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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)

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slide1

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

norman.dewhurst@utoronto.ca

May 7th, 2014

Evolutions Critical

Care Conference

slide2
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
learning objectives
Learning Objectives

By the end of this session, attendees should be

able to:

  • Review basic microbiologic principles
  • Provide an overview of commonly used ICU antimicrobials
  • Explore clinical syndromes from an antibiotic perspective
  • Highlight the importance of antimicrobial stewardship
outline
Outline
  • Microbiology Review
  • General Considerations
  • Antibiotic Options
  • Clinical Applications
  • Allergies
  • Dosing & Monitoring
microbiology review
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
gram staining
Gram Staining

Gram Stain

Gram Positives

Gram Negatives

gram positives
Gram Positives (+)

Gram Positive

Cocci

Bacilli

Pairs

Clusters/

Clumps

Pairs/

Chains

Staphylococcus

(MSSA, MRSA

Coagulase negative)

Streptococcus

Enterococcus

(E. faecalis)

(E. faecium)

Listeria

Bacillus spp.

Corynebacterium

Lactobacillus

Clostridium

gram negatives
Gram Negatives (-)

Gram Negative

Bacilli

(GNB)

Coccobacilli

Diplococci

Haemophilus

Pasteurella

Enterobacteriaceae

Pseudomonas

Neisseria

Moraxella

Acinetobacter

Fermenter

Enterobacteriaceae

COLIFORM

Non-fermenter

Pseudomonas

Stenotrophomonas

GNB

10

primary site of infection
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
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
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.

slide17

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

slide18

Cultures

before treatment

icu treatment principles
ICU Treatment Principles
  • Bactericidal
  • High doses
  • Intravenous
    • Serious infection
  • Non-toxic
other considerations
Other Considerations
  • Allergies
  • Local antibiogram
  • Is oral route feasible?
  • IV to PO stepdown?
mechanism of action
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

how do i treat this

“How do I treat this?”

IV. Clinical Applications

staphylococcus aureus
Staphylococcus aureus
  • Gram positive
  • Skin & soft tissue infections
  • VAP
  • Line infections
primary site of infection1
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

slide30

Staphylococcus aureus

Methicillin Sensitive

S. aureus

(MSSA)

Methicillin Resistant

S. aureus

(MRSA)

Cloxacillin

Cefazolin

Vancomycin

primary site of infection2
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
Community Acquired Pneumonia
  • S. pneumoniae
  • S. aureus
  • Gram-negative bacilli
  • H. influenzae
  • Legionella species

Ceftriaxone

Levofloxacin

Azithromycin

hap vap
HAP/VAP
  • S. pneumoniae
  • S. aureus
  • Gram-negative bacilli
  • H. influenzae
  • Legionella species
  • ? MRSA
  • ? Pseudomonas

Ceftriaxone

Levofloxacin

Azithromycin

Vancomycin

Anti-pseudomonal

slide41

HAP/VAP

< 5 days

> 5 days

Pseudomonas coverage

Ceftriaxone

Levofloxacin

? MRSA

Vancomycin

slide47

HAP/VAP

< 5 days

> 5 days

Pseudomonas coverage

Ceftriaxone

Pip/Tazo

Tobramycin

Levofloxacin

Ceftazidime

? MRSA

Vancomycin

primary site of infection3
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
MDRs / “Super bugs”
  • MRSA
    • Methicillin Resistant Staphylococcus aureus
  • VRE
    • Vancomycin Resistant Enterococcus
  • ESBL
    • Extended spectrum beta-lactamases
  • CRE / CRP
    • Carbapenemase Resistant Enterobacteriaceae
the antimicrobial pipeline
The Antimicrobial Pipeline

www.antibiotic-action.com

mdrs super bugs1
MDRs / “Super bugs”
  • MRSA
    • Methicillin Resistant Staphylococcus aureus
  • VRE
    • Vancomycin Resistant Enterococcus
  • ESBL
    • Extended spectrum beta-lactamases
  • CRE [ CRP / KPC / NDM ]
    • Carbapenemase Resistant Enterobacteriaceae
primary site of infection4
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

slide65

Clostridium difficile infection

Severe

  • Cr  1.5 times
  • WBC ≥ 15

Mild-moderate

Severe,

uncomplicated

Severe,

complicated

  • Ileus, megacolon
  • Hypotension/ shock

Metronidazole PO

Vancomycin PO

Vancomycin PO

+ Metronidazole IV

STOP unnecessary

antibiotics!

(+ consider rectal vancomycin if ileus)

allergies
“Allergies”

I’m allergic to…

Intolerance

Drug Allergy

Side Effect

Nausea

Vomiting

Diarrhea

Hyperkalemia

Bradycardia

Rash / Hives

SOB

Anaphylaxis

Consider:

Who is reporting the reaction

Timeframe (child vs. adult)

Nature of reaction

lactam allergy
-Lactam Allergy
  • 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%
drug dosing
Drug Dosing

Age

Weight

Drug Interactions

Indication / Severity

Consider

Drug Levels

Adverse Effects

Liver Dysfunction

Renal Dysfunction

Cannot always use a cookie cutter approach

Serum creatinine, BUN, urine output, dehydration, acute versus chronic, dialysis modality

therapeutic drug monitoring
Therapeutic Drug Monitoring
  • Guide and monitor dosing changes
  • Evaluate efficacy and toxicity
  • To assess penetration into body fluids (sites of infection)
drug levels
Drug Levels
  • Levels are typically done after 3 doses, with the 4th dose
  • Will be at steady-state equilibrium
slide76

Drug Levels

Stable Patient

Unstable Patient

Renal Failure

Talk to Pharmacist First

Wait until steady state

(With the 4th dose)

Check levels earlier

Check more frequently

outline1
Outline
  • Microbiology Review
  • General Considerations
  • Antibiotic Options
  • Clinical Applications
  • Allergies
  • Dosing & Monitoring