Putative biomarkers for evaluating antibiotic treatment: an experimental model of porcine Actinobacillus pleuropneumoniae infection.
Biomarkers of infection were screened for their possible role as evaluators of antibiotic treatment in an aerosol infection model of porcine pneumonia caused by Actinobacillus pleuropneumoniae (Ap). Following infection of 12 pigs, clinical signs of pneumonia developed within 20 h, whereafter the animals received a single dose of either danofloxacin (2.5mg/kg) or tiamulin (10 mg/kg). To test the discriminative properties of the biomarkers, the dosage regimens were designed with an expected difference in therapeutic efficacy in favour of danofloxacin. Accordingly, the danofloxacin-treated pigs recovered clinically within 24h after treatment, whereas tiamulin-treated animals remained clinically ill until the end of the study, 48 h after treatment. A similar picture was seen for the biomarkers of infection. During the infection period, plasma C-reactive protein (CRP), interleukin-6 and haptoglobin increased, whereas plasma zinc, ascorbic acid and alpha-tocopherol decreased. In the danofloxacin-treated animals, CRP, interleukin-6, zinc, ascorbic acid and alpha-tocopherol reverted significantly towards normalisation within 24h of treatment. In contrast, signs of normalisation were absent (CRP, zinc and ascorbic acid) or less marked (interleukin-6 and alpha-tocopherol) in the tiamulin-treated animals. Plasma haptoglobin remained elevated throughout the study in both groups. This indicates that CRP, zinc, ascorbic acid and to a lesser extent interleukin-6 and alpha-tocopherol might be used to evaluate antibiotic treatment of acute Ap-infection in pigs. The present model provides a valuable tool in the evaluation of antibiotic treatments, offering the advantage of clinical and pathological examinations combined with the use of biochemical infection markers.
Department of Pharmacology and Pathobiology, The Royal Veterinary and Agricultural University, Copenhagen, Denmark. bla@kvl.dk
B
B
Lauritzen
J
J
Lykkesfeldt
M T
MT
Skaanild
Ø
Ø
Angen
J P
JP
Nielsen
C
C
Friis
D000189:Actinobacillus Infections / Q000097:blood / Q000188:drug therapy / Q000382:microbiology / Q000662:veterinary*; D016977:Actinobacillus pleuropneumoniae; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D024841:Fluoroquinolones; D006242:Haptoglobins / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D007958:Leukocyte Count / Q000662:veterinary; D008168:Lung / Q000473:pathology; D018942:Macrolides; D008297:Male; D011001:Pleuropneumonia / Q000097:blood / Q000188:drug therapy / Q000382:microbiology / Q000662:veterinary*; D011897:Random Allocation; D013552:Swine; D013553:Swine Diseases / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology*; D015032:Zinc / Q000097:blood; D024502:alpha-Tocopherol / Q000097:blood
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D015415:Biomarkers; D004224:Diterpenes; D024841:Fluoroquinolones; D006242:Haptoglobins; D015850:Interleukin-6; D018942:Macrolides; C068581:danofloxacin; D002097:C-Reactive Protein; C014224:tiamulin; D024502:alpha-Tocopherol; D015032:Zinc; D001205:Ascorbic Acid