Electron microscopic analysis of Mycobacterium avium complex isolates exposed to ciprofloxacin, rifabutin, ethambutol and clarithromycin.
METHODS
Mycobacterium avium complex (MAC) isolates grown in the presence of clarithromycin, ciprofloxacin, ethambutol or rifabutin were examined by electron microscopy for drug-induced ultrastructural changes.


OBJECTIVE
To further the understanding of the activity of clarithromycin, ciprofloxacin, ethambutol and rifabutin against MAC.


METHODS
Four MAC isolates, 1 control and 3 patient, were cultured for 24 or 72 hours in liquid medium containing one of two concentrations of an antimicrobial agent prior to examination by electron microscopy.


RESULTS
One or more of the following ultrastructural changes was observed after exposure to the antimicrobial agent: disorganized nucleoid and cytoplasm, condensation of nucleoid, vacuolization, enlargement of the periplasmic space with or without vesicles, intracytoplasmic lipid-like inclusions, and cell lysis. Changes were seen after as little as 24 hours of exposure to the antimicrobial agent and were more evident with the higher of the two concentrations of the drug. Changes were present regardless of the minimum inhibitory concentration (MIC) of the antimicrobial agent against the isolates tested, but were more pronounced if the MIC was less than the concentration of drug tested.


CONCLUSIONS
Consistent ultrastructural changes were observed following exposure to a given antimicrobial agent. No drug-specific changes were identified.
Reisner
B S
BS
Department of Pathology, University of Texas Medical Branch, Galveston 77555-0740, USA.
Woods
G L
GL
Popov
V L
VL
D000995:Antitubercular Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology*; D017291:Clarithromycin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004977:Ethambutol / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008854:Microscopy, Electron; D015269:Mycobacterium avium Complex / Q000187:drug effects*; D015270:Mycobacterium avium-intracellulare Infection / Q000382:microbiology; D017828:Rifabutin / Q000494:pharmacology*
D000995:Antitubercular Agents; D017828:Rifabutin; D002939:Ciprofloxacin; D004977:Ethambutol; D017291:Clarithromycin