Principles of antimicrobial

therapy
Dr. Suzy FitzGerald
Consultant Microbiologist
26th January 2022

suzy.fitzgerald@ucd.ie
 Learning objectives
Development of antimicrobial chemotherapy

Classification of antimicrobial agents

Factors influencing selection of antimicrobial agents

Complications of antimicrobial therapy

 What is antimicrobial chemotherapy?
Treatment of infectious disease by administration of drugs (antimicrobial
agents) which have a lethal or inhibitory effect on the micro-organism causing
the infection

Ideal agent has selective toxicity - toxic to the micro-organism, but not
harmful to the cells of the host

Antimicrobial agents target metabolic channels, metabolic pathways or

structures present in the micro-organism, but not in the host
e.g., bacterial cell wall synthesis
 Antibiotic versus antimicrobial
Antibiotic
• Substance produced by a micro-organism (natural origin)

Antimicrobial
• Substance of natural, synthetic or semi-synthetic origin
Why do we need antimicrobial therapy?
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 History of antimicrobial therapy
Paul Ehrlich (1854-1915)
• Father of modern chemotherapy
• ‘magic bullet’ theory
• Discovered compounds active against trypanosomes and syphilis
• Salvarsan 1909 (arsenic derivative)
 Prontosil
Gerhard Domagk (1895-1964)
• Industrial red dye
• Active against haemolytic streptococci
• First sulphonamide
Discovery of penicillin
Development of penicillin
 Classification of antimicrobial agents
Target organism

Cytostatic versus cytocidal

Mechanism of action

Spectrum of activity
 Targets of antimicrobial agents
Bacteria

Fungi

Viruses

Protozoa
Bacteriostatic versus bactericidal
Bacteriostatic Bactericidal
inhibits the growth kills bacteria
of bacteria
Mechanisms of antibacterial agents
 Spectrum of activity
Broad spectrum
Activity against a broad range of bacteria – Gram positive and Gram negative
• Carbapenems
• Fluoroquinolones
• 3rd and 4th generation cephalosporins

Narrow spectrum
Limited activity
• Nitroimidazoles active only against anaerobic bacteria
• Glycopeptides active only against Gram positive bacteria
 Antimicrobial therapy
• Reduced mortality
• Reduced morbidity
• Safer surgery
• Transplant

• Resistance
• Toxicity
• Secondary infection
• Hypersensitivity
 Antimicrobial treatment
Empiric
• Initial treatment, before causative organism identified
• ‘Best guess’

Definitive
• Targeted at identified organism
Selection of an antimicrobial agent
Site of infection

Likely causative organism(s)

Oral or intravenous therapy

Pharmacodynamic characteristics of agent

Therapeutic drug monitoring (TDM)

 MIC
(minimum inhibitory concentration)

Lowest concentration of the antimicrobial which results in inhibition of

detectable growth of the organism
 Pharmacodynamics
Time-dependent killing
Bactericidal effect is dependent on the length of time that the bacteria are
exposed to concentrations of drug above the MIC

• Penicillins
• Cephalosporins
• Carbapenems
 Pharmacodynamics
Concentration-dependent killing
Bactericidal effect increases with the concentration of the drug

• Fluoroquinolones
• Aminoglycosides
 Host factors
Age

Renal and hepatic function

Underlying disease

Antimicrobial allergy

Genetic variation (e.g., G6PD deficiency)

Pregnancy, breastfeeding

Recent antimicrobial therapy

Recent microbiology results

 Complications of antimicrobial therapy
Development of antimicrobial resistance

Drug toxicity

Side effects (adverse reactions)

Interactions with other medications

Allergy (hypersensitivity reactions)

Secondary infections

Treatment failure
 Allergy (hypersensitivity reactions)
Immediate, IgE mediated, type 1
• Within 1 hour
• Urticarial rash, itch, flushing, wheeze, angioedema, hypotension, anxiety

Delayed, non-IgE mediated, usually type 4

• More than 1 hour
• Rash, fever, Stevens-Johnson syndrome

Detailed history important

Need to distinguish
• Nature of allergy
• Between allergy and side effect
 Treatment failure
Incorrect diagnosis

Drug resistance

Inappropriate choice of agent

Suboptimal dose, frequency or duration

Inadequate source control

 Principles of antimicrobial prescribing
Treat only if evidence of infection

Use as narrow-spectrum as possible

Send appropriate microbiology samples, ideally prior to treatment

Follow antimicrobial prescribing guidelines

• Use local guidelines if available

Document indication and review/stop date

Review with results

Modify treatment – de-escalate if possible

Document indication and review/stop date
Review with results