title: Rifabutin and rifampin resistance levels and associated rpoB mutations in clinical isolates of Mycobacterium tuberculosis complex.
abstract: Cross-resistance in rifamycins has been observed in rifampin (RIF)-resistant Mycobacterium tuberculosis complex isolates; some rpoB mutations do not confer broad in vitro rifamycin resistance. We examined 164 isolates, of which 102 were RIF-resistant, for differential resistance between RIF and rifabutin (RFB). A total of 42 unique single mutations or combinations of mutations were detected. The number of unique mutations identified exceeded that reported in any previous study. RFB and RIF MICs up to 8 μg/mL by MGIT 960 were studied; the cut-off values for susceptibility to RIF and RFB were 1 μg/mL and 0.5 μg/mL, respectively. We identified 31 isolates resistant to RIF but susceptible to RFB with the mutations D516V, D516F, 518 deletion, S522L, H526A, H526C, H526G, H526L, and two dual mutations (S522L + K527R and H526S + K527R). Clinical investigations using RFB to treat multidrug-resistant tuberculosis cases harboring those mutations are recommended.
authors.affiliation: California Department of Public Health, Microbial Diseases Laboratory, Richmond, CA, USA. Electronic address: zberrada@smcgov.org.
authors.forename: Zenda L
authors.initials: ZL
authors.lastname: Berrada
authors.affiliation: California Department of Public Health, Microbial Diseases Laboratory, Richmond, CA, USA.
authors.forename: Shou-Yean Grace
authors.initials: SY
authors.lastname: Lin
authors.affiliation: University of California, San Diego, CA, USA.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Rodwell
authors.affiliation: California Department of Public Health, Microbial Diseases Laboratory, Richmond, CA, USA.
authors.forename: Duylinh
authors.initials: D
authors.lastname: Nguyen
authors.affiliation: California Department of Public Health, Microbial Diseases Laboratory, Richmond, CA, USA.
authors.forename: Gisela F
authors.initials: GF
authors.lastname: Schecter
authors.affiliation: California Department of Public Health, Microbial Diseases Laboratory, Richmond, CA, USA.
authors.forename: Lucy
authors.initials: L
authors.lastname: Pham
authors.affiliation: California Department of Public Health, Microbial Diseases Laboratory, Richmond, CA, USA.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Janda
authors.affiliation: University of California, San Diego, CA, USA.
authors.forename: Wael
authors.initials: W
authors.lastname: Elmaraachli
authors.affiliation: University of California, San Diego, CA, USA.
authors.forename: Antonino
authors.initials: A
authors.lastname: Catanzaro
authors.affiliation: California Department of Public Health, Microbial Diseases Laboratory, Richmond, CA, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Desmond
mesh_terms: D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D012321:DNA-Directed RNA Polymerases / Q000235:genetics*; D006801:Humans; D008826:Microbial Sensitivity Tests; D020125:Mutation, Missense; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000302:isolation & purification; D017828:Rifabutin / Q000494:pharmacology*; D012293:Rifampin / Q000494:pharmacology*; D014376:Tuberculosis / Q000382:microbiology*
chemical_list: D000904:Antibiotics, Antitubercular; D017828:Rifabutin; D012321:DNA-Directed RNA Polymerases; C105078:RNA polymerase beta subunit; D012293:Rifampin
keywords: Mycobacterium tuberculosis; molecular drug-susceptibility; multi-drug resistant tuberculosis; rifabutin