Serial analysis of blood biomarker concentrations in dogs with pneumonia, septic peritonitis, and pyometra

Abstract

Background Prolonged antimicrobial drug (AMD) treatment is associated with antimicrobial resistance development. Biomarker measurement may aid treatment decision‐making. Objectives Investigate temporal changes in blood biomarker concentrations in dogs undergoing treatment for pulmonary and intra‐abdominal infections; compare time to biomarker concentration normalization with duration of clinician‐directed AMD treatment. Animals Forty‐two client‐owned dogs with pneumonia (n = 22), septic peritonitis (n = 10), or pyometra (n = 10). Methods Plasma concentrations of C‐reactive protein (CRP), serum amyloid A (SAA), haptoglobin, procalcitonin, nucleosomes, cell‐free DNA (cfDNA), high‐mobility group box‐1 (HMGB1), CC‐motif chemokine ligand‐2 (CCL2), CXC‐motif chemokine ligand‐8 (CXCL8), and keratinocyte chemoattractant‐like (KC‐Like) were quantitated in samples collected on days 1, 3, 7, 14, 28, and 60. Treatment was directed by clinicians blinded to biomarker concentrations. Results Concentrations of CCL2, CRP, and KC‐Like were maximal on D1, concentrations of SAA, cfDNA, HMGB1, and nucleosomes were maximal on D3 and haptoglobin concentrations were maximal on D7. These maximal concentrations were significantly different from those on D60. Concentrations of CRP and SAA decreased by 80% from peak and into respective reference intervals before AMDs were discontinued. For CRP, the median (interquartile range [IQR]) times to 20% peak and normal were 7 (6‐9) and 7 (6‐12) days, respectively, and for SAA they were 4 (4, 5) and 6 (5‐8) days, respectively, compared to a median (IQR) duration of AMD prescribing of 16 (12‐23) days (all P < .0001). Conclusions and Clinical Importance Biomarker concentrations normalized within 7 to 14 days. Serial measurements of CRP and SAA might aid identification of disease resolution and could help guide AMD prescription decision‐making.

Change over time and agreement between clinical markers of disease resolution in dogs with aspiration‐induced lung injury

“…Compared to the previous reports evaluating markers of disease recovery in dogs with pneumonia or aspiration pneumonia, this cohort of dogs is an older population, with many of the dogs having a more complicated clinical course due to their concurrent systemic or focal neuropathy. [21][22][23][24][25][26]28,38 The studies to date have primarily focused on cohorts of younger dogs, with reported median ages ranging from 5 to 5.5 years, and of the combined total of 46 dogs studied, only three dogs were described to have concurrent GLOPP (n = 1) or megaoesophagus (2). 21,22,24 This study population therefore represents a subpopulation of dogs at risk for A-ILI that is not well represented in the recent studies investigating acute-phase protein monitoring in dogs with aspiration pneumonia.…”

“…Alternatively, as in people and recently investigated in dogs, after initiating treatment, the change in CRP concentrations over time rather than CRP normalisation may be more important, especially in patient populations with confounding clinical factors that could influence systemic inflammatory markers. 14,25 In people with acute respiratory infections, acute-phase protein-guided clinical algorithms have been used in many studies, targeting defined cut-off points or using the percent change in acute-phase protein concentrations. 14 For example, studies have reported using a greater than or equal to 80% reduction in acute-phase protein concentrations as a treatment endpoint.…”

“…For example, reported high C-reactive protein (CRP) concentrations in dogs with bacterial pneumonia have led to others investigating CRP normalisation as a marker to guide antibiotic treatment durations. [21][22][23][24][25][26][27] In addition, TXR as a marker of disease resolution in dogs with pneumonia has been challenged, with a recent study suggesting thoracic ultrasound as an alternative imaging tool. 22,24,26 Much of this recent work has focused on dogs with pneumonia of varying aetiologies, with only a few studies focused explicitly on dogs with aspiration pneumonia.…”

Association of the origin of contamination and species of microorganisms with short‐term survival in dogs with septic peritonitis

“…39 Another study investigated other biomarkers including C-reactive protein and serum amyloid A in dogs with systemic infection including septic peritonitis and their concentrations decreased with treatment. 40 Other studies investigated biomarkers in peritoneal fluid including lactate, glucose and cytokines for diagnostic purpose. [41][42][43] It is, however, uncertain whether these biomarkers correlate with the severity of peritonitis.…”

“…However, multiple pathophysiologies of hyperlactatemia are possible in septic peritonitis, and it is unlikely that hyperlactatemia alone can correlate with the severity of peritonitis 39 . Another study investigated other biomarkers including C‐reactive protein and serum amyloid A in dogs with systemic infection including septic peritonitis and their concentrations decreased with treatment 40 . Other studies investigated biomarkers in peritoneal fluid including lactate, glucose and cytokines for diagnostic purpose 41–43 .…”