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. Author manuscript; available in PMC: 2021 Dec 1.
Published in final edited form as: Infect Dis Clin North Am. 2020 Sep 30;34(4):773–819. doi: 10.1016/j.idc.2020.05.001

Table 4.

Mechanisms of resistance to ceftazidime-avibactam

Type Organism Mechanism(s) Relevant Amino Acid Substitutions in β-Lactamase Minimum Inhibitory Concentration of Isolatea Minimum Inhibitory Concentration in a Susceptible Backgroundb Reference
Laboratory E coli KPC-2 R164A N/A 16 102
Laboratory E coli KPC-2 R164P N/A 64 102
Laboratory E coli KPC-2 D179A N/A 64 102
Laboratory E coli KPC-2 D179Q N/A 32 102
Laboratory E coli KPC-2 D179N N/A 32 102
Laboratory E coli KPC-2 D179Y N/A 32 106
Survey K pneumoniae KPC-2, SHV-12, TEM-1, and loss of ompK35, ompk36, and ompK37 16 N/A 166
Survey E coli KPC-2, TEM-1, 344_ins_TIPY_345_PBP3 8 N/A 153
Case K pneumoniae Overexpression of KPC-2, loss of ompK35 and ompK36 12 N/A 108
Laboratory C freundii KPC-2, overexpression of acrA, loss of ompF D176Y 32 8 110
Laboratory C freundii KPC-2, overexpression of acrA, loss of ompF R146S, P147L 64 8 110
Laboratory C freundii KPC-2, overexpression of acrA, loss of ompF D179Y 64 8 110
Case K pneumoniae KPC-2, SHV-11, SHV-12, TEM-1, loss of ompK35, ompK36, and ompK37 D179Y >256 120
Survey K pneumoniae KPC-2 E166_ins_EL_L167, V278_ins_ SEAV_A281 128 64 117
Case K pneumoniae KPC-2 L169P 16 4 125
Case K pneumoniae KPC-2, SHV-11 L259_ins_AVYTRAPNKDDKHSE_V260 >16 127
Laboratory E coli KPC-2 ΔG242-T243 N/A 24 126
Laboratory K pneumoniae KPC-3 S181_ins_S_S182 64 103
Laboratory K pneumoniae KPC-3 D179Y 8–64 103
Laboratory K pneumoniae KPC-3 D163G 32 103
Laboratory Enterobacter cloacae KPC-3 S181_ins_SS_S182 32 103
Laboratory Enterobacter cloacae KPC-3 P174L 8–16 103
Laboratory Enterobacter cloacae KPC-3 T243P 32 103
Laboratory Enterobacter cloacae KPC-3 T265_ins_AR_R266 16 103
Laboratory Enterobacter cloacae KPC-3 P183_ins-RAVTTSSP_R184 128 103
Case K pneumoniae KPC-3, SHV-11, TEM-1, OXA-9 and loss of ompk36 D179Y 64–256 8 104
Case K pneumoniae KPC-3, SHV-11, TEM-1, OXA-9 and loss of ompk36 D179Y, T243M 256 64 104
Case K pneumoniae KPC-3, SHV-11, TEM-1, OXA-9 V240G 32 2 104
Case K pneumoniae KPC-3, SHV-11, TEM-1, OXA-9 and loss of ompk35 A177E, D179Y 128 N/A 107
Case K pneumoniae Overexpression of KPC-3, loss of ompk35 and ompk35, SHV-11, SHV-12 32 145
Survey K pneumoniae KPC-3 ΔE166-L167 16–32 8–16 117
Survey K pneumoniae KPC-3 L7P, D179Y, T243M 256 N/A 117
Case K pneumoniae KPC-3, SHV-11, TEM-1A, OXA-9 loss of ompK35 and ompK36 V240A 16 N/A 118
Laboratory E coli KPC-3 ΔG242-T243 N/A 12 126
Laboratory K pneumoniae KPC-3 D163G 32 N/A 109
Laboratory K pneumoniae KPC-3 R164S 64 N/A 109
Laboratory K pneumoniae KPC-3 E168_ins_EL_L169 32 N/A 109
Laboratory K pneumoniae KPC-3 L169_ins-KL_N170 64 N/A 109
Laboratory K pneumoniae KPC-3 N170D 32 N/A 109
Laboratory K pneumoniae KPC-3 N170D + ΔS171 >256 N/A 109
Laboratory K pneumoniae KPC-3 A172S 64 N/A 109
Laboratory K pneumoniae KPC-3 A172T + T243A 64 N/A 109
Laboratory K pneumoniae KPC-3 A172P 64 N/A 109
Laboratory K pneumoniae KPC-3 P174L 64 N/A 109
Laboratory K pneumoniae KPC-3 P174_ins_PGDARD_D179 64 N/A 109
Laboratory K pneumoniae KPC-3 G175V 64 N/A 109
Laboratory K pneumoniae KPC-3 D176Y 32 N/A 109
Laboratory K pneumoniae KPC-3 D179A >256 N/A 109
Laboratory K pneumoniae KPC-3 D179H >256 N/A 109
Laboratory K pneumoniae KPC-3 D179N 32 N/A 109
Laboratory K pneumoniae KPC-3 D179Y >256 N/A 109
Laboratory K pneumoniae KPC-3 ΔV240 128 N/A 109
Laboratory K pneumoniae KPC-3 Y241N 64 N/A 109
Laboratory K pneumoniae KPC-3 T243M 32 N/A 109
Laboratory K pneumoniae KPC-3 Y263_ins_YTRAPN_N269 >256 N/A 109
Laboratory K pneumoniae KPC-3 Y263_ins_YTRAPNKDDKYSEAV_V278 >256 N/A 109
Laboratory K pneumoniae KPC-3 R266_ins_RAS_P268 >256 N/A 109
Laboratory K pneumoniae KPC-3 R266_ins_RAPNKDDKYS_S275 >256 N/A 109
Laboratory K pneumoniae KPC-3 P268_ins_PN_N269 64 N/A 109
Laboratory K pneumoniae KPC-3 K270_ins_ KD_D271 128 N/A 109
Case K pneumoniae KPC-3 K270_PNK_D271 >128 128 128
Case K pneumoniae KPC-3 L169P, A172T >16 122
Case K pneumoniae KPC-3 A172T, T243A >16 122
Case K pneumoniae KPC-3 A172T >16 122
Survey K oxytoca SHV-12, TEM-1 16 134
Laboratory E coli CTX-M-15 S130G, L169Q N/A 16 133
Case K pneumoniae CTX-M-14, OXA-48 CTX-M-14: P167S, T264I 32 132
Laboratory E coli GES-5 N/A 0.5 31
Laboratory E coli PER-1 N/A 8 31
Laboratory E coli GES-19, GES-26 N/A 256 77
Case K pneumoniae VEB-1, TEM-1, 0XA-10 K234R 32–128 138
Survey E coli CMY-42, CTX-M-15, OXA-1, 333_ins_YRIK_334_PBP3 8 N/A 154
Survey E coli CMY-42, CMY-2, OXA-1, OXA-9, TEM-1, 333_ins_YRIK_334_PBP3 8 N/A 154
Survey K pneumoniae DHA-1, loss of ompK35 and ompK36 16 N/A 41
Survey Enterobacter cloacae AmpC ΔS289-A294 64 N/A 140
Laboratory Enterobacter cloacae AmpC G156R 64 N/A 139
Laboratory Enterobacter cloacae AmpC G156D 16 N/A 139
Laboratory C freundii AmpC N346Y 16 N/A 139
Laboratory C freundii AmpC R148P 16 N/A 139
Laboratory C freundii AmpC R148H 32 N/A 139
Survey K pneumoniae OXA-48, SHV 16 N/A 161
Survey S marcescens OXA-48, CTX-M-22, SHV 64 N/A 161
Survey P aeruginosa GES-5 16 N/A 31
Case P aeruginosa GES-19, GES-26 128 to >256 N/A 77
Survey P aeruginosa PER-1 64 N/A 31
Laboratory P aeruginosa PDC ΔR210-E219 64–256 N/A 141
Laboratory P aeruginosa PDC ΔK204a-G222 64 N/A 141
Laboratory P aeruginosa PDC ΔD217-Y221 256 N/A 141
Laboratory/Case P aeruginosa PDC G156D 128 >32 57,60,141,142
Case P aeruginosa Overexpression of PDC, loss of oprD T96I 16–32 8 52
Case P aeruginosa Overexpression of PDC, loss of oprD E219K >32 16 52
Case P aeruginosa Overexpression of PDC, loss of oprD ΔG202-E219 32 16 52
Survey P aeruginosa Overexpression of PDC and MexAB-OprM, loss of oprD 512 N/A 52
Case P aeruginosa Overexpression of PDC V211A >64 N/A 50
Case P aeruginosa PDC, mutation in mexR ΔP208-G214 >64 N/A 50
Survey P aeruginosa Overexpression of PDC, loss of oprD Q128R, V211T, S279T 256 N/A 54
Survey P aeruginosa Overexpression of PDC, loss of oprD Q128R, V211A, G220S 256 N/A 54
Survey P aeruginosa Overexpression of PDC, loss of oprD V211A 256 N/A 54
Case P aeruginosa PAC-1 >128 >128 74
Case P aeruginosa FOX-4 32 32 34
Case P aeruginosa OXA-2, loss of oprD Duplication D149 >32 32 78
Case P aeruginosa OXA-10, loss of oprD N146S 32 N/A 52
Case P aeruginosa OXA-2, VIM-20, mutation of mexZ mexX, and mexB, loss of oprD ΔI159 + E160K in OXA-2 32 32 79

Avibactam is maintained at 4 μg/mL when in combination with ceftazidime.81

P aeruginosa breakpoint: resistant greater than 8 μg/mL.

Enterobacterales breakpoint: resistant greater than 8 μg/mL.

Abbreviation: NA, not available.

a

The MIC values for the isolate represent the MIC values obtained for either a clinical isolate obtained from a patient in a case study or part of a surveillance study or a laboratory-selected strain.

b

The MIC values in a clean background represent the MIC value after the bla gene for the β-lactamase of interest was cloned and expressed in a susceptible strain.

Data from Clinical and Laboratory Standards Institute (CLSI). M100: Performance Standards for Antimicrobial Susceptibility Testing. 30th ed.; 2020.