CS-023 (RO4908463, formerly R-115685) is a novel 1␤-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), ␤-lactamase-negative ampicillin-resistant Haemophilus influenzae, and Pseudomonas aeruginosa. CS-023 showed the most potent activity among the compounds tested against P. aeruginosa and MRSA, with MICs at which 90% of isolates tested were inhibited of 4 g/ml and 8 g/ml, respectively. CS-023 was stable against hydrolysis by the ␤-lactamases from Enterobacter cloacae and Proteus vulgaris. CS-023 also showed potent activity against extended-spectrum ␤-lactamase-producing Escherichia coli. The in vivo efficacy of CS-023 was evaluated with a murine systemic infection model induced by 13 strains of gram-positive and -negative pathogens and a lung infection model induced by 2 strains of PRSP (serotypes 6 and 19). Against the systemic infections with PRSP, MRSA, and P. aeruginosa and the lung infections, the efficacy of CS-023 was comparable to those of imipenem/cilastatin and vancomycin (tested against lung infections only) and superior to those of meropenem, ceftriaxone, and ceftazidime (tested against P. aeruginosa infections only). These results suggest that CS-023 has potential for the treatment of nosocomial bacterial infections by gram-positive and -negative pathogens, including MRSA and P. aeruginosa.

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The authors report a Japanese family segregating autosomal recessive Charcot-Marie-Tooth disease (CMT) with focally folded myelin, juvenile-onset glaucoma, and a nonsense mutation of SET binding factor 2 (SBF2). The consistent phenotypic features associated with SBF2 mutations are early-onset demyelinating neuropathy, myelin folding, and markedly decreased motor nerve conduction velocities; glaucoma associates with SBF2 nonsense mutations.

Current Japanese clinical practice involves the usage of large amounts of new macrolides such as clarithromycin and roxithromycin for the treatment of diffuse panbronchiolitis, Helicobacter pylori and Mycobacterium avium complex infections. In this study, the phenotypes, genotypes, and macrolide resistance mechanisms of macrolide-inactivating Escherichia coll recovered in Japan from 1996 to 1997, were investigated.The isolation rate of erythromycin A highly-resistant E. coli (MIC > 1600 /xg/ml) in Japan slightly increased from 0.5% in 1986 to 1.2% in 1997. In six macrolide-resistant strains, recovered from the strains collected for this study during 1996 to 1997, the inactivation of macrolide could be detected with or without added ATPin the assay system. The appearance of erythromycin A-inactivating enzyme independent of ATPwas novel from Japanese isolates, and the ]H NMRspectra of oleandomycin hydrolyzed by the three ATP-independent isolates were examined. It was clearly shown that the lactone ring at the position of C-13 was cleaved as 13-H signal in aglycon of oleandomycin upper shifted. These results suggested the first detection of macrolide-lactone ring-hydrolase from clinical isolates in Japan. These results suggested the first detection of an ATP-independent macrolide-hydrolyzing enzyme from Japanese clinical isolates. Substrate specificity of the macrolide-hydrolyzing enzyme was determined with twelve macrolides including the newer membersof this group and it was found that not only erythromycin A but also the new macrolides, such as clarithromycin, roxithromycin, and azithromycin were inactivated. The NMRdata, broad spectrum of activity, and independence of co-enzymesupported our namingof the enzymeas a macrolide esterase. PCRmethodology was employed to detect an ereB-like gene from the 3 isolates producing macrolide esterase, and one of these was subsequently shown to contain both ereB-like and ermB-Wksgenes. It was also clearly shown that the other three isolates, which inactivated macrolide in the presence of ATP, had an mphA-liko gene.

Objectives: Rectus sheath hematoma (RSH) can result from bleeding into the rectus abdominis muscle or a direct muscular tear; nontraumatic spontaneous RSH is a rare condition. Here, we report a case of spontaneous RSH associated with warfarin administration for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH).Patient: An 87-year-old woman was referred to our hospital because of abdominal pain, nausea, and vomiting for 3 days. She was receiving warfarin for treating CTEPH. She had a bulging and hard lower abdomen with ecchymosis. Moreover, the bulging portion was highly tender, and a positive Carnett’s sign was also observed. She reported no history of abdominal trauma. Abdominal computed tomography (CT) scan revealed right RSH.Results: She was diagnosed with spontaneous RSH and admitted to our hospital. Warfarin was antagonized with an intravenous injection of vitamin K; hemostatic agents were intravenously administered. Gradually, her abdominal pain improved. She was finally discharged 12 days after the admission. Abdominal CT scan performed 17 days after the discharge revealed a reduction in the size of RSH.Conclusion: Despite not having a history of trauma, it is necessary to consider the possibility of RSH for patients receiving warfarin and complaining of abdominal pain.