
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• 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
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• Injection:
– From 1% to 10%:
Central nervous system: Chills, drug fever
Dermatologic: Rash
Hematologic: Eosinophilia, reversible neutropenia
Local: Phlebitis

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

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