CARPETIMYCINS A AND B, NEW &amp;beta;-LACTAM ANTIBIOTICS

Nakayama, Masahito; Iwasaki, Akio; Kimura, Shigeru; Mizoguchi, Toshimi; Tanabe, Seiichi; Murakami, Akira; Watanabe, Isamu; Okuchi, Masao; Itoh, Hisakatsu; Saino, Yushi; Kobayashi, Fujio; Mori, Toshihito

doi:10.7164/antibiotics.33.1388

Cited by 64 publications

(11 citation statements)

References 5 publications

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“…Thienamycin was the first "carbapenem" and would eventually serve as the parent or model compound for all carbapenems. A series of other carbapenems were also identified (30,92,107,147,149,162,163,172,233); however, the discovery of thienamycin was paramount.…”

Section: In the Beginning…mentioning

confidence: 99%

Carbapenems: Past, Present, and Future

Papp-Wallace

Endimiani

Taracila

et al. 2011

Antimicrob Agents Chemother

1,159

962

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In this review, we summarize the current "state of the art" of carbapenem antibiotics and their role in our antimicrobial armamentarium. Among the ␤-lactams currently available, carbapenems are unique because they are relatively resistant to hydrolysis by most ␤-lactamases, in some cases act as "slow substrates" or inhibitors of ␤-lactamases, and still target penicillin binding proteins. This "value-added feature" of inhibiting ␤-lactamases serves as a major rationale for expansion of this class of ␤-lactams. We describe the initial discovery and development of the carbapenem family of ␤-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.Carbapenems play a critically important role in our antibiotic armamentarium. Of the many hundreds of different ␤-lactams, carbapenems possess the broadest spectrum of activity and greatest potency against Gram-positive and Gram-negative bacteria. As a result, they are often used as "last-line agents" or "antibiotics of last resort" when patients with infections become gravely ill or are suspected of harboring resistant bacteria (23,(174)(175)(176)229). Unfortunately, the recent emergence of multidrug-resistant (MDR) pathogens seriously threatens this class of lifesaving drugs (189). Several recent studies clearly show that resistance to carbapenems is increasing throughout the world (35,64,73,123,151,155,173,200). Despite this menacing trend, our understanding of how to best use these agents is undergoing a renaissance, especially concerning their role with regard to ␤-lactamase inhibition. In this context, we view the number, type, and diversity of carbapenems as compelling reasons to explore these compounds for new insights into drug development.

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Section: In the Beginning…mentioning

confidence: 99%

Carbapenems: Past, Present, and Future

Papp-Wallace

Endimiani

Taracila

et al. 2011

Antimicrob Agents Chemother

1,159

962

View full text Add to dashboard Cite

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“…A wide variety of carbapenem drugs, including asparenomycins (7), carpetimycins (6), olivanic acids (2), pluracidomycins (17), PS-series compounds (11,14,15), and thienamycins (4,5,16), have been derived from strains of Streptomyces spp. Similar antimicrobial agents have also been produced by strains of Serratia and Erwinia spp.…”

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confidence: 99%

Multicenter in vitro evaluation of SM-7338, a new carbapenem

Jones¹,

Aldridge²,

Allen³

et al. 1989

Antimicrob Agents Chemother

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A new carbapenem, SM-7338, was compared with imipenem, cefotaxime, and ceftazidime at five medical centers. Nearly 6,000 strains were tested by reference methods of the National Committee for Clinical Laboratory Standards, and SM-7338 inhibited the largest percentage of gram-negative bacilli. Its spectrum included all members of the family Enterobacteriaceae (99.7% were susceptible to c4 ,Lg/ml), Pseudomonas spp. (but not Xanthomonas maltophilia), and Acinetobacter spp. The potency and spectrum of SM-7338 against the gram-positive organisms were less than those of imipenem and superior to those of ceftazidime. Only the enterococci and some oxacillin-resistant staphylococci were less susceptible to SM-7338 (MICs for 90% of isolates, .8 ,ug/ml). Organisms resistant to ceftazidime were generally susceptible to SM-7338 and imipenem (76%). However, for one-third of the imipenem.resistant gram-negative bacilli (MICs, >8 ,ug/ml), SM-7338 MICs were -4 ,ug/ml. Some endemic differences in patterns of SM-7338 activity against selected gram-negative species were found among some medical centers.

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“…According to the procedure reported for the synthesis of 6A-a from 5A-al), the keto-esters (6A-b, c, 6B-a -c) were prepared by successive treatment of the corresponding acids (5) with N,N'-carbonyldiimidazole (1.3 equiv.) and the magnesium salt of the mono p-nitrobenzyl ester of malonic acid (1.1 equiv.)…”

Section: Methodsmentioning

confidence: 99%