Synovial fluid pH, cytologic characteristics, and gentamicin concentration after intra-articular administration of the drug in an experimental model of infectious arthritis in horses

K. C. Kent Lloyd From the Veterinary Medical Teaching Hospital (Lloyd) and the Departments of Anatomy (Stover), Surgery (Pascoe), and Pharmacology and Toxicology (Adams), School of Veterinary Medicine, University of California, Davis, CA 95616.

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Susan M. Stover From the Veterinary Medical Teaching Hospital (Lloyd) and the Departments of Anatomy (Stover), Surgery (Pascoe), and Pharmacology and Toxicology (Adams), School of Veterinary Medicine, University of California, Davis, CA 95616.

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John R. Pascoe From the Veterinary Medical Teaching Hospital (Lloyd) and the Departments of Anatomy (Stover), Surgery (Pascoe), and Pharmacology and Toxicology (Adams), School of Veterinary Medicine, University of California, Davis, CA 95616.

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Paul Adams From the Veterinary Medical Teaching Hospital (Lloyd) and the Departments of Anatomy (Stover), Surgery (Pascoe), and Pharmacology and Toxicology (Adams), School of Veterinary Medicine, University of California, Davis, CA 95616.

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SUMMARY

Chemical and cytologic effects and bactericidal activity of gentamicin in septic synovial fluid were evaluated in an experimental model of infectious arthritis in horses. Septic arthritis was induced by inoculation of approximately 7.5 × 106 colony-forming units of Escherichia coli into 1 antebrachiocarpal joint in each of 16 clinically normal adult horses. Clinical signs of septic arthritis were evident 24 hours after inoculation. Horses were allotted to 3 groups: group-1 horses (n = 5) each were given 150 mg of gentamicin (50 mg/ml; 3 ml) intra-articularly (ia); group-2 horses (n = 5) each were given 2.2 mg of gentamicin/kg of body weight, iv, every 6 hours; and group-3 horses (n = 6) each were given buffered gentamicin, consisting of 3 mEq of sodium bicarbonate (1 mEq/ml; 3 ml) and 150 mg of gentamicin (50 mg/ml; 3 ml), ia. Synovial fluid specimens were obtained at posttreatment hour (pth) 0, 0.25, 1, 4, 8, 12, and 24 via an indwelling intra-articular catheter. Synovial fluid pH was evaluated at pth 0, 0.25, and 24. Microbiologic culture and cytologic examination were performed on synovial fluid specimens obtained at pth 0 and 24, and gentamicin concentration was measured in all synovial fluid specimens.

At pth 0, E coli was isolated from synovial fluid specimens obtained from all horses. Synovial fluid pH was lower (range, 7.08 to 7.16) and wbc count was higher (range, 88,000 to 227,200 cells/μl) and predominantly neutrophilic (95 to 99%) at pth 0 than before inoculation. Synovial fluid pH was lowered further (mean, pH 6.63) after ia administration of gentamicin in group-1 horses; mean pH remained unchanged (7.07) after buffered-gentamicin administration in group-3 horses. At pth 0.25, mean peak synovial fluid gentamicin concentration in horses of groups 1 and 3 (4,745 and 6,190 μg/ml, respectively) was 1,000 times greater than that in group-2 horses (5.1 μg/ml) at the same time. Synovial fluid gentamicin concentration in group-1 and group-3 horses was always greater than that in group-2 horses and remained greater than a minimal inhibitory concentration of gentamicin (2 μg/ml) against many common equine bacterial pathogens for at least 24 hours after injection. Further, the calculated apparent half-life and clearance of gentamicin in synovial fluid calculated after ia administration were similar in horses of groups 1 and 3. By pth 24, E coli could not be isolated from synovial fluid specimens obtained from group-1 horses. However, moderate to heavy growth of E coli was isolated from synovial fluid specimens obtained at pth 24 from horses in groups 2 and 3 (80 and 66%, respectively).

In selected cases, ia administration of unbuffered gentamicin may be a useful supplement to drainage, lavage, and systemic antibacterial and anti-inflammatory treatment in horses with naturally acquired infectious arthritis.

SUMMARY

Chemical and cytologic effects and bactericidal activity of gentamicin in septic synovial fluid were evaluated in an experimental model of infectious arthritis in horses. Septic arthritis was induced by inoculation of approximately 7.5 × 106 colony-forming units of Escherichia coli into 1 antebrachiocarpal joint in each of 16 clinically normal adult horses. Clinical signs of septic arthritis were evident 24 hours after inoculation. Horses were allotted to 3 groups: group-1 horses (n = 5) each were given 150 mg of gentamicin (50 mg/ml; 3 ml) intra-articularly (ia); group-2 horses (n = 5) each were given 2.2 mg of gentamicin/kg of body weight, iv, every 6 hours; and group-3 horses (n = 6) each were given buffered gentamicin, consisting of 3 mEq of sodium bicarbonate (1 mEq/ml; 3 ml) and 150 mg of gentamicin (50 mg/ml; 3 ml), ia. Synovial fluid specimens were obtained at posttreatment hour (pth) 0, 0.25, 1, 4, 8, 12, and 24 via an indwelling intra-articular catheter. Synovial fluid pH was evaluated at pth 0, 0.25, and 24. Microbiologic culture and cytologic examination were performed on synovial fluid specimens obtained at pth 0 and 24, and gentamicin concentration was measured in all synovial fluid specimens.

At pth 0, E coli was isolated from synovial fluid specimens obtained from all horses. Synovial fluid pH was lower (range, 7.08 to 7.16) and wbc count was higher (range, 88,000 to 227,200 cells/μl) and predominantly neutrophilic (95 to 99%) at pth 0 than before inoculation. Synovial fluid pH was lowered further (mean, pH 6.63) after ia administration of gentamicin in group-1 horses; mean pH remained unchanged (7.07) after buffered-gentamicin administration in group-3 horses. At pth 0.25, mean peak synovial fluid gentamicin concentration in horses of groups 1 and 3 (4,745 and 6,190 μg/ml, respectively) was 1,000 times greater than that in group-2 horses (5.1 μg/ml) at the same time. Synovial fluid gentamicin concentration in group-1 and group-3 horses was always greater than that in group-2 horses and remained greater than a minimal inhibitory concentration of gentamicin (2 μg/ml) against many common equine bacterial pathogens for at least 24 hours after injection. Further, the calculated apparent half-life and clearance of gentamicin in synovial fluid calculated after ia administration were similar in horses of groups 1 and 3. By pth 24, E coli could not be isolated from synovial fluid specimens obtained from group-1 horses. However, moderate to heavy growth of E coli was isolated from synovial fluid specimens obtained at pth 24 from horses in groups 2 and 3 (80 and 66%, respectively).

In selected cases, ia administration of unbuffered gentamicin may be a useful supplement to drainage, lavage, and systemic antibacterial and anti-inflammatory treatment in horses with naturally acquired infectious arthritis.

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