Bacteria exposed to subinhibitory and sublethal concentrations of antibiotics may show a number of morphologic changes on Gram stain.



Seen in

mottled Gram positivity

Gram-positive bacteria (due to antibiotics affecting the cell wall)

loss of acid-fastness


filamentous forms

Gram-negative bacteria (due to inhibition of enzymes that initiate septation)

rod-shaped forms

Streptococcus pneumoniae

granular or bipolar staining

Enterobacteriaceae (may be associated with density and distribution of ribosomes)

focal dilatations (globules)

Gram negative bacteria; Streptococcus pneumoniae

tetrads or conglomerates

diplococci (such as Neisseria gonorrhoeae)

enlargement (giant forms)

Staphylococcus aureus (inhibition of cytoplasmic division)

greater retention of crystal violet-iodine complex

Staphylococcus aureus (due to thickening of cross walls)



(1) These findings indicate subinhibitory concentration of antibiotics.

(2) The type of organism causing an infection may be misidentified (for example, Streptococcus pneumoniae).

(3) Therapy may be assumed to be more effective than it really is (for example, acid fast bacteria may disappear if acid-fastness is lost).

(4) Cultures may give false negative results if media is hypotonic. In addition, cultures should be held for a longer period (in the event of delayed proliferation).


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