[Concentrations of fosfomycin in serum and lung tissue].
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The present work analyzes pt44 mutation in Sh. flexneri resulting in the appearance of the following phenotypical properties: resistance to phosphomycin, avirulence, pleiotropic disturbances in carbohydrate utilization. The data provided by the biochemical and genetic analysis have indicated that pts44 mutation occupies the region between purC and ptsI loci on the chromosome of Sh. flexneri. Merodiploids containing the mutant allele pts44 and the plasmid including purC-ptsI-ptsH genes from E. coli K12 acquired the capacity for fermenting carbohydrates, but at the same time retained resistance to phosphomycin and avirulent properties. The presence of phosphoenol pyruvate-dependent carbohydrate phosphotransferase system in Sh. flexneri has been proved.
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FOM-Na was investigated on its distribution after a continuous intravenous drip infusion in 3 healthy adult volunteers, and its serum levels and urinary excretion were pharmacokinetically analyzed, while the excreted substance into urine was also analyzed with GC/MS. The results obtained are summarized as follows: 1. The distribution volume of FOM-Na in one-compartment open model was 0.183 L/kg, half life in human body 1.66 hours and renal clearance 0.0737 L/hr/kg. 2. With these pharmacokinetic constants, the mean values following various doses demonstrated almost equal irrespective of its dosage schedule, keeping an almost constant level in each individual tested. 3. The area under serum level-time curve was approximately 216 microgram.hr/ml per 1 g (potency), and increased in proportion to an infused dose within the range of 1 approximately 6 g (potency). Three consecutive administrations showed no trend of accumulation of the agent in the serum. 4. Urinary excretion of the agent was found to be very fast, and its recovery rate from urine within 10 approximately 11 hours after the completion of an i. v. drip infusion was approximately 95 approximately 99%. 5. As a result of GC/MS on the substance excreted into urine, it was noted that FOM-Na was not metabolized in human body and excreted into urine in its original form. 6. There was seen no specific change in electrocardiogram during and/or after an intravenous drip infusion in 1 hour of 2 g (potency) FOM-Na dissolved in a 300 ml 5% glucose solution.
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The in vitro activity of phosphomycin has been compared with other antibiotics in 1703 bacterial strains isolated from pathological specimens sent to the Laboratory from various divisions of the hospital. Results were first class on both gram-positive and gram-negative flora. It was in first place as regards staphylococcus (97.4% sensitive strains), citrobacter (68.6%), proteus mirabilis (73.1%), indole positive proteus (48.2%). It also predominated in pseudomonas (54.6%) and E. coli (86.7%). In view of the fact that gram-negative infections are taking on a predominant position within the hospital environment, it is considered that phosphomycin should be rightfully included among the antibacterial drugs in routine use.
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