Muraminomicins, novel ester derivatives: in vitro and in vivo antistaphylococcal activity.

Novel muraminomicin derivatives with antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) were synthesized by esterification of the hydroxy group on the diazepanone ring of muraminomicin Z. Compound 1b (DS14450354) possessed a diheptoxybenzyl-β-Alanyl-β-Alanyl group and exhibited minimum inhibitory concentrations (MICs) against MRSA comparable to those against methicillin-susceptible S. aureus (MSSA).

Muraminomicins, new lipo-nucleoside antibiotics from Streptosporangium sp. SANK 60501-structure elucidations of muraminomicins and supply of the core component for derivatization.

We screened for bacterial phospho-N-acetylmuramyl-pentapeptide-translocase (MraY: EC 2.7.8.

Spontaneous Infection Caused by in KK-A Mice.

During 2006 through 2012, spontaneous group B Streptococcus infections were reported in 22 female KK-Ay mice, an animal model of type 2 diabetes. The affected mice were 5 to 27 wk old, and the cases involved various body sites, including cases of submandibular, caudal, and lumbar abscesses (n =18) or led to torticollis (n = 2), hydrocephalus (n = 1), or moribund clinical signs (n = 1). At necropsy, the mouse with hydrocephalus also demonstrated retained exudate in the uterus, and the moribund mouse showed renal inflammation.

Antimicrobial resistance in Campylobacter coli and Campylobacter jejuni in cynomolgus monkeys (Macaca fascicularis) and eradication regimens.

Background: Campylobacter spp. are zoonotic pathogens, however, knowledge about their presence and antimicrobial resistance in nonhuman primates is limited. Our animal facility purchased cynomolgus monkeys (Macaca fascicularis) from various Asian countries: China, Cambodia, Indonesia, the Philippines, and Vietnam.

Absorption, elimination, and metabolism of CS-1036, a novel α-amylase inhibitor in rats and monkeys, and the relationship between gastrointestinal distribution and suppression of glucose absorption.

The absorption, metabolism, and excretion of (2R,3R,4R)-4-hydroxy-2-(hydroxymethyl)pyrrolidin-3-yl 4-O-(6-deoxy-β-d-glucopyranosyl)-α-d-glucopyranoside (CS-1036), a novel and potent pancreatic and salivary α-amylase inhibitor, were evaluated in F344/DuCrlCrlj rats and cynomolgus monkeys. The total body clearance and volume of distribution of CS-1036 were low (2.67-3.

Synthesis and SAR of 1,3-thiazolyl thiophene and pyridine derivatives as potent, orally active and S1P₃-sparing S1P₁ agonists.

We have previously disclosed 1,2,4-oxadiazole derivative 3 as a potent S1P(3)-sparing S1P(1) agonist. Although compound 3 exhibits potent and manageable immunosuppressive efficacy in various in vivo models, recent studies have revealed that its 1,2,4-oxadiazole ring is subjected to enterobacterial decomposition. As provisions for unpredictable issues, a series of alternative compounds were synthesized on the basis of compound 3.

Efficacy of human-simulated exposures of tomopenem (formerly CS-023) in a murine model of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus infection.

Tomopenem (formerly CS-023) is a novel carbapenem with improved activity against diverse hospital pathogens, including Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA), and has a half-life about twice longer than the half-lives of other carbapenems such as imipenem and meropenem. Our objective in this study was to estimate the efficacy of tomopenem in humans by human-simulated exposures in a neutropenic murine thigh infection model against 9 clinical isolates of P. aeruginosa with MICs of 4 to 32 μg/ml and 9 clinical isolates of MRSA with MICs of 4 to 16 μg/ml.

In vivo pharmacodynamic activity of tomopenem (formerly CS-023) against Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus in a murine thigh infection model.

Tomopenem (formerly CS-023) is a novel carbapenem with broad-spectrum activities against diverse hospital pathogens, including Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA). We examined the in vivo pharmacodynamic characteristics of tomopenem against P. aeruginosa and MRSA by using a neutropenic murine thigh infection model with P.

In vitro postantibiotic effects of tomopenem (CS-023) against Staphylococcus aureus and Pseudomonas aeruginosa.

The postantibiotic effect (PAE) of tomopenem was determined after a 2 h exposure of two strains of meticillin-susceptible and meticillin-resistant Staphylococcus aureus (MSSA and MRSA), and imipenem-susceptible and imipenem-resistant Pseudomonas aeruginosa, to tenfold the respective MIC. The PAEs on MSSA and P. aeruginosa were approximately 1 h and they were comparable to those of meropenem.

Affinity of Tomopenem (CS-023) for penicillin-binding proteins in Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.

Tomopenem (formerly CS-023), a novel 1beta-methylcarbapenem, exhibited high affinity for penicillin-binding protein (PBP) 2 in Staphylococcus aureus, PBP 2 in Escherichia coli, and PBPs 2 and 3 in Pseudomonas aeruginosa, which are considered major lethal targets. Morphologically, tomopenem induced spherical forms in E. coli and short filamentation with bulges in P.

[In-vitro activity of panipenem against clinical isolates in 2006].

The antimicrobial activity of various antibiotics against clinical bacterial isolates recovered from patients with infectious diseases at the medical facilities in the Kanto region between March and September 2006 was evaluated. A total of 1030 clinical isolates were available for susceptibility tests: 420 aerobic Gram-positive organisms, 520 aerobic Gram-negative organisms, 30 anaerobic Gram-positive organisms and 60 anaerobic Gram-negative pathogens. Antimicrobial susceptibility data for Streptococcus pneumoniae and Haemophilus influenzae isolates from pediatric and adult patients were analyzed separately.

Potent in vitro activity of tomopenem (CS-023) against methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa.

Tomopenem (formerly CS-023) is a novel 1beta-methylcarbapenem with broad-spectrum coverage of gram-positive and gram-negative pathogens. Its antibacterial activity against European clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa was compared with those of imipenem and meropenem. The MICs of tomopenem against MRSA and P.

[Surveillance of susceptibility of clinical isolates to cefmetazole between 2000 and 2003].

For the post-marketing surveillance of cefmetazole (CMZ, Cefmetazon), MICs of injectable beta-lactam antibacterials including CMZ against clinical isolates from 15 medical institutions all over Japan are measured yearly and the incidence rates of resistance in various species are also evaluated. In the first surveillance from June 2000 to March 2001, 574 isolates of 13 species were tested, 548 isolates of the same 13 species were tested in the second surveillance from April 2001 to March 2002, and 654 isolates of the same 13 species were tested in the third surveillance from April 2002 to March 2003. No remarkable changes in the activity of CMZ were observed in these surveillances spanning three years.

[Surveillance of susceptibility of clinical isolates to cefpodoxime between 2000 and 2003].

For the post-marketing surveillance of cefpodoxime proxetil (CPDX-PR, Banan), MICs of oral cephem antibacterials including CPDX against clinical isolates from 15 medical institutions all over Japan are measured yearly and the incidence rates of resistance in various species are also evaluated. In the first surveillance from June 2000 to March 2001, 1,091 isolates of 22 species were tested, 993 isolates of the same 22 species were tested in the second surveillance from April 2001 to March 2002, and 1,115 isolates of the same 22 species were tested in the third surveillance from April 2002 to March 2003. No remarkable changes in the activity of CPDX were observed against most of the species in these surveillances spanning three years and in comparison with that in the studies conducted before Banan was launched.

[Surveillance of susceptibility of clinical isolates to panipenem between 2000 and 2003].

For the post-marketing surveillance of panipenem/betamipron (PAPM/BP, Carbenin), MICs of injectable beta-lactam antibacterials including PAPM against clinical isolates from 15 medical institutions all over Japan are measured yearly and the incidence rates of resistance in various species are also evaluated. In the first surveillance from June 2000 to March 2001, 1,356 isolates of 28 species were tested, 1,221 isolates of the same 28 species were tested in the second surveillance from April 2001 to March 2002, and 1,403 isolates of the same 28 species were tested in the third surveillance from April 2002 to March 2003. No remarkable changes in the activity of PAPM were observed in these surveillances spanning three years.

In vitro and in vivo antibacterial activities of CS-023 (RO4908463), a novel parenteral carbapenem.

CS-023 (RO4908463, formerly R-115685) is a novel 1beta-methylcarbapenem with 5-substituted pyrrolidin-3-ylthio groups, including an amidine moiety at the C-2 position. Its antibacterial activity was tested against 1,214 clinical isolates of 32 species and was compared with those of imipenem, meropenem, ceftazidime, ceftriaxone, ampicillin, amikacin, and levofloxacin. CS-023 exhibited a broad spectrum of activity against gram-positive and -negative aerobes and anaerobes, including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis, penicillin-resistant Streptococcus pneumoniae (PRSP), beta-lactamase-negative ampicillin-resistant Haemophilus influenzae, and Pseudomonas aeruginosa.

Activity of capuramycin analogues against Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium intracellulare in vitro and in vivo.

Objectives: The antimycobacterial activities of RS-112997, RS-124922 and RS-118641, three capuramycin analogues that inhibit phospho-N-acetylmuramyl-pentapeptide translocase, were tested against clinical isolates of Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium intracellulare.

Methods And Results: MICs were determined by the broth microdilution method using a modified Middlebrook 7H9 broth. RS-118641 was the most potent compound overall.

Temporal increase in the gastric colonization of Helicobacter pylori after healing of acetic acid-induced gastric ulcer in a miniature pig.

While the eradication of Helicobacter pylori has been reported to reduce the frequency of ulcer relapse, the preventative mechanism remains unknown. We investigated the changes in the level of gastric colonization 140 days after inducing gastric ulcer by acetic acid in the antral mucosa of a miniature pig infected with H. pylori.

Essential role of magnesium ion in water for colonization of Helicobacter pylori in 2-week-old miniature pigs.

This study was designed to determine whether magnesium ion in water would influence the colonization of Helicobacter pylori in 2-week-old miniature pigs. Groups A (2 pigs) and B (1 pig) were both fed a milk diet dissolved in drinking water, Group C (2 pigs) was fed a milk diet dissolved in deionized distilled water (DDW), and Group D (1 pig) was fed a milk diet dissolved in DDW supplemented with MgCl2. Groups B, C, and D were all challenged with H.

Contribution of ferrous iron to maintenance of the gastric colonization of Helicobacter pylori in miniature pigs.

Our previous study showed that the colonization levels of Helicobacter pylori were higher in the stomachs of 5-day-old miniature pigs than in 2-week-old ones. As dietary factors can cause these differences, we compared two diets, i.e.

Effect of plaunotol in combination with clarithromycin or amoxicillin on Helicobacter pylori in vitro and in vivo.

Plaunotol, a cytoprotective anti-ulcer agent, has antibacterial activity against Helicobacter pylori. The purpose of the present study was to investigate the effect of plaunotol when combined with clarithromycin or amoxicillin against H. pylori.