Abstract
The efficacy of an early and low inoculum-adjusted marbofloxacin treatment was evaluated on microbiological and clinical outcomes in calves infected with 4.107 CFU of Mannheimia haemolytica A1. Twenty-two calves were included based on their rectal temperature rise in the 10 h after challenge and allocated in four groups, receiving a single intramuscular injection of saline (CON), 2 mg/kg marbofloxacin 2–4 h after inclusion (early treatment, E2), 2 or 10 mg/kg marbofloxacin 35–39 h after inclusion (late treatments, L2, L10). In CON calves, M. haemolytica DNA loads in bronchoalveolar lavages continuously increased from inclusion to day 4, and were associated with persistent respiratory clinical signs and lung lesions. At times of early and late treatments, M. haemolytica loads ranged within 3.5–4 and 5.5–6 log10 DNA copies/mL, respectively. Early 2 mg/kg marbofloxacin treatment led to rapid and total elimination of bacteria in all calves. The late treatments induced a reduction of bacterial loads, but 3 of 6 L2 and 1 of 6 L10 calves were still positive for M. haemolytica at day 4. Except for CON calves, all animals exhibited clinical improvement within 24 h after treatment. However, early 2 mg/kg treatment was more efficacious to prevent pulmonary lesions, as indicated by the reduction of the extension and severity of gross lesions and by the histopathological scores. These results demonstrated for the first time that a reduced antibiotic regimen given at an early stage of the disease and targeting a low bacterial load could be efficacious in a natural bovine model of pneumonia.
Highlights
Bovine respiratory disease (BRD) is a major economic concern in young beef cattle production, with a huge economic impact on the farming industry due to production losses and disease treatment and prevention (United State Department of Agriculture, 2013)
The mean DNA loads of M. haemolytica in bronchoalveolar lavages (BAL) over time as well as the mean accumulated bacterial shedding (ABS) scores are presented in Figure 2 for three calves of each group (Supplementary Material)
The bacterial load decreased in both groups, and this decrease appeared to be higher in the L10 group treated with 10 mg/kg marbofloxacin
Summary
A second therapeutic approach consists in treating only the affected animals, regardless of the severity of their clinical signs (O’Connor et al, 2013; Heins et al, 2014) This approach limits exposure to antibiotics and decreases the risk of developing resistant strains. It is usually seen as the “late approach” because the clinical signs and possibly extensive pulmonary damage have had time to develop prior to treatment, as demonstrated for Pasteurellaceae (Ackermann and Brogden, 2000; Dagleish et al, 2010). Considering the uncertainty regarding the causal agent and time of disease onset, labeled doses are determined by pharmacokinetics (PK) and pharmacodynamics (PD) and dose determination experiments These doses generally target a cluster of pathogens and consider the highest minimal inhibiting concentration (MIC) reported (Toutain et al, 2002; Valle et al, 2012). These conditions lead to routine use of a “high” antibiotic dose
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