Compositions, methods, systems and/or kits for detecting antimicrobial resistance in bacteria

The method of any of the preceding claims, wherein the antibiotic and carbapenamase inhibitor in at least one test composition comprises, consists of, or consists essentially of, a first concentration of DOR, a carbapenemase inhibitor of ambler class C, and a carbapenemase inhibitor of ambler class B.

The method of any of the preceding claims, wherein the antibiotic and carbapenamase inhibitor in at least one test composition comprises, consists of, or consists essentially of, a first concentration of MEM, a carbapenemase inhibitor of ambler class C, and a carbapenemase inhibitor of ambler A.

The method of any of the preceding claims, wherein the antibiotic in at least one test composition comprises, consists of, or consists essentially of, a second concentration of DOR.

The method of any of the preceding claims, comprising determining the one or more Ambler class carbapenemases expressed by enteric bacteria is Class D by detecting:

• the presence of growth in a first test composition, wherein the antibiotic and inhibitor comprise, consist of, or consist essentially of, a first concentration of TEM and a carbapenemase inhibitor of ambler class B.

The method of any of the preceding claims, comprising determining the one or more Ambler class carbapenemases expressed by enteric bacteria is Class A by detecting:

• the inhibition of growth in the first test composition, wherein the antibiotic and inhibitor comprise, consist of, or consist essentially of, a first concentration of TEM, and a carbapenemase inhibitor of ambler class B,
• the presence of growth in a second test composition, wherein the antibiotic and inhibitors comprise, consist of, or consist essentially of, a first concentration of DOR, a carbapenemase inhibitor of ambler class C, and a carbapenemase inhibitor of ambler class B, and
• the inhibition of growth in a third test composition, wherein the antibiotic and inhibitors comprise, consist of, or consist essentially of, a first concentration of MEM, a carbapenemase inhibitor of ambler class C, and a carbapenemase inhibitor of ambler class A.

The method of any of the preceding claims, comprising determining the one or more Ambler class carbapenemases expressed by enteric bacteria is Class B by detecting:

• the inhibition of growth in the first test composition, wherein the antibiotic and inhibitors comprise, consist of, or consist essentially of, a first concentration of TEM as the antibiotic and further comprising a carbapenemase inhibitor of ambler class B,
• the inhibition of growth in the second test composition, wherein the antibiotic and inhibitors comprise, consist of, or consist essentially of, a first concentration of DOR, a carbapenemase inhibitor of ambler class C, and a carbapenemase inhibitor of ambler class B, and
• the presence of growth in a fourth test composition, wherein the antibiotic comprises, consists of, or consists essentially of, a second concentration of DOR.

The method of any of the preceding claims, comprising determining the one or more Ambler class carbapenemases expressed by enteric bacteria is Class D by detecting:

• the inhibition of growth in the first test composition, wherein the antibiotic and inhibitor comprise, consist of, or consist essentially of, a first concentration of lEM, and a carbapenemase inhibitor of ambler class B,
• the inhibition of growth in the second test composition, wherein the antibiotic and inhibitors comprise, consist of, or consist essentially of, a first concentration of DOR, a carbapenemase inhibitor of ambler class C, and a carbapenemase inhibitor of ambler class B, and
• the inhibition of growth in the fourth test composition, wherein the antibiotic comprises, consists of, or consists essentially of, a second concentration of DOR.

The method of any of the preceding claims, comprising determining the presence of one or more Ambler class carbapenemases expressed by enteric bacteria , wherein the Ambler class is not identified, by detecting:

• the inhibition of growth in the first test composition, wherein the antibiotic and inhibitor comprise, consist of, or consist essentially of, a first concentration of lEM, and a carbapenemase inhibitor of ambler class B,
• the presence of growth in the second test composition, wherein the antibiotic and inhibitors comprise, consist of, or consist essentially of, a first concentration of DOR, a carbapenemase inhibitor of ambler class C, and a carbapenemase inhibitor of ambler class B, and
• the presence of growth in the third test composition of the plurality of at least four test compositions, wherein the antibiotic and inhibitors comprise, consist of, or consist essentially of, a first concentration of MEM as the antibiotic and further comprising a carbapenemase inhibitor of ambler class C and a carbapenemase inhibitor of ambler class A.

The method of any of the preceding claims, comprising determining the presence of one or more Ambler class A, B or D carbapenemases expressed by enteric bacteria by detecting:

• the inhibition of growth in the first test composition, wherein the antibiotic and inhibitor comprise, consist of, or consist essentially of, a first concentration of lEM, a carbapenemase inhibitor of ambler class B,
• the presence of growth in the second test composition, wherein the antibiotic and inhibitors comprise, consist of, or consist essentially of, a first concentration of, comprising DOR, a carbapenemase inhibitor of ambler class C, and a carbapenemase inhibitor of ambler class B, and
• the presence of growth in the third test composition, wherein the antibiotic and inhibitors comprise, consist of, or consist essentially of, a first concentration of MEM, a carbapenemase inhibitor of ambler class C, and a carbapenemase inhibitor of ambler class A.

The method of any of the preceding claims, wherein the antibiotic and carbapenamase inhibitor in at least one test composition comprises, consists of, or consists essentially of, a third concentration of MEM, and a carbapenemase inhibitor of ambler class C.

A method for determining the presence of none, one, or more Ambler class carbapenemases expressed by non-fermenting bacteria, the method comprising:

• providing a sample comprising the non-fermenting bacteria,
• applying the non-fermenting bacteria in the test sample to a plurality of at least three test compositions for a duration of time, wherein each of the plurality of at least three test compositions comprises a growth medium and an antibiotic, and at least one of the at least three test compositions further comprises at least one carbapenemase inhibitor, and
• determining the presence of none, one, or more one or more Ambler class carbapenemases expressed by the non-fermenting bacteria by detecting a presence or an inhibition of growth of the non-fermenting bacteria in each of the plurality of at least three test compositions after the duration of time.

The method of any of the preceding claims, further comprising determining whether a bacteria in a sample is enteric, non-fermenting, or both.

The method of any of the preceding claims, wherein the first concentration of TEM is about 6 μg/ml to about 128 μg/ml, about 32 μg/ml to about 128 μg/ml, about 32 μg/ml to about 80 μg/ml, or about 64 μg/ml.

The method of any of the preceding claims, wherein the first concentration of DOR is about 0.006 μg/ml to about 0.75 μg/ml, about 0.03125 μg/ml to about 0.1 μg/ml, or about 0.0625 μg/ml or about 0.06 μg/ml.

The method of any of the preceding claims, wherein the second concentration of DOR is about 0.0125 μg/ml to about 2 μg/ml, 0.0625 μg/ml to about 0.25 μg/ml, or about 0.125 μg/ml.

The method of any of the preceding claims, wherein the third concentration of DOR is about 0.1 μg/ml to about 400 μg/ml, about 0.5 μg/ml to about 3 μg/ml, or about 1 μg/ml.

The method of any of the preceding claims, wherein the fourth concentration of DOR is about 0.2 μg/ml to about 40 μg/ml, about 0.5 μg/ml to about 4 μg/ml, or about 2 μg/ml.

The method of any of the preceding claims, wherein the fifth concentration of DOR is about 0.03125 μg/ml to about 80 μg/ml, about 2 μg/ml to about 24 μg/ml, or about 8 μg/ml.

The method of any of the preceding claims, wherein the first concentration of MEM is 0.03125 μg/ml to 1 μg/ml, 0.03125 μg/ml to 0.125 μg/ml, 0.015625 μg/ml to 0.125 μg/ml, about 0.006 μg/ml to about 0.60 μg/ml, about 0.015 μg/ml to about 0.24 μg/ml, about 0.03 μg/ml to about 0.25 μg/ml, about 0.03 μg/ml to about 0.2 μg/ml, about 0.0625 μg/ml or about 0.060 μg/ml.

The method of any of the preceding claims, wherein the second concentration of MEM is about 0.015625 μg/ml to about 0.125 μg/ml, about 0.003 μg/ml to about 0.3 μg/ml, about 0.0075 μg/ml to about 0.12 μg/ml, about 0.01 μg/ml to about 0.12 μg/ml, or about 0.03 μg/ml.

The method of any of the preceding claims, wherein the third concentration of MEM is about 0.0125 μg/ml to about 5 μg/ml, about 0.125 μg/ml to about 1 μg/ml, or about 0.5 μg/ml.

The method of any of the preceding claims, wherein the fourth concentration of MEM is about 0.4 μg/ml to about 40 μg/ml, about 1 μg/ml to about 16 μg/ml, about 2 μg/ml to about 8 μg/ml, or about 4 μg/ml.

The method of any of the preceding claims, wherein the carbapenemase inhibitor of ambler class D comprises a compound selected from the group consisting AVI, Clavulanic acid, boronic acid, tazobactam, sulbactam, vaborbactam (RPX-7009) and BLI-489.

The method of any of the preceding claims, wherein the carbapenemase inhibitor of ambler class B is a metal chelator.

The method of any of the preceding claims, wherein the carbapenemase inhibitor of ambler class B comprises a compound selected from the group consisting EDTA, DPA and deferoxamine.

The method of any of the preceding claims, wherein the carbapenemase inhibitor of ambler class C comprises a compound selected from the group consisting CLOX, dicloxacillin and flucloxacillin.

The method of any of the preceding claims, wherein the carbapenemase inhibitor of ambler class A comprises a compound selected from the group consisting of vaborbactam (RPX-7009), AVI, Clavulanic acid, boronic acid, tazobactam, sulbactam, and BLI-489.

The method of any of the preceding claims, wherein the carbapenemase inhibitor of ambler class D comprises a compound selected from the group consisting BLI, AVI, Clavulanic acid, boronic acid, tazobactam, sulbactam, vaborbactam and (RPX-7009).

The method of any of the preceding claims, wherein the carbapenemase inhibitor of ambler class B in combination with the first concentration of TEM and/or the first concentration of DOR comprises, consists of, or consists essentially of, EDTA.

The method of any of the preceding claims, wherein the carbapenemase inhibitor of ambler class C comprises, consists of, or consists essentially of, CLOX.

The method of any of the preceding claims, wherein the carbapenemase inhibitor of ambler class A in combination with the first and/or second concentration of MEM comprises, consists of, or consists essentially of, RPX.

The method of any of the preceding claims, wherein the carbapenemase inhibitor of ambler class B in combination with the first concentration of MEM and/or the third concentration of DOR comprises, consists of, or consists essentially of, DPA.

The method of any of the preceding claims, wherein the carbapenemase inhibitor of ambler class D in combination with the first and/or fifth concentration of DOR comprises, consists of, or consists essentially of, AVI.

The method of any of the preceding claims, wherein the carbapenemase inhibitor of ambler class D in combination with the fourth concentration of MEM comprises, consists of, or consists essentially of, a first concentration of BLI.

The method of any of the preceding claims, wherein the concentration of EDTA is about 0.025 mg/ml to about 10 mg/ml, about 0.05 mg/ml to about 1.25 mg/ml, or about 0.25 mg/ml.

The method of any of the preceding claims, wherein the concentration of CLOX is about 0.0025 mg/ml to about 40 mg/ml, about 0.020 mg/ml to about 0.5 mg/ml, or about 0.1 mg/ml.

The method of any of the preceding claims, wherein the concentration of RPX is about 0.2 μg/ml to about 320 μg/ml, about 1.5 μg/ml to about 40 μg/ml, or about 8 μg/ml.

The method of any of the preceding claims, wherein the concentration of DPA is about 0.018 mg/ml to about 1.8 mg/ml, about 0.07 mg/ml to about 0.73 mg/ml, or about 0.178 mg/ml.

The method of any of the preceding claims, wherein the concentration of AVI is about 0.1 μg/ml to about 40 μg/ml, about 0.5 μg/ml to about 20 μg/ml, or about 4 μg/ml.

The method of any of the preceding claims, wherein the concentration of BLI is about 0.1 μg/ml to about 200 μg/ml, about 1 μg/ml to about 25 μg/ml, or about 5 μg/ml.

The method of any of the preceding claims, wherein the duration of time for detecting a presence or an inhibition of growth less than about 24 hours, less than about 18 hours, less than about 16, or less than about 14 hours.

The method of any of the preceding claims, wherein the duration of time for detecting a presence or an inhibition of growth of enteric bacteria is about 6 hours to about 8 hours.

The method of any of the preceding claims, wherein the duration of time for detecting a presence or an inhibition of growth of enteric bacteria is about 7 hours.

The method of any of the preceding claims, wherein the duration of time for detecting a presence or an inhibition of growth of non-fermenting bacteria is about 8 hours to about 11 hours.

The method of any of the preceding claims, wherein the duration of time for detecting a presence or an inhibition of growth of non-fermenting bacteria is about 10 hours.

The method of any of the preceding claims, wherein the enteric bacteria comprises a bacteria selected from the group consisting of Klebsiella pneumoniae, Escherichia coli, and Enterobacter aerogenes.

The method of any of the preceding claims, wherein the non-fermenting bacteria comprises a bacteria selected from the group consisting of Pseudomonas aeruginosa, and Acinetobacter baumanii complex.

The method of any of the preceding claims, wherein detecting a presence or an inhibition of growth is not performed by imaging a change in cell morphology.

The methods, systems or kits of any of the preceding claims, comprising a plurality of test compositions, wherein the test compositions comprise, consist of, or consist essentially of, test compositions selected from the test compositions disclosed in Boxes 1-14.