Disease relevance of S-4661

• Doripenem versus Pseudomonas aeruginosa in vitro: activity against characterized isolates, mutants, and transconjugants and resistance selection potential [1].
• ESBL production did not raise the MICs of doripenem for Escherichia coli transconjugants, and studies with known expression mutants confirmed that neither inducible nor depressed AmpC beta-lactamase expression was protective in Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, or Morganella morganii [2].
• Comparative activities of doripenem versus isolates, mutants, and transconjugants of Enterobacteriaceae and Acinetobacter spp. with characterized beta-lactamases [2].
• Similarly, MICs of doripenem for both AmpC-inducible and -derepressed Enterobacter isolates were 0.06 to 0.5 microg/ml [2].
• Resistance to all carbapenems, including doripenem (MICs of mostly 16 to 64 microg/ml, compared with 0.25 to 1 microg/ml for typical strains), was seen in Acinetobacter isolates with metallo-beta-lactamases or OXA-carbapenemases [2].

High impact information on S-4661

• In vitro activity of doripenem against Pseudomonas aeruginosa and Burkholderia cepacia isolates from both cystic fibrosis and non-cystic fibrosis patients [3].
• In vitro activity of doripenem (S-4661) against multidrug-resistant gram-negative bacilli isolated from patients with cystic fibrosis [4].
• Against imipenem-resistant Pseudomonas aeruginosa, S-4661 was the most active among test agents (MIC90, 8 microg/ml) [5].
• METHODS: The in vitro susceptibilities of 2137 bacterial isolates, representing 28 different species, to doripenem, imipenem and meropenem were determined by the NCCLS broth microdilution and disc diffusion testing methods [6].
• Doripenem exhibits excellent activity against extended-spectrum beta-lactamase-producing strains of Escherichia coli and Klebsiella spp [6].

Chemical compound and disease context of S-4661

• The model was applied to analysis of the in vitro time-killing data of beta-lactam antibiotics, S-4661, meropenem, imipenem, cefpirome, and ceftazidim against three types of bacteria, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus [7].
• Multiple beta-lactamase (TEM, SHV, CTX-M, OXA, CMY types)-producing Escherichia coli had doripenem MIC values at </=0.016 mug/mL (with higher values for ertapenem) [8].
• Doripenem (formerly S-4661), a parenteral carbapenem, was tested in combination with an aminoglycoside (gentamicin) to determine the resistance selection of these codrugs during subinhibitory passaging using 6 Pseudomonas aeruginosa isolates [9].
• Using reference broth microdilution methods, doripenem was found to be highly active against oxacillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci (2705 and 297 isolates, respectively; MIC90s 0.06 mg/L), with a potency greater than that of other carbapenem antibiotics [10].
• When P. aeruginosa or multidrug-resistant Gram-positive pathogens such as methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococci are involved, doripenem must be used in combination [11].

Biological context of S-4661

• These results suggest that S-4661 may be useful for treating polymicrobial infections in the fields of obstetrics and gynaecology [12].
• Ertapenem exhibited minimum inhibitory concentration (MIC) elevations for some isolates producing AmpC and extended-spectrum beta-lactamases, in contrast to greater enzyme stability for doripenem and other carbapenems tested [8].
• A novel 1 beta-methylcarbapenem antibiotic, S-4661. Synthesis and structure-activity relationships of 2-(5-substituted pyrrolidin-3-ylthio)-1 beta-methylcarbapenems [13].
• Serum protein binding rates (%) of doripenem were 25.2 in mice, 35.2 in rats, 11.8 in rabbits, 10.2 in dogs, 6.1 in monkeys and 8.1 in humans, respectively [14].
• Pharmacokinetics and tissue penetration of a new carbapenem, doripenem, intravenously administered to laboratory animals [14].

Anatomical context of S-4661

• The accumulation of neutrophils in the uterus in the S-4661-treated group was less marked and the number of bacteria significantly lower than those in the untreated group [12].
• The antibacterial activity of S-4661, a new parenteral carbapenem antibiotic, was assessed against the major urological pathogens isolated from patients with complicated urinary tract infections [15].
• In mice, the doripenem level was highest in the blood plasma, followed by the kidney, liver, lung, heart and spleen [14].

Associations of S-4661 with other chemical compounds

• In in vitro binding studies, imipenem, panipenem, cefazolin and meropenem inhibited [(3)H]muscimol binding to the GABA(A) receptor in mouse brain homogenates while doripenem did not cause any inhibition at up to 10mM [16].

Gene context of S-4661

• Study of the synergism between carbapenems and vancomycin or teicoplanin against MRSA, focusing on S-4661, a carbapenem newly developed in Japan [17].
• Empiric therapy with doripenem, as with other antipseudomonal carbapenems, may be useful in hospital and intensive care unit settings where multidrug resistance has emerged, especially in Gram-negative enteric pathogens [11].

Analytical, diagnostic and therapeutic context of S-4661

• S-4661, a new injectable carbapenem antibiotic, has favourable pharmacokinetic properties and is not hydrolysed by dehydropeptidase I [12].
• Doripenem caused no changes in the EEG and behavior in rats at 400mg/kg [16].
• The concentrations of doripenem in plasma, urine and tissue samples were determined by bioassay [14].

References