Frequency and mechanism of spontaneous resistance to sulbactam combined with the novel β-lactamase inhibitor ETX2514 in clinical isolates of acinetobacter baumannii

Antimicrobial Agents and Chemotherapy

Volumn 62, Issue 2, 2018, Pages

  McLeod, Sarah M ^a   Shapiro, Adam B ^a   Moussa, Samir H ^a   Johnstone, Michele ^c,d   McLaughlin, Robert E ^b   De Jonge, Boudewijn L M ^c   Millera, Alita A ^c  

^a Entasis Therapeutics   (United States)

^b ASTRAZENECA   (United Kingdom)

^c Macrolide Pharmaceuticals   (United States)

^d NONE   (United States)

Author keywords

Acinetobacter baumannii; Antibiotic resistance; ETX2514; Sulbactam; lactamase inhibitor

Indexed keywords

BACTERIAL PROTEIN; BETA LACTAMASE; BETA LACTAMASE INHIBITOR; ETX 2514; MUTANT PROTEIN; PENICILLIN BINDING PROTEIN; PENICILLIN BINDING PROTEIN 2; PENICILLIN BINDING PROTEIN 3; SULBACTAM; UNCLASSIFIED DRUG; ANTIINFECTIVE AGENT; AZABICYCLO DERIVATIVE; ETX2514; ISOPROTEIN; PROTEIN BINDING;

ACINETOBACTER BAUMANNII; ANTIBIOTIC RESISTANCE; ARTICLE; BACTERIAL GENE; BACTERIAL GENOME; BACTERIUM ISOLATE; BINDING AFFINITY; DRUG POTENTIATION; ENZYME INHIBITION; GENE MUTATION; IN VITRO STUDY; MINIMUM INHIBITORY CONCENTRATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN PURIFICATION; ACINETOBACTER INFECTION; ALPHA HELIX; ANTAGONISTS AND INHIBITORS; BETA SHEET; BINDING SITE; CHEMISTRY; COMBINATION DRUG THERAPY; DRUG EFFECT; GENE EXPRESSION REGULATION; GENETICS; HUMAN; ISOLATION AND PURIFICATION; METABOLISM; MICROBIAL SENSITIVITY TEST; MICROBIOLOGY; MOLECULAR MODEL; MULTIDRUG RESISTANCE; MUTATION; PROTEIN DOMAIN;

ACINETOBACTER BAUMANNII; ACINETOBACTER INFECTIONS; ANTI-BACTERIAL AGENTS; AZABICYCLO COMPOUNDS; BETA-LACTAMASE INHIBITORS; BETA-LACTAMASES; BINDING SITES; DRUG RESISTANCE, MULTIPLE, BACTERIAL; DRUG THERAPY, COMBINATION; GENE EXPRESSION REGULATION, BACTERIAL; HUMANS; MICROBIAL SENSITIVITY TESTS; MODELS, MOLECULAR; MUTATION; PENICILLIN-BINDING PROTEINS; PROTEIN BINDING; PROTEIN CONFORMATION, ALPHA-HELICAL; PROTEIN CONFORMATION, BETA-STRAND; PROTEIN INTERACTION DOMAINS AND MOTIFS; PROTEIN ISOFORMS; SULBACTAM;

EID: 85040985768     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.01576-17     Document Type: Article

References (22)

1. Wong D, Nielsen TB, Bonomo RA, Pantapalangkoor P, Luna B, Spell-berg B. 2017. Clinical and pathophysiological overview of Acinetobacter infections: a century of challenges. Clin Microbiol Rev 30:409–447.
2. WHO. 2017. Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics. http://www.who.int/medicines/publications/WHO-PPL-Short_Summary_25Feb-ET_NM _WHO.pdf.
3. Poirel L, Nordmann P. 2006. Carbapenem resistance in Acinetobacter baumannii: mechanisms and epidemiology. Clin Microbiol Infect 12: 826–836. https://doi.org/10.1111/j.1469-0691.2006.01456.x.
4. Potron A, Poirel L, Nordmann P. 2015. Emerging broad-spectrum resistance in Pseudomonas aeruginosa and Acinetobacter baumannii: mechanisms and epidemiology. Int J Antimicrob Agents 45:568–585. https://doi.org/10.1016/j.ijantimicag.2015.03.001.
5. Poirel L, Naas T, Nordmann P. 2010. Diversity, epidemiology, and genetics of class D β-lactamases. Antimicrob Agents Chemother 54:24–38. https://doi.org/10.1128/AAC.01512-08.
6. Bush K, Bradford PA. 2016. -Lactams and β-lactamase inhibitors: an overview. Cold Spring Harb Perspect Med 6:piia025247. https://doi.org/10.1101/cshperspect.a025247.
7. Papp-Wallace KM, Bonomo RA. 2016. New β-lactamase inhibitors in the clinic. Infect Dis Clin North Am 30:441–464. https://doi.org/10.1016/j.idc.2016.02.007.
8. Durand-Reville TF, Guler S, Comita-Prevoir J, Chen B, Bifulco N, Huynh H, Lahiri S, Shapiro AB, Mcleod SM, Carter NM, Moussa SH, Velez-Vega C, Olivier NB, McLaughlin R, Gao N, Thresher J, Palmer T, Andrews B, Giacobbe RA, Newman JV, Ehmann DE, de Jonge B, O’Donnell J, Mueller JP, Tommasi RA, Miller AA. 2017. ETX2514 is a broad-spectrum β-lactamase inhibitor for the treatment of drug-resistant Gram-negative bacteria, including Acinetobacter baumannii. Nat Microbiol 2:17104. https://doi.org/10.1038/nmicrobiol.2017.104.
9. Lickliter KL, O’Donnell JJ, Isaacs R. 2017. Safety and pharmacokinetics (PK) in humans of intravenous ETX2514, a β-lactamase inhibitor (BLI) which broadly inhibits Ambler class A, C and D β-lactamases, poster 1836. ID Week, San Diego, CA, 4 to 8 October 2017.
10. Penwell WF, Shapiro AB, Giacobbe RA, Gu RF, Gao N, Thresher J, McLaughlin RE, Huband MD, DeJonge BL, Ehmann DE, Miller AA. 2015. Molecular mechanisms of sulbactam antibacterial activity and resistance determinants in Acinetobacter baumannii. Antimicrob Agents Chemother 59:1680–1689. https://doi.org/10.1128/AAC.04808-14.
11. Krizova L, Poirel L, Nordmann P, Nemec A. 2013. TEM-1 β-lactamase as a source of resistance to sulbactam in clinical strains of Acinetobacter baumannii. J Antimicrob Chemother 68:2786–2791. https://doi.org/10.1093/jac/dkt275.
12. Kuo SC, Lee YT, Yang Lauderdale TL, Huang WC, Chuang MF, Chen CP, Su SC, Lee KR, Chen TL. 2015. Contribution of Acinetobacter-derived cephalosporinase-30 to sulbactam resistance in Acinetobacter baumannii. Front Microbiol 6:231. https://doi.org/10.3389/fmicb.2015.00231.
13. Clinical and Laboratory Standards Institute. 2015. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard. CLSI document M07-A10. Clinical and Laboratory Standards Institute, Wayne, PA.
14. Han S, Caspers N, Zaniewski RP, Lacey BM, Tomaras AP, Feng X, Geoghe-gan KF, Shanmugasundaram V. 2011. Distinctive attributes of -lactam target proteins in Acinetobacter baumannii relevant to development of new antibiotics. J Am Chem Soc 133:20536–20545. https://doi.org/10.1021/ja208835z.
15. Shapiro AB, Gu RF, Gao N, Livchak S, Thresher J. 2013. Continuous fluorescence anisotropy-based assay of BOCILLIN FL penicillin reaction with penicillin binding protein 3. Anal Biochem 439:37–43. https://doi.org/10.1016/j.ab.2013.04.009.
16. Shapiro AB, Gao N, Gu RF, Thresher J. 2014. Fluorescence anisotropy-based measurement of Pseudomonas aeruginosa penicillin-binding protein 2 transpeptidase inhibitor acylation rate constants. Anal Biochem 463:15–22. https://doi.org/10.1016/j.ab.2014.06.004.
17. Bouloc P, Vinella D, D’Ari R. 1992. Leucine and serine induce mecillinam resistance in Escherichia coli. Mol Gen Genet 235:242–246. https://doi.org/10.1007/BF00279366.
18. Vinella D, D’Ari R, Jaffe A, Bouloc P. 1992. Penicillin binding protein 2 is dispensable in Escherichia coli when ppGpp synthesis is induced. EMBO J 11:1493–1501.
19. Thulin E, Sundqvist M, Andersson DI. 2015. Amdinocillin (mecillinam) resistance mutations in clinical isolates and laboratory-selected mutants of Escherichia coli. Antimicrob Agents Chemother 59:1718 –1727. https://doi.org/10.1128/AAC.04819-14.
20. Doumith M, Mushtaq S, Livermore DM, Woodford N. 2016. New insights into the regulatory pathways associated with the activation of the stringent response in bacterial resistance to the PBP2-targeted antibiotics, mecillinam and OP0595/RG6080. J Antimicrob Chemother 71: 2810–2814. https://doi.org/10.1093/jac/dkw230.
21. Livermore DM, Warner M, Mushtaq S, Woodford N. 2015. Interactions of OP0595, a novel triple-action diazabicyclooctane, with -lactams against OP0595-resistant Enterobacteriaceae mutants. Antimicrob Agents Chemother 60:554 –560. https://doi.org/10.1128/AAC.02184-15.
22. Morinaka A, Tsutsumi Y, Yamada M, Suzuki K, Watanabe T, Abe T, Furuuchi T, Inamura S, Sakamaki Y, Mitsuhashi N, Ida T, Livermore DM. 2015. OP0595, a new diazabicyclooctane: mode of action as a serine β-lactamase inhibitor, antibiotic and -lactam “enhancer.” J Antimicrob Chemother 70:2779–2786. https://doi.org/10.1093/jac/dkv166.