Fluconazole
Diflucan
Triazole antifungal
Inhibits fungal CYP450 14-α-demethylase → blocks ergosterol synthesis. Also a potent human CYP2C9/3A4 inhibitor.
Indications
- •Candidiasis (mucosal, invasive), cryptococcal meningitis prophylaxis/maintenance
Dosing
| Context | Adult | Pediatric |
|---|---|---|
| Invasive candidiasis | 800 mg IV load, then 400 mg daily (renally adjusted) | — |
Pharmacokinetics
Long half-life ~30 h → once-daily. Renally cleared. Excellent CSF/tissue penetration.
Side effects
- !QT prolongation
- !Hepatotoxicity
- !Major CYP interactions (↑ warfarin, ↑ many drug levels)
Contraindications
- ×Long QT / with QT-prolonging drugs
- ×Co-administration with drugs that dangerously accumulate via CYP3A4/2C9
Clinical pearls
- ★Potent CYP2C9/3A4 inhibitor → raises warfarin (INR), phenytoin, and many others; check interactions.
- ★QT prolongation is a class effect of the azoles.
Other drugs in Antibiotics
- Cefazolin
β-lactam — inhibits bacterial cell wall PBPs.
- Vancomycin
Inhibits cell wall synthesis (binds D-Ala-D-Ala). Active against MRSA + gram-positives.
- Clindamycin
Binds 50S ribosomal subunit, blocks peptide-bond formation. Bacteriostatic against most organisms; bactericidal against susceptible streptococci. Excellent activity against anaerobes and gram-positive cocci including community-acquired MRSA.
- Gentamicin
Binds 30S ribosomal subunit, causes misreading of mRNA → defective bacterial protein synthesis. Bactericidal, concentration-dependent killing. Synergy with cell-wall agents (β-lactams, vancomycin) for gram-positive endocarditis.
- Cefuroxime
β-lactam — inhibits cell-wall synthesis (PBP binding). 2nd-gen: gram-positive + expanded gram-negative.
- Cefepime
β-lactam cell-wall inhibitor. Broad gram-negative (incl. Pseudomonas) + gram-positive coverage.
- Cefotetan
β-lactam; adds anaerobic (B. fragilis) coverage → colorectal/gynecologic prophylaxis.
Suggested reading
- •Miller's Anesthesia, 9e
- •FDA package insert
