786. Ceftaroline and Avibactam? Is this a potential combination for Mycobacterium abscessus infection?
Session: Poster Abstract Session: Tuberculosis and Other Mycobacterial Infections
Thursday, October 4, 2018
Room: S Poster Hall
Ceftaroline and Avibactam? Is this a potential combination for Mycobacterium abscessus infection?

Background:

Mycobacterium abscessus harbors a β-lactamase enzyme, BlaMab, able to hydrolyze penicillins, most cephalosporins and carbapenems. As of today, management of M. abscessus with β-lactams does not include combination of β-lactamase inhibitors. The potential benefit of combinations of several β-lactams with new diazabicyclooctane (DBO) inhibitors, such as relebactam and avibactam, has not been well studied. Based upon the ability to inhibit BlaMab by highly potent DBO inhibitors, our goal herein was to investigate the efficacy of a novel combination, ceftaroline (CEF) and avibactam (AVI), to restore susceptibility to β-lactam antibiotics and inhibit growth.

Methods:

Minimum inhibitory concentrations (MICs) of CEF with or without AVI was examined using the microdilution method.

Results:

MIC50 and MIC90 of CEF is 8 mg/L; in the presence of 4 μg/ml of AVI, the MICs of CEF decreased to ≤ 4 mg/L in 31 of 35 cases (Table).

 

Conclusion:

Our results add to the growing evidence of using b-lactams as agents effective against Mycobacterial infections. Inhibition of the hydrolytic activity of (BlaMab) using DBOs such as AVI suggest that this combination should be evaluated in animal and clinical models.

Table 1(a): MICs of M. abscessus strains (mg/L).

Avibactam (AV), Ceftaroline (CEF)

 

CEF

CEF+AVI

 

CEF

CEF+AVI

M. ab 15-103

8

0.25

M. ab (ATCC)

16

0.25

M. ab 15-442

8

1

M. ab IDR1400012185

32

0.25

M. ab 137-10561

8

0.5

M. ab IDR1400011191

8

<0.25

M. ab 15-305

16

2

M. ab IDR130008519

16

2

M. ab (bolletti) 15-148

16

1

M. ab 138-4796

2

0.25

M. ab 16-49

2

1

16-49

16

1

M. ab (ATCC)

32

<2

15-228

16

1

M. ab 16-21

8

0.5

15-235

8

0.5

M. ab 15-228

8

0.5

137-1061

>128

8

M. ab 15-206

128

1

M. ab 15-206

32

<0.25

M. ab 15-235

8

0.5

M. ab 15-86

64

0.5

M. ab 138-4796

32

<2

15-305

16

1

M. ab IDR130008519

16

16

M. ab 16-21

2

0.5

M. ab IDR1400012185

16

4

M. ab 15-103

4

0.5

M. ab 15-86

16

2

M. ab 15-148

8

1

M. ab 132-10561

4

1

15-442

32

1

M. ab #3

4

1

M. ab 132-10561

4

0.5

M. ab N1

4

0.5

M. ab #1

4

0.5

M. ab 60-2016

32

32

M. ab #2

8

2

M. ab IDR1400011191

16

16

M. ab #3

4

0.5

M. ab #14

16

1

M. ab #4

16

2

M. ab W2

8

1

M. ab #5

>128

4

M. ab #12

0.5

<0.125

M. ab #6

64

4

M. ab #13

32

2

M. ab #7

4

0.5

M. ab #11

16

0.5

M. ab #8

8

1

M. ab #10

32

2

M. ab #9

64

8

M. ab #7

4

1

M. ab #10

64

8

M. ab #1

16

0.5

M. ab #11

4

0.5

M. ab #8

18

0.25

M. ab #12

4

0.5

M. ab #9

32

4

M. ab #13

4

0.5

M. ab #6

32

1

M. ab #14

8

1

M. ab #4

8

0.5

M. ab 60-2016

32

32

M. ab #2

4

0.5

M. ab W2

8

0.5

M. ab #5

>64

4

M. ab N1

4

0.5

 

Khalid M. Dousa, MD, FACP, CABIM, Infectious Disease, University Hospitals, Case Western Reserve University, Cleveland, OH, Barry N. Kreiswirth, PhD, Public Health Research Institute, Rutgers New Jersey Medical School, Newark, NJ, Sebastian Kurz, MD, PhD, Department of Pulmonary Medicine and Critical Care, New York University, New York, NY and Robert A. Bonomo, MD, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH

Disclosures:

K. M. Dousa, None

B. N. Kreiswirth, None

S. Kurz, None

R. A. Bonomo, None

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