Multicenter Evaluation of the Novel ETEST Fosfomycin for Antimicrobial Susceptibility Testing of Enterobacterales, Enterococcus faecalis, and Staphylococcus Species.

Fosfomycin is a phosphonic acid derivative active against a wide spectrum of Gram-positive and Gram-negative pathogens. It is used for the treatment of uncomplicated urinary tract infections (uUTI) or severe infections by oral or intravenous (i.v.) administration. In order to improve its performance and robustness, the fosfomycin strip, an antibiotic gradient diffusion strip, was redeveloped and evaluated in the multicenter study summarized in this paper. ETEST fosfomycin (ETEST FO) clinical performance was evaluated by three study sites on 152 Enterococcus faecalis, 100 Staphylococcus spp. and 330 Enterobacterales in comparison with the CLSI and EUCAST agar dilution reference method. Referring to FDA performance criteria, the ETEST FO achieved 91.0% of essential (EA) and 99.0% of categorical agreement (CA) for Escherichia coli. In addition, 98.0% EA and 93.4% CA were achieved for E. faecalis, with no very major errors (VME) or major errors (ME). According to EUCAST breakpoints for intravenous fosfomycin use, Enterobacterales and Staphylococcus spp. also met ISO acceptance criteria for EA and CA (EA 91.5%, 94.0%, respectively, and CA 98.0% for both). A VME rate of 8.8% was observed for Enterobacterales but the MICs were within EA. A trend to predict lower MICs for Citrobacter spp., E. coli and Salmonella enterica and to predict higher MICs for Klebsiella pneumoniae MICs was observed, while ETEST FO should not be used for Enterobacter cloacae, because of low EA and a high VME rate. The study results support the efficiency of the novel ETEST FO, making it an easy-to-handle tool as a substitute to the classical agar dilution method.

Circadian rhythms of thyroid secretion, morphometry, and cell division in prometamorphic and climax Rana tadpoles.

Rhythmicity of thyroid follicle structure, cell division, and T4 secretion in vitro was studied in anuran tadpoles on a 12L:12D cycle with light onset at 0800 hr. Stage XIII Rana pipiens larvae had a significant circadian rhythm of follicle lumen diameter (acrophase 1052 hr). Follicle cell height was higher at 0900 hr than at other times but the rhythm was not significant. At Stage XX, both follicle cell height (acrophase 2318 hr) and cell division (acrophase 1929 hr) were rhythmic while lumen diameter, though highest at 0900 hr, showed no significant daily changes. Thyroids from Rana catesbeiana larvae at Stages XVII to XVIII had a significant circadian rhythm of T4 secretion (acrophase 2034 hr) in vitro as measured by radioimmunoassay of media collected every 6 hr for 24 hr. The findings indicate that the daily sequence of thyroid structure and function in preclimax Rana tadpoles includes larger follicle lumina early in the light and maximum cell division, T4 secretion, and follicle cell height within a 4-hr interval beginning around the onset of dark.

Metamorphic rate as a function of the light/dark cycle in Rana pipiens larvae.

1. The rate of development of Rana pipiens tadpoles in spontaneous and thyroxine (T4)-induced metamorphosis was studied on light/dark (LD) cycles in which the photophase was held constant while the scotophase was progressively extended or vice versa. 2. Metamorphic rate fluctuated in both types of experiments as the LD cycle lengthened. However, the pattern of resonance differed with the length of the photophase. For example, with an 8 hr light phase, development rate slowed and then increased as the cycle was extended from 24 to to 36 hr, whereas with a 12 hr photophase the reverse took place. 3. The findings are compatible with the occurrence of a rhythm of light sensitivity in photoperiodic time measurement in this amphibian. 4. From the viewpoint of hormonal mechanisms, it is suggested that photoperiodic effects on metamorphic rate result from different patterns of melatonin secretion under the various LD cycles, since melatonin can modify the action of T4 in metamorphosis.

Effect of a light pulse during the dark on photoperiodic regulation of the rate of thyroxine-induced, spontaneous, and prolactin-inhibited metamorphosis in Rana pipiens tadpoles.

Since Rana pipiens tadpoles injected with thyroxine (T4) early in the dark develop more slowly than those injected in the light, we studied the effect of giving a light pulse of 1 hr early in the dark. Tadpoles injected under a 7.5-W red light bulb in a darkened room with 0.2 microgram T4 daily at 2200 hr went through metamorphosis faster on a 12L:3D:1L:8D cycle with a light pulse after injection than on a 12L:12D cycle without a light pulse, and even faster on a 12L:1.5D:1L:9.5D cycle with a light pulse before the injection. Thus a 1-hr light pulse counteracted the metamorphic delay resulting from administration of T4 in the dark, and set in motion the conditions that resulted in a more rapid response to an injection of T4. However, a 1-hr light pulse in the early dark had no effect on growth and development of older or younger untreated tadpoles or those constantly immersed in 30 micrograms/liter T4. Larvae on 21L:3D with T4 injection in the dark and on 12L:3D:1L:8D with T4 injection at 0700 hr just before the start of the main light phase progressed faster than 12L:3D:1L:8D with injection at 2200 hr in the dark before only a 1-hr light pulse. Thus the length of the light phase immediately after T4 injection was significant. There was no difference on 12L:12D and 12L:3D:1L:8D cycles in the effectiveness of daily injections of 10 micrograms prolactin (PRL) in the early dark at 2200 hr in promoting tail growth or antagonizing tail resorption induced by T4 immersion. Under these conditions, PRL utilization did not appear to be inhibited by the light pulse.