Regarding the pharmacology of aminoglycosides, all of the following statements are true EXCEPT:

Explanation

## Aminoglycosides: Mechanism and Spectrum ### Bactericidal Mechanism **Key Point:** Aminoglycosides bind to the bacterial 30S ribosomal subunit, causing misreading of mRNA codons and incorporation of incorrect amino acids, leading to bacterial cell death. ### Concentration-Dependent Pharmacodynamics **High-Yield:** Aminoglycosides exhibit **concentration-dependent killing** — the rate and extent of bacterial killing increase with drug concentration. This principle supports once-daily dosing regimens (e.g., gentamicin 5–7 mg/kg once daily) rather than divided doses, which improves efficacy and reduces nephrotoxicity. ### Oxygen-Dependent Uptake **Clinical Pearl:** Aminoglycosides require an **oxygen-dependent active transport mechanism** for entry into bacterial cells. This is why they are **ineffective against anaerobic bacteria** — anaerobes lack the aerobic respiration machinery needed to generate the electrochemical gradient required for drug uptake. ### Spectrum of Activity | Organism Type | Susceptibility | Reason | | --- | --- | --- | | Gram-negative aerobes (E. coli, Klebsiella, Pseudomonas) | Excellent | Oxygen-dependent uptake intact | | Gram-positive aerobes (Staphylococcus) | Moderate | Less efficient uptake; synergy with β-lactams | | Anaerobes (Bacteroides, Clostridium, Peptostreptococcus) | Resistant | No aerobic respiration; cannot activate drug | | Streptococci | Resistant | Inefficient uptake; poor ribosomal binding | **Warning:** Aminoglycosides **cannot be used as monotherapy for polymicrobial infections** (e.g., intra-abdominal sepsis, aspiration pneumonia) because anaerobic coverage is mandatory. They must be combined with agents active against anaerobes (e.g., clindamycin, metronidazole, or β-lactam/β-lactamase inhibitor combinations). ### Why Option 3 Is Incorrect Option 3 falsely claims aminoglycosides are effective against anaerobes and suitable for monotherapy in polymicrobial infections. This is the **single statement that is NOT true** — the defining limitation of aminoglycosides is their inability to kill anaerobes due to their dependence on aerobic respiration for cellular uptake.