Browsing by Subject "Macrolides"

Now showing 1 - 5 of 5
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    23S rRNA and L22 ribosomal protein are involved in the acquisition of macrolide and lincosamide resistance in Mycoplasma capricolum subsp. capricolum
    (Elsevier, ) Prats-van der Ham, Miranda; Tatay-Dualde, Juan; Gómez-Martín, Angel; Corrales, Juan Carlos; Contreras de Vera, Antonio; Sánchez López, Antonio; de la Fe, Christian; Sanidad Animal
    Mycoplasma capricolum subsp. capricolum (Mcc) is one of the causative agents of contagious agalactia, and antimicrobial treatment is the most commonly applied measure to treat outbreaks of this disease. Macrolides and lincosamides bind specifically to nucleotides at domains II and V of the 23S rRNA gene. Furthermore, rplD and rplV genes encode ribosomal proteins L4 and L22, which are also implicated in the macrolide binding site. The aim of this work was to study the relationship between these genes and the acquisition of macrolide and lincosamide resistance in Mcc. For this purpose, in vitro selected resistant mutants and field isolates were studied. This study demonstrates the appearance of DNA point mutations at the 23S rRNA encoding genes (A2058G, A2059G and A2062C) and rplV gene (Ala89Asp) in association to high minimum inhibitory concentration values. Hence, it proves the importance of 23S rRNA domain V and ribosomal protein L22 as molecular mechanisms responsible for the acquisition of macrolide and lincosamide resistance in both field isolates and in vitro selected mutants. Furthermore, these mutations enable us to provide an interpretative breakpoint of antimicrobial resistance for Mcc at MIC 0.8 µg/ml.
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    Antimicrobial susceptibility of Rhodococcus equi strains isolated from foals in Chile
    (2023-06-22) Badillo Puerta, Elena; Zúñiga, María Paz; Abalos, Pedro; Valencia, Eduardo David; Marín, Pedro; Escudero, Elisa; Galecio, Juan Sebastián; Farmacología
    Rhodococcus equi is responsible for foal pneumonia worldwide, with a significant economic impact on the production and breeding of horses. In Chile, the first case was reported in 2000, and since then, its incidence has been increasing. Distinctive characteristics of R. equi as an intracellular pathogen in macrophages, emergence of virulence plasmids encoding surface lipoprotein antigens, and appearance of antibiotic resistance against macrolides and rifampicin have significantly complicated the treatment of R. equi pneumonia in foals. Therefore, in vitro susceptibility studies of first-line and newer antibiotics against R. equi are the first step to establishing effective treatments and optimizing new therapeutic options. The aim of the present study is to determine the susceptibility profile of fourteen strains of R. equi isolated from foals in Chile to several antibiotics of the macrolide group including azithromycin, amikacin, tildipirosin and gamithromycin as well as others such as rifampicin, doxycycline and ceftiofur. Identification of R. equi in collected isolates from foals in Chile has been performed by CAMP test and PCR based on detecting of the gene encoding the 16 S rRNA. The presence of genes encoding virulence plasmids was also determined using PCR. Results obtained have demonstrated presence of virulent R. equi strains in Chile. In vitro susceptibility pattern to different antibiotics has shown better results for doxycycline and rifampicin similar to previous studies performed. Current macrolides have been evaluated in order to consider alternative treatment options in a context of emerging resistance to classic macrolides and rifampicin, obtaining better results with gamithromycin (MIC range of 0.125 to 128 mg/ml) than with tildipirosin (MIC range of 16 to 128 mg/ml). An adequate diagnosis of bacterial susceptibility based on antibiograms is necessary to treat the Rhodococcus equi infection in foals.
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    Disposition kinetics of tildipirosin in alpacas after parenteral administrations
    (Elsevier, 2023-11-10) Galecio, Juan Sebastian; Escudero, Elisa; Egas, David; Mena, Luis; Badillo Puerta, Elena; Marin, Pedro; Hernandis, Verónica; Farmacología
    Tildipirosin is a macrolide antibiotic marketed in veterinary medicine to treat respiratory infections in pigs and calves. There are no pharmacokinetics studies of tildipirosin after parenteral administration in alpacas which is an extremely decisive step for determining dosage regimen. Thus, the aim of the present study was to establish the disposition fate of tildipirosin following intravenous (IV), intramuscular (IM) and subcutaneous (SC) administrations in alpacas. A crossover study was used, and each alpaca received a single dose of tildipirosin by IV and IM or SC. All the routes of administration were adequately tolerated, and no adverse reactions was observed in any alpaca. Tildipirosin in alpacas reached peak concentrations (Cmax = 0.68 µg/mL vs. 0.79 µg/mL) at 0.22 and 0.50 h (tmax) after IM and SC administration, respectively, with an absolute bioavailability of >100 % for both routes of administration. Steady-state volume of distribution and clearance were 6.02 ± 1.34 L/kg and 2.76 ± 0.28 L/h/kg, respectively. Tildipirosin presents a particular pharmacokinetic behaviour in alpacas, distinctive from other ruminant species, confirming the need to perform studies in the target species in order to promote rational dose regimens of this antimicrobial to maximize its efficacy, minimize its toxicity and avoid the emergence of resistant bacteria.
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    Is Azithromycin the first-choice macrolide for treatment of community-acquired pneumonia?
    (Infectious Diseases Society of America, 2003-05-06) Sánchez, F.; Mensa, J.; Martínez, J.A.; García-Vázquez, Elisa; Marco, F.; González, J.; Marcos, F.A.; Soriano, A.; Torres, A.; Medicina
    Combination treatment with ab-lactam plus a macrolide may improve the outcome for elderly patients with community-acquired pneumonia (CAP). The prognoses and mortality rates for elderly patients with CAP who receive ceftriaxone combined with a 3-day course of azithromycin or a 10-day course of clarithromycin were compared in an open-label, prospective study. Of 896 assessable patients, 220 received clarithromycin and 383 received azithromycin. There were no significant differences between groups with regard to the severity score defined by the Pneumonia Patient Outcomes Research Team (PORT) study group; the incidence of bacteremia was also not significantly different. However, for patients treated with azithromycin, the length of hospital stay was shorter (mean+_ SD, 7.4+_5 vs 9.4+_7 days; P<.01) and the mortality rate was lower (3.6% vs. 7.2%; P<.05); compared with those treated with clarithromycin. There might be a difference in the outcome for patients with CAP depending on the macrolide used. A shorter treatment course with azithromycin may result in better compliance with therapy
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    Pharmacokinetics of tildipirosin in horses after intravenous and intramuscular administration and its potential muscle damage
    (Elsevier, 2022-07-23) Galecio Naranjo, Juan Sebastian; Escudero Pastor, Elisa; Badillo Puerta, Elena; Marín Carrillo, Pedro; Farmacología
    Tildipirosin is a novel semisynthetic macrolide antibiotic exclusively used in veterinary practice to treat respiratory infections. There are no pharmacokinetic or safety information available regarding the use of tildipirosin after intramuscular administration in horses. Thus, the objective of this work was to determine the disposition kinetics of tildipirosin after intravenous (IV) and intramuscular (IM) administration in horses and its potential muscle damage and cardiotoxicity. Six mature, Spanish-breed horses were used in a crossover study with a washout period of 30 days. Tildipirosin (18%) was administered at single doses by IV (2 mg/kg) and IM (4 mg/kg) routes. Tildipirosin plasma concentrations were determined by HPLC assay with ultraviolet detection. Muscle damage and inflammation were assessed by creatine kinase (CK) and haptoglobin (Hp), respectively. Creatine kinase myocardial band (CK-MB) and troponin (Tn) were used to evaluate cardiotoxicity. Tildipirosin in horses reached peak concentrations (Cmax = 1.13 μg/mL) at 0.60 h (tmax) after IM administration with an absolute bioavailability of 109.2%. Steady-state volume of distribution and clearance were 3.31 ± 0.57 L/kg and 0.22 ± 0.02 L/h/kg, respectively. Tildipirosin did not cause cardiotoxicity since CK-MB and Tn basal levels were not significantly different from those obtained after several days post-administration. Mild local reactions were observed after IM administration. This local inflammation was associated with mild myolysis (CK 239–837 UI/L), which was detectable for 48 h. In brief, tildipirosin could help to treat respiratory infections in horses because it showed extensive distribution, high bioavailability and did not provoke general adverse reactions.