College Answer

Patient Factors

• History of current acute illness
• Allergies
• Previous antibiotic exposure
• Co-morbidities like immunocompetence, Diabetes.
• Social history e.g. nursing home resident, alcohol/drug abuse, occupation, contact with birds/animals, travel

Organism

• Sensitivity profile
• Inducible beta-lactamase producers (e.g. ESCAPPM)
• Tendency to develop resistance to antimicrobial during treatment course e.g. Pseudomonas aeruginosa
• Intracellular (e.g. aminoglycosides poorly active against strictly intracellular bacteria e.g. Rickettsia, Chlamydia, Coxiella burnetti)

Site of infection

• Organs with non-fenestrated capillaries (e.g. brain, prostate, anterior chamber of eye) – poor penetration of non lipid-soluble drugs
• Biliary and urinary sepsis – select drugs with hepatic (e.g. ceftriaxone) and urinary excretion (cefotaxime) respectively
• Lung – e.g. daptomycin inactivated by surfactant, vancomycin poor penetration

Organ dysfunction

• Renal or hepatic dysfunction may result in decreased elimination and increased toxicity

Toxicity

• Renal and ototoxicity of aminoglycosides
• Renal toxicity of vancomycin
• Neurotoxicity of imipenem

Drug interactions

• Synergy – beta lactams and aminoglycosides
• Pharmacodynamic interactions e.g. macrolides plus other agents causing prolongation of QT

Non anti-microbial effects of antimicrobial

• Anti-inflammatory effect of macrolides – may underlie outcome benefit when combined with beta lactams for bacteraemic pneumococcal pneumonia
• Inhibition of toxin synthesis in toxic-shock syndrome by clindamycin and linezolid

Additional comments:

Candidates were not expected to provide long lists of antimicrobial agents but to mention some examples where relevant. Overall, the question was poorly answered with superficial answers showing a lack of depth of understanding of the topic. Some wrote about dosing and dose adjustment but not about the choice of antimicrobial agent. Some candidates included key phrases e.g., “time dependent killing” without any demonstration of understanding of how that concept affected the choice of antibiotic.

Discussion

This vaguely worded broad question was answered poorly. This is not because the trainees were unaware of the influence of susceptibilities or drug interactions on antibiotic choice, but because they could not guess what exactly the examiners wanted from them.

The tabulated answer below was largely derived from an article by  Surbhi et al (2011) from the Mayo Clinic Proceedings.