In vitro activity of biapenem against clinical isolates of gram-positive and gram-negative bacteria

Malanoski, Gregory J.; Collins, L A; Wennersten, Christine; Moellering, Robert C.; Eliopoulos, George M.

doi:10.1128/aac.37.9.2009

Cited by 27 publications

(18 citation statements)

References 7 publications

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“…Biapenem has a broad spectrum of in vitro antibacterial activity against gram-negative (including blactamase-producing strains and P. aeruginosa ), grampositive, and anaerobic bacteria (10,11). A previous study demonstrated that biapenem is as effective and well tolerated as imipenem/cilastatin in the treatment of intermediate and severe bacterial infections (11).…”

Section: Discussionmentioning

confidence: 99%

In Vitro Analysis of Activities of 16 Antimicrobial Agents against Gram-Negative Bacteria from Six Teaching Hospitals in China

Chen

Wang

et al. 2015

Jpn J Infect Dis

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SUMMARY:To evaluate the in vitro antimicrobial activities of biapenem, arbekacin, and cefminox against different gram-negative bacterial isolates in China, a total of 100 non-duplicated Escherichia coli, 100 Acinetobacter baumannii, 100 Pseudomonas aeruginosa, and 99 Klebsiella pneumoniae isolates were collected from 6 teaching hospitals in China in 2012. The minimal inhibitory concentrations (MICs) of biapenem, arbekacin, cefminox and 13 other antibiotics were determined by the broth microdilution method. The carbapenems (biapenem, meropenem, and imipenem) exhibited high antimicrobial activity against E. coli (98z) and K. pneumoniae (95z), followed by colistin and amikacin. The MIC 50 and MIC 90 of biapenem against E. coli were 0.06 mg/L and 0.25 mg/L, respectively. For K. pneumoniae, the MIC 50 and MIC 90 of biapenem were 0.25 mg/L and 1.0 mg/L, respectively. The MIC 50 and MIC 90 of cefminox against E. coli were 1.0 mg/L and 4.0 mg/L, respectively. The resistance rates of A. baumannii to most of the antibiotics were more than 50z, except for colistin. Amikacin was the most active antibiotic against P. aeruginosa (97z), followed by colistin (93z). The MIC 50 and MIC 90 of arbekacin against P. aeruginosa were 2.0 mg/L and 8.0 mg/L, respectively. In conclusion, carbapenems, colistin, amikacin, and arbekacin exhibited high antimicrobial activities against gramnegative bacteria, except A. baumannii.

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Section: Discussionmentioning

confidence: 99%

In Vitro Analysis of Activities of 16 Antimicrobial Agents against Gram-Negative Bacteria from Six Teaching Hospitals in China

Chen

Wang

et al. 2015

Jpn J Infect Dis

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“…Several recent observations have prompted us to investigate in detail the kinetics of interaction between the novel carbapenem antibiotic biapenem (8,27,41) and active-site serine and metallo-␤-lactamases. These observations include the discovery of a plasmid-mediated metallo-␤-lactamase in P. aeruginosa (40); the emergence of strains of Bacteroides spp.…”

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Interactions of biapenem with active-site serine and metallo-beta-lactamases

Felici

Perilli

Segatore

et al. 1995

Antimicrob Agents Chemother

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Biapenem, formerly LJC 10,627 or L-627, a carbapenem antibiotic, was studied in its interactions with 12 ␤-lactamases belonging to the four molecular classes proposed by R. P. Ambler (Philos. Trans. R. Soc. Lond. Biol. Sci. 289:321-331, 1980). Kinetic parameters were determined. Biapenem was readily inactivated by metallo-␤-lactamases but behaved as a transient inhibitor of the active-site serine enzymes tested, although with different acylation efficiency values. Class A and class D ␤-lactamases were unable to confer in vitro resistance toward this carbapenem antibiotic. Surprisingly, the same situation was found in the case of class B enzymes from Aeromonas hydrophila AE036 and Bacillus cereus 5/B/6 when expressed in Escherichia coli strains.It has been clearly shown that bacterial resistance to ␤-lactam antibiotics is often a multifactorial event in which outer membrane impermeability and ␤-lactamase production by gram-negative bacteria play central roles (39).␤-Lactamase degradation of ␤-lactam antibiotics represents one of the most important biochemical mechanisms of resistance to these molecules in bacteria (19). These enzymes, which are bacterial hydrolases (EC 3.5.2.6), have been classified into four different molecular classes on the basis of their primary structures and catalytic mechanisms (1). Enzymes of classes A, C, and D exert their catalytic activity by a reactive serine residue in the active site, while class B ␤-lactamases are metalloproteins which require a divalent transition metal ion for their activity, most often Zn 2ϩ . Antibiotic pressure has often selected bacteria able to elaborate two or more specific chromosomally encoded or plasmidmediated ␤-lactamases which are active against a wide range of ␤-lactam compounds.An expanded spectrum of ␤-lactams has been developed over the past 20 years in order to overcome bacterial resistance to molecules previously developed for clinical use. Carbapenem antibiotics are reported to be very stable in the presence of active-site serine ␤-lactamases, with the exception of class C enzymes produced by members of the family Enterobacteriaceae which exhibit slow antibiotic hydrolysis (25). This phenomenon, combined with a reduced permeability of the bacterial outer membrane, leads to resistance in hyperproducing strains of Enterobacter cloacae and Pseudomonas aeruginosa. These novel antibiotics also show a broad range of activity against gram-negative and gram-positive bacteria (22,30), with the exception of Xanthomonas maltophilia, which produces a chromosomally encoded class B ␤-lactamase (4, 36) which is able to inactivate all ␤-lactam antibiotics except aztreonam (14). Moreover, carbapenem antibiotics have variable stability to hydrolysis by mammalian dehydropeptidase-I (18,20,21,34). For this reason, imipenem, the first carbapenem molecule to be introduced in the clinical setting, is administered in combination with cilastatin, a dehydropeptidase-I inhibitor. Despite the antimicrobial efficacy of imipenem, it is only relatively recently that reports ...

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“…In both instances, resistance to ␤-lactams can be attributed to the presence of penicillin-binding proteins with reduced affinities for these agents (7,8,14,16,22). Neither of the two more recently developed carbapenems, meropenem and biapenem, offers any activity advantage over imipenem against these organisms in particular or against gram-positive bacteria in general (13,20).…”

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confidence: 99%

“…Strains of streptococci demonstrating resistance to ␤-lactams and strains of vancomycinresistant enterococci had been referred to our collection from a variety of sources (13,20). L-695,256 and imipenem were provided by Merck, Sharp & Dohme Research Laboratories, Rahway, N.J. Other susceptibility reference powders were gifts from the indicated sources: oxacillin, Bristol-Myers Squibb Co., Syracuse, N.Y.; clindamycin, Upjohn Co., Kalamazoo, Mich.; erythromycin and vancomycin, Eli Lilly & Co., Indianapolis, Ind.…”

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Comparative in vitro activities of L-695,256, a novel carbapenem, against gram-positive bacteria

Malanoski

Collins

Eliopoulos

et al. 1995

Antimicrob Agents Chemother

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The in vitro activity of a prototype 2-aryl carbapenem, L-695,256, against gram-positive bacteria was examined. All streptococci and oxacillin-susceptible and -resistant staphylococci were inhibited at concentrations of Յ0.125, Յ0.125, and 4 g/ml, respectively. The activity of L-695,256 was superior to that of imipenem against other organisms intrinsically resistant to ␤-lactams.The introduction of imipenem into clinical practice represented a major advance. Its broad antibacterial spectrum is potentially advantageous for empiric treatment of infections prior to identification of causative organisms and for treatment of polymicrobial infections. In addition, because of resistance to hydrolysis by most clinically important ␤-lactamases and other favorable characteristics, this carbapenem often retains activity against nosocomial isolates of gram-negative bacteria resistant to other ␤-lactam antibiotics (3,4,18). Two notable exceptions to this favorable pattern of activity are methicillinresistant staphylococci and penicillin-resistant enterococci, both of which display reduced susceptibility to imipenem (20). In both instances, resistance to ␤-lactams can be attributed to the presence of penicillin-binding proteins with reduced affinities for these agents (7,8,14,16,22). Neither of the two more recently developed carbapenems, meropenem and biapenem, offers any activity advantage over imipenem against these organisms in particular or against gram-positive bacteria in general (13,20).L-695,256 ( Fig. 1) is one of a series of novel 2-aryl carbapenems selected for evaluation because of its unusually good activity against methicillin-resistant staphylococci (19). This drug binds to PBP 2a of Staphylococcus aureus and to PBP 5 of Enterococcus hirae with substantially greater affinity than comparable ␤-lactams (6, 9). The present study was undertaken to examine the in vitro activity of L-695,256 against a variety of gram-positive bacteria, including strains specifically collected because of their resistance to ␤-lactams or other antibiotics.(This work was presented in part at the 34th Interscience Conference on Antimicrobial Agents and Chemotherapy, Orlando, Fla., October 1994 [12].)Most of the organisms included in this study were clinical isolates obtained at Deaconess Hospital and Massachusetts General Hospital, Boston, Mass. Strains of streptococci demonstrating resistance to ␤-lactams and strains of vancomycinresistant enterococci had been referred to our collection from a variety of sources (13,20). L-695,256 and imipenem were provided by Merck, Sharp & Dohme Research Laboratories, Rahway, N.J. Other susceptibility reference powders were gifts from the indicated sources: oxacillin, Bristol-Myers Squibb Co., Syracuse, N.Y.; clindamycin, Upjohn Co., Kalamazoo, Mich.; erythromycin and vancomycin, Eli Lilly & Co., Indianapolis, Ind.; and teicoplanin, Marion Merrell Dow, Inc., Cincinnati, Ohio.Antimicrobial susceptibility was determined by an agar dilution technique as previously described (13). Mueller-Hinton II agar ...

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In vitro activity of biapenem against clinical isolates of gram-positive and gram-negative bacteria

Abstract: The in vitro activity of biapenem, a new carbapenem previously designated L-627, was

Cited by 27 publications

References 7 publications

In Vitro Analysis of Activities of 16 Antimicrobial Agents against Gram-Negative Bacteria from Six Teaching Hospitals in China

In Vitro Analysis of Activities of 16 Antimicrobial Agents against Gram-Negative Bacteria from Six Teaching Hospitals in China

Interactions of biapenem with active-site serine and metallo-beta-lactamases

Comparative in vitro activities of L-695,256, a novel carbapenem, against gram-positive bacteria

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