C2-1988. Diversity of Clarithromycin Resistance Mechanisms in Mycobacterium abscessus Complex Isolates
Session: Poster Session: Resistance in Mycobacteria
Monday, October 27, 2008: 12:00 AM
Room: Hall C
Background: M abscessus complex (MabC) members [M abscessus (Mab), M bolletii (Mbo), M massiliense (Mma)] are MDR species and more closely related to true respiratory pathogens than to opportunistic pathogens unlike MAC. For patients with pulmonary disease, the only oral antimicrobial to which MabC is susceptible is clarithromycin (Clr). Relapses have been reported and no alternative has been recommended. In vitro study at CDC showed that 35% of MabC isolates were resistant to this drug and 16% appeared to have intermediate resistance using the CLSI guideline. The aim of this study is to investigate whether the Clr resistance mechanism is the same among MabC isolates Methods: We studied 16 clr-R (MIC>8µg/ml), 7 clr-I (MIC=4µg/ml) and 23 clr-S (MIC<2 µg/ml) isolates using broth microdilution method according to CLSI guideline. These isolates were initially identified by HPLC and PRA. Definitive identification was done by rpoB sequencing. Riboproteins L22, L4 and 23S rRNA (domains II and V) were sequenced to screen for mutations Results: Among the 23 clr-S (MIC<2 µg/ml), 19 were identified as Mab and 4 as Mma based on rpoB sequencing. Among the 16 clr-R (MIC >8µg/ml) and at high clr resistance level [MIC>64µg/ml (n=8)] 4 were identified as Mab and 4 as Mbo. These 4 Mab isolates have 4 different mutations in the domain V of 23S rRNA (A2058C, A2059G, C2442T and T2611C) whereas the 4 Mbo isolates have no mutation. In the remaining 8 clr-R [MIC=16µg/ml (n=3), MIC=8µg/ml (n=5)], the 7 clr-I (MIC=4µg/ml) and the 23 clr-S (MIC<2 µg/ml) isolates, no mutation in 23S rRNA, L22 or L4 have been detected Conclusions: RpoB sequencing identified 50% of MabC isolates with MIC>64µg/ml as Mbo and 17% of the clr-S isolates as Mma. At high clr resistance level, while Mab isolates have different mutations in 23S rRNA, no mutation could be detected in Mbo isolates. The disruption of the A2057-T2611C and C2442T mutation seem to be new clr resistance mechanisms in Mab isolates. More studies are needed to find macrolides resistance mechanisms in Mbo isolates
Mitchell Yakrus, MS, MPH1, Thomas Shinnick, PhD1, Toidi Adekambi, PhD2 and  T. Adekambi, None., (1)Center of Diseases Control and Prevention, (2)Center of Diseases Control and Prevention, Atlanta, GA

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