Carprofen Potentiates Activity of Doxycycline Against Methicillin-Resistant Staphylococcus pseudintermedius In Vitro

Carprofen enhances the in vitro antimicrobial effect of doxycycline against methicillin-resistant Staphylococcus pseudintermedius (MRSP), according to a study recently published in BMC Veterinary Research.

MRSP poses a health risk to both humans and animals. Certain strains of MRSP are resistant to all of the main antibiotic classes used in veterinary patients. Some drugs used to treat noninfectious conditions also have in vitro antimicrobial activity, so using combinations of non-antimicrobial and antimicrobial drugs could potentially overcome bacterial resistance, write the authors.

The study included 6 antibacterial drugs (ampicillin, oxacillin, ciprofloxacin, clindamycin, doxycycline, and trimethoprim/sulfamethoxazole) and 36 non-antibacterial drugs chosen for their availability and frequency of use in veterinary practice. Investigators performed double disk infusion tests on agar plates inoculated with MRSP to identify non-antibacterial drugs that extended the antibacterial drugs’ inhibition zones. This initial screening revealed 7 non-antibacterial drugs (acepromazine, amitriptyline, bromhexine, clomipramine, carprofen, fluoxetine, and ketoconazole) that showed activity against MRSP and also appeared to potentiate the activity of at least 1 antibiotic.

Minimum inhibitory concentration test results showed that of the 7 non-antibacterial drugs, ketoconazole had the highest anti-MRSP activity and bromhexine had the lowest. Checkerboard assays were used to investigate the synergy of these 7 drugs with the antibiotic that they appeared to potentiate to the greatest degree. The combination of carprofen and doxycycline was the only one to show synergy.

The carprofen/doxycycline combination had a synergistic effect against strains of MRSP carrying the tetracycline resistance gene tetK but not against other strains. Synergy was achieved with concentrations of carprofen and doxycycline that were compatible with the recommended oral doses of these drugs in dogs.

The authors point out that the drug combination will not necessarily work the same way in vivo as it does in vitro. They suggest further in vitro tests to investigate serum protein binding, which could alter the in vivo effectiveness of the drug combination. A carprofen/doxycycline combination could be useful in the treatment of upper respiratory infections, they write, and topical formulations could also potentially be used to treat skin and soft-tissue infections.

The study was funded by the University of Copenhagen Research Center for Control of Antibiotic Resistance and by a grant from Zoetis.

Dr. Laurie Anne Walden received her doctorate in veterinary medicine from North Carolina State University. After an internship in small animal medicine and surgery at Auburn University, she returned to North Carolina, where she has been in small animal primary care practice for over 20 years. Dr. Walden is also a board-certified editor in the life sciences and owner of Walden Medical Writing, LLC.