Pharmacokinetics of macrolides in foals

Villarino, Nicolás F.; Martı́n-Jiménez, Tomás

doi:10.1111/jvp.12010

Cited by 25 publications

(29 citation statements)

References 67 publications

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“…Macrolide antibiotics are a major part of the standard therapy , as they widely distribute into pulmonary compartments (Gaynor and Mankin 2003). In foals, macrolides show unique pharmacokinetic features such as rapid and extensive distribution and long persistence in pulmonary epithelial lining fluid (PELF) and in bronchoalveolar cells (Villarino et al 2013). For all the macrolides, the rate of elimination is slow, and drugs tend to persist for a long period of time in bronchoalveolar cells when compared with PELF and plasma (Villarino et al 2013).…”

Section: Introductionmentioning

confidence: 99%

“…After intramuscular administration, TUL is rapidly and nearly completely absorbed from the injection site. It is widely distributed and accumulates in lung tissue, but the plasma concentrations and the lung tissue concentrations are far below the MIC for R. equi, which brings into question the value of TUL as an alternative to treat pneumonia caused by R. equi in foals (Villarino et al 2013). But as shown by in vitro studies, TUL accumulates also in leukocytes and macrophages to concentrations several times above the serum levels.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy of treatment and survival rate of foals with pneumonia: Retrospective comparison of rifampin/azithromycin and rifampin/tulathromycin

Arnold-Lehna¹,

Venner²,

Berghaus³

et al. 2019

PHK

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Rhodococcus equi (R. equi), a Gram-positive facultative intracellular pathogen is one of the most common causes of pneumonia in foals. The retrospective study compares the efficacy of rifampin/azithromycin versus rifampin/tulathromycin for the treatment of R. equi pneumonia in foals. Weekly medical data of foals born in the seasons 2012 to 2016 (i.e. five foaling seasons) that developed pneumonia were collected and analysed. Foals 21 days of age or older with a pulmonary consolidation of more than 1 cm (abscess score ≥ 1 cm) were enrolled for participation in the study. All foals meeting the criteria for inclusion were listed in a spreadsheet and 330 foals affected with pneumonia each year were randomly selected by an online research randomizer. Foals with incorrect or missing data and those that were included in previous treatment studies were excluded from the analysis, resulting in a total enrolment of 1544 foals with pneumonia. The farm established a screening program in 2003 in order to detect foals in the early course of pneumonia, so all foals were examined once weekly starting at the age of two weeks until four and a half months of age. A physical examination of the respiratory tract, body temperature, haematology and an ultrasonographic examination of the lungs were included. Sonography areas with visible consolidation were measured and added to calculate an "abscess score" which represents the extent of pulmonary damage. Weekly medical data were analysed retrospectively. The risk of therapy failure, which means either death or worsening of pneumonia requiring that the foal be switched to another therapy, showed in a univariate comparison of the two treatments, that there was a higher incidence of treatment failure in foals treated with RIF/AZM (32/353, 9.1 %) than in foals that were treated with RIF/TUL (19/406, 4.7 %; Pearson's χ 2 , P = 0.016). In a Kaplan-Meier analysis, there was also a significant difference between the two treatments with respect to their survival functions (Log-rank test, P = 0.045; Figure 1). The incidence of mortality due to R. equi pneumonia was higher in foals that were treated with RIF/AZM (8/353, 2.3 %) than in those that were treated with RIF/TUL (0/406, 0.0 %; Fisher's exact test, P = 0.002). After adjusting for year, age of foals at the beginning of treatment, and abscess score at the beginning of treatment, the risk of treatment failure was not significantly lower for foals that were treated with RIF/TUL compared to those that were treated with RIF/AZM [Hazard Ratio (95 % CI) = 0.75 (0.38, 1.5)]. Age of foals was negatively associated with treatment failure, with the risk of failure decreasing by 30 % for every one-month increase in age at the beginning of treatment [HR (95 % CI) = 0.70 (0.54, 0.91)]. Abscess score was positively associated with treatment failure, with the risk of failure increasing by 4 % for every one cm increase in score [HR (95 % CI) = 1.04 (1.01, 1.07)]. Year was also associated with the risk of treatment failure but it did not meet the proportiona...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Efficacy of treatment and survival rate of foals with pneumonia: Retrospective comparison of rifampin/azithromycin and rifampin/tulathromycin

Arnold-Lehna¹,

Venner²,

Berghaus³

et al. 2019

PHK

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“…Der Wirkstoff Gamithromycin gehört neben Azithromycin, Clarithromycin und Tulathromycin zu den neueren Makrolidantibiotika. Neben einer besseren Bioverfügbarkeit und Stabilität als Erythromycin haben sie ein höheres Verteilungsvolumen, eine längere Plasmahalbwertszeit und erreichen eine höhere Konzentration im Gewebe und in den phagozytären Zellen [15][29] [31]. Durch die Anreicherung in Makrophagen wird eine hohe Konzentration im Entzündungsgebiet erreicht.…”

Section: Diskussionunclassified

Praktische Erfahrungen zur Behandlung einer mandibulären Osteomyelitis („lumpy jaw“) mit Gamithromycin bei einem Muntjak

Wagener

Schwennen

Punsmann

et al. 2020

Tierarztl Prax Ausg G

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ZusammenfassungMandibuläre Osteomyelitiden kommen sowohl bei Haus- als auch bei Wildwiederkäuern immer wieder vor. Die entzündlichen Veränderungen des Kiefers werden dabei nicht nur von Actinomyces ssp. verursacht, sondern es kommen auch andere bakterielle Erreger ursächlich in Betracht. Im Fall eines Muntjaks aus privater Haltung, der mit Fressunlust und einer soliden Umfangsvermehrung am Körper des rechten Unterkiefers vorgestellt wurde, ließ sich röntgenologisch eine mandibuläre Osteomyelitis diagnostizieren. Eine antibiotische Behandlung mit Gamithromycin (Zactran®) über 50 Tage führte zu einer Verbesserung des Fressverhaltens und einem Rückgang der Umfangsvermehrung an der Mandibula. Bei Kontrolluntersuchungen nach 18 und 28 Monaten zeigte sich eine gute Remodellierung des betroffenen Unterkieferkörpers, die allerdings mit dem Verlust aller Backenzähne einherging. Die alleinige Langzeitverabreichung von Gamithromycin ist möglicherweise eine erfolgreiche Behandlungsmethode für die mandibuläre Osteomyelitis bei Wiederkäuern.

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“…However, there are also reports on clinical use of GAM in other species (e.g., chicken, foals) (Berghaus et al., ; Giguere et al., ; Watteyn et al., ). A single‐dose administration seems to be sufficient to ensure effective antimicrobial concentrations in pulmonary target compartments for more than one week (Berghaus et al., ; Giguere et al., ; Huang, Letendre, Banav, Fischer, & Somerville, ; Villarino & Martin‐Jimenez, ). However, subcutaneous administration in horses leads to severe pain and local tissue lesions at the injection site likely caused by hyperosmolality of the commercially available formulation (Hildebrand, Venner, & Giguere, ; Merial Ltd. ).…”

Section: Introductionmentioning

confidence: 99%

“…week Giguere et al, 2011;Huang, Letendre, Banav, Fischer, & Somerville, 2010;Villarino & Martin-Jimenez, 2013).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and pulmonary distribution of gamithromycin after intravenous administration in foals

Berlin

Randow²,

Scheuch

et al. 2017

Vet Pharm & Therapeutics

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The long-acting azalide antibiotic gamithromycin is marketed for intramuscular treatment of bovine and swine infections. Off-label use in foals leads to severe local lesions likely caused by hyperosmolality of the injected solution. We provide evidence from a pharmacokinetic study in 10 warm-blooded healthy foals for intravenous bolus injection of gamithromycin diluted in distilled water to be a safe and well tolerated alternative. By intravenous dosing, markedly higher plasma exposure and better penetration into bronchoalveolar lavage cells but lower distribution into epithelial lining fluid are achieved as after intramuscular or subcutaneous administration. Intravenously injected gamithromycin was tolerated without any adverse drug reactions. The protocols for treatment of equine pulmonary infections caused by Rhodococcus equi should be revised accordingly.

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Pharmacokinetics of macrolides in foals

Cited by 25 publications

References 67 publications

Efficacy of treatment and survival rate of foals with pneumonia: Retrospective comparison of rifampin/azithromycin and rifampin/tulathromycin

Efficacy of treatment and survival rate of foals with pneumonia: Retrospective comparison of rifampin/azithromycin and rifampin/tulathromycin

Praktische Erfahrungen zur Behandlung einer mandibulären Osteomyelitis („lumpy jaw“) mit Gamithromycin bei einem Muntjak

Pharmacokinetics and pulmonary distribution of gamithromycin after intravenous administration in foals

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