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Single-Dose Pharmacokinetics and Safety of a Novel Broad-Spectrum Cephalosporin (BAL5788) in Healthy Volunteers. Anne Schmitt-Hoffmann, 2004.BAL5788 is the water-soluble prodrug of BAL9141, a novel broad-spectrum cephalosporin with potent bactericidal activities against methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae . We investigated the safety and pharmacokinetics of BAL5788 in a double-blind, single-ascending-dose study with 40 healthy male subjects . The subjects were randomized to receive placebo (n = 2 subjects per dose) or BAL5788 (n = 6 subjects per dose) as a 200-ml intravenous infusion over 30 min . The BAL5788 doses used were 125, 250, 500, 750, and 1,000 mg (BAL9141 equivalents) . All doses were well tolerated, with no severe or serious adverse events (AEs) . The most frequent AE was taste disturbance . No electrocardiographic abnormalities and no trends or clinically significant changes in laboratory parameters or vital signs were observed . The maximum concentration of drug in serum and the area under the concentration-time curve for BAL9141 were dose proportional over the dosing range . The elimination half-life of BAL9141 was about 3 h . The volume of distribution at steady state was equal to the volume of the adult extracellular water compartment, and the rate of renal clearance of free drug corresponded to the normal glomerular filtration rate for adults . More than 70% of the administered dose was excreted as BAL9141 in the urine, and almost no prodrug was detected . After the infusion of 750 mg, the mean plasma BAL9141 concentrations exceeded the MIC at which 100% of MRSA isolates are inhibited (4 µg/ml) for approximately 7 h, or 58% of a 12-h dosing interval . These results indicate that infusions of 750 mg twice a day should be adequate for the treatment of infections caused by MRSA . Evidence for the Presence of Simkania negevensis in Drinking Water and in Reclaimed Wastewater in Israel. Simona Kahane, 2004.Simkania negevensis is a recently discovered chlamydia-like intracellular microorganism which has been associated with bronchiolitis in infants and with community-acquired pneumonia in adults; a high seroprevalence of antibodies to the microorganism has been found in various population groups . S . negevensis can be grown in various cell lines as well as in free-living amoebae such as Acanthamoeba polyphaga . In this study, evidence for the existence of Simkania or Simkania-like microorganisms in drinking water and in reclaimed wastewater is presented for the first time . Detection of the microorganism was made possible by the development of a specific and sensitive filter membrane immunoassay and was confirmed by PCR detection of microbial DNA in the water samples . The common presence of S . negevensis in water sources together with the high seroprevalence of antibodies to it and early age of acquisition of infection may implicate water as a source of infection . The possible significance of this finding for public health and for municipal water testing and treatment needs to be further examined . Ribonuclease M5 Has Few, If Any, mRNA Substrates in Bacillus subtilis. Ciarán Condon, 2002.In Bacillus subtilis, maturation of 5S rRNA is catalyzed by an enzyme called RNase M5 . We searched for potential mRNA substrates for RNase M5 by gene array technology, based on the premise that most endonucleolytic cleavages have an effect on the stability of RNA and hence on steady-state levels of expression . Only a handful of genes had significantly altered expression in rnmV mutants compared to wild-type strains that could subsequently be confirmed by Northern blotting . The effect of RNase M5 on the expression of the best candidates, the odhAB and sucCD operons, is indirect, by a mechanism we do not yet understand . We show that an effect of RNase M5 on the expression of the remaining candidate, ctsR, is due to the failure to process the 5S rRNA contained in the rrnW lying directly upstream . We thus conclude that RNase M5 has very few or possibly no mRNA substrates in B . subtilis .
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