Discuss the factors that may affect your choice of antimicrobial agent in a critically ill septic patient, giving examples where relevant.
- 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
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.
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.
|Factors||Discussion and examples|
|Disease specifics||Travel history||
|Recent antimicrobial use||
|Empiric vs. definitive||
|Urgency and timing||
|Reliability of cultures||
|Pregnancy and lactation||
|Duration of therapy||
|Assessment of response||
|Bactericidal vs bacteriostatic||
LONGACRE, AB. "Factors influencing the choice of antibiotics in therapy." The New Orleans medical and surgical journal 103.4 (1950): 160-167.
Leekha, Surbhi, Christine L. Terrell, and Randall S. Edson. "General principles of antimicrobial therapy." Mayo Clinic Proceedings. Vol. 86. No. 2. Elsevier, 2011.