Related Experiment Videos
Antimicrobial safety and tolerability: differences and dilemmas
L A Mandell1, P Ball, G Tillotson
1McMaster Medical Unit, Henderson General Hospital, 711 Concession Street, Hamilton, Ontario L8V 1C3, Canada. lmandell@fhs.csu.mcmaster.ca
Abstract:
The adverse drug reactions associated with antimicrobials have become a topic of major importance and concern in the last few years. Antimicrobial toxicity may take many forms, varying from mild, transient phenomena to dramatic, life-threatening events such as seizures or cardiac arrhythmias. We review the toxicity of antimicrobials in general and of the fluoroquinolones in particular and attempt to explain the adverse events by use of structure-adverse event relationships where possible. There are currently 5 main mechanisms that can be invoked to explain antimicrobial toxicity: direct effects, hypersensitivity, changes in microbial flora, drug interactions, and microbial lysis. The adverse drug reactions seen with fluoroquinolones are explained on the basis of these 5 mechanisms. The various organ systems affected by the fluoroquinolones are considered; then individual members of the fluoroquinolone class are reviewed. The unexpected and dramatic problems encountered with temafloxacin and trovafloxacin are discussed as well.
Insights
Antimicrobial toxicity, including severe adverse drug reactions, is a growing concern. This review examines antimicrobial toxicity mechanisms and fluoroquinolone adverse events, linking them to drug structures.
Area of Science:
- Pharmacology
- Toxicology
- Infectious Diseases
Background:
- Adverse drug reactions (ADRs) from antimicrobials are a significant clinical concern.
- Antimicrobial toxicity ranges from mild effects to life-threatening events like seizures and cardiac arrhythmias.
Purpose of the Study:
- To review general antimicrobial toxicity.
- To specifically examine fluoroquinolone toxicity and adverse events.
- To explore structure-adverse event relationships for explaining toxicity.
Main Methods:
- Review of existing literature on antimicrobial and fluoroquinolone toxicity.
- Categorization of toxicity mechanisms (direct effects, hypersensitivity, flora changes, drug interactions, lysis).
- Analysis of organ system involvement and individual fluoroquinolone drugs.
Main Results:
- Five primary mechanisms explain antimicrobial toxicity.
- Fluoroquinolone ADRs are explained using these mechanisms.
- Specific fluoroquinolones like temafloxacin and trovafloxacin exhibited significant adverse events.
Conclusions:
- Understanding antimicrobial toxicity mechanisms is crucial for patient safety.
- Fluoroquinolone-associated adverse events require careful consideration.
- Structure-activity relationships can help predict and explain drug toxicity.