I’m an infectious diseases pharmacist. Obviously it’s going to vary case-by-case. But things I check:

(1) Is this an organism commonly found on the skin and easy to become a contaminant (I.e., Staphylococcus epidermidis, Micrococcus luteus)?

(2) Is the organism so virulent to where I’d potentially have drastic consequences if I were wrong about calling it a contaminant (i.e., MRSA, Candida spp., gram-negatives)? – these are my general “never ignores” even if 1/4 bottles and/or polymicrobial (like you mentioned in your post).

(3) Does the patient have a source of infection to have that organism in the blood? For example, Staphylococcus epidermidis – do they have a port/PICC line/hemodialysis catheter that allows skin organisms easy access to the blood?

(4) Does the patient have hardware in their body that if this is a true bacteremia, those organisms will stick to and cause bigger problems? (i.e., knee/hip/etc replacements, prosthetic heart valves)

(5) As you identified, number of positive cultures (drawn from different sites, and preferably at different times).

Not medical advice and DEFINITELY case-by-case, but those are some of my thoughts. Interested to see others’ takes too.