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Antimicrobial Agents and Chemotherapy, June 2008, p. 2019-2026, Vol. 52, No. 6
0066-4804/08/$08.00+0     doi:10.1128/AAC.00986-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Differential Antibiotic Susceptibility of Mycobacterium abscessus Variants in Biofilms and Macrophages Compared to That of Planktonic Bacteria

The University of New Mexico School of Medicine, Albuquerque, New Mexico 87131,¹ Department of Medicine, New Mexico Veterans Affairs Health Care System, Albuquerque, New Mexico 87108²

Received 30 July 2007/ Returned for modification 14 September 2007/ Accepted 24 March 2008

Mycobacterium abscessus causes refractory pulmonary infections requiring surgery for cure. It exists as a smooth biofilm-forming phenotype which is noninvasive and a rough, non-biofilm-forming phenotype which can invade macrophages and cause persistent pulmonary infection in mice. We have postulated that the dissociation of the smooth phenotype to the rough phenotype may lead to invasive lung disease following initial colonization of the airways. Amikacin, cefoxitin, and clarithromycin are standard therapies for this infection. We determined the MICs of these antibiotics against this pathogen in biofilms and macrophages, the niches that it likely occupies in the human host. Our results demonstrate that even though the MICs indicate sensitivity to these antibiotics, the minimal bactericidal concentrations for amikacin and clarithromycin were substantially higher and were out of the range of the concentrations achievable in serum. Cefoxitin demonstrated only bacteriostatic activity. In addition, although amikacin had modest activity against M. abscessus in biofilms, clarithromycin demonstrated only minimal activity at the highest concentrations tested. Our results indicate that M. abscessus in mature biofilms is in a stationary-phase state and that clarithromycin is relatively inactive against stationary-phase M. abscessus. In human macrophages, all three antibiotics were only bacteriostatic for M. abscessus variants at 10 times their MICs. These results suggest why treatment failure with antibiotics alone is common in the clinical setting of M. abscessus pulmonary infection. Determination of the efficacies of new antibiotics should include an assessment of their activities against the smooth and rough M. abscessus morphotypes in biofilms and macrophages.

Published ahead of print on 31 March 2008.