Susceptible, intermediate or resistant, defined against a breakpoint
Expansion
How it is determined: the minimum inhibitory concentration is the lowest concentration preventing visible growth. This is compared with a breakpoint, the concentration achievable at the site of infection with standard dosing.
- S, susceptible: standard dosing should work
- I, susceptible at increased exposure: needs higher dose or a site where the drug concentrates, classically urine
- R, resistant: unlikely to work whatever the dose
Why the site matters: the breakpoint differs by compartment. Many agents concentrate tenfold or more in urine, so an organism reported sensitive for a urinary isolate may be untreatable in bacteraemia, and very few agents cross into the cerebrospinal fluid at therapeutic concentrations.
Selective reporting: laboratories deliberately report only a narrow panel, to steer prescribing towards narrow spectrum agents and away from broad ones. The absence of a drug from the report does not mean the organism is resistant to it.
Key resistance mechanisms
- Beta lactamases, including ESBL (extended spectrum), which inactivate penicillins and cephalosporins. ESBL producers are usually treated with a carbapenem
- AmpC induction, in Enterobacter, Serratia, Citrobacter and Providencia, where the organism may test sensitive to cephalosporins yet develop resistance during treatment
- Carbapenemases, the most concerning, requiring infection control isolation
- Altered target: MRSA through an altered penicillin binding protein, macrolide resistance through methylation
- Efflux pumps and porin loss, particularly Pseudomonas
- Inducible clindamycin resistance, detected by the D test
Practical points: always de-escalate to the narrowest effective agent once sensitivities return, treat the patient rather than the culture, and remember that growth from a swab, a catheter or sputum may represent colonisation rather than infection.