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  1. Home
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Browsing by Subject "Aminoglycosides"

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    Empiric therapy with Carbapenem-sparing regimens for bloodstream infections due to Extended-Spectrum β-Lactamase-producing Enterobacteriaceae: results from the INCREMENT cohort
    (Oxford University Press, 2017-08-19) Hernández Torres, Alicia; Palacios-Baena, Zaira Raquel; Gutiérrez Gutiérrez, Belén; Calbo, Esther; Almirante, Benito; Viale, Pierluigi; Oliver, Antonio; Pintado, Vicente; Gasch, Oriol; Martínez Martínez, Luis; Pitout, Johann; Akova, Murat; Peña, Carmen; Molina Gil-Bermejo, José; Venditti, Mario; Prim, Nuria; Bou, German; Tacconelli, Evelina; Tumbarello, Mario; Hamprecht, Axel; Giamarellou, Helen; Almela, Manel; Pérez, Federico; Schwaber, Mitchell J.; Bermejo, Joaquín; Lowman, Warren; Hsueh, Po-Ren; Paño-Pardo, José Ramón; Torre-Cisneros, Julián; Souli, Maria; Bonomo, Robert A.; Carmeli, Yehuda; Paterson, David L.; Pascual, Álvaro; Rodríguez-Baño, Jesús; Spanish Network for Research in Infectious Diseases (REIPI); European Study Group of Bloodstream Infections and Sepsis (ESGBIS); INCREMENT Group; Medicina
    Background There is little information about the efficacy of active alternative drugs to carbapenems except β-lactam/β-lactamase inhibitors for the treatment of bloodstream infections (BSIs) due to extended-spectrum β-lactamase–producing Enterobacteriaceae (ESBL-E). The objective of this study was to assess the outcomes of patients with BSI due to ESBL-E who received empiric therapy with such drugs (other active drugs [OADs]) or carbapenems. Methods A multinational retrospective cohort study of patients with BSI due to ESBL-E who received empiric treatment with OADs or carbapenems was performed. Cox regression including a propensity score for receiving OADs was performed to analyze 30-day all-cause mortality as main outcome. Clinical failure and length of stay were also analyzed. Results Overall, 335 patients were included; 249 received empiric carbapenems and 86 OADs. The most frequent OADs were aminoglycosides (43 patients) and fluoroquinolones (20 patients). Empiric therapy with OADs was not associated with mortality (hazard ratio [HR], 0.75; 95% confidence interval [CI], .38–1.48) in the Cox regression analysis. Propensity score–matched pairs, subgroups, and sensitivity analyses did not show different trends; specifically, the adjusted HR for aminoglycosides was 1.05 (95% CI, .51–2.16). OADs were neither associated with 14-day clinical failure (adjusted odds ratio, 0.62; 95% CI, .29–1.36) nor length of hospital stay. Conclusions We were unable to show that empiric treatment with OAD was associated with a worse outcome compared with carbapenems. This information allows more options to be considered for empiric therapy, at least for some patients, depending on local susceptibility patterns of ESBL-E.
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    Inhibition of gentamicin-induced nephrotoxicity by lithium in rat
    (Murcia : F. Hernández, 1993) Samadian, T.; Dehpour, A.R.; Amini, Sh.; Nouhnejad, P.
    Daily intraperitoneal injection of gentamicin in doses of 2,4 and 10 mglkglday for 5 consecutive days produced proximal tubular necrosis in male albino rats as assessed by ultrastructural findings from electron microscopic observations. With respect to nephrotoxicity, aminoglycoside antibiotics (AGs) have been shown to concentrate in the lysosomes of kidney proximal tubular cells to inhibit the activities of phospholipases A and C, including a phospholipidosis, characterized by the formation of myeloid bodies. It has been suggested that the nephrotoxicity of AGs is related to the extent of this phospholipidosis. The concurrent therapy of lithium in doses of 5 and 10 mEqIkglday, administered subcutaneously, 24 hours prior to gentamicin administration for the same period, proved effective in reducing the gentamicin-induced phospholipidosis in kidney as judged by reduction in lysosomal myeloid bodies to an amount of 26-45 percent. It is well known that lithium interferes with phosphatidylinositol turnover and reduces the cellular availability of myoinositol which is needed for the resynthesis of membrane poliphosphoinositides. Thus, the inhibitory effect of lithium on gentamicin-induced nephrotoxicity may be due to interference of lithium with phosphoinositide cycle.
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    Ultrastructural localization of calcium in neuromuscular junctions of smooth and skeletal muscles after aminoglycoside antibiotics treatment
    (Murcia : F. Hernández, 1994) Nouhnejad, P.; Dehpour, A.R.; Samadian, T.; Amini, Sh.
    Aminoglycoside antibiotics are all capable of producing clinically significant neuromuscular paralysis. Since part of the mechanism of action of these antibiotics at neuromuscular junction is a calciumdependent inhibition of acetylcholine release, so this experiment was carried out in vitro on both somatic (isolated rat phrenic-nerve hemidiaphragm) and autonomic neuro-effector transmission (guinea-pig ileum) using gentamicin and amikacin, to determine the calcium contents at this level. Electron microscopic observations on gentamycinandlor amikacin-treated materials, using potassium pyroantimonate method suggest a reduction of internal calcium in nerve terminals of both preparations.
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    Vestibular histofluorescence could be due to accumulation of both the antibiotic and its derivative, streptidine, after acute streptomycin treatment in the guinea pig
    (Murcia : F. Hernández, 2001) Meza Ruiz, G.; Barba-Behrens, N.; Granados, O.; Hernandez-Cruz, A.; Toxqui, A.
    Acute treatment with 300 mglkg of pigmented guinea pigs with streptomycin sulfate induces an elevation of endogenous fluorescence in vestibular ampullary cristae. Fluorescence accumulates in all compartments of the epithelium, i.e., vestibular sensory and supporting cells and nerve fibers of the stroma and it was very intense 1 and 12 hours after its administration. Fli~orescence decreased to control levels 24 hours following streptomycin injection. Fluorescence levels were very low either in untreated animals or in animals injected with s a l i n e physiological solution. To investigate whether this fluorescence was an intrinsic property of the antibiotic or whether it was due to a derivative of it, or both, an in vitro fluorescence spectrum was performed with I00 ,LIM solutions of streptomycin or streptidine, or both, dissolved in various buffer solutions at 488 nm of excitation. A discrete level of fluorescence was observed in the spectrum regardless of media when separate solutions of both streptomycin or streptidine were s t u d i e d . Fluorescence notably increased at 522-532 nm when the solutions contained both streptomycin and streptidine toget her. These results suggest that streptidine putatively derived from streptomycin may contribute to the observed fluorescence accumulation in vestibular preparations after acute treatment. Thus, these metabolic properties of the inner ear which transform streptomycin into streptidine, something never considered earlier, could be claimed as partially responsible for converting a therapeutic agent into a compound which could be as harmful as STP to the inner ear.

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