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This is essentially a summary of the first half of Jeffrey Lipman's chapter for Oh's Manual. He offers a point-form guide to the use of antibiotics, which seems well suited to the easy generation of SAQs. In order to simplify panicked last-minute cramming, this already laconic list of instructions has been abbreviated yet further. But if brevity is not your thing, you may revel in the excess of the Required Reading section for Infectious Diseases Antibiotics and Sepsis, where antibiotic use is serenaded in the following associated chapters:
- Pharmacokinetics of antibiotics in critical illness
- Antibiotic dosing in renal failure
- Antibiotic dosing during dialysis
- Kill characteristics of antibiotic agents
- Causes of antibiotic treatment failure
- The minimum inhibitory concentration (MIC)
- Post-antibiotic effect
- Antibiotic agents classified by mechanism of action
- Specific antibiotic choices for selected pathogens
- Pharmacology of antifungal agents
General principles of antibiotic use
- Send cultures before you start the antibiotics
- Take two sets of cultures, not from a line.
- Timing with fever is not critical.
- Do not delay the administration of antibiotics
- Use empirical therapy first; narrow the spectrum later
- Use a proper dose first up. No point under-doing your patients.
- Where possible, use monotherapy (it reduces cost and toxicity).
- If the microbiology suggests reduced susceptibility, think: are the antibiotics working clinically? Is there direct bedside evidence that they are working? if the answer is yes, then you should continue them in spite of laboratory evidence. In vitro sensitivity does not predict in vivo effect.
- A shorter course is probably as good as a standard 2-week course
- Infectious diseases specialists should be involved in managing serious infections.
- Know your antimicrobial pharmacokinetics and pharmacodynamics; consider tissue penetration and dose adjustment to correct for altered clearance.
- Monitor the monitorable levels.
- Limit "prophylactic" use to appropriate situations.
- Consider non-infective causes of inflammation (it's not always sepsis)
- Give a strong emhasis to infection control policies.
Common errors of antibiotic use
- Antibiotics given before cutures are taken
- Poor quality blood culture collection
- Ridiculously long courses of antibiotics
- Wildly erratic changes of antibiotics ("antibiotic surfing") when the sepsis is not improving
- Inadequate doses
- Poor choice of empirical antibiotics, failing to account for resident flora
- Failure to predict toxicity or account for interactions
- Inappropriate use of antibiotic polypharmacy
Factors which should influence the choice of antibiotic agent
This issue has come up in Question 27 from the first paper of 2015. It was a very general question ("Discuss the factors that may affect your choice of antimicrobial agent in a critically ill septic patient, giving examples where relevant") and the college were very disappointed with the pass rate (23%). The examiners complained that the trainees gave "superficial answers", including key phrases (eg. "time-dependent killing") without demonstration of understanding. In all fairness, ICU is a business of offering specific answers for specific problems, and the candidates probably do much better with direct knowledge-based questions, eg . "how to kill this Vibrio vulnificus?", or "what is time-dependent killing"? Looking for answers in Oh's Manual also proved fruitless, as even the all-encompassing Lipman chapter ("Principles of antibiotic use", p. 738) is not as broad as the college answer.
A Google search for "factors which influence antibiotic choices" comes up with useless Medscape snippets and studies which were published in1950. It is impossible to say precisely where the college got their answer from, probably because the topic is so diffuse that no author would publish a article about it specifically. Fortunately, a good review from the Mayo Clinic Proceedings is available ( Surbhi et al, 2011). Meat from this article has been grafted to the disarticulated carcass of the college answer for Question 27, forming the table offered below. For rapid revision, the long form of the table can be distilled into a short series of points.
Factors which influence antibiotic choice Disease factors Host factors Organism factors Drug factors
- Travel history
- Occupation
- Recreational exposure
- IVDU
- Severity of illness, urgency of therapy
- Reliability of cultures
- Age
- Clearance organ function
- Allergies
- Immune status, HIV
- Pregnancy and lactation
- Source control
- Susceptibility
- Empiric vs specific
- Intra vs. extracellular
- Duration of therapy
- Assessment of response
- Cost
- Toxicity
- Bioavaiability
- Source site penetration
- Drug synergy
- Bacteriostatic vs bactericidal
Factors | Discussion and examples | |
Disease specifics |
Travel history |
|
Occupational exposure |
|
|
Recreational exposure |
|
|
Recent antimicrobial use |
|
|
Empiric vs. definitive |
|
|
Urgency and timing |
|
|
Reliability of cultures |
|
|
Host factors |
Clearance |
|
Age |
|
|
Genetic variation |
|
|
Pregnancy and lactation |
|
|
Immunocomptence |
|
|
Allergies |
|
|
Organism factors |
Susceptibility |
|
Biology |
|
|
Source control |
|
|
Duration of therapy |
|
|
Assessment of response |
|
|
Drug factors |
Cost |
|
Toxicity |
|
|
Bioavailability |
|
|
Site penetration |
|
|
Bactericidal vs bacteriostatic |
|
|
Synergistic combination |
|
References
Oh's Intensive Care Manual: Chapter 72 (pp. 738) Principles of antibiotic use by Jeffrey Lipman
Roberts, Jason A., and Jeffrey Lipman. "Pharmacokinetic issues for antibiotics in the critically ill patient." Critical care medicine 37.3 (2009): 840-851.
Craig, William A. "Basic pharmacodynamics of antibacterials with clinical applications to the use of β-lactams, glycopeptides, and linezolid." Infectious disease clinics of North America 17.3 (2003): 479-501.
Craig, William A. "Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men." Clinical infectious diseases (1998): 1-10.
Craig, William A. "Interrelationship between pharmacokinetics and pharmacodynamics in determining dosage regimens for broad-spectrum cephalosporins." Diagnostic microbiology and infectious disease 22.1 (1995): 89-96.
Weinstein, Melvin P., et al. "Multicenter collaborative evaluation of a standardized serum bactericidal test as a predictor of therapeutic efficacy in acute and chronic osteomyelitis." The American journal of medicine 83.2 (1987): 218-222.
Leggett, J. E., et al. "Comparative antibiotic dose-effect relations at several dosing intervals in murine pneumonitis and thigh-infection models." Journal of infectious diseases 159.2 (1989): 281-292.
Moore, Richard D., Paul S. Lietman, and Craig R. Smith. "Clinical response to aminoglycoside therapy: importance of the ratio of peak concentration to minimal inhibitory concentration." Journal of Infectious Diseases 155.1 (1987): 93-99.
Daikos, GEORGE L., VALENTINA T. Lolans, and G. G. Jackson. "First-exposure adaptive resistance to aminoglycoside antibiotics in vivo with meaning for optimal clinical use." Antimicrobial agents and chemotherapy 35.1 (1991): 117-123.
MacKenzie, F. M., and I. M. Gould. "The post-antibiotic effect." Journal of Antimicrobial Chemotherapy 32.4 (1993): 519-537.
Athamna, A., et al. "In vitro post-antibiotic effect of fluoroquinolones, macrolides, β-lactams, tetracyclines, vancomycin, clindamycin, linezolid, chloramphenicol, quinupristin/dalfopristin and rifampicin on Bacillus anthracis."Journal of Antimicrobial Chemotherapy 53.4 (2004): 609-615.
Stubbings, William J., et al. "Assessment of a microplate method for determining the post-antibiotic effect in Staphylococcus aureus and Escherichia coli." Journal of Antimicrobial Chemotherapy 54.1 (2004): 139-143.
Woodnutt, Gary. "Pharmacodynamics to combat resistance." Journal of antimicrobial chemotherapy 46.suppl 3 (2000): 25-31.
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.