Antibiotic therapy in critical care

Question 1

What factors influence choice of antibiotic in critically ill patients?

Answer 1

1. Site infection
2. Likely organisms
3. Culture results and sensitivities
4. Any known drug resistance on swabs or previous cultures
5. Any immunocompromised
6. Severity of infection
7. Patient allergies
8. Potential drug interactions and pharmacokinetic considerations.

Question 2

How do antibiotics work?

Answer 2

Broadly speaking antibiotics are either bacteriostatic or bactericidal.

Bactericidal:

• Penicillins
• carbapenems
• cephalosporins
• glycopeptides
• aminoglycosides
• quinolones
• rifampicin
• nitrofurantoin
• metronidazole

Bacteriostatic:

• macrolides
• tetracyclines
• sulphonamides
• trimethoprim
• clindamycin
• linezolid

Question 3

By what mechanisms do antibiotics achieve their antibacterial effect?

Answer 3

4 main mechanisms:

1. Inhibition of cell wall synthesis
   - penicillins
   - carbapenems
   - Glycopeptides (Vancomycin and teicoplanin)
   - cephalosporins
   - colistin
2. Inhibition of DNA synthesis
   - Metronidazole
   - Rifampicin
   - Ciprofloxacin (quinolones)
3. Inhibition of protein synthesis
   - tetracyclines
   - macrolides (erythromycin, clarithromycin)
   - clindamycin
   - linezolid
4. Inhibition of tetrahydrofolate synthesis
   - trimethoprim
   - sulphonamides

Question 4

What is time-dependent and concentration-dependent killing with respect to antibiotics?

Answer 4

Time-dependent killing refers to agents that have maximal antibacterial effect by keeping duration above MIC as long as possible.
This often correlates with frequent dosing (e.g. beta-lactam pencillins such as flucloxacillin) or infusions (e.g. vancomycin).

Concentration-dependent killing refers to agents that have their maximal antibacterial effect by having peak serum concentrations far above the MIC.
They are often given at less frequent intervals (e.g. Gentamicin) limited by their tissue toxicity (e.g. Gentamicin).

Question 5

What is Gram staining?

Answer 5

Gram staining refers to the identification of bacterial subsets based on the ability of their cell wall to take up certain dyes and whether or not these dyes can be washed out.
This helps identify them as gram positive or gram negative and helps differentiate between bacteria on microscopy.
Bacteria can further be separated on their shape, cocci or bacilli.

The 4 classical groups are:

Gram positive cocci:

• Staphylococci
• Streptococci (progenies, enterococci, pneumonia)

Gram positive bacilli:

• Actinomyces
• Bacillus
• Clostridia
• Diptheria
• Listeria

Gram negative cocci:

• Neisseria
• Moraxella

Gram negative bacilli:

• Pseudomonas
• Klebsiella
• salmonella
• citrobacter
• E.coli
• shigella
• proteus
• yersinia
• serratia