AB: pharmacology and treatment

What is a common empiric antibiotic regimen for suspected community-acquired bacterial meningitis in older children and adults?

IV vancomycin plus ceftriaxone or cefotaxime, adjusted for age, risk factors, local resistance patterns, and clinical circumstances.

Why is ampicillin added to empiric meningitis therapy in older adults or patients with specific risk factors?

To cover Listeria monocytogenes, which is intrinsically resistant to cephalosporins. Risk factors include older age, pregnancy, and impaired cellular immunity.

What is the major mechanism of bacterial resistance to aminoglycosides?

Aminoglycoside-modifying enzymes that acetylate, phosphorylate, or adenylate the antibiotic, reducing its ability to bind its ribosomal target.

How do aminoglycosides inhibit bacterial protein synthesis?

They irreversibly bind the 30S ribosomal subunit, interfering with initiation and causing misreading of mRNA. They are bactericidal.

What is the mechanism of action of vancomycin?

What are important adverse effects of vancomycin?

Nephrotoxicity, infusion-related flushing and pruritus, thrombophlebitis, rare ototoxicity, and rare severe hypersensitivity reactions including DRESS.

What causes vancomycin infusion reaction ('red man syndrome')?

Rate-dependent, non-IgE-mediated mast cell activation with histamine release. Prevention includes slower infusion, with antihistamines considered in selected patients.

What is the mechanism of action of azithromycin?

A macrolide that binds the bacterial 50S ribosomal subunit and inhibits protein synthesis by interfering with translocation during elongation.

Why can linezolid precipitate serotonin syndrome?

Linezolid has reversible monoamine oxidase-inhibiting activity and can increase serotonergic activity, especially when combined with SSRIs or other serotonergic medications.

What is the classic triad of serotonin syndrome?

Altered mental status (agitation/confusion), autonomic hyperactivity (fever, tachycardia, diaphoresis), and neuromuscular hyperactivity (clonus, hyperreflexia, tremor).

What is the mechanism of action of rifampin (rifampicin)?

It binds the β subunit of bacterial DNA-dependent RNA polymerase and inhibits transcription, preventing bacterial RNA synthesis.

When is rifampin used for meningitis-related chemoprophylaxis?

For eligible close contacts of patients with meningococcal disease or invasive Haemophilus influenzae type b disease, according to public health recommendations.

Why is rifampin not usually used as monotherapy for active bacterial infections?

Resistance can develop rapidly through mutations in the bacterial rpoB gene encoding the β subunit of RNA polymerase.

Why does rifampin reduce bacterial RNA synthesis?

It blocks RNA chain elongation by bacterial RNA polymerase. This inhibits transcription rather than directly inhibiting RNA nucleotide production or uracil synthesis.