Imipenem/Cilastatin

Clissold, Stephen P.; Todd, Peter A.; Campoli-Richards, Deborah M.

doi:10.2165/00003495-198733030-00001

Cited by 119 publications

(18 citation statements)

References 246 publications

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“…1b). Imipenem is an inhibitor of β-lactamases that inhibits cell wall synthesis in Gram-positive and Gram-negative bacteria [25]. Stressor molecules d -cycloserine, polymyxin and hydrogen peroxide were also tested, and d -cycloserine caused the largest increase in OMV production (Fig.…”

Section: Resultsmentioning

confidence: 99%

Antibiotic treatment modulates protein components of cytotoxic outer membrane vesicles of multidrug-resistant clinical strain, Acinetobacter baumannii DU202

et al. 2018

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BackgroundOuter membrane vesicles (OMVs) of Acinetobacter baumannii are cytotoxic and elicit a potent innate immune response. OMVs were first identified in A. baumannii DU202, an extensively drug-resistant clinical strain. Herein, we investigated protein components of A. baumannii DU202 OMVs following antibiotic treatment by proteogenomic analysis.MethodsPurified OMVs from A. baumannii DU202 grown in different antibiotic culture conditions were screened for pathogenic and immunogenic effects, and subjected to quantitative proteomic analysis by one-dimensional electrophoresis and liquid chromatography combined with tandem mass spectrometry (1DE-LC-MS/MS). Protein components modulated by imipenem were identified and discussed.ResultsOMV secretion was increased > twofold following imipenem treatment, and cytotoxicity toward A549 human lung carcinoma cells was elevated. A total of 277 proteins were identified as components of OMVs by imipenem treatment, among which β-lactamase OXA-23, various proteases, outer membrane proteins, β-barrel assembly machine proteins, peptidyl-prolyl cis–trans isomerases and inherent prophage head subunit proteins were significantly upregulated.ConclusionIn vitro stress such as antibiotic treatment can modulate proteome components in A. baumannii OMVs and thereby influence pathogenicity.Electronic supplementary materialThe online version of this article (10.1186/s12014-018-9204-2) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Antibiotic treatment modulates protein components of cytotoxic outer membrane vesicles of multidrug-resistant clinical strain, Acinetobacter baumannii DU202

et al. 2018

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“…Imipenem exhibits its antimicrobial action through inhibiting cell wall synthesis of bacteria and is very stable in the presence of b-lactamase produced by some bacteria. Since it is rapidly degraded by the renal enzyme dehydropeptidase 1 when administered alone, therefore it is always co-administered with cilastatin to prevent this inactivation [30]. Compounds 1e (4-F on aroyl 2-F on aryl ring; zone of inhibition 14 mm against B. subtilis) and 1f (2-Cl on aroyl, 3-F on aryl, zone of inhibition 14 mm against P. aureginosa) possess antibacterial action close to that of Imipenem having zone of inhibition 18 mm for each of these strains.…”

Section: Staphylococcus Aureusmentioning

confidence: 99%

Synthesis, characterization and antimicrobial activity of some new 1-(fluorobenzoyl)-3-(fluorophenyl)thioureas

Saeed

Shaheen

Hameed

et al. 2009

Journal of Fluorine Chemistry

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“…Carbapenems such as imipenem (Scheme 1) have proven useful for the treatment of a variety of Gram-negative and Gram-positive infections (1,2). Carbapenems and other ␤-lactam antibiotics covalently modify penicillin-binding proteins (PBPs) 1 involved in the peptidoglycan biosynthetic pathway of cell wall assembly in bacteria (3,4).…”

Section: Imp-1 Metallo-␤-lactamase (Class B) Is a Plasmid-borne Zinc mentioning

confidence: 99%

“…Recently, members of this class of inhibitors were reported to reverse imipenem resistance in clinical isolates of P. aeruginosa expressing IMP-1. 2 The structure-activity relationships for succinic acids as inhibitors of IMP-1 can be understood by comparing the crystal structures of enzyme-inhibitor complexes and by molecular modeling of the inhibitors docked into the active site.…”

Section: Imp-1 Metallo-␤-lactamase (Class B) Is a Plasmid-borne Zinc mentioning

confidence: 99%

Succinic Acids as Potent Inhibitors of Plasmid-borne IMP-1 Metallo-β-lactamase

Toney

Hammond

Fitzgerald

et al. 2001

Journal of Biological Chemistry

190

174

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IMP-1 metallo-␤-lactamase (class B) is a plasmid-borne zinc metalloenzyme that efficiently hydrolyzes ␤-lactam antibiotics, including carbapenems, rendering them ineffective. Because IMP-1 has been found in several clinically important carbapenem-resistant pathogens, there is a need for inhibitors of this enzyme that could protect broad spectrum antibiotics such as imipenem from hydrolysis and thus extend their utility. We have identified a series of 2,3-(S,S)-disubstituted succinic acids that are potent inhibitors of IMP-1. Determination of high resolution crystal structures and molecular modeling of succinic acid inhibitor complexes with IMP-1 has allowed an understanding of the potency, stereochemistry, and structure-activity relationships of these inhibitors.Carbapenems such as imipenem (Scheme 1) have proven useful for the treatment of a variety of Gram-negative and Gram-positive infections (1, 2). Carbapenems and other ␤-lactam antibiotics covalently modify penicillin-binding proteins (PBPs) 1 involved in the peptidoglycan biosynthetic pathway of cell wall assembly in bacteria (3, 4). Resistance to carbapenems can arise because of acquisition of low affinity PBPs (3) (e.g. PBP2a of Staphylococcus aureus), altered membrane permeability (5), and expression of class A, B, and D ␤-lactamases (6 -10). Class B ␤-lactamases (metallo-␤-lactamases or MBLs) can hydrolyze a wide variety of substrates of the ␤-lactam class, including carbapenems, penicillins, and cephalosporins, rendering them ineffective as antibiotics.The IMP-1 gene encoding an MBL has been identified on a plasmid and in Japan has transferred among clinical isolates such as Pseudomonas aeruginosa (11,12), Klebsiella pneumoniae, Serratia marcescens, and other members of the Enterobacteriaceae (13,14). In addition, carbapenem-resistant clinical isolates expressing MBLs related to IMP-1 have been identified recently in Singapore (15), Italy (16), and Hong Kong (10). Such reports of plasmid-borne imipenem resistance highlight the need for inhibitors of IMP-1 that can restore the activity of carbapenems in resistant bacteria.Several classes of MBL inhibitors have been reported (for reviews, see Refs. 17 and 18)) including phenazines (19), trifluoromethyl alcohol and ketone derivatives of L-and D-alanine (20), thioesters (18, 21-23), thiols (24 -28), biphenyl tetrazoles (29, 30), and amino acid-derived hydroxamates (31). Biphenyl tetrazoles have been shown to reverse imipenem resistance in a clinical isolate of Bacteroides fragilis (29), and thioesters have been shown to reverse resistance to the carbapenem L-742,728 in a laboratory strain of Escherichia coli expressing IMP-1 (32). A 1␤-methylcarbapenem substituted at C-2 with a benzothienylthio moiety has been reported to be a potent IMP-1 inhibitor that can reverse resistance to imipenem in an IMP-1-producing strain of Serratia marcescens (33). Although the inhibitors described above have been reported to have good activity against a specific MBL, only certain thiols (e.g. SB 264218) exhibit broad spe...

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Imipenem/Cilastatin

Cited by 119 publications

References 246 publications

Antibiotic treatment modulates protein components of cytotoxic outer membrane vesicles of multidrug-resistant clinical strain, Acinetobacter baumannii DU202

Antibiotic treatment modulates protein components of cytotoxic outer membrane vesicles of multidrug-resistant clinical strain, Acinetobacter baumannii DU202

Synthesis, characterization and antimicrobial activity of some new 1-(fluorobenzoyl)-3-(fluorophenyl)thioureas

Succinic Acids as Potent Inhibitors of Plasmid-borne IMP-1 Metallo-β-lactamase

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