Antibiotics

Drugs

Background of antimicrobial drugs and resistance

Author

Chi Zhang

Published

February 21, 2024

Economics and production

Drug-resistant diseases kill 700k people (Plackett2020) yearly, however fewer new antibiotic drugs are reaching the market.

Development cost: 1.5 billion USD (for one drug, based on 2017 study) while revenue is 45 million USD.

  • not enough demand: physicians prescribe less, treatment cycle is short compared to chronic diseases
  • price is low
  • development is difficult

https://www.nature.com/articles/s41429-023-00629-8

Antibiotics stewardship

Coursera course: Antibiotics stewardship

Antimicrobials are the 2nd most frequently prescribed claass of pharmaceuticals. As much as 50% of antibiotic use is inappropriate.

Five D’s: (if it is the right) drug, dose, delivery, deescalation, duration.

Impact of inappropriate AB use: poor patient outcomes (adverse reactions, organ toxicity, AB resistance, increased mortality); excess costs (drug acquisition cost, complication management, prolonged hospital stays, costs associated with AB resistance)

Principles

Prophylactic to prevent infection, preemptive to abort infection, empiric to provide initial control in absence of knowledge of its etiology, definitive to cure infectiou of a knownn etiology or its antimicrobial susceptibility

Empiric use is very common - e.g. community and hospital acquired pneumonia, sepsis.

PKPD

Pharmacokinetics (PK): what the body does to the drug - absorption, distribution, metabolism, elimination

Pharmacodynamics (PD): what the drug does to the body / target organism - measured drug concentration and antimicrobial effect (e.g. adverse effect, safety)

MIC: minimum inhibitory concentration, from no visible growth to 99.9% bacteria kill (MBC)

Pharmacodynamic measures

  • Cmax, AB peak concentration
  • Cmin, AB trough concentration
  • Cmax / MIC, AUC / MIC, T>MIC (on concentration time curve)

Concentration-dependent AB classes: large, infrequent doses

  • aminoglycosides (e.g. gentamicin, tobramycin, aminkacin for life-threatening nosocomial infections)
  • fluoroquinolonse (e.g. norfloxacin, ciprofloxacin, levofloxacin)
  • polymyxin

Time-dependent AB classes (beta-lactam): optimize the duration

  • penicillins
  • cephalosporins
  • carbapenems
  • macrolides

Research on antibiotics use

(relevant to my research)

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2814214

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2814216

https://pubmed.ncbi.nlm.nih.gov/37760690/