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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.

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Macrolide antibiotics penetrate in the lung against steep concentration gradients into the epithelial lining fluid (ELF) and broncho-alveolar cells (BAC). Since they interact with ABCB1, ABCC2, and organic anion transporting proteins (OATPs), which are localized to lung tissue, pulmonary concentration may be influenced by rifampicin (RIF), an inducer and modulator of efflux and uptake transporters. We measured concentrations of tulathromycin (TM) in plasma, ELF and BAC in 21 warm-blooded foals 24 and 192 h after first and last intramuscular injection of 2.5 mg/kg TM once weekly for 6 weeks. In 11 foals, TM was combined with RIF (10 mg/kg twice daily), and mRNA expression of ABCB1 and ABCC2 in BAC was assessed before and after RIF. Affinity of TM to ABCB1 and ABCC2 was measured by transport assays using cell monolayers and membrane vesicles of MDCKII and 2008 cells transfected with ABCB1 and ABCC2, respectively. At steady state, TM concentrated manifold in ELF and BAC. Comedication of RIF significantly decreased the AUC of TM (18.5 +/- 4.0 versus 24.4 +/- 3.7 microg x h/ml, p < 0.05) and lowered its concentrations in plasma (24 h, 0.17 +/- 0.05 versus 0.24 +/- 0.05 microg/ml; 192 h, 0.05 +/- 0.01 versus 0.06 +/- 0.01 microg/ml) and BAC (24 h, 0.84 +/- 0.36 versus 1.56 +/- 1.02 microg/ml; 192 h, 0.60 +/- 0.23 versus 1.23 +/- 0.90 microg/ml, all p < 0.05). Treatment with rifampicin did not markedly induce ABCB1 and ABCC2 expression. TM had no affinity to ABCB1 and ABCC2 in vitro. Concentration of TM in the lung of foals was significantly lowered by comedication of rifampicin most likely caused by extrapulmonary mechanisms leading to lower plasma concentrations.

BackgroundGamithromycin is active in vitro against the bacterial agents most commonly associated with bronchopneumonia in older foals. However, the clinical efficacy and safety of this drug have not been investigated.HypothesisGamithromycin is effective for the treatment of bronchopneumonia in foals.AnimalsOne hundred and twenty‐one foals on a farm endemic for infections caused by Rhodococcus equi.MethodsIn a controlled, randomized, and double blinded clinical trial, foals with ultrasonographic evidence of pulmonary abscesses (abscess score 8.0–20 cm) were randomly allocated in 3 treatment groups: (1) gamithromycin IM q7 days (n = 40); (2) azithromycin with rifampin, PO q24h (n = 40); or (3) no antimicrobial treatment (controls; n = 41). Physical examination and thoracic ultrasonography were performed by individuals unaware of treatment group assignment. Foals that worsened were removed from the study.ResultsThe proportion of foals that recovered without the need to be removed from the study was significantly higher for foals treated with gamithromycin (38 of 40) or azithromycin with rifampin (39 of 40) than for controls (32 of 41). Treatment with gamithromycin or with azithromycin‐rifampin resulted in a significantly faster decrease in the clinical score and abscess score compared to the controls. Adverse reactions characterized by colic (n = 18) and hind limb lameness (n = 14) were observed only in foals treated with gamithromycin.Conclusion and Clinical ImportanceGamithromycin was noninferior to azithromycin with rifampin for the treatment of bronchopneumonia in the study population but had a higher frequency of adverse reactions.

Summary This study compared the study of a pectin‐lecithin complex (Pronutrin)1 on gastric ulcer healing during an 11 day period in 2 groups of 12 horses each. Twenty‐four horses suffering from gastric lesions of differing severity were selected from a larger group of clinical cases on the basis of gastroscopic examination. Both gastric mucosal erosions as well as gastric ulcers were found in the 2 mucosal regions (pars nonglandularis and pars glandularis). The gastric mucosal lesions occurred predominantly in the pars nonglandularis in the vicinity of the margo plicatus. The 24 horses were divided equally into a treated group (Group A) and a control group (Group B). Twelve horses in Group A received Pronutrin, in a dose of 300 g/horse/day over a period of 10 days, whereas horses in Group B received no active substance. Gastroscopic examination was performed on Days 0 and 11. The degree of severity of the gastric erosions or gastric ulcers was evaluated independently in the 2 mucosal regions with the aid of a scoring system. Group A horses showed good acceptance of the product and no side effects were recorded. After the 10 day treatment phase, Group A showed a marked reduction in gastric mucosal lesions or disappearance of lesions, while untreated horses showed no change or, even, a deterioration on Day 11. Statistical calculation of efficacy revealed a highly significant reduction in gastric mucosal lesions in the pars nonglandularis and a significant reduction in gastric mucosal lesions in the pars glandularis in the treated horses. It would appear, however, that the treatment period of 10 days was too short, since the gastric mucosal lesions had often not completely healed in all horses. The results of this study in 24 horses with gastric lesions suggest that a pectin‐lecithin complex can have a beneficial effect on the healing of gastric ulcers.