2022
DOI: 10.1128/aac.02179-21
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Klebsiella pneumoniae Mutants Resistant to Ceftazidime-Avibactam Plus Aztreonam, Imipenem-Relebactam, Meropenem-Vaborbactam, and Cefepime-Taniborbactam

Abstract: We show that a previously described Klebsiella pneumoniae variant that is resistant to ceftazidime-avibactam plus meropenem-vaborbactam, has a ramR plus ompK36 mutation, and produces the V239G variant KPC-3 (V240G per the standard numbering system) exhibits resistance to ceftazidime-avibactam plus aztreonam and imipenem-relebactam but not cefepime-taniborbactam. The V239G variant does not generate collateral β-lactam susceptibility like ma… Show more

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Cited by 16 publications
(5 citation statements)
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“…With the recent emergence of aztreonam-avibactam resistance among carbapenemase-producing Enterobacterales [11,29,30], these tripartite associations of aztreonam-imipenem-relebactam and aztreonam-meropenem-vaborbactam have to be taken into consideration as last-resort treatment options. Unfortunately, resistance to aztreonam-meropenem-vaborbactam has already been reported in a KPC variant producing K. pneumoniae [31]. Accordingly, the rapid development of additional options, such as new combinations with more potent inhibitors (e.g., zidebactam and taniborbactam) are mandatory [32][33][34].…”
Section: Discussionmentioning
confidence: 99%
“…With the recent emergence of aztreonam-avibactam resistance among carbapenemase-producing Enterobacterales [11,29,30], these tripartite associations of aztreonam-imipenem-relebactam and aztreonam-meropenem-vaborbactam have to be taken into consideration as last-resort treatment options. Unfortunately, resistance to aztreonam-meropenem-vaborbactam has already been reported in a KPC variant producing K. pneumoniae [31]. Accordingly, the rapid development of additional options, such as new combinations with more potent inhibitors (e.g., zidebactam and taniborbactam) are mandatory [32][33][34].…”
Section: Discussionmentioning
confidence: 99%
“…This is a relatively new addition to CARD’s Relationship Ontology, with the MCR gene family serving as a trial before potential further implementation for other AMR gene families, including particularly β-lactam resistance determinants, e.g. V240G variants of bla KPC-3 ( 21 ).…”
Section: Expansion Of Card Curationmentioning
confidence: 99%
“…Notably, taniborbactam remains active against novel KPC-variants, which are resistant to CAZ/AVI. However, the accumulation of mutations can confer CEFI/TANI non-activity against K. pneumoniae [ 140 ].…”
Section: Antimicrobials In Phase 3 Clinical Trialsmentioning
confidence: 99%