Microbiological Characteristics of the 32 Isolates Obtained from 16 Patients for Whom Additional Analysis was Performed on Initial and Subsequent Ceftolozane-tazobactam (TOL-TAZ) Exposed Pseudomonas aeruginosa Isolates
| Isolate Number . | Index Isolate TOL-TAZ MIC (mcg/mL) . | Subsequent Isolate TOL-TAZ MIC (mcg/mL) . | Index Isolate CAZ-AVI MIC (mcg/mL) . | Subsequent Isolate CAZ-AVI MIC (mcg/mL) . | Sequence Type . | Resistance Genes/Enzymes Identified in Both Index and Subsequent Isolates . | Chromosomal Mutations Leading to Amino Acid Variants in Subsequent Isolates Likely Contributing to TOL-TAZ Resistance . |
|---|---|---|---|---|---|---|---|
| 1a/1b | 0.5 | 256 | 2 | 1 | ST-244 | fosA, catB7, crpP, aph(3′)-IIb, blaOXA-847, PDC-1 | OprD stop mutation (E426) |
| Membrane transport protein: ATB-binding component of ABC transporter (G326A) | |||||||
| 2a/2b | 4 | 256 | 16 | 64 | ST-9 | fosA, catB7, aph(3′)-IIb, blaOXA-486, PDC-3 | AmpC (G183D) |
| Penicillin binding protein 3 (E466K) | |||||||
| DNA polymerase subunits gamma and tau (disruption in frame insertion) | |||||||
| 3a/3b | 2 | 8 | 2 | 16 | ST-2053 | fosA, crpP, catB7, aph(3′)-IIb, blaOXA-50, PDC-3 | Not analyzed |
| 4a/4b | 4 | 256 | 64 | 64 | ST-179 | fosA, catB7, crpP, aph(3′)-IIb, blaOXA-396, PDC-57 | DNA polymerase subunits gamma and tau (V406G) |
| Probable multidrug resistant efflux pump (PAO434) | |||||||
| 5a/5b | 1 | 16 | 4 | 256 | Unknown | fosA, catB7, aph(3′)-IIb, blaOXA-50, PDC-101 | AmpR (D135G) |
| Cell shape-determining protein: MreC (A298G, P313L) | |||||||
| Protein involved in energy-dependent receptor-mediated ligand uptake: TonB2 (A163T, P164Q, P177A) | |||||||
| Probable porin: PA3588 (R241fs) | |||||||
| Membrane transport protein: major facilitator superfamily transporter PA4113 (A371V) | |||||||
| 6a/6b | 4 | 8 | 2 | 8 | Unknown | fosA, catB7, aph(3′)-IIb, blaOXA-50, PDC-3 | Not analyzed |
| 7a/7b | 1 | 1 | 4 | 4 | ST-1568 | fosA, catB7, crpP, aph(3′)-IIb, blaOXA-395, PDC-98 | Not analyzed |
| 8a/8b | 1 | 4 | 2 | 8 | ST-683 | fosA, crpP, catB7, aph(3′)-IIb, blaOXA-50, PDC-3 | Not analyzed |
| 9a/9b | 0.5 | 256 | 16 | 256 | ST-281 | crpP, catB7, aph(3′)-IIb, blaOXA-486, PDC-1 | AmpC (E247K) |
| DNA polymerase subunits gamma and tau (V477I) | |||||||
| Outer membrane protein: Opr86 (Q678_G679insIV, N669_K676delinsDGKD) | |||||||
| 10a/10b | 1 | 2 | 2 | 2 | Unknown | fosA, crpP, catB7, aph(3′)-IIb, blaOXA-50, PDC-3 | Not analyzed |
| 11a/11b | 2 | 1 | 4 | 2 | ST-2613 | fosA, crpP, catB7, aph(3′)-IIb, aadA6, blaOXA-488, sul1, qacEdelta1, PDC-35 | Not analyzed |
| 12a/12b | 4 | 2 | 32 | 4 | ST-253 | fosA, crpP, aph(3′)-IIb, blaOXA-488, PDC-34 | Not analyzed |
| 13a/13b | 1 | 0.5 | 16 | 4 | ST-395 | fosA, catB7, aph(3′)-IIb, blaOXA-851, PDC-8 | Not analyzed |
| 14a/14b | 2 | 8 | 16 | 16 | ST-677 | fosA, crpP, catB7, aph(3′)-IIb, blaOXA-396, PDC-5 | Not analyzed |
| 15a/15b | 1 | 256 | 2 | 256 | ST-309 | fosA, crpP, catB7, aph(3′)-IIb, blaOXA-846, PDC-19a | Not analyzed |
| 16a/16b | 1 | 256 | 8 | 32 | Unknown | fosA, crpP, catB7, aph(3′)-IIb, blaOXA-50, PDC-3 | Not analyzed |
| Isolate Number . | Index Isolate TOL-TAZ MIC (mcg/mL) . | Subsequent Isolate TOL-TAZ MIC (mcg/mL) . | Index Isolate CAZ-AVI MIC (mcg/mL) . | Subsequent Isolate CAZ-AVI MIC (mcg/mL) . | Sequence Type . | Resistance Genes/Enzymes Identified in Both Index and Subsequent Isolates . | Chromosomal Mutations Leading to Amino Acid Variants in Subsequent Isolates Likely Contributing to TOL-TAZ Resistance . |
|---|---|---|---|---|---|---|---|
| 1a/1b | 0.5 | 256 | 2 | 1 | ST-244 | fosA, catB7, crpP, aph(3′)-IIb, blaOXA-847, PDC-1 | OprD stop mutation (E426) |
| Membrane transport protein: ATB-binding component of ABC transporter (G326A) | |||||||
| 2a/2b | 4 | 256 | 16 | 64 | ST-9 | fosA, catB7, aph(3′)-IIb, blaOXA-486, PDC-3 | AmpC (G183D) |
| Penicillin binding protein 3 (E466K) | |||||||
| DNA polymerase subunits gamma and tau (disruption in frame insertion) | |||||||
| 3a/3b | 2 | 8 | 2 | 16 | ST-2053 | fosA, crpP, catB7, aph(3′)-IIb, blaOXA-50, PDC-3 | Not analyzed |
| 4a/4b | 4 | 256 | 64 | 64 | ST-179 | fosA, catB7, crpP, aph(3′)-IIb, blaOXA-396, PDC-57 | DNA polymerase subunits gamma and tau (V406G) |
| Probable multidrug resistant efflux pump (PAO434) | |||||||
| 5a/5b | 1 | 16 | 4 | 256 | Unknown | fosA, catB7, aph(3′)-IIb, blaOXA-50, PDC-101 | AmpR (D135G) |
| Cell shape-determining protein: MreC (A298G, P313L) | |||||||
| Protein involved in energy-dependent receptor-mediated ligand uptake: TonB2 (A163T, P164Q, P177A) | |||||||
| Probable porin: PA3588 (R241fs) | |||||||
| Membrane transport protein: major facilitator superfamily transporter PA4113 (A371V) | |||||||
| 6a/6b | 4 | 8 | 2 | 8 | Unknown | fosA, catB7, aph(3′)-IIb, blaOXA-50, PDC-3 | Not analyzed |
| 7a/7b | 1 | 1 | 4 | 4 | ST-1568 | fosA, catB7, crpP, aph(3′)-IIb, blaOXA-395, PDC-98 | Not analyzed |
| 8a/8b | 1 | 4 | 2 | 8 | ST-683 | fosA, crpP, catB7, aph(3′)-IIb, blaOXA-50, PDC-3 | Not analyzed |
| 9a/9b | 0.5 | 256 | 16 | 256 | ST-281 | crpP, catB7, aph(3′)-IIb, blaOXA-486, PDC-1 | AmpC (E247K) |
| DNA polymerase subunits gamma and tau (V477I) | |||||||
| Outer membrane protein: Opr86 (Q678_G679insIV, N669_K676delinsDGKD) | |||||||
| 10a/10b | 1 | 2 | 2 | 2 | Unknown | fosA, crpP, catB7, aph(3′)-IIb, blaOXA-50, PDC-3 | Not analyzed |
| 11a/11b | 2 | 1 | 4 | 2 | ST-2613 | fosA, crpP, catB7, aph(3′)-IIb, aadA6, blaOXA-488, sul1, qacEdelta1, PDC-35 | Not analyzed |
| 12a/12b | 4 | 2 | 32 | 4 | ST-253 | fosA, crpP, aph(3′)-IIb, blaOXA-488, PDC-34 | Not analyzed |
| 13a/13b | 1 | 0.5 | 16 | 4 | ST-395 | fosA, catB7, aph(3′)-IIb, blaOXA-851, PDC-8 | Not analyzed |
| 14a/14b | 2 | 8 | 16 | 16 | ST-677 | fosA, crpP, catB7, aph(3′)-IIb, blaOXA-396, PDC-5 | Not analyzed |
| 15a/15b | 1 | 256 | 2 | 256 | ST-309 | fosA, crpP, catB7, aph(3′)-IIb, blaOXA-846, PDC-19a | Not analyzed |
| 16a/16b | 1 | 256 | 8 | 32 | Unknown | fosA, crpP, catB7, aph(3′)-IIb, blaOXA-50, PDC-3 | Not analyzed |
Abbreviations: CAZ-AVI, ceftazidime-avibactam; del, deletion; fs, frameshift mutation; ins, insertion; MIC, minimum inhibitory concentration.
Microbiological Characteristics of the 32 Isolates Obtained from 16 Patients for Whom Additional Analysis was Performed on Initial and Subsequent Ceftolozane-tazobactam (TOL-TAZ) Exposed Pseudomonas aeruginosa Isolates
| Isolate Number . | Index Isolate TOL-TAZ MIC (mcg/mL) . | Subsequent Isolate TOL-TAZ MIC (mcg/mL) . | Index Isolate CAZ-AVI MIC (mcg/mL) . | Subsequent Isolate CAZ-AVI MIC (mcg/mL) . | Sequence Type . | Resistance Genes/Enzymes Identified in Both Index and Subsequent Isolates . | Chromosomal Mutations Leading to Amino Acid Variants in Subsequent Isolates Likely Contributing to TOL-TAZ Resistance . |
|---|---|---|---|---|---|---|---|
| 1a/1b | 0.5 | 256 | 2 | 1 | ST-244 | fosA, catB7, crpP, aph(3′)-IIb, blaOXA-847, PDC-1 | OprD stop mutation (E426) |
| Membrane transport protein: ATB-binding component of ABC transporter (G326A) | |||||||
| 2a/2b | 4 | 256 | 16 | 64 | ST-9 | fosA, catB7, aph(3′)-IIb, blaOXA-486, PDC-3 | AmpC (G183D) |
| Penicillin binding protein 3 (E466K) | |||||||
| DNA polymerase subunits gamma and tau (disruption in frame insertion) | |||||||
| 3a/3b | 2 | 8 | 2 | 16 | ST-2053 | fosA, crpP, catB7, aph(3′)-IIb, blaOXA-50, PDC-3 | Not analyzed |
| 4a/4b | 4 | 256 | 64 | 64 | ST-179 | fosA, catB7, crpP, aph(3′)-IIb, blaOXA-396, PDC-57 | DNA polymerase subunits gamma and tau (V406G) |
| Probable multidrug resistant efflux pump (PAO434) | |||||||
| 5a/5b | 1 | 16 | 4 | 256 | Unknown | fosA, catB7, aph(3′)-IIb, blaOXA-50, PDC-101 | AmpR (D135G) |
| Cell shape-determining protein: MreC (A298G, P313L) | |||||||
| Protein involved in energy-dependent receptor-mediated ligand uptake: TonB2 (A163T, P164Q, P177A) | |||||||
| Probable porin: PA3588 (R241fs) | |||||||
| Membrane transport protein: major facilitator superfamily transporter PA4113 (A371V) | |||||||
| 6a/6b | 4 | 8 | 2 | 8 | Unknown | fosA, catB7, aph(3′)-IIb, blaOXA-50, PDC-3 | Not analyzed |
| 7a/7b | 1 | 1 | 4 | 4 | ST-1568 | fosA, catB7, crpP, aph(3′)-IIb, blaOXA-395, PDC-98 | Not analyzed |
| 8a/8b | 1 | 4 | 2 | 8 | ST-683 | fosA, crpP, catB7, aph(3′)-IIb, blaOXA-50, PDC-3 | Not analyzed |
| 9a/9b | 0.5 | 256 | 16 | 256 | ST-281 | crpP, catB7, aph(3′)-IIb, blaOXA-486, PDC-1 | AmpC (E247K) |
| DNA polymerase subunits gamma and tau (V477I) | |||||||
| Outer membrane protein: Opr86 (Q678_G679insIV, N669_K676delinsDGKD) | |||||||
| 10a/10b | 1 | 2 | 2 | 2 | Unknown | fosA, crpP, catB7, aph(3′)-IIb, blaOXA-50, PDC-3 | Not analyzed |
| 11a/11b | 2 | 1 | 4 | 2 | ST-2613 | fosA, crpP, catB7, aph(3′)-IIb, aadA6, blaOXA-488, sul1, qacEdelta1, PDC-35 | Not analyzed |
| 12a/12b | 4 | 2 | 32 | 4 | ST-253 | fosA, crpP, aph(3′)-IIb, blaOXA-488, PDC-34 | Not analyzed |
| 13a/13b | 1 | 0.5 | 16 | 4 | ST-395 | fosA, catB7, aph(3′)-IIb, blaOXA-851, PDC-8 | Not analyzed |
| 14a/14b | 2 | 8 | 16 | 16 | ST-677 | fosA, crpP, catB7, aph(3′)-IIb, blaOXA-396, PDC-5 | Not analyzed |
| 15a/15b | 1 | 256 | 2 | 256 | ST-309 | fosA, crpP, catB7, aph(3′)-IIb, blaOXA-846, PDC-19a | Not analyzed |
| 16a/16b | 1 | 256 | 8 | 32 | Unknown | fosA, crpP, catB7, aph(3′)-IIb, blaOXA-50, PDC-3 | Not analyzed |
| Isolate Number . | Index Isolate TOL-TAZ MIC (mcg/mL) . | Subsequent Isolate TOL-TAZ MIC (mcg/mL) . | Index Isolate CAZ-AVI MIC (mcg/mL) . | Subsequent Isolate CAZ-AVI MIC (mcg/mL) . | Sequence Type . | Resistance Genes/Enzymes Identified in Both Index and Subsequent Isolates . | Chromosomal Mutations Leading to Amino Acid Variants in Subsequent Isolates Likely Contributing to TOL-TAZ Resistance . |
|---|---|---|---|---|---|---|---|
| 1a/1b | 0.5 | 256 | 2 | 1 | ST-244 | fosA, catB7, crpP, aph(3′)-IIb, blaOXA-847, PDC-1 | OprD stop mutation (E426) |
| Membrane transport protein: ATB-binding component of ABC transporter (G326A) | |||||||
| 2a/2b | 4 | 256 | 16 | 64 | ST-9 | fosA, catB7, aph(3′)-IIb, blaOXA-486, PDC-3 | AmpC (G183D) |
| Penicillin binding protein 3 (E466K) | |||||||
| DNA polymerase subunits gamma and tau (disruption in frame insertion) | |||||||
| 3a/3b | 2 | 8 | 2 | 16 | ST-2053 | fosA, crpP, catB7, aph(3′)-IIb, blaOXA-50, PDC-3 | Not analyzed |
| 4a/4b | 4 | 256 | 64 | 64 | ST-179 | fosA, catB7, crpP, aph(3′)-IIb, blaOXA-396, PDC-57 | DNA polymerase subunits gamma and tau (V406G) |
| Probable multidrug resistant efflux pump (PAO434) | |||||||
| 5a/5b | 1 | 16 | 4 | 256 | Unknown | fosA, catB7, aph(3′)-IIb, blaOXA-50, PDC-101 | AmpR (D135G) |
| Cell shape-determining protein: MreC (A298G, P313L) | |||||||
| Protein involved in energy-dependent receptor-mediated ligand uptake: TonB2 (A163T, P164Q, P177A) | |||||||
| Probable porin: PA3588 (R241fs) | |||||||
| Membrane transport protein: major facilitator superfamily transporter PA4113 (A371V) | |||||||
| 6a/6b | 4 | 8 | 2 | 8 | Unknown | fosA, catB7, aph(3′)-IIb, blaOXA-50, PDC-3 | Not analyzed |
| 7a/7b | 1 | 1 | 4 | 4 | ST-1568 | fosA, catB7, crpP, aph(3′)-IIb, blaOXA-395, PDC-98 | Not analyzed |
| 8a/8b | 1 | 4 | 2 | 8 | ST-683 | fosA, crpP, catB7, aph(3′)-IIb, blaOXA-50, PDC-3 | Not analyzed |
| 9a/9b | 0.5 | 256 | 16 | 256 | ST-281 | crpP, catB7, aph(3′)-IIb, blaOXA-486, PDC-1 | AmpC (E247K) |
| DNA polymerase subunits gamma and tau (V477I) | |||||||
| Outer membrane protein: Opr86 (Q678_G679insIV, N669_K676delinsDGKD) | |||||||
| 10a/10b | 1 | 2 | 2 | 2 | Unknown | fosA, crpP, catB7, aph(3′)-IIb, blaOXA-50, PDC-3 | Not analyzed |
| 11a/11b | 2 | 1 | 4 | 2 | ST-2613 | fosA, crpP, catB7, aph(3′)-IIb, aadA6, blaOXA-488, sul1, qacEdelta1, PDC-35 | Not analyzed |
| 12a/12b | 4 | 2 | 32 | 4 | ST-253 | fosA, crpP, aph(3′)-IIb, blaOXA-488, PDC-34 | Not analyzed |
| 13a/13b | 1 | 0.5 | 16 | 4 | ST-395 | fosA, catB7, aph(3′)-IIb, blaOXA-851, PDC-8 | Not analyzed |
| 14a/14b | 2 | 8 | 16 | 16 | ST-677 | fosA, crpP, catB7, aph(3′)-IIb, blaOXA-396, PDC-5 | Not analyzed |
| 15a/15b | 1 | 256 | 2 | 256 | ST-309 | fosA, crpP, catB7, aph(3′)-IIb, blaOXA-846, PDC-19a | Not analyzed |
| 16a/16b | 1 | 256 | 8 | 32 | Unknown | fosA, crpP, catB7, aph(3′)-IIb, blaOXA-50, PDC-3 | Not analyzed |
Abbreviations: CAZ-AVI, ceftazidime-avibactam; del, deletion; fs, frameshift mutation; ins, insertion; MIC, minimum inhibitory concentration.
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