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.
Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.
After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.
He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE. He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.
His one great achievement is being the father of three amazing children.
On Twitter, he is @precordialthump.