Background: Mass antimicrobial treatment of foals with small subclinical ultrasonographic pulmonary lesions is empirical practice on many farms with endemic disease caused by Rhodococcus equi.Hypothesis: Mass antimicrobial treatment of foals with subclinical ultrasonographic pulmonary lesions is unnecessary. Animals: One hundred and eight foals on a farm endemic for infections caused by R. equi. Methods: Controlled, randomized, and double-blinded prospective study. Foals with ultrasonographic evidence of pulmonary abscesses 5.0-10 cm in diameter (n = 108) were randomly allocated in 5 treatment groups: (1) tulathromycin IM; (2) doxycycline monotherapy PO; (3) doxycycline with rifampin PO; (4) azithromycin with rifampin PO, and (5) saline IM as a placebo. Physical examination and thoracic ultrasonography were performed by individuals unaware of treatment group assignment. Foals with evidence of disease progression were removed from the study and treated with azithromycinrifampin.Results: Overall, 22/25 (88%) foals in the placebo group recovered without the need for treatment. The proportion of foals that had evidence of disease progression did not differ significantly between the treatment groups (P > .05). Although the median duration of treatment was significantly (P < .05) shorter in foals treated with azithromycin-rifampin (46 days) compared with foals treated with the placebo (73 days), the time frame of ultrasonographic lesion resolution did not differ significantly between the treatment groups.Conclusions and Clinical Importance: The majority of foals with subclinical pulmonary abscesses <10 cm in diameter recover without antimicrobial treatment and treatment of affected foals does not provide a clear benefit over administration of a placebo.

ABSTRACT:The delivery of clarithromycin (CRL) to its site of action in bronchial/alveolar epithelial cells (EC), bronchial epithelial lining fluid (ELF), and bronchoalveolar lavage cells (BALC) may be influenced by CYP3A4 and the drug transporters, ATP-binding cassette (ABC) B1 and ABCC2 and organic anion-transporting polypeptides (OATPs), which can be modulated and/or up-regulated via the nuclear pregnane X receptor (PXR) by rifampicin (RIF). Therefore, we evaluated the disposition and pulmonary distribution of CLR (7.5 mg/kg b.i.d., 21 days) and expression of ABCB1, ABCC2, OATP1A2, and OATP2B1 in EC and BALC before and after comedication of RIF (10 mg/kg b.i.d., 11 days) in nine healthy foals (41-61 days, 115-159 kg) in which the genetic homology of drug transporters is close to that of their human analogs. After RIF comedication, relative bioavailability of CLR decreased by more than 90%. Concentrations in plasma (29.8 ؎ 26.3 versus 462 ؎ 368 ng/ml), ELF (0.69 ؎ 0.66 versus 9.49 ؎ 6.12 g/ml), and BALC (10.2 ؎ 10.2 g/ml 264 ؎ 375 g/ml; all P < 0.05) were lowered drastically, whereas levels of the metabolite 14-hydroxyclarithromycin were not elevated despite higher 4␤-hydroxycholesterol/cholesterol plasma concentration ratio, a surrogate for CYP3A4 induction. In the presence of CLR, ABCC2 and PXR mRNA contents were significantly and coordinately (r 2 ‫؍‬ 0.664, P < 0.001) reduced in BALC after RIF. In EC, mRNA expression of OATP1A2 increased but that of OATP2B1 decreased (both P < 0.05). RIF interrupts oral absorption and decreases CRL plasma levels below the minimal inhibitory concentration for eradication of Rhodococcus equi. Evidence that RIF influences the cellular uptake of CLR in bronchial cells and the PXR expression in BALC in the presence of high CLR concentrations exists.

ABSTRACT:Pulmonary penetration of clarithromycin (CLR) in epithelial lining fluid (ELF) and bronchoalveolar lavage cells (BALCs) can be influenced by CYP3A4, by P-glycoprotein, and, according to our hypothesis, by a member of the organic anion-transporting protein (OATP) family, for which rifampicin (RIF) is inhibiting in single doses but inducing after long-term coadministration. To assess the partial inhibitory effect, we measured absorption and pulmonary distribution of CLR after short-term (2.5-day) coadministration of RIF, after which up-regulation is not expected. The drug interaction study was performed with five doses (12-h interval) of CLR (7.5 mg/kg) and RIF (10 mg/kg) in nine healthy foals; horse transporters are very similar in protein sequence and transcriptional regulation to the human analogs. RIF was equally distributed in ELF but reached half the plasma levels in BALCs. The deacetylated metabolite accumulated 1.4-to 6-fold in ELF and 8-to 60-fold in BALCs. CLR did not significantly influence the distribution of RIF. CLR and 14-hydroxyclarithromycin (14OH-CLR) accumulated approximately

The objectives of the present study were to determine the relative efficacy of tulathromycin, azithromycin, or azithromycin with rifampin for the treatment of pulmonary abscesses on a farm with endemic infections caused by Rhodococcus equi. Foals with ultrasonographic evidence of pulmonary abscesses (abscess score 8.0-15 cm; n=120) were randomly allocated in four equal treatment groups: (1) tulathromycin intramuscularly; (2) azithromycin monotherapy, orally; (3) azithromycin with rifampin, orally; (4) saline intramuscularly as a placebo. Physical examination and thoracic ultrasonography were performed by individuals unaware of treatment group assignment. Foals that worsened were removed from the study. The proportion of foals that recovered without the need for a change in therapy was significantly higher for foals treated with azithromycin (29 of 30) or azithromycin with rifampin (28 of 30) than for foals treated with a placebo (20 of 30). Additionally, azithromycin or azithromycin with rifampin resulted in a significantly faster decrease in the number of abscesses and abscess score compared with a placebo. The proportion of foals treated with tulathromycin that recovered (27 of 30) was not significantly different from that of foals treated with a placebo. Azithromycin alone or in combination with rifampin was beneficial in the study population.

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Atemwegserkrankungen bei Fohlen stellen ein ernst zu nehmendes Problem im Hinblick auf Gesundheit und Wirtschaftlichkeit in der Fohlenaufzucht dar. Erkrankungen des Respirationstraktes können bei Fohlen durch Infektion mit Bakterien und Viren hervorgerufen werden. Zu den häufigsten Erregern zählen Herpes-und Influenza-Viren, Klebsiellen, Streptokokken, Actinobacillus und Rhodokokken (Varga et al. 1997, Chapman 2000, Timoney 2004). Rhodococcus equi: der Erreger und seine Eigenschaften Rhodococcus equi (R. equi) ist der am häufigsten vorkommende Erreger von schweren, oft lebensbedrohlichen Pneumonien bei Fohlen im Alter von vier bis zwölf Wochen. Es ist ein grampositives Bakterium und ein ubiquitär vorkommender Bodensaprophyt mit ausgesprochen hoher Tenazität. R. equi ist weltweit im Erdreich nachzuweisen, nicht betroffen ist allein die Antarktis (Knottenbelt 1993, Makrai et al. 2002, Muscatello et al. 2006). Das Überleben des Erregers in der Umwelt ist von verschiedenen Faktoren abhängig. Trockenheit und hohe Temperaturen beeinflussen das Wachstum positiv. Kälte und gängige Desinfektionsmittel machen den Erreger unschädlich. Gegen Alkohole ist der Erreger allerdings nicht sensibel. Des Weiteren vermehren sich Rhodokokken im Darmlumen von erwachsenen Pferden und in der Lunge von Fohlen (Takai et al. 1987, Prescott und Hoffman 1993). Der Nachweis von R. equi lässt sich nicht nur bei Pferden führen, sondern auch bei anderen Tierarten wie Rindern, Hunden, Katzen und Geflügel (Barton und Hughes 1984). R. equi verursacht bei Fohlen unterschiedliche Krankheitsformen. Am häufigsten kommen Erkrankungen im Respirationstrakt, insbesondere in Form einer abszedierenden Bronchopneumonie vor. Nur seltener treten extrapulmonale Erkrankungsbilder u.a. Enteritis, Polysynoviitis, Osteomyelitis und Abszesse in allen Körperregionen auf (Prescott und Hoffman 1993, Ainsworth 1999). Die Morbidität durch R. equi liegt zwischen 5% und 60%, bei einer Letalität von 40% bis 80% und einer Mortalität von 5% bis 17% (Elissalde et al. 1980, Higuchi et al. 1997). Betroffen sind Fohlen bis zum siebten Lebensmonat, wobei sich Todesfälle im Alter von vier bis 12

The bronchoalveolar lavage (BAL) is a procedure, which is used to differentiate and evaluate various lower airway diseases in adult horses. In foals this method is the best way to diagnose a Pneumocystis carinii infection in vivo. Bronchoalveolar lavages are also useful for pharmacokinetic studies to determine concentrations of agents in the tissue of the lung or in the bronchoalveolar cells. The method of performing BAL was evaluated in a total number of 34 foals and 168 BALs. To ensure a recovery rate of more than 60% BALF the bronchoalveolar lavage was performed endoscopically in general anaesthesia. The cell count was determined, the bronchoalveolar fluid was centrifuged and a slide was made to differentiate the cells. The total cell count was 14±5, 8 G/L and most numerous cell populations were macrophages (73±14 %) and lymphocytes (18±12 %) in healthy foals (n=25) in the age of 8 to 12 weeks.