Efficacy of Ceftazidime-Avibactam Salvage Therapy in Patients With Infections Caused by<i>Klebsiella pneumoniae</i>Carbapenemase–producing<i>K. pneumoniae</i>

Tumbarello, Mario; Trecarichi, Enrico Maria; Corona, Alberto; Rosa, Francesco Giuseppe De; Bassetti, Matteo; Mussini, Cristina; Menichetti, Francesco; Viscoli, Claudio; Campoli, Caterina; Venditti, Mario; Gasperi, Andrea De; Mularoni, Alessandra; Tascini, Carlo; Parruti, Giustino; Pallotto, Carlo; Sica, Simona; Concia, Ercole; Cultrera, Rosario; Pascale, Gennaro De; Capone, Alessandro; Antinori, Spinello; Corcione, Silvia; Righi, Elda; Losito, Angela Raffaella; Digaetano, Margherita; Amadori, Francesco; Giacobbe, Daniele Roberto; Ceccarelli, Giancarlo; Mazza, E.; Raffaelli, Francesca; Spanu, Teresa; Cauda, Roberto; Viale, Pierluigi

doi:10.1093/cid/ciy492

Cited by 300 publications

(234 citation statements)

References 35 publications

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confidence: 99%

“…Mounting real-world evidence shows improved clinical outcomes in CRE-infected patients treated with ceftazidime-avibactam compared to those treated with alternative agents (3)(4)(5). Despite these encouraging findings, the emergence of ceftazidimeavibactam resistance has been reported (5)(6)(7)(8)(9)(10)(11). Resistance is most commonly due to mutations in plasmid-borne bla KPC that encode variant Klebsiella pneumoniae carbapenemase (KPC) enzymes (7,9,12,13) and results in the restoration of carbapenem susceptibility in some isolates (8,14,15).…”

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confidence: 99%

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Effects of KPC Variant and Porin Genotype on the In Vitro Activity of Meropenem-Vaborbactam against Carbapenem-Resistant Enterobacteriaceae

Wilson

Kline

Jones

et al. 2019

Antimicrob Agents Chemother

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Meropenem-vaborbactam is a new agent with the potential to treat carbapenem-resistant Enterobacteriaceae (CRE) infections. We describe the in vitro activity of meropenem-vaborbactam against representative CRE genotypes and laboratory-engineered Escherichia coli isolates harboring mutant blaKPC genes associated with ceftazidime-avibactam resistance. We also compared disk diffusion and gradient strip testing methods to standard broth microdilution methods. Against 120 CRE isolates, median ceftazidime-avibactam and meropenem-vaborbactam MICs were 1 and 0.03 µg/ml, respectively. Ninety-eight percent (117/120) of isolates were susceptible to meropenem-vaborbactam (MICs ≤ 4 µg/ml). Against Klebsiella pneumoniae isolates harboring mutant blaKPC, the addition of vaborbactam lowered the meropenem MICs in 78% of isolates (14/18); 100% were susceptible to meropenem-vaborbactam. Median meropenem-vaborbactam MICs were higher against K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae isolates with mutant ompK36 porin genes (n = 26) than against those with wild-type ompK36 porin genes (n = 54) (0.25 versus 0.03 µg/ml; P < 0.0001). Against E. coli TOP10 isolates with plasmid constructs containing wild-type blaKPC or mutant blaKPC, the addition of vaborbactam at 8 µg/ml lowered the meropenem MICs 2- to 512-fold, resulting in meropenem-vaborbactam MICs of 0.03 µg/ml. The rates of categorical agreement with broth microdilution for disk diffusion or gradient strips ranged from 90 to 95%. Essential agreement rates were higher for research-use-only (RUO) gradient strips manufactured by bioMérieux (82%) than for those manufactured by Liofilchem (48%) (P < 0.0001). Taken together, our data highlight the potent in vitro activity of meropenem-vaborbactam against CRE, including isolates resistant to ceftazidime-avibactam. Vaborbactam inhibited both wild-type and variant KPC enzymes. On the other hand, KPC-producing K. pneumoniae isolates with ompK36 mutations displayed higher meropenem-vaborbactam MICs than isolates with wild-type ompK36. The results of susceptibility testing with RUO bioMérieux gradient strips most closely aligned with those of broth microdilution methods.

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confidence: 99%

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confidence: 99%

Effects of KPC Variant and Porin Genotype on the In Vitro Activity of Meropenem-Vaborbactam against Carbapenem-Resistant Enterobacteriaceae

Wilson

Kline

Jones

et al. 2019

Antimicrob Agents Chemother

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“…T he worldwide spread of multiresistant bacteria, especially carbapenemaseproducing Enterobacteriaceae, can lead to situations for which no antibiotic therapy option is available. The novel combination ceftazidime-avibactam (CZA) has a broad antibacterial spectrum that led to an increase in its use, notably for immunosuppressed patients treated with anticancer chemotherapy (1), and is associated with a decreased mortality rate in treated patients (2). It demonstrates excellent in vitro activity against bacteria producing Ambler class A, C, and D ␤-lactamases, including extendedspectrum ␤-lactamases (ESBLs), cephalosporinases, and carbapenemases, such as KPCtype and OXA-48-like carbapenemases (3), but not against those producing class B metallo-␤-lactamases (MBLs), such as New Delhi metallo-beta-lactamase (NDM).…”

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confidence: 99%

Successful Treatment of Bacteremia Due to NDM-1-Producing Morganella morganii with Aztreonam and Ceftazidime-Avibactam Combination in a Pediatric Patient with Hematologic Malignancy

Hobson

Bonacorsi

Fahd

et al. 2019

Antimicrob Agents Chemother

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“…Different new antibiotics have recently become available for carbapenem-resistant Enterobacteriaceae. However, the experience with these molecules in real-life settings is still scarce, as is the evidence of their superiority versus old schemes [83][84][85]. Data are even more scarce in the setting of SOTRs, as they are mainly limited to small series rather than large cohorts [10,[86][87][88].…”

Section: Management Of Lung Infections In Solid Organ Transplant Recimentioning

confidence: 99%

Challenges in the Diagnosis and Management of Bacterial Lung Infections in Solid Organ Recipients: A Narrative Review

Carugati

Morlacchi

Peri

et al. 2020

IJMS

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Respiratory infections pose a significant threat to the success of solid organ transplantation, and the diagnosis and management of these infections are challenging. The current narrative review addressed some of these challenges, based on evidence from the literature published in the last 20 years. Specifically, we focused our attention on (i) the obstacles to an etiologic diagnosis of respiratory infections among solid organ transplant recipients, (ii) the management of bacterial respiratory infections in an era characterized by increased antimicrobial resistance, and (iii) the development of antimicrobial stewardship programs dedicated to solid organ transplant recipients.

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Efficacy of Ceftazidime-Avibactam Salvage Therapy in Patients With Infections Caused byKlebsiella pneumoniaeCarbapenemase–producingK. pneumoniae

Abstract: CAZ-AVI appears to be a promising drug for treatment of severe KPC-Kp infections, especially those involving bacteremia.

Cited by 300 publications

References 35 publications

Effects of KPC Variant and Porin Genotype on the In Vitro Activity of Meropenem-Vaborbactam against Carbapenem-Resistant Enterobacteriaceae

Effects of KPC Variant and Porin Genotype on the In Vitro Activity of Meropenem-Vaborbactam against Carbapenem-Resistant Enterobacteriaceae

Successful Treatment of Bacteremia Due to NDM-1-Producing Morganella morganii with Aztreonam and Ceftazidime-Avibactam Combination in a Pediatric Patient with Hematologic Malignancy

Challenges in the Diagnosis and Management of Bacterial Lung Infections in Solid Organ Recipients: A Narrative Review

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