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Principles of antimicrobial therapy

How an antibiotic is chosen: likely microbe, site, patient and killing pattern, using the narrowest effective drug for the shortest effective time.

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Antimicrobial therapy succeeds when the right drug reaches the site of infection at an effective concentration for long enough, in a patient who can tolerate it. Each choice also selects for resistance, in the patient and in the community, so good practice balances the individual's need with stewardship of a shared resource.

Choosing the drug

  • Which organism is likely, given the site, the setting (community or hospital) and local resistance data?
  • Will the drug reach the site? Bone, prostate, eye, abscesses and the cerebrospinal fluid are hard to reach
  • Is the patient allergic, pregnant, very young or old, or with kidney or liver failure?
  • Can the patient take it by mouth? Switching from intravenous to oral once stable is often possible
  • What is the shortest duration that works? Many common infections need fewer days than once thought

How antibiotics kill: pharmacodynamics

The minimum inhibitory concentration (MIC) measures how much drug stops growth in the laboratory. β-lactams and vancomycin depend mainly on the time the free drug stays above the MIC, which favours frequent dosing or prolonged infusions. Aminoglycosides and fluoroquinolones depend on the peak or total exposure relative to the MIC and have a post-antibiotic effect (bacteria stay suppressed after levels fall), which allows widely spaced dosing. Bactericidal drugs kill; bacteriostatic drugs stop growth and rely more on host defences, which matters in endocarditis, meningitis and neutropenia.

Combinations and prophylaxis

Combinations are used to broaden empirical cover, to gain synergy (a β-lactam with an aminoglycoside in some endocarditis), or to prevent resistance (tuberculosis is always treated with several drugs). Combinations can also antagonise each other or add toxicity. Prophylaxis prevents infection in defined situations: surgical prophylaxis is given shortly before the incision and kept short; other examples are post-exposure prophylaxis and prevention in immunosuppressed patients.

AWaRe and stewardship

The WHO AWaRe classification groups antibiotics as Access (first or second choice for common infections, such as amoxicillin), Watch (higher resistance potential, for specific indications, such as ceftriaxone or ciprofloxacin) and Reserve (last-resort drugs for multidrug-resistant infections). The WHO AWaRe antibiotic book gives empirical choices for common infections. Hospital stewardship programmes add leadership, pharmacy expertise, audit and feedback, tracking of use and resistance, and education.

Test yourself

Think of the answer, then tap the question to see it.

Why are cultures taken before the first dose of an antibiotic when possible?

Antibiotics can sterilise cultures; an organism and its susceptibility allow treatment to be narrowed later.

Which pharmacodynamic parameter best predicts β-lactam effect?

The fraction of the dosing interval during which the free drug concentration stays above the MIC (time-dependent killing).

Why is tuberculosis treated with several drugs at once?

To prevent resistant mutants, which arise spontaneously in large bacterial populations, from being selected by a single drug.

What do the three AWaRe groups mean?

Access: first-line for common infections; Watch: higher resistance potential, restricted indications; Reserve: last-resort drugs for multidrug-resistant infections.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: The WHO AWaRe (Access, Watch, Reserve) antibiotic book (World Health Organization, 2022); AWaRe classification of antibiotics for evaluation and monitoring of use, 2023 (World Health Organization, 2023); Core Elements of Hospital Antibiotic Stewardship Programs (Centers for Disease Control and Prevention (CDC), 2025).

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