Patients in the ICU can require antimicrobial therapy for numerous reasons. Patients may be admitted to the ICU with an ongoing
infection or they may develop an infection while in the ICU, such infections are referred to as hospital-acquired infections.
Early appropriate antimicrobial treatment is essential since incorrect antimicrobial choices are associated with increased
mortality. While it might seem prudent to put all ICU patients on antibiotics, this will ultimately lead to an increase in
antimicrobial resistance.
Antimicrobial therapy should be tailored to maximize benefits while minimizing risks. Ideally, therapy should be based upon
results of an antimicrobial culture and sensitivity report. In cases where such a report is not available rational empiric
therapy requires knowledge of the likely infecting organism(s) as well as the spectrum of activity of potential antimicrobial
therapy. Only by assimilation of this knowledge can the clinician consistently make rational antimicrobial choices. It is
the responsibility of the clinician to collect appropriate samples for culture and sensitivity in all cases where feasible.
Random changes in antimicrobial therapy not guided by antimicrobial cultures can result in inadequate antimicrobial coverage
as well as leading to the development of antimicrobial resistance
- Empirical antimicrobial therapy – The use of an antimicrobial in the absence of an etiologic diagnosis.
o Life-threatening infections
o Failure to culture an organism
o Economic considerations
- Selection of an empirical agent
o Knowledge of likely pathogens
o Knowledge of drug pharmacokinetics
• Bioavailability
• Concentration at infection site
o Potential toxicities
o Cost of treatment
o Regulatory concerns
Susceptibility testing
Some organisms have highly predictable antimicrobial susceptibility patterns and as a result microbiology laboratories do
not routinely perform susceptibility testing but rather provide a list of antimicrobials that are predictably efficacious
(coagulase-negative Staph., Rickettsia). Susceptibility testing is generally performed by either the disk diffusion or dilution methods. The distinction between
antimicrobial sensitivity and resistance is based upon the determination of a minimum inhibitory concentration (MIC). The
MIC is the minimum antimicrobial concentration required to inhibit growth. The MIC is established by the National Committee
for Clinical Laboratory Standards based upon available pharmacokinetic and microbial data. Intermediate sensitivities represent
organisms resistant to typical therapeutic concentrations that may be sensitive to maximally achievable concentrations (i.e.
urine concentration).
Antimicrobial dosing regimens
Typically, antimicrobial dosing regimens are designed to maintain tissue and plasma drug concentrations above the target organisms
MIC. This approach usually necessitates repeated dosing throughout the course of a day. Recently, the existence of a post-antibiotic
effect (PAE) has been recognized. The PAE refers to the existence of residual antimicrobial effects despite serum and tissue
levels below the MIC. The two drug classes commonly used in veterinary medicine that exhibit a PAE are the fluoroquinolones
and the aminoglycosides.
Antimicrobial resistance
The growing problem of antimicrobial resistance has been identified as one of the greatest threats to human health in the
21st century by the Centers for Disease Control and Prevention. As veterinarians we play a key role in limiting the development
of this problem through our use of antimicrobial drugs. The development of antimicrobial resistance can occur through either
spontaneous chromosomal mutations or the transfer of R plasmids between microorganisms. Plasmid transfer represents the major
source of antimicrobial resistance. R plasmid transfer is uncommon in most Gram positive organisms except for Staph sp. and Enterococcus. R plasmid transfer occurs much more frequently between Gram negative organisms. A single R plasmid may code for the resistance
of up to 10 antimicrobials.
Limiting antimicrobial use and using them appropriately when they are indicated are the two most important strategies to limit
the development of resistance. Antimicrobial therapy should be prescribed for the minimum duration needed to result in a clinical
cure. Therapy beyond this point is not of any benefit and only serves to heighten the problem or resistance. Subtherapeutic
dosing levels also result in the promotion of resistance (such as antimicrobial use as a growth promoter in food animals).
The narrowest spectrum drug available to treat the infection should be chosen and therapeutic choices should be refined once
sensitivity results are available.
