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Mohammed Adel, B.Sc., PharmDClinical Pharmacy Department

Al-Ahrar General Hospital

Antibiotics:Optimization of use & excellence of

outcome

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

Content

Antimicrobi

al Pattern

of killing

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•Vancomycin:• Mechanism of action • Indications • Dosing • ADR

Content

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Principles of antibiotic use

Drug

Dose

Delivery

Duration

De-escalation

The fiveDs

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Principles of antibiotic use

• Prevent infectionProphylactic

• Abort infectionPreemptive

• Initial control of infectionEmpiric

• Cure infection of know etiology Definitive

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Principles of antibiotic use

• Prevent endocarditis• Surgical prophylaxis

Prophylactic

• Against cytomegalovirus in immune suppressed Pts

Preemptive

• CAP / HAP / VAPEmpiric • Known etiologic

organism & susceptibility

Definitive Pt= Patient CAP= Community Acquired pneumonia HAP= Hospital Acquired pneumonia VAP=Ventilator Acquired pneumonia

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Principles of antibiotic use

• Initiate appropriate Abx therapy ASAPEvery 1 Hr delay = 8% increase in

mortality•Be aware of the site of infection

Local controlTreating most likely organism

ABX= antibiotics ASAP= as soon as possible

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Principles of antibiotic use

• Possibility of resistance Abx exposureKnown resistant colonizationExposure to heath care facilitiesLocal Abx resistance pattern

•Host factor:Allergy Organ function status

ABX= antibiotics

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Principles of antibiotic use

• Severity of illnessUsing IV vs POChoosing upper end of the dosing range

Consider loading dose Consider combination therapy

ABX= antibiotics IV= Intravenous PO= Oral route

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Principles of antibiotic use

• Treat infection… not colonization• Cultures before Abx

Without delay•Administer the 1st dose ASAP•Monitor response to your Abx therapy

After 48-72 HrsTake routine Abx time out

ABX= antibiotics ASAP= as soon as possible

Recommendati

on for practice

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Principles of antibiotic use

•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?

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Principles of antibiotic use

•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)?

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Principles of antibiotic use

•Re-evaluation of therapy depends on:– Clinical response– Microbiologic dataOrganism IDLocal anti-biogramIsolate susceptibility

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Principles of antibiotic use

Chk your Pt-ve Culture

No change Worse Improve

d

+ve Culture

Optimize

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Principles of antibiotic use

Improving ptRe-evaluate the dose

Evaluate Adverse effects

1- If culture +ve: refine your regimen2- If culture –ve: decide the duration

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Principles of antibiotic use

Refining / de-

escalating regimen

• Resolve bug drug mismatch

• Plan the likely duration• De-escalation:

• Narrowing spectrum• Eliminate

redundancies• Consider PO route

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Time dependent activity

• 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?

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Time dependent activity

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Concentration dependent activity• 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?

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Concentration dependent activity

This is Genta !

:D

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Concentration dependent activity

Which kill better?

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Mixed pattern activity• 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:DaptomycinTigecyclinevancomycin

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Indications for antibiotic prophylaxis

•Before dental procedures against IE•Before surgical procedures•Before GI endoscopy• For SBP• For recurrent UTIIE= infective endocarditis GI= Gastro-intestinal SBP= Spontaneous Bacterial Pretonitis UTI= Urinary tract infection

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Vancomycin

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

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Vancomycin

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Vancomycin

• 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

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Vancomycin

•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]);

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Vancomycin

• *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]);

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Vancomycin

• 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)

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Vancomycin

• Injection:– From 1% to 10%:Central nervous system: Chills, drug feverDermatologic: RashHematologic: Eosinophilia, reversible

neutropeniaLocal: Phlebitis

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Vancomycin

•Oral:– More than10%: Gastrointestinal: Abdominal pain, bad

taste (with oral solution), nausea

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Thank

you