General Principles of Antimicrobial Selection - 2018

GENERAL PRINCIPLES OF
ANTIMICROBIAL SELECTION
Arwa M. Amin Mostafa
PhD & M.Pharm Clinical Pharmcy, DipMgt, B.Pharm.

ARWA M. AMIN
WHAT WE WILL DISCUSS TODAY?
Types of Antimicrobial Therapy
Systematic approach for Antimicrobial selection
• Confirming the Presence of Infection
• Identifying the Pathogen
• Selecting Rational Antimicrobial Therapy
• Monitoring Therapeutic Response

ARWA M. AMIN
ANTIMICROBIAL THERAPY
Antimicrobial Therapy is the use of Antimicrobial Drug to
treat Infections
Antimicrobial Drugs Kill or Inhibit the growth of Microbes such
as Bacteria
Antimicrobial

ARWA M. AMIN
TYPES OF ANTIMICROBIAL THERAPY
Antimicrobial
Microbes

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ANTIMICROBIAL
Therapy Definitive Therapy
Empiric Therapy
Prophylactic Therapy

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ANTIMICROBIAL
Therapy
Empiric Therapy
Antimicrobial Therapy begun BEFORE
Identifying the Microbe

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ANTIMICROBIAL
Therapy
Empiric Therapy
Antimicrobial Therapy begun BEFORE
Identifying the Microbe
Use Broad Spectrum Antibiotic
(Fight all possible Microbes)

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Definitive Therapy
ANTIMICROBIAL
Therapy
Antimicrobial Therapy begun AFTER Identifying
the Microbe

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Definitive Therapy
ANTIMICROBIAL
Therapy
Antimicrobial Therapy begun AFTER Identifying
the Microbe
Use Narrow Spectrum Antibiotic
(Fight only the Identified Microbe)

ARWA M. AMIN
ANTIMICROBIAL
Therapy
Antimicrobial Therapy Given before
surgery/Procedure to Prevent a Bacterial Infection

ARWA M. AMIN
ANTIMICROBIAL
Therapy
Antimicrobial Therapy Given before
surgery/Procedure to Prevent a Bacterial Infection
Give Antibiotic before surgery
(Fight possible infection due to surgery)

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SYSTEMATIC APPROACH FOR ANTIMICROBIAL SELECTION
A. Confirm the Presence of Infection
B. Identify the Pathogen
C. Select Rational Antimicrobial Therapy
D. Monitor Therapeutic Response

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A- Confirm the Presence of Infection
How to confirm that the patient has an
Infection?
1. History and Physical Examination
➢ Traveling
➢ Playing with Pets
➢ Eating Food which contains Infection
➢ Family illness
➢ Other family members has certain infection.

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A- Confirm the Presence of Infection
2. Signs and Symptoms
 Fever (Temp > 37 °C) Orally
 Elevated White Blood Cells (WBCs) or Leukocytosis
 Pain
 Inflammation
 Swelling, Erythema, Tenderness and Purulent
drainage.

ARWA M. AMIN
WHAT MAY CAUSE FEVER OTHER THAN INFECTION?
Fever can be due to other conditions
such as,
Malignant Tumors
Rheumatoid Arthritis
Liver Cirrhosis
Some drugs may induce Fever:
Some Drugs may induce fever which
should NOT be confused with Infectious
fever.
Drug Induced fever is persistent fever in
the absence of Infection or any other
cause.

ARWA M. AMIN
WHAT CAN CAUSE FEVER OTHER THAN INFECTION?
Medications which may cause fever:
Antimicrobials
 e.g. Vancomycin, Streptomycin
Cardiovascular Medication
 e.g. Captopril
Anticonvulsant
 e.g. Phenytoin
Analgesics
 e.g. Ibuprofen
Immunization (Vaccines):
Pneumococcal vaccine

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B- Identify the Pathogen
Infected body material should be sampled
(e.g. Urine, Blood, spinal fluids, CSF, Throat
swap) and analyzed to indicate the
infecting pathogen.
Gram Stain: G +, G - Bacteria
Acid-fast Stain: Mycobacteria
or Actinomycetes
Culture & Sensitivity Testing
A: Non Acid-Fast,
B: Acid-FastCulture

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GRAM STAINING
Is the Bacteria G + or G - ?

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ACID-FAST STAIN
Acid-Fast or Non-Acid-Fast?

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CULTURE AND ANTIMICROBIAL SENSITIVITY TESTING
Which Antibiotic the Bacteria is sensitive for ?
Antimicrobial Susceptibility
test tell us which Antibiotic
(AB) the Bacteria or fungal
Infection is sensitive for
(R, I, S), particularly in
difficult-to-treat infections
A: In-effective Antibiotic; Bacteria is Resistant (R)
B: Intermediately effective Antibiotic, Bacteria is intermediately susceptible (I)
C: Very Effective Antibiotic, Bacteria is susceptible (S)
Disk Diffusion (Kirby-Bauer disks)

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B- Identify the Pathogen
After Identifying the Pathogen (Microbe), Antimicrobial
Therapy should be directed based on the culture and
Antimicrobial Sensitivity results (Definitive Therapy), but the
Antimicrobial drug should be Rationally selected.

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C- Select Rational Antimicrobial Therapy
Factors which should be considered for the Rational
selection of Antimicrobial Therapy:
Host Factors
Drug Factors
The need for using Combination Antimicrobial Therapy

ARWA M. AMIN
Host Factors
When Initiating antimicrobial therapy in a patient, the following
factors should be considered:
 Allergy or history of adverse drug reaction
 If the patient has history of Allergic Anaphylaxis to Penicillin’s,
Avoid penicillin’s, Cephalosporins and Carbapenems.
Age of the patient
 Renal Function affected by Age
Metabolic or Genetic Variation

ARWA M. AMIN
Host Factors… cont.
Pregnancy/Lactation
Antibiotics which are considered generally safe
in Pregnancy:
 Penicillin’s
 Cephalosporins
 Erythromycin
 Clindamycin (with caution)
Antibiotics to Avoid in Pregnancy:
 Tetracyclines

ARWA M. AMIN
Host Factors cont..
Renal and Hepatic Function
Patient with renal or Hepatic dysfunction may have higher
serum concentration of the Antimicrobial Drug (Drug
Accumulation) which necessitates dose adjustment
Concomitant Diseases
Is the patient having Cardiovascular diseases (CVDs) or
currently taking any medications for any other condition?
Concomitant Drug Therapy: To avoid Drug-Drug
Interaction

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Drug Factors
Pharmacodynamics and Pharmacokinetics Parameters
Side Effect
Tissue Penetration
Bacterial Resistance

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Drug Factors:
Pharmacodynamics and Pharmacokinetics Parameters
Antimicrobial Bactericidal Activity is affected by certain
parameters:
 Minimum Inhibitory Concentration (MIC):
The lowest concentration of antibiotics that inhibits bacterial growth.
 Area Under the Curve (AUC) of the antibiotic
 Maximum Plasma Concentration

ARWA M. AMIN
Concentration Or Time-dependent Antimicrobial Bactericidal
Effect
 Bactericidal Effect of some Antibiotics is Concentration dependent
 Depends on Peak/MIC (AUC/MIC)
 e.g. Aminoglycosides and Fluoroquinolones
 Bactericidal Effect of some Antibiotics is Time dependent
 Depends on the duration that drug concentration exceed the MIC
 e.g. β-Lactams: Penicillin's and cephalosporins

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Peak/MIC , AUC/MIC, T>MIC
Aminoglycosides &
Fluoroquinolones
β-Lactams

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Pharmacodynamics and Pharmacokinetics Parameters
 Drug-Drug Interaction and Drug-Food Interaction
 Penicillin's and Cephalosporins with Aspirin may block excretion of β-
lactams
Use together if prolonged ↑↑ Concentration of β-lactams is required
Avoid if prolonged ↑↑ Concentration of β-lactams is NOT required
 Tetracyclines with Antacids or Iron or Calcium may decrease the
absorption of Tetracyclines
Separate by 2 h
 Macrolides or Tetracyclines with Digoxin may reduce digoxin
bioavailability and metabolism
Monitor Digoxin Serum Drug concentration (SDC) or Avoid using together
if possible.

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Drug Factors:
Side-Effects
 Allergic Reaction
e.g. Penicillin's
 Risk of reduction in renal function while using
Aminoglycosides or Vancomycin, particularly in patients
with renal impairment
Avoid if possible or Reduce the Dosage

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Drug Factors:
Tissue Penetration
Importance of Tissue penetration depends
on the site of Infection.
e.g. Central Nervous System (CNS) Infection
(e.g. Meningitis) requires Antimicrobial which
have high penetration and concentration in
the cerebrospinal fluids (CSF)
 If the drug does NOT penetrate CSF with
sufficient concentration; either to avoid
using it or it should be instilled directly.

ARWA M. AMIN
Drug Factors
 Bacterial Resistance
 In Empiric Therapy; Avoid using Antimicrobial
drug when resistant pathogen is suspected for
that Antimicrobial Drug.
 Use Antimicrobial Drug with broader spectrum
activity.
 Or Use Combination Antimicrobial Therapy to
broaden the spectrum of coverage.

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The Need for using Combination Antimicrobial Therapy
Combination of Antimicrobial Therapy is the use of ≥ 2
Antimicrobial drugs to treat patient’s infection.

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Reasons of using Combination Antimicrobial Therapy
To Broaden the spectrum of coverage in Empiric
Therapy.
To Avoid toxic doses of single Antimicrobial
e.g. Avoiding high dose of Aminoglycosides in
patients with Renal Impairment.
Achieve Synergistic Activity against the infecting
microbe.
e.g.1 Infections caused by G (-) Bacilli in
Immunosuppressed patients.
e.g.2 Infections caused by Pseudomonas aeruginosa (G -)
and some Enterococcus species (G +).

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Reasons of using Combination Antimicrobial Therapy
Polymicrobial infections
Multiple Organisms causing the infection (e.g.
Intraabdominal and female pelvic infections)
To Prevent the Emergence of Resistance.
e.g. Tuberculosis (TB)

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Disadvantages of Combination Antimicrobial Therapy
Increased Cost.
Higher risk of Drug Toxicity and adverse effect.
Superinfection with more resistant Bacteria

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Disadvantages of Combination
Antimicrobial Therapy
Antagonizing effect from some
combinations
E.g. Bactericidal Antibiotics with
Bacteriostatic Antibiotics
Tetracyclines (Bacteriostatic AB) and
Penicillin (Bactericidal) can’t be given
concurrently, why?
Tetracyclines decrease the
synthesis of Penicillin binding
Protein.
AB-A AB-B

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D- Monitor Therapeutic Response
What we should Monitor?
 The Three main Elements.
Host
Microbe Drug

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How to assess Response to Antimicrobial Treatment?
Assessing Response to
Antimicrobial Therapy
Clinical Microbiological

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Clinical Assessment of Antimicrobial Therapy Response
 Monitor Signs and Symptoms of infection, temperature,
appetite, pain and radiologic studies as appropriate.
 Reduction of swelling, erythema and Tenderness.
 Lab Data:
 ↓ WBC; NO leukocytosis
 Renal Function
 Liver Function
 Serum Antimicrobial Concentrations.
Vancomycin
Aminoglycosides

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Microbiological Assessment of Antimicrobial Therapy
Obtain 1st Culture and sensitivity Report if Empiric Therapy has
already started
Obtain 2nd Culture and sensitivity Reports (48 – 72) hours if patient
on Definitive Therapy.
Empiric Therapy: use Antimicrobials with the Narrowest
spectrum of activity against the identified pathogens.
Definitive Therapy: Evaluate the Culture for Negative and
Positive Bacterial Growth

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Route of Antimicrobial Drug Administration
Criteria to favor the switching IV antimicrobial to
Oral Therapy:
 Overall Clinical Improvement
 Lack of fever for 8 -24 hours
 Decreased WBCs
 Functioning Gastrointestinal tract

ARWA M. AMIN
FAILURE OF ANTIMICROBIAL THERAPY
Reasons of Antimicrobial Therapy Failure:
 Wrong Diagnosis of the Infection
 Probably No infection
 In appropriate Antimicrobial Drug Selection
 Drug was not selected according to the guidance of Culture and
Antimicrobial sensitivity results or common infection in the country/place.
 Wrong Identification of the microbial Infection
 Probable wrong results in Culture and Antimicrobial Sensitivity lab data
 Polymicrobial infection

ARWA M. AMIN
FAILURE OF ANTIMICROBIAL THERAPY
Reasons of Antimicrobial Therapy Failure .. cont.:
 Inappropriate Combination was used
 Antagonism
 Malabsorption of the Drug
 Tetracyclines interaction with Food
 Drug interaction of fluoroquinolones with multivalent
Cations → reduced absorption
 Patient has impaired Immune System
 Development of Bacterial Resistance or Super Infection
 Collection Requiring Drainage

ARWA M. AMIN
When to Stop the Antimicrobial Therapy?
When Infection is Cured and the use of Antimicrobial is
Unnecessary.
When Culture Results are Negative
When Patient is clinically Improved and Infection diagnosis is
unlikely
 Signs, Symptoms and Lab data show Improvement.

ARWA M. AMIN
ANTIMICROBIAL STEWARDSHIP PROGRAM (ASP)
 Antimicrobial Stewardship Program (ASP) is a program which
intends to guide the use of Antimicrobials and prevent Bacterial
Resistance.
 The program encourages Judicious use of Antimicrobials.
 Infectious Diseases specialists Staff from many professions are
involved in the program.
 ASP aims to:
 Optimize Antimicrobials Clinical Outcomes
 Minimizing Unintended consequences of Antimicrobial use

General Principles of Antimicrobial Selection - 2018

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