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Impact of Timing and Dosage of a Fluoroquinolone Treatment on the Microbiological, Pathological, and Clinical Outcomes of Calves Challenged with Mannheimia haemolytica.

ABSTRACT: The efficacy of an early and low inoculum-adjusted marbofloxacin treatment was evaluated on microbiological and clinical outcomes in calves infected with 4.10(7) 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.

SUBMITTER: Lhermie G

PROVIDER: S-EPMC4773444 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Impact of Timing and Dosage of a Fluoroquinolone Treatment on the Microbiological, Pathological, and Clinical Outcomes of Calves Challenged with Mannheimia haemolytica.

Lhermie Guillaume G Ferran Aude A AA Assié Sébastien S Cassard Hervé H El Garch Farid F Schneider Marc M Woerhlé Frédérique F Pacalin Diane D Delverdier Maxence M Bousquet-Mélou Alain A Meyer Gilles G

Frontiers in microbiology 20160302

The efficacy of an early and low inoculum-adjusted marbofloxacin treatment was evaluated on microbiological and clinical outcomes in calves infected with 4.10(7) 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 inclus ...[more]

PMID: 26973615

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Project description:Six Lactobacillus strains originating from the nasopharyngeal microbiota of cattle were previously characterized in vitro and identified as candidate bacterial therapeutics (BTs) for mitigating the bovine respiratory pathogen Mannheimia haemolytica In the present study, these BT strains were evaluated for their potential to (i) reduce nasal colonization by M. haemolytica, (ii) modulate the nasal microbiota, and (iii) stimulate an immune response in calves experimentally challenged with M. haemolytica. Twenty-four Holstein bull calves (1 to 3 weeks old) received either an intranasal BT cocktail containing 6 Lactobacillus strains (3?×?109 CFU per strain; BT + Mh group) 24?h prior to intranasal M. haemolytica challenge (3?×?108 CFU) or no BTs prior to challenge (Mh, control group). Nasal swab, blood, and transtracheal aspiration samples were collected over the course of 16?days after BT inoculation. Counts of M. haemolytica were determined by culturing, and the nasal and tracheal microbiotas were evaluated using 16S rRNA gene sequencing. Serum cytokines (interleukin-6 [IL-6], IL-8, and IL-10) were quantified by enzyme-linked immunosorbent assay (ELISA). Administration of BT reduced nasal colonization by M. haemolytica (P?=?0.02), modified the composition and diversity of the nasal microbiota, and altered interbacterial relationships among the 10 most relatively abundant genera. The BT + Mh calves also had a lower relative abundance of Mannheimia in the trachea (P?<?0.01) but similar cytokine levels as Mh calves. This study demonstrated that intranasal BTs developed from the bovine nasopharyngeal Lactobacillus spp. were effective in reducing nasal colonization by M. haemolytica in dairy calves.IMPORTANCE Bovine respiratory disease (BRD) is one of the significant challenges for the modern dairy industry in North America, accounting for 23 to 47% of the total mortality among pre- and postweaned dairy heifers. Mass medication with antibiotics is a common practice to control BRD in dairy cattle. However, the emergence of multidrug-resistant BRD pathogens highlights the importance of developing alternatives to antibiotics for BRD mitigation. Using a targeted approach, we recently identified 6 Lactobacillus strains originating from the bovine respiratory microbiota as candidates to be used as bacterial therapeutics (BTs) for the mitigation of the BRD pathogen Mannheimia haemolytica Here, we demonstrated that intranasal inoculation of the BT strains reduced nasal colonization by M. haemolytica in dairy calves experimentally challenged with this pathogen. This study, for the first time, shows the potential use of intranasal BTs as an alternative to mitigate BRD pathogens in cattle.

Dataset Information

Impact of Timing and Dosage of a Fluoroquinolone Treatment on the Microbiological, Pathological, and Clinical Outcomes of Calves Challenged with Mannheimia haemolytica.

Publications

Impact of Timing and Dosage of a Fluoroquinolone Treatment on the Microbiological, Pathological, and Clinical Outcomes of Calves Challenged with Mannheimia haemolytica.

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