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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 2.

Mechanisms of resistance to ceftolozane-tazobactam

Type Organism Mechanism(s) Relevant Amino Acid Substitutions in β-Lactamase Minimum Inhibitory Concentration of Isolatea Minimum Inhibitory Concentration in a Susceptible Backgroundb Reference
Case report P aeruginosa PDC G156D ≥64 ≥64 57
Case report P aeruginosa Overexpression of PDC, loss of oprD T96I >32 32 52
Case report P aeruginosa Overexpression of PDC, loss of oprD E219K >32 16 52
Case report P aeruginosa Overexpression of PDC, loss of oprD ΔG202-E219 32 32 52
Case report P aeruginosa Overexpression of PDC, loss of oprD, mutations in mexD, mexT, mexI and mexR R52Q, T79 A, G156D ≥256 N/A 61
Case report P aeruginosa Overexpression of PDC V211A 64 N/A 50
Case report P aeruginosa PDC, mutation in mexR ΔP208-G214 >128 N/A 50
Case report P aeruginosa PDC, loss of oprD G156D 32–48 N/A 60
Laboratory strain P aeruginosa Overexpression of PDC G156D 64 32 55
Laboratory strain P aeruginosa Overexpression of PDC E219K, V329I 32 64 55
Laboratory strain P aeruginosa Overexpression of PDC F121L, Q130R, E219K, V329I 128 128 55
Survey P aeruginosa Overexpression of PDC, loss of oprD Q128R, V211T, S279T 256 N/A 54
Survey P aeruginosa PDC, loss of oprD and mutations in mexT A5V, V211A, G214R, G220S 12 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
Survey P aeruginosa PDC P153L N/A 8 51
Survey P aeruginosa PDC G214R N/A 8 51
Survey P aeruginosa PDC N346I N/A 4–8 51
Survey P aeruginosa PDC R100H, G214R N/A 16 51
Survey P aeruginosa PDC E219K N/A 64 to >64 51
Survey P aeruginosa PDC E219G N/A 32 51
Survey P aeruginosa PDC F121L, M174L N/A 16 51
Survey P aeruginosa PDC V211A, N346I N/A 16 51
Survey P aeruginosa PDC ΔT289-M291 N/A 4–8 51
Survey P aeruginosa PDC ΔT289-A292 N/A 16 51
Case report P aeruginosa Overexpression of PDC, loss of oprD ΔG202-E219 32 N/A 56
Survey P aeruginosa Overexpression of PDC and/or MexAB-OprM or MexXY-OprM and/or loss of oprD 8–16 N/A 68
Case report P aeruginosa PAC-1 >128 >128 74
Case report P aeruginosa FOX-4 16 16 34
Laboratory strain P aeruginosa GES-1 N/A 32 34
Laboratory strain P aeruginosa GES-2 G170N N/A 16 34
Laboratory strain P aeruginosa GES-5 G170S N/A 8 34
Laboratory Strain P aeruginosa GES-6 E104K, G170S N/A 32 34
Case report P aeruginosa GES-6 E104K, G170S 32 64 75
Laboratory strain P aeruginosa PER-1 N/A 512 34
Laboratory strain P aeruginosa BEL-1 N/A 8 34
Laboratory strain P aeruginosa BEL-2 N/A 32 34
Survey P aeruginosa BEL-3 P160S 16 N/A 80
Laboratory strain P aeruginosa VEB-1 N/A 64 34
Case report P aeruginosa OXA-2, loss of oprD Duplication D149 >32 16 78
Case report P aeruginosa OXA-2, VIM-20, mutation of mexZ mexX, and mexB, loss of oprD ΔI159 + E160 K in OXA-2 >32 32 79
Survey P aeruginosa OXA-2 W159R 16–32 16 68,80
Survey P aeruginosa OXA-10 N73S 64 N/A 80
Survey P aeruginosa OXA-101 32 N/A 80
Case report P aeruginosa OXA-10, loss of oprD N146S 32 N/A 52
Laboratory strain E coli GES-1 N/A 8 31
Laboratory strain E coli GES-5 G170S N/A 8 31
Laboratory strain E coli GES-6 E104K, G170S N/A 64 31
Case report E coli GES-19, GES-26 N/A 48 77
Laboratory strain E coli PER-1 N/A 128 31
Laboratory strain E coli BEL-1 N/A 4 31
Laboratory strain E coli BEL-2 N/A 8 31

Tazobactam is maintained at 4 μg/mL when in combination with ceftolozane.81

P aeruginosa breakpoints: intermediate = 8 μg/mL; resistant ≥16 μg/mL.

Enterobacterales breakpoints: intermediate = 4 μg/mL; resistant ≥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 susceptible 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.