Efficacy in US cattle of a novel fixed-dose combination injectable (0.2 mg/kg doramectin + 6.0 mg/kg levamisole hydrochloride) against naturally acquired gastrointestinal nematode infections.

Reports of macrocyclic lactone (ML) loss of efficacy suggest ML resistance in gastrointestinal nematodes (GINs) is a growing problem in the US cattle industry. Empirical and modeling data support combining an ML and second anthelmintic from a different drug class to help ML resistance development while effectively treating existing resistant parasite populations. Here, we present a novel fixed-dose combination injectable (FDCI) solution for cattle that delivers 0.2 mg of doramectin and 6.0 mg of levamisole hydrochloride (HCl) per kg of body weight. Field studies were conducted at six sites across the Midwest United States to investigate the efficacy of a single administration of the FDCI in treating common cattle GINs. Cattle (n = 425) with GIN infections confirmed by fecal egg count (FEC) on Day -10( ± 2) were randomly allocated to the control (saline) or treatment (FDCI) group. On Day 0, pre-treatment fecal samples were collected, and cattle were administered a single subcutaneous injection of saline (n = 106) or FDCI (n = 319). Post-treatment fecal samples were collected on Day 14. Fecal egg count reduction tests (FECRTs) were conducted using Day 0 and Day 14 FECs. Efficacy was evaluated using Day 14 FECs (FDCI-treated versus saline-treated). Within treatment, samples collected on Days 0 and 14 with ≥ 20 eggs per gram (EPG) were cultured for nematode larvae recovery and identification. Day -10 FECs for enrolled animals were similar between treatment groups. Coprocultures from cattle with FEC ≥ 20 EPG (n = 68 saline; n = 211, FDCI) on Day 0 showed the presence of Cooperia punctata, Ostertagia spp., Haemonchus spp., C. oncophora, Oesophagostomum spp. and Trichostrongylus spp. Day 14 FECs for FDCI-treated cattle were significantly reduced (0-3 EPG) compared to saline-treated cattle (0-1252 EPG) (p ≤ 0.0042). At all study sites, the efficacy of the new FDCI was ≥ 99.4% and the FECR was 0.99 or 1.00. Day 14 coprocultures from control cattle showed infections of common GIN genera, confirming the efficacy of the FDCI against GINs in the field. A single administration of the doramectin + levamisole HCl combination injectable effectively treats common and economically important cattle GINs.

Dose confirmation of a novel fixed dose combination injectable (0.2 mg/kg doramectin + 6.0 mg/kg levamisole hydrochloride) against naturally acquired gastrointestinal nematodes in US cattle.

Macrocyclic lactone (ML) resistance in cattle gastrointestinal nematodes (GINs) is an increasing problem. Concurrent combination anthelmintic therapy incorporating an existing ML with a second drug class has been proposed to control cattle GINs while slowing the development of ML resistance. Two dose confirmation studies were conducted to investigate the efficacy of a new fixed-dose combination injectable (FDCI) anthelmintic against common cattle GINs known to negatively impact production. The FDCI is formulated with 5 mg/ml doramectin and 150 mg/ml levamisole hydrochloride (HCl). Cattle enrolled in the two studies were sourced from either the Southern (Study 1, n = 30) or Midwest (Study 2, n = 36) United States. Animals with GIN infections confirmed by fecal egg count (FEC) were randomly allocated to one of three treatment groups. On Day 0, cattle with positive FECs on Day -5( ± 2) were weighed and administered a single subcutaneous injection of either saline (0.9% sodium chloride) at 0.04 ml/kg, 10 mg/ml doramectin at 0.02 ml/kg (to provide 0.2 mg/kg doramectin) or the FDCI at 0.04 ml/kg (to provide 0.2 mg/kg doramectin and 6.0 mg/kg levamisole HCl). On Day 14, fecal samples were collected, animals were euthanized, and worms were collected from the intestinal tract of each animal. Treatment efficacy was calculated using worm burdens and the fecal egg count reduction test (FECRT). Pre-treatment (Day -5, Study 1; Day -3, Study 2) mean FECs were 999.4-1136.2 eggs per gram (EPG) in Study 1 and 137.1-226.6 EPG in Study 2. The FDCI was active against cattle GIN populations in both studies, with FECRT ≥ 99.98% in both studies. Compared to saline-treated cattle, FDCI-treated cattle had significantly fewer adult and immature worms of all identified species on Day 14. In Study 1, Day 14 efficacy of the FDCI was 96.9% for Cooperia spp. (C. oncophora (99.7%) and C. punctata (95.9%)), 99.1% for Nematodirus helvetianus, and 99.8% for Ostertagia spp. In Study 2, the FDCI provided 100% efficacy against all adult GIN species identified, including all GINs identified in Study 1 and Trichostrongylus axei. The FDCI also provided 95.5% efficacy against immature Ostertagia spp. and 100% efficacy against immature Cooperia spp. (Study 2). Doramectin was effective against all adult cattle GINs (except N. helvetianus) in Study 2 but was only effective against adult Ostertagia spp. in Study 1. Additionally, doramectin was only effective against immature Cooperia spp. (and not immature Ostertagia spp.) in Study 2. A single administration of the doramectin + levamisole HCl FDCI provides a new and effective approach to the treatment and control of common cattle GINs, including those exhibiting decreased susceptibility to doramectin alone.

Synovex ONE Grower improves growth performance for at least 200 days in growing beef steers and heifers fed in confinement for slaughter.

Growth-promoting implants are broadly used in the feedlot industry to improve growth performance and to increase production efficiencies. With cattle being fed longer and to heavier weights, there is demand for extended-release implants that payout for at least 200 d. Our objective was to evaluate feedlot growth of Synovex ONE Grower, a moderate potency (150 mg trenbolone acetate [TBA] and 21 mg estradiol benzoate [EB]), extended-release, growth-promoting implant for 200 d. At four locations (Texas, Idaho, California, and Nebraska), 200 steers (n = 800; d 0 body weight [BW] = 320.2 ± 9.5 kg) and 200 heifers (n = 800; d 0 BW = 311.5 ± 9.5 kg) were blocked by BW and randomized to 1 of 2 treatments: 1) Control, empty subcutaneous needle inserted and extracted from the middle third of one ear; 2) ONE Grower, 150 mg TBA and 21 mg EB extended-release implant administered in middle third of one ear. Treatments were commingled within pen of the same sex (n = 4/site; 2/sex/site) in a split plot design replicated across four sites. Cattle were fed finishing ration ad libitum common to each geographical region at least once daily and were observed for any abnormal health events twice daily. Treatments were administered on d 0. Mid-study implant site evaluations were performed on d 35 or 41. Initial BW was recorded on d 0 and final BW was recorded on d 200 to 204. Cattle were harvested from d 201 to 231; however, carcass data were not collected due to slaughter facility complications brought on by the COVID-19 pandemic. Data were analyzed using the PROC MIXED and PROC GLIMMIX procedures of SAS (Version 9.4, SAS Institute, Cary, NC; P < 0.05), and animal was the experimental unit. There were no treatment × sex interactions (P ≥ 0.052) for any variable. Final BW on d 200 was greater (P < 0.01) for steers and heifers implanted with ONE Grower compared to Control; ONE Grower improved final BW by 5.7% for steers and 3.9% for heifers. Overall average daily gain (ADG) from d 0 to 200 was greater (P < 0.01) for ONE Grower steers and heifers compared to Control with an increase in ADG of 13.1% for steers and 8.9% for heifers. For cattle implanted with ONE Grower, implant retention rates at d 35 or 41 were 95.7% and 96.3% for steers and heifers, respectively. There was no difference (P ≥ 0.32) in percentage deads, removals, or bullers (steers) between treatments. Synovex ONE Grower improved final BW and ADG in feedlot steers and heifers fed for at least 200 d.