Carbapenems: Past, Present, and Future
Krisztina M. Papp-Wallace,Andrea Endimiani,Andrea Endimiani,Andrea Endimiani,Magdalena A. Taracila,Robert A. Bonomo +5 more
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TLDR
The current “state of the art” of carbapenem antibiotics and their role in the antimicrobial armamentarium are summarized and the medicinal chemist is urged to continue development of these versatile and potent compounds.Abstract:
In this review, we summarize the current "state of the art" of carbapenem antibiotics and their role in our antimicrobial armamentarium. Among the β-lactams currently available, carbapenems are unique because they are relatively resistant to hydrolysis by most β-lactamases, in some cases act as "slow substrates" or inhibitors of β-lactamases, and still target penicillin binding proteins. This "value-added feature" of inhibiting β-lactamases serves as a major rationale for expansion of this class of β-lactams. We describe the initial discovery and development of the carbapenem family of β-lactams. Of the early carbapenems evaluated, thienamycin demonstrated the greatest antimicrobial activity and became the parent compound for all subsequent carbapenems. To date, more than 80 compounds with mostly improved antimicrobial properties, compared to those of thienamycin, are described in the literature. We also highlight important features of the carbapenems that are presently in clinical use: imipenem-cilastatin, meropenem, ertapenem, doripenem, panipenem-betamipron, and biapenem. In closing, we emphasize some major challenges and urge the medicinal chemist to continue development of these versatile and potent compounds, as they have served us well for more than 3 decades.read more
Citations
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β-Lactams and β-Lactamase Inhibitors: An Overview
Karen Bush,Patricia A. Bradford +1 more
TL;DR: This work provides a comprehensive overview of β-lactam antibiotics that are currently in use, as well as a look ahead to several new compounds that are in the development pipeline.
Journal ArticleDOI
Carbapenem Resistance: A Review
Francis S. Codjoe,Eric S. Donkor +1 more
TL;DR: In this paper, an in-depth review of carbapenem resistance is provided providing up-to-date information on the subject.
Journal ArticleDOI
Epidemic of carbapenem-resistant Klebsiella pneumoniae in Europe is driven by nosocomial spread
Sophia David,Sandra Reuter,Simon R. Harris,Corinna Glasner,Theresa Feltwell,Silvia Argimón,Khalil Abudahab,Richard Goater,Tommaso Giani,Giulia Errico,Marianne Aspbury,Sara Sjunnebo,Edward J. Feil,Gian Maria Rossolini,David M. Aanensen,Hajo Grundmann,Hajo Grundmann +16 more
TL;DR: Combined analysis of the genetic and geographic distances between isolates with different β-lactam resistance determinants suggests that the propensity of K. pneumoniae to spread in hospital environments correlates with the degree of resistance and that carbapenemase-positive isolates have the highest transmissibility.
Journal ArticleDOI
Metallo-β-lactamase structure and function
TL;DR: This review summarizes the numerous studies that have yielded insights into the structure, function, and mechanism of action of metallo‐β‐lactamase.
Journal ArticleDOI
New antibiotics for bad bugs: where are we?
TL;DR: The need of new antibiotics still does not cover the increasing prevalence of antibiotic-resistant bacterial infections, so the management of antimicrobial resistance should also include fostering coordinated actions by all stakeholders, creating policy guidance, support for surveillance and technical assistance.
References
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TL;DR: Extended-spectrum β-lactamases represent an impressive example of the ability of gram-negative bacteria to develop new antibiotic resistance mechanisms in the face of the introduction of new antimicrobial agents.
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Carbapenemases: the versatile beta-lactamases.
Anne Marie Queenan,Karen Bush +1 more
TL;DR: The characteristics, epidemiology, and detection of the carbapenemases found in pathogenic bacteria are updates and metallo-β-lactamases are detected primarily in Pseudomonas aeruginosa.
Journal ArticleDOI
Characterization of a New Metallo-β-Lactamase Gene, blaNDM-1, and a Novel Erythromycin Esterase Gene Carried on a Unique Genetic Structure in Klebsiella pneumoniae Sequence Type 14 from India
Dongeun Yong,Mark Toleman,Christian G. Giske,Hyun Sun Cho,Kristina Sundman,Kyungwon Lee,Timothy R. Walsh +6 more
TL;DR: A Swedish patient of Indian origin traveled to New Delhi, India, and acquired a urinary tract infection caused by a carbapenem-resistant Klebsiella pneumoniae strain that typed to the sequence type 14 complex, showing broad resistance carried on these plasmids.
Journal ArticleDOI
Updated Functional Classification of β-Lactamases
Karen Bush,George A. Jacoby +1 more
TL;DR: The functional classification scheme updated herein is based on the 1995 proposal and includes group 1 (class C) cephalosporinases; group 2 (classes A and D) broad-spectrum, inhibitor-resistant, and extended-spectrums β-lactamases and serine carbapenemases; and group 3 metallo-β-lacticamases.
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Multidrug efflux pumps of gram-negative bacteria.
TL;DR: Recent studies showed that multipledrug efflux pumps, many with unusually broad specificities, play a major role in the intrinsic resistance of gram-negative bacteria.
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