Relebactam is a potent inhibitor of the kpc-2 -lactamase and restores imipenem susceptibility in kpc-producing enterobacteriaceae

Antimicrobial Agents and Chemotherapy

Volumn 62, Issue 6, 2018, Pages

  Papp Wallace, Krisztina M ^a,b   Barnes, Melissa D ^a,b   Alsop, Jim ^c   Taracila, Magdalena A ^a,b   Bethel, Christopher R ^a   Becka, Scott A ^a   van Duin, David ^d   Kreiswirth, Barry N ^e   Kaye, Keith S ^f   Bonomo, Robert A ^a,b  

^a DEPARTMENT OF VETERANS AFFAIRS   (United States)

^b CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF MINNESOTA   (United States)

^d UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^e PUBLIC HEALTH RESEARCH INSTITUTE   (United States)

^f UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AVIBACTAM; AVIBACTAM PLUS CEFTAZIDIME; BETA LACTAMASE; CARBAPENEMASE; IMIPENEM; KLEBSIELLA PNEUMONIAE CARBAPENEMASE; RELEBACTAM; UNCLASSIFIED DRUG; ANTIINFECTIVE AGENT; AZABICYCLO DERIVATIVE; BACTERIAL PROTEIN; BETA LACTAMASE INHIBITOR; BETA-LACTAMASE KPC-2, KLEBSIELLA PNEUMONIAE; MK-7655;

ACYLATION; ANTIBIOTIC SENSITIVITY; ANTIMICROBIAL ACTIVITY; ARTICLE; BACTERIUM ISOLATE; CITROBACTER FREUNDII; CITROBACTER KOSERI; CONTROLLED STUDY; ENTEROBACTER AEROGENES; ENTEROBACTER CLOACAE; ENZYME INACTIVATION; ESCHERICHIA COLI; KLEBSIELLA OXYTOCA; KLEBSIELLA PNEUMONIAE; MASS SPECTROMETRY; MINIMUM INHIBITORY CONCENTRATION; MOLECULAR DYNAMICS; NONHUMAN; PRIORITY JOURNAL; RATE CONSTANT; ANTAGONISTS AND INHIBITORS; CARBAPENEM-RESISTANT ENTEROBACTERIACEAE; DRUG COMBINATION; DRUG EFFECT; ENZYME ACTIVE SITE; GENETICS; HUMAN; ISOLATION AND PURIFICATION; METABOLISM; MICROBIAL SENSITIVITY TEST;

ANTI-BACTERIAL AGENTS; AZABICYCLO COMPOUNDS; BACTERIAL PROTEINS; BETA-LACTAMASE INHIBITORS; BETA-LACTAMASES; CARBAPENEM-RESISTANT ENTEROBACTERIACEAE; CATALYTIC DOMAIN; DRUG COMBINATIONS; HUMANS; IMIPENEM; KLEBSIELLA PNEUMONIAE; MICROBIAL SENSITIVITY TESTS; MOLECULAR DYNAMICS SIMULATION;

EID: 85047624882     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.00174-18     Document Type: Article

References (19)

1. Papp-Wallace KM, Bethel CR, Distler AM, Kasuboski C, Taracila M, Bonomo RA. 2010. Inhibitor resistance in the KPC-2 -lactamase, a preeminent property of this class A -lactamase. Antimicrob Agents Chemother 54:890–897. https://doi.org/10.1128/AAC.00693-09.
2. Blizzard TA, Chen H, Kim S, Wu J, Bodner R, Gude C, Imbriglio J, Young K, Park YW, Ogawa A, Raghoobar S, Hairston N, Painter RE, Wisniewski D, Scapin G, Fitzgerald P, Sharma N, Lu J, Ha S, Hermes J, Hammond ML. 2014. Discovery of MK-7655, a -lactamase inhibitor for combination with Primaxin(R). Bioorg Med Chem Lett 24:780–785. https://doi.org/10 .1016/j.bmcl.2013.12.101.
3. Ehmann DE, Jahic H, Ross PL, Gu RF, Hu J, Durand-Reville TF, Lahiri S, Thresher J, Livchak S, Gao N, Palmer T, Walkup GK, Fisher SL. 2013. Kinetics of avibactam inhibition against class A, C, and D -lactamases. J Biol Chem 288:27960–27971. https://doi.org/10.1074/jbc.M113.485979.
4. Hirsch EB, Ledesma KR, Chang KT, Schwartz MS, Motyl MR, Tam VH. 2012. In vitro activity of MK-7655, a novel -lactamase inhibitor, in combination with imipenem against carbapenem-resistant Gram-negative bacteria. Antimicrob Agents Chemother 56:3753–3757. https://doi.org/10 .1128/AAC.05927-11.
5. Livermore DM, Warner M, Mushtaq S. 2013. Activity of MK-7655 combined with imipenem against Enterobacteriaceae and Pseudomonas aeruginosa. J Antimicrob Chemother 68:2286–2290. https://doi.org/10.1093/jac/dkt178.
6. Bhagunde P, Chang KT, Hirsch EB, Ledesma KR, Nikolaou M, Tam VH. 2012. Novel modeling framework to guide design of optimal dosing strategies for -lactamase inhibitors. Antimicrob Agents Chemother 56:2237–2240. https://doi.org/10.1128/AAC.06113-11.
7. Powles M, Galgoci A, Misura A, Liberator P, Hammond M. 2010. Abstr 50th Intersci Conf Antimicrob Agents Chemother, Boston, MA, abstr F1-2140.
8. Papp-Wallace KM, Taracila MA, Smith KM, Xu Y, Bonomo RA. 2012. Understanding the molecular determinants of substrate and inhibitor specificities in the carbapenemase KPC-2: exploring the roles of Arg220 and Glu276. Antimicrob Agents Chemother 56:4428–4438. https://doi.org/10.1128/AAC.05769-11.
9. Papp-Wallace KM, Winkler ML, Taracila MA, Bonomo RA. 2015. Variants of -lactamase KPC-2 that are resistant to inhibition by avibactam. Antimicrob Agents Chemother 59:3710–3717. https://doi.org/10.1128/AAC.04406-14.
10. Krishnan NP, Nguyen NQ, Papp-Wallace KM, Bonomo RA, van den Akker F. 2015. Inhibition of Klebsiella -lactamases (SHV-1 and KPC-2) by avibactam: a structural study. PLoS One 10:e0136813. https://doi.org/10.1371/journal.pone.0136813.
11. Yigit H, Queenan AM, Anderson GJ, Domenech-Sanchez A, Biddle JW, Steward CD, Alberti S, Bush K, Tenover FC. 2001. Novel carbapenem-hydrolyzing -lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae. Antimicrob Agents Chemother 45:1151–1161. https://doi.org/10.1128/AAC.45.4.1151-1161.2001.
12. Papp-Wallace KM, Taracila M, Hornick JM, Hujer AM, Hujer KM, Distler AM, Endimiani A, Bonomo RA. 2010. Substrate selectivity and a novel role in inhibitor discrimination by residue 237 in the KPC-2 -lactamase. Antimicrob Agents Chemother 54:2867–2877. https://doi.org/10.1128/ AAC.00197-10.
13. KPC in the United States. Antimicrob Agents Chemother 52:2680 –2682. https://doi.org/10.1128/AAC.00158-08.
14. KPC-containing Klebsiella pneumoniae isolates detected in different institutions in the eastern USA. J Antimicrob Chemother 63:427–437. https://doi.org/10.1093/jac/dkn547.
15. Clinical and Laboratory Standards Institute. 2006. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard, 7th ed. CLSI document M7-A7. Clinical and Laboratory Standards Institute, Wayne, PA.
16. Reference deleted.
17. Papp-Wallace KM, Winkler ML, Gatta JA, Taracila MA, Chilakala S, Xu Y, Johnson JK, Bonomo RA. 2014. Reclaiming the efficacy of -lactam–-lactamase inhibitor combinations: avibactam restores the susceptibility of ceftazidime against CMY-2-producing Escherichia coli. Antimicrob Agents Chemother 58:4290–4297. https://doi.org/10.1128/AAC.02625-14.
18. Papp-Wallace KM, Becka SA, Taracila MA, Winkler ML, Gatta JA, Rholl DA, Schweizer HP, Bonomo RA. 2016. Exposing a -lactamase “twist”: the mechanistic basis for the high level of ceftazidime resistance in the C69F variant of the Burkholderia pseudomallei PenI -lactamase. Antimicrob Agents Chemother 60:777–788. https://doi.org/10.1128/AAC.02073-15.
19. Levitt PS, Papp-Wallace KM, Taracila MA, Hujer AM, Winkler ML, Smith KM, Xu Y, Harris ME, Bonomo RA. 2012. Exploring the role of a conserved class A residue in the -loop of KPC-2 -lactamase: a mechanism for ceftazidime hydrolysis. J Biol Chem 287:31783–31793. https://doi.org/10.1074/jbc.M112.348540.