Discuss the factors that may affect your choice of antimicrobial agent in a critically ill septic patient, giving examples where relevant.
Answer and interpretation
- History of current acute illness
- Previous antibiotic exposure
- Co-morbidities like immunocompetence, Diabetes.
- Social history e.g. nursing home resident, alcohol/drug abuse, occupation, contact with birds/animals, travel
- 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
- Renal or hepatic dysfunction may result in decreased elimination and increased toxicity
- Renal and ototoxicity of aminoglycosides
- Renal toxicity of vancomycin
- Neurotoxicity of imipenem
- 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
- Local microbiology/ecology
- Ability of monitoring drug levels (TDM)
- Presence of an ID physician / Antibiotic Stewardship team in the hospital and their policies
Route of administration
- Certain routes of administration may be unreliable in critically ill patients and drugs which can only be administered by that route are less desirable e.g. inhaled zanamivir
- Cost-effectiveness of the antibiotic
Bactericidal vs bacteriostatic
- Theoretical benefit from bactericidal drugs. Controversial whether there is a clinical benefit
- Pass rate: 23%
- Maximum mark: 6.0
- 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.