Archive for May 28, 2013

Carbapenems: past, present, and future.

Antimicrob Agents Chemother. 2011 Nov;55(11):4943-60.

Papp-Wallace KM, Endimiani A, Taracila MA, Bonomo RA.

Source

Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio 44106, USA.

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.

PDF

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3195018/pdf/zac4943.pdf

May 28, 2013 at 11:21 pm

Emergence of Klebsiella pneumoniae carbapenemase-producing bacteria.

South Med J. 2011 Jan;104(1):40-5.

Arnold RS, Thom KA, Sharma S, Phillips M, Kristie Johnson J, Morgan DJ.

Source

Department of Medicine, University of Maryland, Baltimore, MD 21201, USA.

Abstract

Klebsiella pneumoniae carbapenemase (KPC)-producing bacteria are a group of emerging highly drug-resistant Gram-negative bacilli causing infections associated with significant morbidity and mortality. Once confined to outbreaks in the northeastern United States (US), they have spread throughout the US and most of the world. KPCs are an important mechanism of resistance for an increasingly wide range of Gram-negative bacteria and are no longer limited to K pneumoniae. KPC-producing bacteria are often misidentified by routine microbiological susceptibility testing and incorrectly reported as sensitive to carbapenems; however, resistance to the carbapenem antibiotic ertapenem is common and a better indicator of the presence of KPCs. Carbapenem antibiotics are generally not effective against KPC-producing organisms. The best therapeutic approach to KPC-producing organisms has yet to be defined; however, common treatments based on in vitro susceptibility testing are the polymyxins, tigecycline, and less frequently, aminoglycoside antibiotics. The purpose of this review is to identify the various challenges that KPC-producing bacteria present to clinicians. These include the need for special techniques for microbiological detection, the potential for nosocomial transmission, and therapeutic challenges related to limited, relatively unproven antimicrobial treatment options.

PDF

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3075864/pdf/nihms-253051.pdf

May 28, 2013 at 11:19 pm


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