Antibacterials

Under construction

Antibacterials (Figure 1) are drugs used to treat bacterial infections. We often use the words antimicrobials, antibacterials, and antibiotics for these compounds. They are similar terms, but each has a specific meaning:

The term “antibiotic” comes from the Greek words anti (“against”) and biotikos (“concerning life”). Strictly speaking, antibiotics refers only to naturally produced substances, and not synthetic or semi-synthetic types (e.g., quinolones). However, it is commonly used interchangeably with antibacterials.

How do antibacterials work?

Antibacterials interfere with vital processes in bacterial cells. They may kill the bacteria (bactericidal) or stop their growth (bacteriostatic).

Bactericidal and bacteriostatic antibacterials

Bactericidal antibacterials kill bacteria. Bacteriostatic antibacterials prevent bacteria from multiplying. The immune system then clears the infection.

Antibiotic targets in bacteria

Different classes of antibacterials act on different parts of bacterial cells. They mainly target:

  1. The cell wall or membranes surrounding the cell.
  2. The DNA and RNA production machinery.
  3. The protein production machinery (ribosomes and related proteins).

These structures do not exist in human or animal cells, so antibacterials typically do not harm our cells. However, side effects can still occur.

Figure 1: Types and classes of antibacterials.

Narrow-spectrum and broad-spectrum antibacterials

Some antibacterials have a narrow spectrum, meaning they act on only certain groups of bacteria. Others are broad spectrum and affect many bacterial species. Narrow-spectrum antibacterials are often preferred since they leave non-disease causing bacteria alone. However, broad-spectrum antibacterials are sometimes used when doctors are unsure of the exact bacteria causing the infection.

Resistance

Antibiotic resistance is a bacterias ability to survive the effects of an antibiotic. In the presence of the antibiotic, resistant bacteria live and multiply. Clinically, resistance means the bacterium can grow at drug exposures reached during standard treatment, leading to treatment failure.

Bacteria gain resistance through:

  1. Mutations in their own DNA.
  2. Horizontal gene transfer, where they acquire DNA from other bacteria.

If the new trait offers an advantage, the bacterium may pass it on to future generations or spread it through horizontal transfer. Resistant bacteria travel through food, water, global trade, or human travel.

AMR Terminology:

  • MDR: Resistant to ≥1 agent in ≥3 classes
  • XDR: Resistant to ≥1 agent in all but 2 classes
  • PDR: Resistant to all agents in all classes

PD-targets (indices)

Time-dependent or concentration-dependent effect.

  • AUC/MIC
  • Cmax/MIC
  • time above MIC

Decided by plotting log-kill against AUC, and fitting a non-linear regression. Highest R^2 decides the index.