Anti-infective Pharmacology

Anti-infective pharmacology covers antibacterials, antivirals, and antifungals — drug classes essential to modern medicine and increasingly threatened by resistance.

Beta-lactam antibiotics share the beta-lactam ring and inhibit bacterial cell wall synthesis by acylating penicillin-binding proteins (PBPs), preventing cross-linking of peptidoglycan. This is bactericidal. Penicillins (amoxicillin, flucloxacillin, benzylpenicillin) are foundational. Flucloxacillin is uniquely stable against staphylococcal beta-lactamase, making it first-line for Staph aureus infections. Amoxicillin-clavulanate combines a broad-spectrum penicillin with a beta-lactamase inhibitor, extending cover to Haemophilus influenzae and some Enterobacteriaceae. Cephalosporins are grouped by generation: first-generation (cephalexin — skin and UTIs), second-generation (cefuroxime), third-generation (ceftriaxone — meningitis, serious gram-negative infections), fourth-generation (cefepime). Carbapenems (meropenem) are reserved for multi-resistant organisms.

Macrolides (erythromycin, azithromycin, clarithromycin) bind the 50S ribosomal subunit, inhibiting translocation. They are bacteriostatic and used for atypical respiratory pathogens (Mycoplasma, Legionella, Chlamydia), as well as penicillin-allergic patients. Azithromycin has excellent tissue penetration and a very long half-life. Macrolides are CYP3A4 inhibitors (except azithromycin), causing clinically significant drug interactions.

Fluoroquinolones (ciprofloxacin, norfloxacin) inhibit bacterial DNA gyrase and topoisomerase IV, preventing DNA supercoiling relief — bactericidal. They have excellent oral bioavailability approaching 100%. Key adverse effects include QT prolongation, tendinopathy (especially Achilles), and seizures. Their use is restricted in New Zealand due to resistance concerns.

Aminoglycosides (gentamicin, tobramycin) inhibit the 30S ribosomal subunit, causing misreading of mRNA. They are concentration-dependent and synergistic with beta-lactams. Nephrotoxicity and ototoxicity are the major adverse effects, requiring therapeutic drug monitoring (trough levels).

Antiviral drugs act on viral-specific targets. Oseltamivir (Tamiflu) inhibits neuraminidase, preventing influenza release from host cells. It must be started within 48 hours of symptom onset for efficacy. Acyclovir is a nucleoside analogue that requires phosphorylation by viral thymidine kinase (selectivity mechanism), then inhibits viral DNA polymerase. It is used for herpes simplex and varicella-zoster infections. Resistance can occur in immunocompromised patients with deficient thymidine kinase.

Antifungals target ergosterol, the predominant sterol in fungal cell membranes (unlike human cholesterol). Azoles (fluconazole, voriconazole) inhibit CYP51 (lanosterol 14α-demethylase), depleting ergosterol. Amphotericin B binds ergosterol directly, forming pores in the fungal membrane — highly effective but nephrotoxic. Echinocandins (caspofungin) inhibit beta-glucan synthase, disrupting the fungal cell wall with minimal mammalian toxicity.