2017
DOI: 10.1128/aac.00777-17
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Avibactam Restores the Susceptibility of Clinical Isolates of Stenotrophomonas maltophilia to Aztreonam

Abstract: is an emerging opportunistic pathogen, classified by the World Health Organization as one of the leading multidrug-resistant organisms in hospital settings. The need to discover novel compounds and/or combination therapies for is urgent. We demonstrate the efficacy of aztreonam-avibactam (ATM-AVI) against and kinetically characterize the inhibition of the L2 β-lactamase by avibactam. ATM-AVI overcomes aztreonam resistance in selected clinical strains of, addressing an unmet medical need.

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Cited by 58 publications
(43 citation statements)
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“…In addition, a modified carbapenemase multiplex PCR that detects bla IMP , bla NDM , bla OXA-48-like, and bla VIM was employed (26). The P. aeruginosa and S. maltophilia ␤-lactamase content was previously determined in other studies (20)(21)(22). In this manner, we identified the relevant ␤-lactamases for the entire collection of 1,086 Gram-negative clinical isolates.…”
mentioning
confidence: 97%
See 1 more Smart Citation
“…In addition, a modified carbapenemase multiplex PCR that detects bla IMP , bla NDM , bla OXA-48-like, and bla VIM was employed (26). The P. aeruginosa and S. maltophilia ␤-lactamase content was previously determined in other studies (20)(21)(22). In this manner, we identified the relevant ␤-lactamases for the entire collection of 1,086 Gram-negative clinical isolates.…”
mentioning
confidence: 97%
“…In addition, there were 116 clinical strains of various enterobacterial species selected from a reference collection with various ␤-lactamases and included the 18 isolates without ESBLs or carbapenemases. The nonfermenter isolates tested were clinical isolates from a worldwide collection of Acinetobacter baumannii complex isolates (n ϭ 200; 101 were resistant to at least one carbapenem), S. maltophilia (n ϭ 25 with bla L1 ), and P. aeruginosa (n ϭ 27) isolates with bla VIM , bla PDC , and/or porin OprD deletions from hospitals in the Cleveland, OH, area (6,(20)(21)(22). All A. baumannii complex isolates and a subset of the K. pneumoniae isolates were sequenced by whole-genome sequencing (WGS) using paired-end NexteraXT libraries and an Illumina NextSeq sequencer (2ϫ 150 bp) to ϳ100-fold coverage.…”
mentioning
confidence: 99%
“…every 8h) in combination with ATM (2g i.v. every 8 h) for 48 days was demonstrated for a young renal transplant patient with S. maltophilia resistant to SXT, meropenem and CAZ [11]. In our research, CAZ/AVI has been demonstrated to inhibit the growth of about half of the CAZ-NS isolates (48.48%, 16/33), still showing high-level resistance (MIC: 64/4 µg/mL) in 10 isolates.…”
Section: Bactericidal Activities Of Caz/avi and Atm/avi Against S Mamentioning
confidence: 54%
“…L1 is a class B3 metallo-β-lactamase (MBL) that hydrolyzes carbapenems and other β-lactams, with the important exception of the monobactam aztreonam (ATM), and is resistant to all clinically available β-lactams [1,8,9]. L2 is a class A cephalosporinase that confers resistance to extended-spectrum cephalosporins and ATM but can be inhibited by commercially available serine-β-lactamase inhibitors such as clavulanic acid and avibactam [1,2,11,12]. Avibactam (AVI) is a non β lactam, βlactamase inhibitor without intrinsic antibacterial activity, but offers a broader β-lactamase inhibition pro le compared with any other recently used serine βlactamase inhibitors [13].…”
Section: Introductionmentioning
confidence: 99%
“…Stenotrophomonas maltophilia is an arising opportunistic pathogenic microorganism, systematic classified by the WHO as one of the governing multidrug-resistant pathogen in a hospital ward (1). Stenotrophomonas maltophilia is a Gram-negative environmental bacterium that can cause respiratory tract infections with cystic fibrosis, associated with bloodstream and urinary tract infections.…”
Section: Introductionmentioning
confidence: 99%