Beta-Lactamase Gene Found in Animal Bite-Associated Capnocytophaga Species

For a study recently published in the European Journal of Clinical Microbiology & Infectious Diseases, authors conducted antibiotic susceptibility testing (AST) of clinical Capnocytophaga isolates and identified a class D beta-lactamase gene in animal bite-associated Capnocytophaga species.

Two species of Capnocytophaga bacteria—C. canimorsus and C. cynodegmi—are commensal bacteria that reside in the oral cavities of healthy dogs and cats. However, they can cause wound infections and serious disease when transmitted to humans via bites and scratches. C. canis, a recently discovered Capnocytophaga species, is also part of the normal oral flora in dogs and has unknown pathogenicity. C. stomatis, also recently discovered, has been found in wound infections from dog bites.

Antibiotics commonly used to treat dog and cat bites, such as penicillin and amoxicillin+clavulanic acid, are effective against bacteria—such as Pasturella and Staphylococcus—typically found in cat and dog bites; these antibiotics may also be effective against C. canimorsus and C. cynodegmi. However, little data is available on antibiotic susceptibility patterns for these two Capnocytophaga species. Interestingly, several species of human Capnocytophaga produce beta-lactamase, which confers resistance to beta-lactam antibiotics like penicillin.

Authors analyzed 24 Capnocytophaga isolates of four Capnocytophaga species (C. canimorsus, C. cynodegmi, C. stomatis, C. canis), obtained from blood and wound cultures after dog and cat bites. Sixteen strains underwent AST, for which the minimal inhibitory concentration was determined against several antibiotics commonly used to treat dog bites; antibiotics used for AST included benzyl penicillin, amoxicillin+clavulanic acid, cefotaxime, and clindamycin. All strains underwent bioinformatic analyses, including identification of antibiotic resistance genes and phylogenetics.

All nine C. canimorsus strains, which were obtained from blood cultures, were susceptible to penicillin, imipenem, and two cephalosporins (cefotaxime, ceftazidime). Similarly, C. canis demonstrated susceptibility to penicillin, imipenem, and cefotaxime. In contrast, several wound strains of C. cynodegmi and C. stomatis demonstrated resistance to penicillin, imipenem, and cephalosporins, suggesting beta-lactamase activity. Notably, the C. cynodegmi and C. stomatis wound strains were also resistant to amoxicillin+clavulanic acid.

Genomic analysis revealed the presence of blaOXA-347, a class D beta-lactamase gene, in four wound strains of C. cynodegmi and C. stomatis. Two of these strains also contained the tet(X) gene, which confers resistance to tetracyclines. Notably, three of the four wound strains with the blaOXA-347 gene demonstrated resistance to imipenem, suggesting blaOXA-347 could also be classified as a carbapenemase. In total, genomic analysis results aligned with AST results for these four strains.

Authors constructed a phylogenetic tree to identify relationships between members of the class D beta-lactamase gene family. Capnocytophaga sequences were clustered uniformly, indicating 100% sequence identity, and were related to other clinically relevant class D beta-lactamases, such as blaOXA-48.

Authors considered it important that C. canimorsus was susceptible to penicillin, which is the first-line antibiotic treatment for infections due to dog and cat bites. Other than penicillin, study results suggest that cephalosporins, tetracyclines, and clindamycin could be used to treat invasive C. canimorsus infections. However, antibiotic wound treatment may be more complex, given the beta-lactamase activity demonstrated by several Capnocytophaga wound strains in this study. For veterinary clinical practice, authors advised veterinarians to conduct full ASTs for animal bite-associated wound cases.

The number of isolates used in this study was small, limiting the amount of epidemiological information that can be obtained from the results. In addition, the identification of several antibiotic resistance genes in the Capnocytophaga species indicates the need for more detailed bioinformatic analysis of this bacteria’s resistome.

Given the study results, authors suggested the commensal bacteria in the oral cavities of healthy dogs and cats could be sources of antibiotic resistance. Further research will be needed to determine the clinical relevance of this antibiotic resistance and learn more about the epidemiology and clinical outcomes of Capnocytophaga infections.

Dr. JoAnna Pendergrass received her doctorate in veterinary medicine from the Virginia-Maryland College of Veterinary Medicine. Following veterinary school, she completed a postdoctoral fellowship at Emory University’s Yerkes National Primate Research Center. Dr. Pendergrass is the founder and owner of JPen Communications, LLC.