Antibiotics

 

Antibiotic resistance

Bacterial resistance can occur via different mechanisms:

1. Intrinsic chromosomal resistance
   • Bacteria has intrinsic resistance to certain antibiotic mechanism
2. Acquired chromosomal resistance
   • During treatment for infection – mutant bacteria selected for (other bacteria killed by treatment) – and so the mutant resistant bacteria replicates
   • Especially if underdosed, poorly compliant
3. Acquired extrachromosomal resistance
   • Most common mechanism
   • Transference of the genetic material responsible for resistance via plasmids – can transfer between species, usually in bowel flora

 

Four mechanisms of antibiotic resistance:

1. Limiting drug uptake
   • g. if no cell wall then penicillins won’t work
   • g. gram negative bacteria have porins which allow access through wall – modification in porins will mediate resistance
2. Modifying drug target
   • g. alteration in number/structure of penicillin binding proteins in cell wall
   • g. ribosomal mutation providing resistance to drugs targeting ribosomal protein synthesis
3. Inactivating a drug
   • g. beta-lactamases which hydrolyse the beta-lactam ring
   • g. acetylation – transferring acetyl group to antibiotic inactivating it
4. Active drug efflux
   • g. efflux pumps commonly found on GNB which efflux certain drugs

 

Multi-drug resistant organisms

Carapenem-resistant Enterobacteriaceae (CRE)

• Enterobacteriaceae are large family of gram negative bacteria – E.coli, Klebsiella, proteus and Enterobacter.
• These bugs produce carbapenemases, beta-lactamases and have efflux pumps which extrude antibiotics.

 

Extended spectrum beta-lactamases (ESBL)

• ESBLs are enzymes acquired by plasmid transfer – Klebiseilla > E.coli – hydrolyse and therefore resistant to beta-lactams
• Increasingly common community-acquired UTI. 50 % infections in SE Asia ICUs.
• Often resistant to gent as well as beta-lactams – Rx cipro, bactrim, carbapenems.

 

Vancomycin resistant enterococcus (VRE)

• High mortality compared to non resistant strains
• Plasmid encoded vanA and vanB ligases – reducing target sites for glycopeptide antibiotics.
• Major reservoir is ICU – found to be on surfaces around patient environment and transmitted via hands – often asymptomatic colonisation

 

ESCAPPM

• Resistant gram negative bugs which all have chromosomal beta-lactamase making them resistant to standard beta-lactam antibiotics – usually treatable with gent, cipro, bactrim

 

Antimicrobial stewardship

Compulsory criteria for hospital accreditation. Led by ID/microbiology and pharmacy.

 

Goals:

• Deliver best clinical outcomes
• Limit selective pressures driving emergence of resistant strains
• Reduce toxicity and adverse effects
• Minimise cost

 

Strategies to minimise development of resistance:

• Optimum choice of antibiotic (both broad spectrum/empiric based on local biome, and when organism isolated)
• Optimal dose, route (IV to oral) and duration
• De-escalating or stopping antibiotics when appropriate
• Only using antibiotics when clinically necessary – i.e. not treating asymptomatic bacteriuria
  • Avoiding testing in asymptomatic/catheterised patients

 

Components of antimicrobial stewardship programs:

• Regular training of staff and education re: best antimicrobial practice
• Adherence to local and national guidelines
• Regular ward visits and accessibility of ID and microbiology
• Audits of treatment and outcomes
• Monitoring and feedback to prescribers both of their prescribing habits, and of local resistance profiles