美罗培南、阿维巴坦和金属-β-内酰胺酶抑制剂三联用药优化对不同β-内酰胺酶病原菌的抗菌覆盖率

Zhuoren Ling, Alistair James Macdonald Farley, Aditya Lankapalli, Yanfang Zhang, Shonnette Premchand-Branker, Kate Cook, Andrei Baran, Charlotte Gray-Hammerton, Claudia Orbegozo Rubio, Edgars Suna, Jordan Mathias, Jürgen Brem, Kirsty Sands, Maria Nieto-Rosado, Maria Mykolaivna Trush, Nadira Naznin Rakhi, Willames Martins, Yuqing Zhou, Christopher Joseph Schofield, Timothy Walsh

工程（英文） ›› 2024, Vol. 38 ›› Issue (7) : 124-132.

PDF(3624 KB)
PDF(3624 KB)
工程（英文） ›› 2024, Vol. 38 ›› Issue (7) : 124-132. DOI: 10.1016/j.eng.2024.02.010
研究论文
Article

美罗培南、阿维巴坦和金属-β-内酰胺酶抑制剂三联用药优化对不同β-内酰胺酶病原菌的抗菌覆盖率

作者信息 +

The Triple Combination of Meropenem, Avibactam, and a Metallo-β-Lactamase Inhibitor Optimizes Antibacterial Coverage Against Different β-Lactamase Producers

Author information +
History +

Abstract

This work explores the potential of a triple combination of meropenem (MEM), a novel metallo-βlactamase (MBL) inhibitor (indole-2-carboxylate 58 (InC58)), and a serine-β-lactamase (SBL) inhibitor (avibactam (AVI)) for broad-spectrum activity against carbapenemase-producing bacteria. A diverse panel comprising MBL- and SBL-producing strains was used for susceptibility testing of the triple combination using the agar dilution method. The frequency of resistance (FoR) to MEM combined with InC58 was investigated. Mutants were sequenced and tested for cross resistance, fitness, and the stability of the resistance phenotype. Compared with the double combinations of MEM plus an SBL or MBL inhibitor, the triple combination extended the spectrum of activity to most of the isolates bearing SBLs (oxacillinase-48 (OXA-48) and Klebsiella pneumoniae carbapenemase-2 (KPC-2)) and MBLs (New Delhi metallo-β- lactamases (NDMs)), although it was not effective against Verona integron-encoded metallo-βlactamase (VIM)-carrying Pseudomonas aeruginosa (P. aeruginosa) and OXA-23-carrying Acinetobacter baumannii (A. baumannii). The FoR to MEM plus InC58 ranged from 2.22×10-7 to 1.13×10-6. The resistance correlated with mutations to ompC and comR, affecting porin C and copper permeability, respectively. The mutants manifested a fitness cost, a decreased level of resistance during passage without antibiotic pressure, and cross resistance to another carbapenem (imipenem) and a β-lactamase inhibitor (taniborbactam). In conclusion, compared with the dual combinations, the triple combination of MEM with InC58 and AVI showed a much wider spectrum of activity against different carbapenemase-producing bacteria, revealing a new strategy to combat β-lactamase-mediated antimicrobial resistance.

Keywords

Carbapenemase / Metallo/serine-β-lactamase inhibitor / Avibactam / Meropenem / Antimicrobial resistance

引用本文

EndNote

Ris (Procite)

Bibtex

导出引用
Zhuoren Ling, Alistair James Macdonald Farley, Aditya Lankapalli. 美罗培南、阿维巴坦和金属β-内酰胺酶抑制剂三联用药对不同β-内酰胺酶的抗菌范围优化. Engineering. 2024, 38(7): 124-132 https://doi.org/10.1016/j.eng.2024.02.010

参考文献

原文顺序 | 文献年度倒序 | 文中引用次数倒序
[1]
K. Bush, P.A. Bradford. β-Lactams and β-lactamase inhibitors: an overview. Cold Spring Harb Perspect Med, 6 (8) (2016), p. a025247
[2]
X.Z. Li, M. Mehrotra, S. Ghimire, L. Adewoye. β-Lactam resistance and β-lactamases in bacteria of animal origin. Vet Microbiol, 121 (3-4) (2007), pp. 197-214
[3]
K. Bush, P.A. Bradford. Epidemiology of β-lactamase-producing pathogens. Clin Microbiol Rev, 33 (2) (2020), pp. e00047-e119
[4]
K. Bush. Past and present perspectives on β-lactamases. Antimicrob Agents Chemother, 62 (10) (2018), pp. e01076-e1118
[5]
K. Bush, P.A. Bradford. Interplay between β-lactamases and new β-lactamase inhibitors. Nat Rev Microbiol, 17 (5) (2019), pp. 295-306
[6]
D.E. Ehmann, H. Jahić, P.L. Ross, R.F. Gu, J. Hu, G. Kern, et al. Avibactam is a covalent, reversible, non-β-lactam β-lactamase inhibitor. Proc Natl Acad Sci USA, 109 (29) (2012), pp. 11663-11668
[7]
D.E. Ehmann, H. Jahic, P.L. Ross, R.F. Gu, J. Hu, T.F. Durand-Réville, et al. Kinetics of avibactam inhibition against Class A, C, and D β-lactamases. J Biol Chem, 288 (39) (2013), pp. 27960-27971
[8]
S.D. Lahiri, S. Mangani, T. Durand-Reville, M. Benvenuti, F. De Luca, G. Sanyal, et al. Structural insight into potent broad-spectrum inhibition with reversible recyclization mechanism: avibactam in complex with CTX-M-15 and Pseudomonas aeruginosa AmpC β-lactamases. Antimicrob Agents Chemother, 57 (6) (2013), pp. 2496-2505
[9]
D.M. Livermore, S. Mushtaq, M. Warner, J. Zhang, S. Maharjan, M. Doumith, et al. Activities of NXL 104 combinations with ceftazidime and aztreonam against carbapenemase-producing Enterobacteriaceae. Antimicrob Agents Chemother, 55 (1) (2011), pp. 390-394
[10]
M.J. Carvalho, K. Sands, K. Thomson, E. Portal, J. Mathias, R. Milton, et al.BARNARDS Group. Antibiotic resistance genes in the gut microbiota of mothers and linked neonates with or without sepsis from low- and middle-income countries. Nat Microbiol, 7 (9) (2022), pp. 1337-1347
[11]
M.R. Meini, L.I. Llarrull, A.J. Vila. Overcoming differences: the catalytic mechanism of metallo-β-lactamases. FEBS Lett, 589 (22) (2015), pp. 3419-3432
[12]
S.M. Drawz, R.A. Bonomo. Three decades of β-lactamase inhibitors. Clin Microbiol Rev, 23 (1) (2010), pp. 160-201
[13]
J. Brem, T. Panduwawala, J.U. Hansen, J. Hewitt, E. Liepins, P. Donets, et al. Imitation of β-lactam binding enables broad-spectrum metallo-β-lactamase inhibitors. Nat Chem, 14 (1) (2022), pp. 15-24
[14]
D. Yahav, C.G. Giske, A. Grāmatniece, H. Abodakpi, V.H. Tam, L. Leibovici. New β-lactam-β-lactamase inhibitor combinations. Clin Microbiol Rev, 34 (1) (2020), pp. e00115-e120
[15]
Y. Wang, J. Wang, R. Wang, Y. Cai. Resistance to ceftazidime-avibactam and underlying mechanisms. J Glob Antimicrob Resist, 22 (2020), pp. 18-27
[16]
Y. Zhang, A. Kashikar, C.A. Brown, G. Denys, K. Bush. Unusual Escherichia coli PBP 3 insertion sequence identified from a collection of carbapenem-resistant Enterobacteriaceae tested in vitro with a combination of ceftazidime-, ceftaroline-, or aztreonam-avibactam. Antimicrob Agents Chemother, 61 (8) (2017), pp. e00389-e417
[17]
R.M. Humphries, P. Hemarajata.Resistance to ceftazidime-avibactam in Klebsiella pneumoniae due to porin mutations and the increased expression of KPC-3.Antimicrob Agents Chemother, 61 (6) (2017), pp. e00537-e00617
[18]
K. Nelson, P. Hemarajata, D. Sun, D. Rubio-Aparicio, R. Tsivkovski, S. Yang, et al. Resistance to ceftazidime-avibactam is due to transposition of KPC in a porin-deficient strain of Klebsiella pneumoniae with increased efflux activity. Antimicrob Agents Chemother, 61 (10) (2017), pp. e00989-e1017
[19]
L. Sun, W. Chen, H. Li, L. Li, X. Zou, J. Zhao, et al. Phenotypic and genotypic analysis of KPC-51 and KPC-52, two novel KPC-2 variants conferring resistance to ceftazidime/avibactam in the KPC-producing Klebsiella pneumoniae ST 11 clone background. J Antimicrob Chemother, 75 (10) (2020), pp. 3072-3074
[20]
P. Gaibani, C. Campoli, R.E. Lewis, S.L. Volpe, E. Scaltriti, M. Giannella, et al. In vivo evolution of resistant subpopulations of KPC-producing Klebsiella pneumoniae during ceftazidime/avibactam treatment. J Antimicrob Chemother, 73 (6) (2018), pp. 1525-1529
[21]
M.J. Giddins, N. Macesic, M.K. Annavajhala, S. Stump, S. Khan, T.H. McConville, et al. Successive emergence of ceftazidime-avibactam resistance through distinct genomic adaptations in blaKPC-2-harboring Klebsiella pneumoniae sequence type 307 isolates. Antimicrob Agents Chemother, 62 (3) (2018), pp. e02101-e2117
[22]
A. Both, H. Büttner, J. Huang, M. Perbandt, C. Belmar Campos, M. Christner, et al. Emergence of ceftazidime/avibactam non-susceptibility in an MDR Klebsiella pneumoniae isolate. J Antimicrob Chemother, 72 (9) (2017), pp. 2483-2488
[23]
Clinical and Laboratory Standards Institute CLSI. Performance standards for antimicrobial susceptibility testing. 30th edition. Wayne: CLSI M100; 2020.
[24]
S. Schwarz, P. Silley, S. Simjee, N. Woodford, E. van Duijkeren, A.P. Johnson, et al. Editorial: assessing the antimicrobial susceptibility of bacteria obtained from animals. J Antimicrob Chemother, 65 (4) (2010), pp. 601-604
[25]
K. Sands, M.J. Carvalho, E. Portal, K. Thomson, C. Dyer, C. Akpulu, et al. Characterization of antimicrobial-resistant Gram-negative bacteria that cause neonatal sepsis in seven low- and middle-income countries. Nat Microbiol, 6 (4) (2021), pp. 512-523
[26]
M. Kolmogorov, J. Yuan, Y. Lin, P.A. Pevzner. Assembly of long, error-prone reads using repeat graphs. Nat Biotechnol, 37 (5) (2019), pp. 540-546
[27]
B.J. Walker, T. Abeel, T. Shea, M. Priest, A. Abouelliel, S. Sakthikumar, et al. Pilon: an integrated tool for comprehensive microbial variant detection and genome assembly improvement. PLoS One, 9 (11) (2014), p. e112963
[28]
R.R. Wick, K.E. Holt. Polypolish: short-read polishing of long-read bacterial genome assemblies. PLoS Comput Biol, 18 (1) (2022), p. e1009802
[29]
A.V. Zimin, G. Marçais, D. Puiu, M. Roberts, S.L. Salzberg, J.A. Yorke. The MaSuRCA genome assembler. Bioinformatics, 29 (21) (2013), pp. 2669-2677
[30]
V. Bortolaia, R.S. Kaas, E. Ruppe, M.C. Roberts, S. Schwarz, V. Cattoir, et al. ResFinder 4.0 for predictions of phenotypes from genotypes. J Antimicrob Chemother, 75 (12) (2020), pp. 3491-3500
[31]
E. Zankari, R. Allesøe, K.G. Joensen, L.M. Cavaco, O. Lund, F.M. Aarestrup. PointFinder: a novel web tool for WGS-based detection of antimicrobial resistance associated with chromosomal point mutations in bacterial pathogens. J Antimicrob Chemother, 72 (10) (2017), pp. 2764-2768
[32]
C. Camacho, G. Coulouris, V. Avagyan, N. Ma, J. Papadopoulos, K. Bealer, et al. BLAST+: architecture and applications. BMC Bioinformatics, 10 (1) (2009), p. 421
[33]
H. Hasman, D. Saputra, T. Sicheritz-Ponten, O. Lund, C.A. Svendsen, N. Frimodt-Møller, et al. Rapid whole-genome sequencing for detection and characterization of microorganisms directly from clinical samples. J Clin Microbiol, 52 (1) (2014), pp. 139-146
[34]
M.V. Larsen, S. Cosentino, O. Lukjancenko, D. Saputra, S. Rasmussen, H. Hasman, et al. Benchmarking of methods for genomic taxonomy. J Clin Microbiol, 52 (5) (2014), pp. 1529-1539
[35]
P.T.L.C. Clausen, F.M. Aarestrup, O. Lund. Rapid and precise alignment of raw reads against redundant databases with KMA. BMC Bioinformatics, 19 (1) (2018), p. 307
[36]
G.G. Zhanel, R. Wiebe, L. Dilay, K. Thomson, E. Rubinstein, D.J. Hoban, et al. Comparative review of the carbapenems. Drugs, 67 (7) (2007), pp. 1027-1052
[37]
J.M. Pagès, C.E. James, M. Winterhalter. The porin and the permeating antibiotic: a selective diffusion barrier in Gram-negative bacteria. Nat Rev Microbiol, 6 (12) (2008), pp. 893-903
[38]
M. Mermod, D. Magnani, M. Solioz, J.V. Stoyanov. The copper-inducible ComR (YcfQ) repressor regulates expression of ComC (YcfR), which affects copper permeability of the outer membrane of Escherichia coli. Biometals, 25 (1) (2012), pp. 33-43
[39]
M.G.P. Page, C. Dantier, E. Desarbre, B. Gaucher, K. Gebhardt, A. Schmitt-Hoffmann. In vitro and in vivo properties of BAL30376, a β-lactam and dual β-lactamase inhibitor combination with enhanced activity against Gram-negative bacilli that express multiple β-lactamases. Antimicrob Agents Chemother, 55 (4) (2011), pp. 1510-1519
[40]
T. Idowu, D. Ammeter, G. Arthur, G.G. Zhanel, F. Schweizer. Potentiation of β-lactam antibiotics and β-lactam/β-lactamase inhibitor combinations against MDR and XDR Pseudomonas aeruginosa using non-ribosomal tobramycin-cyclam conjugates. J Antimicrob Chemother, 74 (9) (2019), pp. 2640-2648
[41]
A. MacGowan, M. Attwood, K. Bowker, A. Noel. Comment on: cefepime/sulbactam as an enhanced antimicrobial combination therapy for the treatment of MDR Gram-negative infections. J Antimicrob Chemother, 75 (9) (2020), pp. 2711-2712
[42]
H. Mansour, A.E.L. Ouweini, E.B. Chahine, L.R. Karaoui. Imipenem/cilastatin/relebactam: a new carbapenem β-lactamase inhibitor combination. Am J Health Syst Pharm, 78 (8) (2021), pp. 674-683
[43]
R.E. Hancock. Resistance mechanisms in Pseudomonas aeruginosa and other nonfermentative Gram-negative bacteria. Clin Infect Dis, 27 (s1) (1998), pp. S93-S99
[44]
Lupo A, Haenni M, Madec JY. Antimicrobial resistance in Acinetobacter spp. and Pseudomonas spp. Microbiol Spectr 2018; 6(3):ARBA.
[45]
E.B. Breidenstein, C. de la Fuente-Núñez, R.E. Hancock. Pseudomonas aeruginosa: all roads lead to resistance. Trends Microbiol, 19 (8) (2011), pp. 419-426
[46]
J.C. Vázquez-Ucha, J. Arca-Suárez, G. Bou, A. Beceiro. New carbapenemase inhibitors: clearing the way for the β-lactams. Int J Mol Sci, 21 (23) (2020), p. 9308
[47]
K.Y. Djoko, M.E.S. Achard, M.D. Phan, A.W. Lo, M. Miraula, S. Prombhul, et al. Copper ions and coordination complexes as novel carbapenem adjuvants. Antimicrob Agents Chemother, 62 (2) (2018), pp. e02280-e2317
[48]
S. Chetri, M. Singha, D. Bhowmik, K. Nath, D.D. Chanda, A. Chakravarty, et al. Transcriptional response of OmpC and OmpF in Escherichia coli against differential gradient of carbapenem stress. BMC Res Notes, 12 (1) (2019), p. 138
[49]
H. Lou, M. Chen, S.S. Black, S.R. Bushell, M. Ceccarelli, T. Mach, et al. Altered antibiotic transport in OmpC mutants isolated from a series of clinical strains of multi-drug resistant E. coli. PLoS One, 6 (10) (2011), p. e25825
PDF(3624 KB)

Accesses

Citation

Detail
段落导航
相关文章

/

〈 〉