Antimicrobials: Mechanisms and Spectrum

• The notes below discuss the mechanisms of action (MOA) of common antimicrobials such as β-lactams, quinolones, and macrolides. It also compares their spectrum of activities, discusses allergic reactions and desensitization, and reviews adverse side effects like seizures and QT prolongation.

β-Lactams

• β-lactams include penicillins, cephalosporins, carbapenems, and monobactams
• These drugs inhibit bacterial cell wall synthesis
• They bind to penicillin-binding proteins (PBPs), which are enzymes responsible for peptidoglycan synthesis
• This binding prevents the cross-linking of peptidoglycans, weakening the cell wall and leading to bacterial cell death
• β-lactams are generally bactericidal

Quinolones

• Quinolones, such as ciprofloxacin and levofloxacin, inhibit bacterial DNA replication and repair
• They target DNA gyrase and topoisomerase IV enzymes, which are essential for DNA supercoiling and segregation during cell division
• By inhibiting these enzymes, quinolones prevent DNA replication and transcription, leading to bacterial cell death
• Quinolones are generally bactericidal

Macrolides

• Macrolides like erythromycin, azithromycin, and clarithromycin inhibit bacterial protein synthesis
• They bind to the 23S rRNA of the 50S ribosomal subunit, blocking the translocation step of protein synthesis
• This action prevents the addition of new amino acids to the growing peptide chain, halting protein synthesis
• Macrolides are generally bacteriostatic but can be bactericidal at high concentrations or against highly susceptible organisms

Spectrum of Activities

β-Lactams

• Penicillins have a broad spectrum, effective against many Gram-positive and some Gram-negative bacteria
• Cephalosporins are classified into generations with increasing activity against Gram-negative bacteria
• Carbapenems have the broadest spectrum of activity, effective against many Gram-positive, Gram-negative, and anaerobic bacteria

Quinolones

• Quinolones are effective against a wide range of Gram-negative and Gram-positive bacteria
• Fluoroquinolones have enhanced activity against Gram-positive bacteria

Macrolides

• Macrolides are effective against Gram-positive bacteria, atypical bacteria (e.g., Mycoplasma, Legionella, Chlamydia), and some Gram-negative bacteria

Allergic Reactions to Antimicrobials

• Allergic reactions to antimicrobials, particularly β-lactams, are common
• Reactions can range from mild rash and hives to severe anaphylaxis
• Desensitization is a process of gradually administering increasing doses of an antimicrobial to induce tolerance in allergic individuals
• It should only be performed under strict medical supervision in a controlled setting due to the risk of anaphylaxis

Adverse Side Effects

• Seizures: Some antimicrobials, like quinolones and carbapenems, can lower the seizure threshold and increase the risk of seizures, especially in patients with pre-existing seizure disorders or renal impairment
• QT Prolongation: Macrolides and quinolones can prolong the QT interval, increasing the risk of torsades de pointes, a life-threatening arrhythmia; caution is advised when prescribing these drugs to patients with risk factors for QT prolongation

Explore the mechanisms of action for common antimicrobials such as β-lactams and quinolones. This review covers their spectrum of activity, allergic reactions, and adverse effects. Learn about their impact on bacterial cell wall synthesis and DNA replication.