Ceftazidime-Avibactam and Aztreonam, an Interesting Strategy To Overcome β-Lactam Resistance Conferred by Metallo-β-Lactamases in Enterobacteriaceae and Pseudomonas aeruginosa

Davido, Benjamin; Fellous, Lesly; Lawrence, Christine; Maxime, Virginie; Rottman, Martin; Dinh, Aurélien

doi:10.1128/aac.01008-17

Cited by 141 publications

(88 citation statements)

References 3 publications

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“…The other three patients died as a result of other underlying conditions and therefore should not be considered a failure of the combination treatment (249). Several case reports have also demonstrated that the combination of aztreonam and ceftazidime-avibactam can successfully treat infections with NDM-positive CRE strains (247,250). This combination could be considered if there are no alternative therapeutic options, and its efficacy warrants further, large-scale studies.…”

Section: Aztreonam-avibactam or Aztreonam Combined With Ceftazidime-amentioning

confidence: 99%

NDM Metallo-β-Lactamases and Their Bacterial Producers in Health Care Settings

et al. 2019

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SUMMARYNew Delhi metallo-β-lactamase (NDM) is a metallo-β-lactamase able to hydrolyze almost all β-lactams. Twenty-four NDM variants have been identified in >60 species of 11 bacterial families, and several variants have enhanced carbapenemase activity.Klebsiella pneumoniaeandEscherichia coliare the predominant carriers ofblaNDM, with certain sequence types (STs) (forK. pneumoniae, ST11, ST14, ST15, or ST147; forE. coli, ST167, ST410, or ST617) being the most prevalent. NDM-positive strains have been identified worldwide, with the highest prevalence in the Indian subcontinent, the Middle East, and the Balkans. MostblaNDM-carrying plasmids belong to limited replicon types (IncX3, IncFII, or IncC). Commonly used phenotypic tests cannot specifically identify NDM. Lateral flow immunoassays specifically detect NDM, and molecular approaches remain the reference methods for detectingblaNDM. Polymyxins combined with other agents remain the mainstream options of antimicrobial treatment. Compounds able to inhibit NDM have been found, but none have been approved for clinical use. Outbreaks caused by NDM-positive strains have been reported worldwide, attributable to sources such as contaminated devices. Evidence-based guidelines on prevention and control of carbapenem-resistant Gram-negative bacteria are available, although none are specific for NDM-positive strains. NDM will remain a severe challenge in health care settings, and more studies on appropriate countermeasures are required.

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Section: Aztreonam-avibactam or Aztreonam Combined With Ceftazidime-amentioning

confidence: 99%

NDM Metallo-β-Lactamases and Their Bacterial Producers in Health Care Settings

et al. 2019

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“…have attracted some attention to the potential effect of combining ceftazidime-avibactam with aztreonam. Synergistic effects have been seen in in vitro and in vivo studies (346,357), and indeed, some patients were successfully treated with this combination (208,397). This raises the possibility of using atypical combinations of BLBLIs and other ␤-lactams, such as piperacillin-tazobactam plus aztreonam, against MBL and ESBL producers, although many of these should be tested in vitro, in vivo, and on patients before any recommendations can be provided.…”

Section: Ceftazidime-avibactammentioning

confidence: 99%

Treatment of Infections Caused by Extended-Spectrum-Beta-Lactamase-, AmpC-, and Carbapenemase-Producing Enterobacteriaceae

et al. 2018

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Therapy of invasive infections due to multidrug-resistant (MDR-E) is challenging, and some of the few active drugs are not available in many countries. For extended-spectrum β-lactamase and AmpC producers, carbapenems are the drugs of choice, but alternatives are needed because the rate of carbapenem resistance is rising. Potential active drugs include classic and newer β-lactam-β-lactamase inhibitor combinations, cephamycins, temocillin, aminoglycosides, tigecycline, fosfomycin, and, rarely, fluoroquinolones or trimethoprim-sulfamethoxazole. These drugs might be considered in some specific situations. AmpC producers are resistant to cephamycins, but cefepime is an option. In the case of carbapenemase-producing (CPE), only some "second-line" drugs, such as polymyxins, tigecycline, aminoglycosides, and fosfomycin, may be active; double carbapenems can also be considered in specific situations. Combination therapy is associated with better outcomes for high-risk patients, such as those in septic shock or with pneumonia. Ceftazidime-avibactam was recently approved and is active against KPC and OXA-48 producers; the available experience is scarce but promising, although development of resistance is a concern. New drugs active against some CPE isolates are in different stages of development, including meropenem-vaborbactam, imipenem-relebactam, plazomicin, cefiderocol, eravacycline, and aztreonam-avibactam. Overall, therapy of MDR-E infection must be individualized according to the susceptibility profile, type, and severity of infection and the features of the patient.

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“…A relatively new option for treatment of NDM-1 infections is the combination of ceftazidime/avibactam with aztreonam. 6, 7 Aztreonam is active against most MBLs, but often the bacteria have other resistance mechanisms (e.g. ESBLs) that inactivate aztreonam.…”

Section: Discussionmentioning

confidence: 99%

“…5,12 This could be expected to be even worse in a black market, unli- aztreonam. 6,7 Aztreonam is active against most MBLs, but often the bacteria have other resistance mechanisms (e.g., ESBLs) that inactivate aztreonam. The use of the β-lactamase inhibitor avibactam enables aztreonam to remain stable against inactivation despite in vitro resistance to both aztreonam and avibactam individually.…”

Section: Discussionmentioning

confidence: 99%

Transplant tourism complicated by life-threatening New Delhi metallo-β-lactamase-1 infection

Stewart

Newman

Jain

et al. 2019

American Journal of Transplantation

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Transplant tourism, the practice of traveling to other countries for transplantation, continues to be a major problem worldwide. We describe a patient who traveled to Pakistan and underwent commercial kidney transplantation. He developed life-threatening infections from New Delhi metallo-beta-lactamase-1-producing Enterobacter cloacae and Rhizopus oryzae resulting in a necrotizing kidney allograft infection and subsequent external iliac artery rupture. He survived after a prolonged course of non-standardized antimicrobial therapy, including a combination of aztreonam and ceftazidime/avibactam, and aggressive surgical debridement with allograft nephrectomy. The early timing of infection with these unusual organisms localized to the allograft suggests contamination and substandard care at the time of transplant. This case highlights the challenges of caring for these infections and serves as a cautionary tale for the potential complications of commercial transplant tourism.

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Ceftazidime-Avibactam and Aztreonam, an Interesting Strategy To Overcome β-Lactam Resistance Conferred by Metallo-β-Lactamases in Enterobacteriaceae and Pseudomonas aeruginosa

Abstract: Ceftazidime-avibactam and aztreonam, an interesting strategy to overcome β-lactam resistance conferred by metallo-β-lactamases in Enterobacteriaceae and Pseudomonas aeruginosa. Antimicrob Agents Chemother 61:e01008-17.

Cited by 141 publications

References 3 publications

NDM Metallo-β-Lactamases and Their Bacterial Producers in Health Care Settings

NDM Metallo-β-Lactamases and Their Bacterial Producers in Health Care Settings

Treatment of Infections Caused by Extended-Spectrum-Beta-Lactamase-, AmpC-, and Carbapenemase-Producing Enterobacteriaceae

Transplant tourism complicated by life-threatening New Delhi metallo-β-lactamase-1 infection

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