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Knowledge is Power:
An Antibiotic Overview to Maximize
Outcomes in the Critically Ill
Norman Dewhurst, BScPhm, ACPR, PharmD, RPh
Clinical Pharmacy Specialist/Leader, Critical Care
St. Michael’s Hospital, Toronto, ON
Assistant Professor (Status)
Leslie Dan Faculty of Pharmacy, University of Toronto
[email protected]
May 7th, 2014
Evolutions Critical
Care Conference
1
Goal
• To review antibiotics & rationalize why we
choose the drugs we do for various
diseases / infection issues which comes
up in the critical care environment
2
Learning Objectives
By the end of this session, attendees should be
able to:
1. Review basic microbiologic principles
2. Provide an overview of commonly used ICU
antimicrobials
3. Explore clinical syndromes from an antibiotic
perspective
4. Highlight the importance of antimicrobial
stewardship
3
4
Outline
I. Microbiology Review
II. General Considerations
III. Antibiotic Options
IV. Clinical Applications
V. Allergies
VI. Dosing & Monitoring
5
“How do microbiology reports
help me treat a patient?”
I. Microbiology Review
6
Microbiology Review
• Gram Stain
• Blue / Purple = Gram positives
• Red / Pink = Gram negatives
• Bacterial Shape
• Bacilli = rods = long, thin
• Cocci = round, oval
• Ability to grow in presence/absence of oxygen
• Aerobes = ability to grow in the presence of oxygen
• Anaerobes = ability to grow in the absence of oxygen
7
Gram Staining
Gram Stain
Gram Positives
Gram Negatives
8
Gram Positives (+)
Gram Positive
Cocci
Bacilli
Pairs
Clusters/
Clumps
Pairs/
Chains
Streptococcus
Staphylococcus
(MSSA, MRSA
Coagulase
negative)
Listeria
Bacillus spp.
Corynebacterium
Lactobacillus
Clostridium
Enterococcus
(E. faecalis)
(E. faecium)
Spectrum
Staph.
(MSSA)
Strep.
Enter.
faecalis
Drug
?
?
?
GNB
Expanded
GNB
Pseudomonas
Gut
Anaerobes
9
Gram Negatives (-)
Gram Negative
Coccobacilli
Diplococci
Bacilli
(GNB)
Haemophilus
Pasteurella
Neisseria
Moraxella
Acinetobacter
Enterobacteriaceae
Pseudomonas
Fermenter
Non-fermenter
Enterobacteriaceae
Pseudomonas
Stenotrophomonas
GNB
COLIFORM
Spectrum
Drug
Staph.
(MSSA)
Strep.
Enter.
faecalis
GNB
Expanded
GNB
Pseudomonas
?
?
?
Gut
Anaerobes
10
10
“What do I need to consider
before treatment?”
II. General Considerations
11
12
Primary Site of Infection
CVC / Line infection
Respiratory tract infection
Intra-abdominal
Urinary Tract
Skin & Soft
Tissue Infection
Other
Unknown Origin
Image: http://en.wikipedia.org/wiki/Commons:File:Human_body_features.svg
Management Decisions
•
•
•
•
•
•
•
•
•
•
Do the bacteria represent infection or colonisation?
Can the condition be treated without antibiotics?
Can this infection be treated with antibiotics alone?
What is the most appropriate antibiotic(s)?
– Pharmacotherapeutic considerations?
– Alternatives in case of allergy?
Side effects, contraindications?
OPAT?
Is it hospital acquired or community acquired?
How to screen patients for MDR organisms?
How to prevent the spread of MDR in wards?
Which antibiotics to avoid in MDR positive patients?
Bhattacharya S. J Med Microbiol. 2006 Jan;24(1):20-4.
Infection versus Colonisation?
• a) Specimen type?
• Physiologically sterile sites
• Non-sterile sites
• Catheterised specimens
• b) Inflammatory parameters of the patient
• WBC, CRP, ESR
• c) General condition of the patient
• Temperature
• Blood pressure, pulse rate
• Arterial oxygen saturation, inotrope requirement,
organ support requirement
Bhattacharya S. J Med Microbiol. 2006 Jan;24(1):20-4.
16
Therapeutic Thought Process
Indication
Know the infection you’re treating
Efficacy / Spectrum
Assess alternatives, drug of choice?
Safety
Maximize dosing, monitor, minimize toxicity
Cost
Address above before considering cost
Convenience
Considerations for discharge
17
Cultures
before
treatment
18
ICU Treatment Principles
• Bactericidal
• High doses
• Intravenous
Serious infection
• Non-toxic
Other Considerations
•
•
•
•
Allergies
Local antibiogram
Is oral route feasible?
IV to PO stepdown?
“What are my antibiotic
options?”
III. Antibiotic Options
21
Mechanism of Action
Cell Wall Synthesis
Penicillins
Cephalosporins
Carbapenems
Vancomycin
Cell Wall Integrity
Beta-lactamases
DNA Synthesis
Metronidazole
DNA Gyrase
Fluoroquinolones
RNA Polymerase
Rifampin
Protein (50S)
Synthesis
Macrolides
Chloramphenicol
Clindamycin
Lincomycin
Protein (30S)
Synthesis
Tetracyclines
Streptomycin
Spectinomycin
Kanamycin
Phospholipid membranes
Polymyxins
Therapeutic Options
Penicillins
Cephalosporins
Carbapenems
Penicillin
Cefazolin (1st)
Imipenem
Cloxacillin
β-Lactamase Inhibitor
Amoxicillin/
Ampicillin
Clavulanate
Ceftazidime (3rd)
Doripenem
Tazobactam
Cefipime (4th)
Ertapenem
Piperacillin
Ceftriaxone
(3rd)
Meropenem
Ceftaroline (5th)
Ticarcillin
Macrolides
Aminoglycosides
Fluoroquinolones
Vancomycin
Erythromycin
Gentamicin
Ciprofloxacin
Metronidazole
Clarithromycin
Tobramycin
Levofloxacin
Clindamycin
Azithromycin
Amikacin
Moxifloxacin
Tigecycline
Linezolid
Fosfomycin
Colistin
Daptomycin
Nitrofurantoin
Trimethoprim/
Sulfamethoxazole
23
24
Therapeutic Options
Penicillins
Cephalosporins
Carbapenems
Penicillin
Cefazolin (1st)
Imipenem
Cloxacillin
β-Lactamase Inhibitor
Amoxicillin/
Ampicillin
Clavulanate
Ceftazidime (3rd)
Doripenem
Tazobactam
Cefipime (4th)
Ertapenem
Piperacillin
Ceftriaxone
(3rd)
Meropenem
Ceftaroline (5th)
Ticarcillin
Macrolides
Aminoglycosides
Fluoroquinolones
Vancomycin
Erythromycin
Gentamicin
Ciprofloxacin
Metronidazole
Clarithromycin
Tobramycin
Levofloxacin
Clindamycin
Azithromycin
Amikacin
Moxifloxacin
Tigecycline
Linezolid
Fosfomycin
Colistin
Daptomycin
Nitrofurantoin
Trimethoprim/
Sulfamethoxazole
25
Therapeutic Options
Penicillins
Cephalosporins
Carbapenems
Cloxacillin
Cefazolin (1st)
Imipenem
Piperacillin
Ceftriaxone (3rd)
Meropenem
β-Lactamase Inhibitor
Ceftazidime (3rd)
Ertapenem
Tazobactam
Macrolides
Aminoglycosides
Fluoroquinolones
Vancomycin
Azithromycin
Gentamicin
Ciprofloxacin
Metronidazole
Tobramycin
Levofloxacin
Trimethoprim/
Sulfamethoxazole
Moxifloxacin
26
“How do I treat this?”
IV. Clinical Applications
27
Staphylococcus aureus
• Gram positive
• Skin & soft tissue infections
• VAP
• Line infections
28
Primary Site of Infection
CVC / Line infection
Respiratory tract infection
Intra-abdominal
Urinary Tract
Skin & Soft
Tissue Infection
Other
Unknown Origin
Image: http://en.wikipedia.org/wiki/Commons:File:Human_body_features.svg
Staphylococcus aureus
Methicillin Sensitive
S. aureus
(MSSA)
Methicillin Resistant
S. aureus
(MRSA)
Cloxacillin
Cefazolin
Vancomycin
30
CLOXACILLIN
Mechanism
of Action
• Cell wall synthesis inhibitor
Spectrum
Staph.
(MSSA)
Strep.
Enter.
faecalis
GNB
Expanded
GNB
Pseudomonas
Gut
Anaerobes
Cloxacillin
+
+
-
-
-
-
-
Uses
• MSSA VAP, Cellulitis
• Endocarditis
Standard
Dosing
• 1-2 g IV q6h
• Endocarditis: 2 g IV q4h
Side Effects • Hypersensitivity reactions
• Seizures
Cautions/
Contraindications
• Allergy / anaphylaxis
• No need to adjust in renal
dysfunction
• Antibiotic Associated Diarrhea
CEPHALOSPORINS
Mechanism
of Action
Cell-wall synthesis inhibitors
Spectrum
Staph.
(MSSA)
Strep.
Enter.
faecalis
GNB
Expanded
GNB
Pseudomonas
Gut
Anaerobes
Cefazolin
+
+
-
+
-
-
-
Ceftriaxone
+
+
-
+
+
-
-
Ceftazidime
-
-
-
+
+
+
-
Uses
• Cefazolin: surgical prophylaxis
• Ceftriaxone: CAP/HAP/VAP
Standard
Dosing
• Cefazolin 1-2 g IV q8h
• Ceftriaxone 1-2 g IV q24h
• Ceftazidime 1-2 g IV q8h
Common
• Hypersensitivity reactions
Side Effects • Seizures
Cautions/
Contraindications
• Allergy / anaphylaxis
• Ceftazidime: VAP
• Thrombocytopenia
• Clostridium difficile
-Lactams
Side Effects
• Hypersensitivity reactions
• Seizures
• Antibiotic Associated Diarrhea
• Thrombocytopenia
• C. difficile
Cautions/
• Allergy / anaphylaxis
Contraindications
VANCOMYCIN
Mechanism
of Action
Spectrum
IV
• Cell wall synthesis inhibitor
Staph.
(MSSA)
Strep.
Enter.
faecalis
GNB
Expanded
GNB
Pseudomonas
Gut
Anaerobes
+
+
+
-
-
-
-
-
-
-
C. diff +
(+ MRSA)
-
Oral
(+ E. faecium)
-
-
Uses
• MRSA infection
• Meningitis (Until resistance R/O)
• C. difficile (oral only)
Standard
Dosing
•
•
•
•
• PO (C.diff): 125 mg PO q6h
IV Load: 15-25 mg/kg (up to 2 g)
IV Maintenance: 1 g IV q8-12h
Level just prior to 4th dose
Random level anytime
On combo:
Caution when
d/c’ing IV or
PO
Side Effects • Nephrotoxicity
• Red Man’s syndrome (facial and torso flushing, hypotension)
Cautions/
CIs
• Dosing in renal failure
35
Primary Site of Infection
CVC / Line infection
Respiratory tract infection
Intra-abdominal
Urinary Tract
Skin & Soft
Tissue Infection
Other
Unknown Origin
Image: http://en.wikipedia.org/wiki/Commons:File:Human_body_features.svg
Community Acquired Pneumonia
• S. pneumoniae
•
•
•
•
S. aureus
Gram-negative bacilli
H. influenzae
Legionella species
Ceftriaxone
Levofloxacin
Azithromycin
37
MACROLIDES
Mechanism
of Action
Spectrum
Protein Synthesis Inhibitor (50S ribosome)
Staph.
(MSSA)
Strep.
Enter.
faecalis
GNB
Erythromycin
+/-
Atypicals +
Clarithromycin
+
Atypicals +
Azithromycin
-
+
-
Expanded
GNB
Pseudomonas
Gut
Anaerobes
-
-
-
Atypicals +
Uses
• CAP (atypical coverage) + beta-lactam
Standard
Dosing
• Azithromycin 500 mg IV/po X 1, then 250 mg IV/po daily (X 4 days)
• Azithromycin 500 mg IV/po q24h (X 5 days)
Common
• QTc prolongation
Side Effects • LFT elevation
Cautions/
Contraindications
• Prolonged QTc
• Diarrhea
• Ototoxicity
FLUOROQUINOLONES
Mechanism
of Action
DNA Synthesis Inhibitor
Spectrum
Staph.
(MSSA)
Strep.
Enter.
faecalis
GNB
Expanded
GNB
Pseudomonas
Gut
Anaerobes
Ciprofloxacin
-
-
-
+
+
+
-
Levofloxacin
+
+
-
+
+
-
-
Moxifloxacin
+
+
-
+
+
-
+
Uses
• Cipro: gram negative
infections
Standard
Dosing
• Ciprofloxacin 400 mg IV q8-12h
• Levofloxacin 750 mg IV q24h
• Moxifloxacin 400 mg IV q24h
Common
• QTc prolongation
Side Effects • Seizure
Cautions/
Contraindications
• Levofloxacin: CAP/HAP/VAP
• Moxifloxacin: Intra-abdominal
• Tendon rupture
• LFT elevation
• QTc prolongation
• Use within previous 3 months (resistance)
HAP/VAP
• S. pneumoniae
•
•
•
•
S. aureus
Gram-negative bacilli
H. influenzae
Legionella species
• ? MRSA
• ? Pseudomonas
Ceftriaxone
Levofloxacin
Azithromycin
Vancomycin
Anti-pseudomonal
40
HAP/VAP
< 5 days
> 5 days
Pseudomonas coverage
Ceftriaxone
Levofloxacin
? MRSA
Vancomycin
Anti-Pseudmonal
Penicillins
Cephalosporins
Carbapenems
Penicillin
Cefazolin (1st)
Imipenem
Cloxacillin
β-Lactamase Inhibitor
Amoxicillin/
Ampicillin
Clavulanate
Ceftazidime (3rd)
Doripenem
Tazobactam
Cefipime (4th)
Ertapenem
Piperacillin
Ceftriaxone
(3rd)
Meropenem
Ceftaroline (5th)
Ticarcillin
Macrolides
Aminoglycosides
Fluoroquinolones
Vancomycin
Erythromycin
Gentamicin
Ciprofloxacin
Metronidazole
Clarithromycin
Tobramycin
Levofloxacin
Clindamycin
Azithromycin
Amikacin
Moxifloxacin
Tigecycline
Linezolid
Fosfomycin
Colistin
Daptomycin
Nitrofurantoin
Trimethoprim/
Sulfamethoxazole
42
Anti-Pseudomonal
Penicillins
Cephalosporins
Carbapenems
Cloxacillin
β-Lactamase Inhibitor
Cefazolin (1st)
Imipenem
Piperacillin
Tazobactam
Ceftriaxone (3rd)
Meropenem
Ceftazidime (3rd)
Ertapenem
Macrolides
Aminoglycosides
Fluoroquinolones
Vancomycin
Azithromycin
Gentamicin
Ciprofloxacin
Metronidazole
Tobramycin
Levofloxacin
Clindamycin
Moxifloxacin
Trimethoprim/
Sulfamethoxazole
43
Anti-Pseudomonal
Penicillins
β-Lactamase Inhibitor
Piperacillin
Tazobactam
Cephalosporins
Ceftazidime
(3rd)
Not empiric
Carbapenems
Imipenem
Meropenem
Aminoglycosides
Tobramycin
Reserve Use
Nephrotoxicity
Ototoxicity
Fluoroquinolones
Ciprofloxacin
High Resistance
44
PIPERACILLIN/TAZOBACTAM
Mechanism
of Action
• Cell wall synthesis inhibitor + beta-lactamase inhibitor
Spectrum
Staph.
(MSSA)
Strep.
Enter.
faecalis
GNB
Expanded
GNB
Pseudomonas
Gut
Anaerobes
Pip/tazo
+
+
+
+
+
+
+
Uses
• Broad spectrum / poly-microbial infections
• Severe intra-abdominal infections
• Pip/tazo: HAP/VAP (requiring pseudomonas coverage)
Standard
Dosing
• Pip/tazo: 4.5 g IV q6h
Side Effects • Hypersensitivity reactions
• Seizures
Cautions/
Contraindications
• Allergy / anaphylaxis
• Antibiotic Associated Diarrhea
AMINOGLYCOSIDES
Mechanism
of Action
Protein Synthesis Inhibitor (30S ribosome)
Spectrum
Staph.
(MSSA)
Strep.
Enter.
faecalis
GNB
Expanded
GNB
Pseudomonas
Gut
Anaerobes
Gentamicin
-
-
-
+
+
+
-
Tobramycin
-
-
-
+
+
++
-
Uses
• Gram negative infections
Standard
Dosing
• 1-2 mg/kg IV q8h
• 5-7 mg/kg IV q24h
Common
• Nephrotoxicity
Side Effects • Ototoxicity
Cautions/
Contraindications
• Renal failure
Traditional drug monitoring:
• Peak – 30 min post infusion
• Trough – just prior to dose
Once daily:
• 8 hour random only
HAP/VAP
< 5 days
> 5 days
Pseudomonas coverage
Ceftriaxone
Pip/Tazo
Levofloxacin
Tobramycin
Ceftazidime
? MRSA
Vancomycin
48
Primary Site of Infection
CVC / Line infection
Respiratory tract infection
Intra-abdominal
Urinary Tract
Skin & Soft
Tissue Infection
Other
Unknown Origin
Image: http://en.wikipedia.org/wiki/Commons:File:Human_body_features.svg
MDRs / “Super bugs”
• MRSA
– Methicillin Resistant Staphylococcus aureus
• VRE
– Vancomycin Resistant Enterococcus
• ESBL
– Extended spectrum beta-lactamases
• CRE / CRP
– Carbapenemase Resistant Enterobacteriaceae
50
51
Resistance Alarms
IDSA
WHO
The Antimicrobial Pipeline
www.antibiotic-action.com
54
ESBL Infections
Therapeutic Options
Penicillins
Cephalosporins
Carbapenems
Penicillin
Cefazolin (1st)
Imipenem
Cloxacillin
β-Lactamase Inhibitor
Amoxicillin/
Ampicillin
Clavulanate
Ceftazidime (3rd)
Doripenem
Tazobactam
Cefipime (4th)
Ertapenem
Piperacillin
Ceftriaxone
(3rd)
Meropenem
Ceftaroline (5th)
Ticarcillin
Macrolides
Aminoglycosides
Fluoroquinolones
Vancomycin
Erythromycin
Gentamicin
Ciprofloxacin
Metronidazole
Clarithromycin
Tobramycin
Levofloxacin
Clindamycin
Azithromycin
Amikacin
Moxifloxacin
Tigecycline
Linezolid
Fosfomycin
Colistin
Daptomycin
Nitrofurantoin
Trimethoprim/
Sulfamethoxazole
56
Therapeutic Options
Penicillins
Cephalosporins
Carbapenems
Penicillin
Cefazolin (1st)
Imipenem
Cloxacillin
β-Lactamase Inhibitor
Amoxicillin/
Ampicillin
Clavulanate
Ceftazidime (3rd)
Doripenem
Tazobactam
Cefipime (4th)
Ertapenem
Piperacillin
Ceftriaxone
(3rd)
Meropenem
Ceftaroline (5th)
Ticarcillin
Macrolides
Aminoglycosides
Fluoroquinolones
Vancomycin
Erythromycin
Gentamicin
Ciprofloxacin
Metronidazole
Clarithromycin
Tobramycin
Levofloxacin
Clindamycin
Azithromycin
Amikacin
Moxifloxacin
Tigecycline
Linezolid
Fosfomycin
Colistin
Daptomycin
Nitrofurantoin
Trimethoprim/
Sulfamethoxazole
57
CARBAPENEMS
Mechanism
of Action
Cell wall synthesis inhibitors
Spectrum
Staph.
(MSSA)
Strep.
Enter.
faecalis
GNB
Expanded
GNB
Pseudomonas
Gut
Anaerobes
Imipenem
+
+
+
+
+
+
+
Meropenem
+
+
+(?)
+
+
+
+
Ertapenem
+
+
-
+
+
-
+
Uses
• ESBL infections
• Beta-lactam allergy
Standard
Dosing
• Imipenem 500 mg IV q6h
• Ertapenem 1 g IV q24h
Common
• Hypersensitivity reactions
Side Effects • Seizures
Cautions/
Contraindications
• Allergy / anaphylaxis
• Polymicrobial infection
BROAD
SPECTRUM
• Thrombocytopenia
• Eosinophilia
MDRs / “Super bugs”
• MRSA
– Methicillin Resistant Staphylococcus aureus
• VRE
– Vancomycin Resistant Enterococcus
• ESBL
– Extended spectrum beta-lactamases
• CRE [ CRP / KPC / NDM ]
– Carbapenemase Resistant Enterobacteriaceae
59
CRE Infections
Therapeutic Options
Penicillins
Cephalosporins
Carbapenems
Penicillin
Cefazolin (1st)
Imipenem
Cloxacillin
β-Lactamase Inhibitor
Amoxicillin/
Ampicillin
Clavulanate
Ceftazidime (3rd)
Doripenem
Tazobactam
Cefipime (4th)
Ertapenem
Piperacillin
Ceftriaxone
(3rd)
Meropenem
Ceftaroline (5th)
Ticarcillin
Macrolides
Aminoglycosides
Fluoroquinolones
Vancomycin
Erythromycin
Gentamicin
Ciprofloxacin
Metronidazole
Clarithromycin
Tobramycin
Levofloxacin
Clindamycin
Azithromycin
Amikacin
Moxifloxacin
Tigecycline
Linezolid
Fosfomycin
Colistin
Daptomycin
Nitrofurantoin
Trimethoprim/
Sulfamethoxazole
61
62
SEPTRA (Trimethoprim & Sulfamethoxazole)
Mechanism
of Action
Spectrum
Septra
Protein Synthesis Inhibitors
(dihydrofolate reductase & dihydropteroate synthetase inhibitors)
Staph.
(MSSA)
+
(+ MRSA)
Strep.
Enter.
faecalis
GNB
Expanded
GNB
Pseudomonas
Gut
Anaerobes
-
-
+
+
-
-
Uses
• Urinary tract infections
• MRSA infections
• Skin and soft tissue infections
Standard
Dosing
• 15 mg/kg of TMP component / 24 hours (divided q6-q8h)
• 2 DS tabs po q8h (~for 60 kg patient, 6 DS tabs per day)
Common
• Hyperkalemia
Side Effects • Hypoglycemia
Cautions/
Contraindications
• Renal failure
• Skin reactions • Bone marrow suppression
• Cystalluria
• Hepatotoxicity
Primary Site of Infection
CVC / Line infection
Respiratory tract infection
Intra-abdominal
Urinary Tract
Skin & Soft
Tissue Infection
Other
Unknown Origin
Image: http://en.wikipedia.org/wiki/Commons:File:Human_body_features.svg
Clostridium difficile infection
Severe
Mild-moderate
• Cr  1.5 times
• WBC ≥ 15
Severe,
uncomplicated
Severe,
complicated
• Ileus, megacolon
• Hypotension/
shock
Metronidazole PO
Vancomycin PO
STOP unnecessary
antibiotics!
Vancomycin PO
+ Metronidazole IV
(+ consider rectal
vancomycin if ileus)
METRONIDAZOLE
Mechanism
of Action
Deactivation of cysteine bearing enzymes, binds to proteins and DNA
Spectrum
Staph.
(MSSA)
Strep.
Enter.
faecalis
GNB
Expanded
GNB
Pseudomonas
Metronidazole
-
-
-
-
-
-
Uses
• Intra-abdominal Infections
• C. difficile infections
Standard
Dosing
• 500 mg IV/po q12h
Common
• Peripheral neuropathy
Side Effects • Disulfiram like-reaction
Cautions/
Contraindications
• Long-term use (> 1 month)
Gut
Anaerobes
+
(C.diff +)
• C. difficile: 500 mg IV/po q8h
“What about allergies?”
V. Allergies
67
“Allergies”
I’m allergic to…
Side Effect
Intolerance
Drug Allergy
Nausea
Vomiting
Diarrhea
Hyperkalemia
Bradycardia
Rash / Hives
SOB
Anaphylaxis
Consider:
Who is reporting the reaction
Timeframe (child vs. adult)
Nature of reaction
-Lactam Allergy
Penicillins
Cephalosporins
Carbapenems
Cloxacillin
Cefazolin
Meropenem
Ampicillin / Amoxicillin
Ceftriaxone
Imipenem
Piperacillin-tazobactam
Ceftazidime
Ertapenem
• Non-pruritic morbilliform & macupaular rash (amoxicillin)
• Idiopathic, not a contraindication to repeat
• Penicillins & Cephalosporins: 8-10% (1970’s) – Flawed studies
• Depends on side chains
• Cefazolin not expected to cross react with any
penicillin or cephalosporin
• Penicillins & Carbapenems ~1%
69
“Is the dose correct?”
“When do I do a drug level?”
VI. Dosing & Monitoring
70
Drug Dosing
Age
Weight
Drug
Interactions
Indication /
Severity
Consider
Adverse
Effects
Drug Levels
Renal
Dysfunction
Liver
Dysfunction
Serum creatinine, BUN, urine output, dehydration, acute versus chronic, dialysis modality
Cannot always
use a cookie
cutter approach
Mistakes happen
Therapeutic Drug Monitoring
• Guide and monitor dosing changes
• Evaluate efficacy and toxicity
• To assess penetration into body fluids
(sites of infection)
73
Drug Levels
• Levels are typically done after 3 doses, with the 4th dose
• Will be at steady-state equilibrium
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Drug Levels
Unstable Patient
Renal Failure
Stable Patient
Talk to
Pharmacist
First
Wait until steady state
(With the 4th dose)
Check levels earlier
Check more
frequently 76
Outline
I. Microbiology Review
II. General Considerations
III. Antibiotic Options
IV. Clinical Applications
V. Allergies
VI. Dosing & Monitoring
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Thank you!
Questions?
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