Overcoming an extreme drug resistant (XDR) pathogen: Avibactam restores susceptibility to ceftazidime for Burkholderia cepacia
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1 Overcoming an extreme drug resistant (XDR) pathogen: Avibactam restores susceptibility to ceftazidime for Burkholderia cepacia complex isolates from Cystic Fibrosis patients Krisztina M. Papp-Wallace, Scott A. Becka, Elise T. Zeiser, Nozomi Ohuchi, Maria F. Mojica, Julian A. Gatta, Monica Falleni, Delfina Tosi, Elisa Borghi, Marisa L. Winkler, Brigid M. Wilson, John J. LiPuma, Michiyoshi Nukaga, and Robert A. Bonomo Number of pages: 7 Number of tables: 2 S1
2 Supplemental Table 1. MICs in mg/l of selected antibiotics against clinical isolates of B. multivorans. a Strain TOB CIP MIN SXT IPM CAZ CAZ-AVI ATCC / AU / AU / AU / AU / AU / AU / AU / AU / AU / AU / AU / AU / AU / AU / AU / AU / AU / AU / AU / AU / AU / AU / AU / AU / AU / AU / AU / AU /76 16 >512 8 S2
3 AU / AU / AU / AU / AU / AU / AU / AU > >16/ AU / AU / AU / AU / AU / AU / AU / AU / AU / AU / AU / AU / AU / AU / E. coli DH10B 0.25 pbc SK+ b / E. coli DH10B 4 1 b / pbc SK+ bla pena a TOB, tobramycin ( 4 mg/l = S); CIP, ciprofloxacin ( 1 mg/l = S); MIN, minocycline ( 4 mg/l = S); SXT, trimethoprimsulfamethoxazole ( 2/38 mg/l = S); CAZ, ceftazidime ( 8 mg/l = S); IPM, imipenem ( 4 mg/l = S); avibactam (AVI) was held at 4 mg/l and CAZ concentrations were varied. MIC breakpoints based on CLSI criteria 15 for Bcc are in parenthesis; S = susceptible; b The bla pena gene was cloned from the B. multivorans ATCC17616 strain into pbc SK(+) and its expression is under the control of the lac promoter and expressed in E. coli DH10B; this is a control strain to reveal expression of bla pena contribution on MICs in a isogenic background. E. coli DH10B pbc SK(+) is the empty vector control. S3
4 Supplemental Table 2. MICs in mg/l against clinical isolates of Burkholderia spp. a Strain TOB CIP MIN IPM SXT CAZ CAZ- AVI B. ambifaria AU / B. ambifaria AU / B. ambifaria AU / B. ambifaria AU >16/ B. arboris AU / B. arboris AU / B. cenocepacia AU / B. cenocepacia AU14109 > / B. cenocepacia AU / B. cenocepacia AU / B. cenocepacia AU / B. cenocepacia AU9215 > >16/ B. cenocepacia AU9512 > / B. cenocepacia AU / B. cenocepacia AU10321 > / B. cenocepacia AU / B. cenocepacia AU / B. cenocepacia AU / B. cenocepacia AU / B. cenocepacia AU / B. cenocepacia AU / B. cenocepacia AU / B. cenocepacia AU / B. cenocepacia AU19530 > / B. cenocepacia AU / B. cenocepacia AU / B. cenocepacia AU / S4
5 B. cenocepacia AU / B. cenocepacia AU / B. cenocepacia AU / B. cenocepacia AU / B. cenocepacia AU >16/ B. cenocepacia AU19684 > / B. cenocepacia AU20998 >512 > / B. cenocepacia AU / B. cenocepacia AU / B. cenocepacia AU >16/ B. cenocepacia AU14093 > / B. cepacia AU / B. cepacia AU / B. cepacia AU / B. cepacia AU / B. cepacia AU / B. cepacia AU / B. cepacia AU / B. cepacia AU / B. cepacia AU / B. cepacia AU / B. cepacia AU / B. cepacia AU / B. cepacia AU / B. cepacia AU / B. cepacia AU / B. contaminans AU / B. contaminans AU / B. contaminans AU / B. contaminans AU / B. contaminans AU / S5
6 B. contaminans AU / B. diffusa AU / B. dolosa AU / B. dolosa AU12872 >512 > / B. dolosa AU / B. dolosa AU29985 > /152 > B. gladioli AU / B. gladioli AU / B. gladioli AU / B. gladioli AU / B. gladioli AU / B. gladioli AU / B. gladioli AU / B. pseudomultivorans AU19682 > / B. pyrrocinia AU / B. pyrrocinia AU / B. seminalis AU / B. stabilis AU9035 > >16/ B. stabilis AU10235 > / B. ubonensis AU7314 > / B. vietnamiensis AU / B. vietnamiensis AU / B. vietnamiensis AU / B. vietnamiensis AU10214 > / B. vietnamiensis AU / B. vietnamiensis AU / B. vietnamiensis AU / B. vietnamiensis AU26096 >512 > >16/ B. vietnamiensis AU / B. vietnamiensis AU28891 > >16/ b Burkholderia spp. AU / S6
7 Burkholderia spp. AU / Burkholderia spp. AU / Burkholderia spp. AU / Burkholderia spp. AU / Burkholderia spp. AU > >16/ Burkholderia spp. AU / Burkholderia spp. AU / a TOB, tobramycin ( 4 mg/l = S); CIP, ciprofloxacin ( 1 mg/l = S); MIN, minocycline ( 4 mg/l = S); SXT, trimethoprim-sulfamethoxazole ( 2/38 mg/l = S); CAZ, ceftazidime ( 8 mg/l = S); IPM, imipenem ( 4 mg/l = S); avibactam (AVI) was held at 4 mg/l and CAZ concentrations were varied. MIC breakpoints based on CLSI criteria 15 for Bcc are in parenthesis; S = susceptible. b Burkholderia spp. are members of Bcc, but are quite distinct from the current species in Bcc, and are not in a large enough number for taxonomic analyses to describe a new species. S7
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