Antimicrobial resistance

Question 1

What mechanisms confer antibiotic resistance?

Answer 1

1. Intrinsic
   - innate resistance
   - membrane impermeability (Gram-negative have a thick cell wall)
2. Acquired
   i) - Drug inactivation e.g. Beta-lactamases
   ii) - Decreased intracellular drug concentration:
   - reduced permeability (pseudomonas has relatively impermeable out membrane).
   - drug efflux (Pseudomonas has pump for penicillins, cephalosporins, chloramphenicol, quinolones)
   iii) - Alteration of molecular target (production of low-affinity penicillin binding protein by MRSA and coagulase-negative Staph, altered cell wall substrate in VRE)

Question 2

How do bacteria acquire resistance to antimicrobial drugs?

Answer 2

1. Intrinsic (innate resistance, gram negatives have a thick cell wall)
2. Sporadic mutation (potential for vertical transmission)
3. Horizontal gene transfer:
   - Transformation: (Free DNA released from lysed bacteria)
   - Transduction: (Bacteriophages (viruses that infect bacteria) transferring DNA to other bacteria)
   - Conjugation: (Plasmids transfer of genetic material)
   - Transposition: (Transposons - small segments of bacterial DNA that can move independently between plasmids or bacterial chromosomes).

Question 3

Why is antibiotic resistance a problem in ICU?

Answer 3

1. Use of broad-spectrum antibiotics
2. Indwelling devices breaching barrier defences
3. Sick, vulnerable and immunocompromised patients
4. Transfer between patients
5. Bed management and isolation

Question 4

What interventions do we use to minimise antibiotic resistance?

Answer 4

1. Antibiotic stewardship:
   - pharmacy and microbiology input
   - Using local microbiological guidelines to guide empirical therapy
   - minimise duration of broad spectrum Abx
   - narrow spectrum once sensitivities known
   - regular resistance swabs
2. Prevention of nosocomial infection:
   - Line Care bundles (Matching michigan) to prevent device infection
   - daily sedation holds to minimise time of invasive ventilation
   - daily line reviews
   - patient isolation
   - SDD:
   i - non-absorbable oral paste: tobramycin, polymixin E, amphotericin
   ii - NG administration: tobramycin, polymixin E, amphotericin
   iii - IV cefotaxime for first four days
   iv - regular throat and rectal swabs for monitoring

Question 5

What resistant bacteria are you aware of? What antimicrobials can you use to treat them?

Answer 5

1. MRSA (PVL - MEC-A gene codes for low-affinity penicillin binding protein) - Mx: i) glycopeptides, ii) linezolid
2. ESBL (plasmid transfer, typically Klebsiella) - Mx: i) meropenem
3. CPE (carbapenemase- producing enterobacteriaceae) - Mx: colistin, amikaicin, tigecycline
4. VRE (vancomycin resistant enterococci: E. faecalis, E. faecium) - Mx: Linezolid, tigecycline

All should be managed by discussion with infection control for isolation of symptomatic patients and ensuring isolated care and good hand hygiene.