ANTIBIOTIC AND ANTIBIOTIC RESISTANCE

Helle Ericsson Unnerstad Veterinarian, Associate Professor Department of Animal Health and Antimicrobial Strategies National Veterinary Institute, Uppsala, Sweden

ITP, SVA, 28 September, 2018 Antibiotics or antimicrobials?

• Old definition: Antibiotics are naturally produced by microorganisms.

• Perhaps more useful definitions today:

Antimicrobials are compounds with direct action on microorganisms. They are used for treatment or prevention of infections. Antimicrobials are inclusive of anti-bacterials, anti-virals, anti-fungals and anti-protozoals.

Antibiotics are synonymous with anti-bacterials.

• “Antibiotic resistance” more familiar for the public than “antimicrobial resistance” according to WHO survey.

• In many contexts antibiotic resistance and antimicrobial resistance are used synonymously. Antibiotics – toxins for bacteria

Antibiotic Antibiotic activity

• Bactericidal activity – kill bacteria

• Bacteriostatic activity – inhibit or delay bacterial growth Mechanisms of action for antibiotics

Inhibition of Inhibition of cell wall synthesis protein synthesis • Aminoglycosides • Beta lactams • Tetracyclines • Cephalosporins • Macrolides • Glycopeptides • Lincosamides • Chloramphenicol • Fusidic acid • Pleuromutilins

Inhibition of Inhibition of folic acid synthesis DNA/RNA synthesis • Sulphonamides • Quinolones • Trimethoprim • Coumarins • Rifamycins Spectra of activity

• Broad-spectrum antibiotics Ex. tetracyclines, fluoroquinolones, 3:d and 4:th gen cephalosporins, carbapenems (G+, G-, aerobes, anaerobes)

• Narrow-spectrum antibiotics Ex. penicillin, glycopeptides (G+), polymyxins (G-) Antibiotic resistance

• Microbiological resistance Grows in higher concentration than other strains of the same species.

• Clinical resistance Survives antimicrobial therapy. Mechanisms of action for antibiotic resistance

Antibiotic Enzymes Impermeable cellwall

Changed target Efflux-pumps Cross-resistance • Resistance to one antibiotic is associated with resistance to other antibiotics due to the same resistance mechanism.

• Often antibiotic substances that belong to the same class. For example resistance in E. coli to enrofloxacin means also resistance to ciprofloxacin.

• Also antibiotics that belong to different classes. For example macrolides and lincosamides. Co-resistance

Resistance to one antibiotic is associated with resistance to other antibiotics due to coexistence of several resistance genes or mutations.

Ex resistance in E. coli

Resistance phenotypes Number of isolates Amp Tsu Str Tet Enr Neo Gen Ctx Col R R R R R R 1 R R R R R 4 R R R R R 3 R R R R 11 R R R R 2 R R R R 4 R R R R 1 R R R R 1 R R R 19 R R R R 1 R R R 3 R R R 2 R R R R 1 R R R R 1 R R R 6 R R R 1 R R R 2 R R R R 1 R R R 1 R R R 1 R R R 1 Sum 67 Antibiotic susceptibility testing

Microdilution Disc-diffusion

Minimum Inhibitory Concentration (MIC) Inhibitory zone diameter (mg/L) (mm) Interpretive criteria:

• Clinical breakpoints → ”Clinical resistance” • Epidemiological cut-off values → ”Acquired resistance mechanisms” Resistance can be:

• Inherent Ex: E. coli is resistant to penicillin.

or

• Acquired Susceptible Resistant

Ex: E. coli can be resistant or sensitive to tetracycline.

Bacteria acquire resistance through mutation or acquisition of genes. Acquired resistance

When a bacterial strain grows at a higher concentration of an antibiotic than related strains of the same species.

Mutation Uptake of resistance genes

For example transfer of mobile plasmids or insertion of mobile DNA elements. Distribution of MICs

15 000 Ampicillin - Escherichia coli (n = 37 590)

10 000

isolates of of

5 000 Number

0

Minimum Inhibitory Concentration MIC (mg/L)

From: EUCAST www.escmid.org/research_projects/eucast/ Drivers of antibiotic resistance

• Selection - survival of the fittest

• Spread - bacteria are contagious - resistance genes can be contagious Selection - when bacteria and antibiotic meet

AB +

Spread - Both resistant and sensitive bacteria are contagious. Co-selection

One antibiotic selects for resistance also to others What can we do?

• Reduce selection by reducing the use of antibiotics. Disease prevention need for antibiotics reduced

• Reduce spread of resistant bacteria by improving biosecurity. Thank You for listening!