rifampin and tulathromycin

There is conflicting data regarding the efficacy of tulathromycin for the treatment of foals with bronchopneumonia.. Tulathromycin is effective for the treatment of bronchopneumonia in foals and noninferior to the combination of azithromycin and rifampin.. A total of 240 foals on a farm endemic for infections caused by Rhodococcus equi.. In a controlled, randomized, and double-blinded clinical trial, foals with ultrasonographic pulmonary lesions (abscess score 10-15 cm) were allocated to 3 groups: 1-tulathromycin IM q 7 days (n = 80); 2-azithromycin-rifampin, orally q24h (n = 80); or 3-untreated controls (n = 80). Physical examination and thoracic ultrasonography were performed by individuals unaware of treatment group assignment. Foals that worsened were considered treatment failures and removed from the study.. The proportion of foals that recovered was significantly higher for foals treated with tulathromycin (70 of 79) or azithromycin-rifampin (76 of 80) compared to that of control foals (22 of 80). The difference in the percentage of efficacy of azithromycin-rifampin versus tulathromycin was 6.4% (90% CI = -0.72-13.5%). Given that the confidence interval crossed the predetermined noninferiority limit of 10%, the null hypothesis that the response rate in the azithromycin-rifampin group is superior to that of the tulathromycin group could not be rejected. Resolution of ultrasonographic lesions occurred faster in foals treated with azithromycin-rifampin than in foals treated with tulathromycin.. Tulathromycin was effective for the treatment of bronchopneumonia in foals at this farm but not as effective as the combination of azithromycin-rifampin.

Topics: Actinomycetales Infections; Animals; Anti-Bacterial Agents; Azithromycin; Bronchopneumonia; Disaccharides; Double-Blind Method; Drug Therapy, Combination; Female; Heterocyclic Compounds; Horse Diseases; Horses; Male; Rhodococcus equi; Rifampin; Treatment Outcome

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.

Topics: Actinomycetales Infections; Animals; Anti-Bacterial Agents; Azithromycin; Disaccharides; Double-Blind Method; Drug Therapy, Combination; Endemic Diseases; Germany; Heterocyclic Compounds; Horse Diseases; Horses; Lung Abscess; Pneumonia, Bacterial; Rhodococcus equi; Rifampin; Severity of Illness Index; Treatment Outcome

Mass antimicrobial treatment of foals with small ultrasonographic pulmonary lesions is common on farms with endemic disease caused by Rhodococcus equi. The objectives of this study were to compare the relative efficacy of three antimicrobial protocols for the treatment of pulmonary abscesses on a farm with endemic infections caused by R. equi and to determine the frequency of spontaneous resolution of subclinical pulmonary lesions. Foals with ultrasonographic evidence of pulmonary abscesses ≥ 1.0 cm in diameter (n=128) were randomly allocated to one of four equal treatment groups. Animals with respiratory distress or severe pulmonary lesions were excluded from the study. Treatment groups consisted of: (1) tulathromycin intramuscularly; (2) azithromycin monotherapy orally; (3) azithromycin in combination with rifampin orally; and (4) glucose orally as a placebo. Physical examination, thoracic ultrasonography and white blood cell (WBC) counts were performed weekly by individuals unaware of treatment group assignment. Foals that worsened were removed from the study and treated with azithromycin and rifampin. Overall, 14/32 (43.8%) foals in the placebo group recovered without the need for therapy. The proportion of foals that responded to the initial therapy, the duration of therapy, the kinetics of ultrasonographic lesion resolution, the proportion of foals that had to be removed from the study and the number of days to removal from the study did not differ significantly between treatment groups. The study showed that many foals with pulmonary abscesses recover without antimicrobial therapy. Moreover, treatment of sub-clinically affected foals with antimicrobial agents did not significantly hasten recovery.

Topics: Actinomycetales Infections; Animals; Anti-Bacterial Agents; Azithromycin; Disaccharides; Double-Blind Method; Drug Therapy, Combination; Endemic Diseases; Female; Heterocyclic Compounds; Horse Diseases; Horses; Lung Abscess; Male; Rhodococcus equi; Rifampin; Time Factors; Treatment Failure

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.

Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antitubercular; Area Under Curve; ATP Binding Cassette Transporter, Subfamily B, Member 1; Bronchi; Bronchoalveolar Lavage Fluid; Cell Line; Disaccharides; Dogs; Drug Interactions; Female; Heterocyclic Compounds; Horses; Male; Multidrug Resistance-Associated Protein 2; Multidrug Resistance-Associated Proteins; Pulmonary Alveoli; Rifampin; RNA, Messenger

Tulathromycin is a new injectable macrolide antibiotic used for the treatment of pulmonary diseases of swine and cattle. In this study, 37 foals with sonographic evidence of lung abscesses were treated with tulathromycin (2.5mg/kg intramuscularly [IM] once weekly, group 1) and 33 foals (group 2) with a combination of azithromycin (10mg/kg per os [PO] once daily for the first seven days of therapy, thereafter every other day) and rifampin (10mg/kg PO twice daily). The bacterial aetiological agent was not determined. The foals were only mildly sick and the median number of pulmonary abscesses was 1.4 (group 1) and 1.6 (group 2). Thirty foals in each group were treated without modifying therapy protocols until all clinical signs of disease had subsided. Tulathromycin was administered for a mean of 53 days, and azithromycin/rifampin for 42 days. The following side effects were associated with tulathromycin (279 IM injections): self-limiting diarrhoea in 11 foals; elevated temperature in six foals, and swellings at the injection site in 12 foals. This study provides some evidence that tulathromycin is well tolerated and appears promising for the treatment of pulmonary abscesses in foals.

Topics: Administration, Oral; Animals; Animals, Newborn; Anti-Bacterial Agents; Azithromycin; Disaccharides; Drug Therapy, Combination; Heterocyclic Compounds; Horse Diseases; Horses; Injections, Intramuscular; Lung Abscess; Random Allocation; Rifampin; Time Factors; Treatment Outcome