Coinfections of Two Strains of NDM-1- and OXA-232-Coproducing Klebsiella pneumoniae in a Kidney Transplant Patient

Contreras, Deisy; Fitzwater, Sean; Nanayakkara, Deepa; Schaenman, Joanna; Aldrovandi, Grace M.; Garner, Omai B.; Yang, Shangxin

doi:10.1128/aac.00948-19

Cited by 36 publications

(52 citation statements)

References 20 publications

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“…Key among these are the carbapenem-inactivating serine ␤-lactamases (SBLs), including KPC and OXA-48, and the emerging metallo-␤-lactamases (MBLs; e.g., NDM and VIM). CRE and carbapenem-resistant Pseudomonas aeruginosa (CRPA) strains producing SBLs and MBLs pose a serious challenge for infectious disease physicians and are a major public health concern (4,(15)(16)(17)(18). One effective strategy to address the upsurge of carbapenemases is the use of a combination of a ␤-lactam (BL) with a ␤-lactamase inhibitor (BLI) to provide protection from these hydrolyzing enzymes (1,2,12).…”

mentioning

confidence: 99%

VNRX-5133 (Taniborbactam), a Broad-Spectrum Inhibitor of Serine- and Metallo-β-Lactamases, Restores Activity of Cefepime in Enterobacterales and Pseudomonas aeruginosa

Hamrick

Docquier

Uehara

et al. 2020

Antimicrob Agents Chemother

134

109

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As shifts in the epidemiology of β-lactamase-mediated resistance continue, carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) are the most urgent threats. Although approved β-lactam (BL)–β-lactamase inhibitor (BLI) combinations address widespread serine β-lactamases (SBLs), such as CTX-M-15, none provide broad coverage against either clinically important serine-β-lactamases (KPC, OXA-48) or clinically important metallo-β-lactamases (MBLs; e.g., NDM-1). VNRX-5133 (taniborbactam) is a new cyclic boronate BLI that is in clinical development combined with cefepime for the treatment of infections caused by β-lactamase-producing CRE and CRPA. Taniborbactam is the first BLI with direct inhibitory activity against Ambler class A, B, C, and D enzymes. From biochemical and structural analyses, taniborbactam exploits substrate mimicry while employing distinct mechanisms to inhibit both SBLs and MBLs. It is a reversible covalent inhibitor of SBLs with slow dissociation and a prolonged active-site residence time (half-life, 30 to 105 min), while in MBLs, it behaves as a competitive inhibitor, with inhibitor constant (Ki) values ranging from 0.019 to 0.081 μM. Inhibition is achieved by mimicking the transition state structure and exploiting interactions with highly conserved active-site residues. In microbiological testing, taniborbactam restored cefepime activity in 33/34 engineered Escherichia coli strains overproducing individual enzymes covering Ambler classes A, B, C, and D, providing up to a 1,024-fold shift in the MIC. Addition of taniborbactam restored the antibacterial activity of cefepime against all 102 Enterobacterales clinical isolates tested and 38/41 P. aeruginosa clinical isolates tested with MIC90s of 1 and 4 μg/ml, respectively, representing ≥256- and ≥32-fold improvements, respectively, in antibacterial activity over that of cefepime alone. The data demonstrate the potent, broad-spectrum rescue of cefepime activity by taniborbactam against clinical isolates of CRE and CRPA.

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mentioning

confidence: 99%

VNRX-5133 (Taniborbactam), a Broad-Spectrum Inhibitor of Serine- and Metallo-β-Lactamases, Restores Activity of Cefepime in Enterobacterales and Pseudomonas aeruginosa

Hamrick

Docquier

Uehara

et al. 2020

Antimicrob Agents Chemother

134

109

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“…Few clinical cases were also published, describing cefiderocol's compassionate use for other types of infection, such as endocarditis, ventilator-associated pneumonia, intra-abdominal infection or bloodstream infection [7][8][9].…”

Section: Discussionmentioning

confidence: 99%

Compassionate Use of Cefiderocol to Treat a Case of Prosthetic Joint Infection Due to Extensively Drug-Resistant Enterobacter hormaechei

et al. 2020

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We report the case of a 67-year old man with a right knee prosthetic joint infection due to extensively drug-resistant Enterobacter hormaechei. The resistance phenotype was due to the overproduction of the intrinsic cephalosporinase (ACT-5) associated with the production of three acquired β-lactamases (CTX-M-15, TEM-1B and OXA-1), and a putative membrane decreased permeability. He was first treated with colistin-tigecyclin due to adverse drug reactions; treatment was switched to cefiderocol for a 12-week antibiotic duration, with a favorable outcome.

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“…Blood culture taken the day of surgery was negative and persisted negative up to day 275. 68, female 55 End-stage renal disease secondary to diabetes who had been on hemodialysis for 8 years. Renal transplant complicated by cardiac arrest with pulseless electronic activity, requiring initiation of extracorporeal membrane oxygenation and continuous renal replacement therapy.…”

Section: Case Reports and Case Seriesmentioning

confidence: 99%

Evaluating Cefiderocol in the Treatment of Multidrug-Resistant Gram-Negative Bacilli: A Review of the Emerging Data

Giacobbe¹,

Ciacco²,

Girmenia³

et al. 2020

IDR

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Coinfections of Two Strains of NDM-1- and OXA-232-Coproducing Klebsiella pneumoniae in a Kidney Transplant Patient

Cited by 36 publications

References 20 publications

VNRX-5133 (Taniborbactam), a Broad-Spectrum Inhibitor of Serine- and Metallo-β-Lactamases, Restores Activity of Cefepime in Enterobacterales and Pseudomonas aeruginosa

VNRX-5133 (Taniborbactam), a Broad-Spectrum Inhibitor of Serine- and Metallo-β-Lactamases, Restores Activity of Cefepime in Enterobacterales and Pseudomonas aeruginosa

Compassionate Use of Cefiderocol to Treat a Case of Prosthetic Joint Infection Due to Extensively Drug-Resistant Enterobacter hormaechei

Evaluating Cefiderocol in the Treatment of Multidrug-Resistant Gram-Negative Bacilli: A Review of the Emerging Data

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