68-year-old Man Bitten on the Thumb by Dog

Presented by:

Dr. K.N. Brown and Dr. R.S Roman

Clinical Case:

A 68 year-old man attended his family practitioner two days after having been bitten on the thumb by his dog. He felt extremely debilitated and was suffering from intermittent chills. On examination, he had a fever and appeared to be very ill. Only a small, apparently almost completely healed lesion was present on his thumb.

The phyisician ordered blood cultures over the next three days. Three of the four bottles inoculated yielded microorganisms, which on gram-stain showed small slender gram-negative, slightly curved rods with pointed ends. The fourth bottle, which was anaerobic, failed to grow any organisms.

On subcultures to blood agar, small non-haemolytic colonies were evident in 24 hours. The organism was very slow growing but produced colonies 2-3 mm. in diameter after 3 days. The colonies were relatively flat with slightly irregular edges displaying spreading growth. Growth was augmented by incubation in carbon-dioxide, but was also seen anaerobically. Growth did not occur on MacConkey agar. The organism was oxidase and catalase positive. It failed to produce any biochemical change when submitted to API testing.

Testing showed the organism to be beta-lactamase begative, but because of its slow growth, disc-diffusion susceptibility testing took three days to perform despite using a heavy inoculum on the test plates. Whilst, in the strict sense, uncontrolled, these susceptibility tests suggested that the organism was resistant to gentamicin and trimethoprim/sulphamethoxazole, but was sensitive to the penicillins, cephalosporins, ciprofloxacin, erythromycin and clindamycin.

The organism was referred to a reference laboratory which confirmed the impressions formed in our own facility.

The patient was treated with oral ampicillin. He was clinically imporved two days later and appeared to be completely recovered a week later.

Questions:

• What genus of organisms is likely implicated in this man's bacteremia?
• What specific member of this genus is most likely involved?
• Apart from a dog bite, what other animal could result in a bacteremia from this genus of organisms?
• Would cloxacillin be a useful drug to use in an infection with this organism?
• What particular group of patients are at increased risk of mortality when infected with this organism?

Discussion:

This case is an illustration of bacteremia due to Capnocytophaga canimorsus originating from a dog bite. Capnocytophaga spp. includes C. gingivalis, C. granulosa, C. haemolytica, C. ochracea and C. sputigena, which are members of the human oral flora. Other Capnocytophaga species include C. canimorsus and C. cynodegmi, which colonize the oral cavities of cats and dogs. C. canimorsus was previously called CDC group dysgonic fermenter-2 or CDC group DF-2.

Capnocytophaga spp. are thin, spindle-shaped, gram negative rods 1-3 mm in length and therefore morphologically resemble Fusobacterium spp. Curved filaments and coccoid forms can also be seen. Movement of the organism under the microscope has been described as 'gliding motility', although most do not have flagella. The organisms grow best at 35-37ºC. Some isolates will grow better anaerobically on primary isolation, but they are best described as capnophilic (grows better in CO2 enriched atmosphere). They are slowing growing, with very small colonies on blood agar after 1 day of incubation and reaching 2-3 mm in size only after 2 to 4 days. Colonial morphology is quite pleomorphic ranging from small discrete colonies to larger flat colonies with irregular finger-like projections spreading from the edges representing 'gliding motility'. The organisms do not grow on MacConkey agar. Colonies are non-hemolytic and often have a yellowish-orange pigment.

Clues to the identification of Capnocytophaga spp. include the characteristic gram stain, colonial morphology and growth requirements. They may be identified with some commercially available anaerobic identification systems. Capnocytophaga species that colonize animals (C. canimorsus and C. cynodegmi) are oxidase positive and catalase positive, while the species colonizing the oral cavities of humans (C. gingivalis, C. granulosa, C. haemolytica, C. ochracea and C. sputigena) are oxidase negative and catalase negative. It can be difficult to differentiate C. canimorsus and C. cynodegmi with routine phenotypic testing.

C. canimorsus and C. cynodegmi can cause infectious complications in humans after animal bites. C. cynodegmi causes localized wound infections, while C. canimorsus can cause severe infections with septicemia. Predisposing factors for severe infection include splenectomy, alcoholism, steroid medication and other immunocompromising factors. Eighty percent of patients with fulminant C. canimorsus infections have an underlying predisposing medical condition. Fulminant illness can include bacteremia, endocarditis, meningitis, shock, renal failure and peripheral gangrene. Fulminant C. canimorsus infection has a 25% mortality rate. Seventy-five percent of cases involve exposure to a dog, through either ownership or a bite. C. canimorsus is carried in the oropharynx of 25% of dogs and 15% of cats.

There are no NCCLS guidelines to interpret disk diffusion susceptibility test results. The organism does not grow well in broth media precluding the use of broth dilution techniques. Antibiotics expected to be active against Capnocytophaga spp. include clindamycin, quinolones, and the expanded spectrum cephalosporins. Activity of the first generation cephalosporins, aminoglycosides and metronidazole is variable. They are generally resistant to cloxacillin. Most strains are still susceptible to penicillin, although recently the prevalence of beta-lactamase producing isolates is increasing. Because penicillin is often used as the empiric therapy of choice in possible infections due to Capnocytophaga spp., testing for beta-lactamase production should be performed in the laboratory. Testing for beta-lactamase production has been shown to be predictive of penicillin resistance, but it does not correlate with resistance to other beta-lactam antibiotics.

References:

• Brenner DJ, Hollis DG, Fanning GR, et al. 1989. Capnocytophaga canimorsus sp. nov. (formerly CDC group DF-2), a cause of septicemia following dog bite, and C. cynodegmi sp. nov., a cause of localized wound infection following dog bite. J Clin Microbiol 27: 231-235.
• Mossad SB, Lichtin AE, Hall GS, Gordon SM. 1997. Diagnosis: Capnocytophaga canimorsus septicemia. Clin Infect Dis Feb; 24 (2): 123-267.
• Pers C, Gahrn-Hansen B, Frederiksen W. 1996. Capnocytophaga canimorsus septicemia in Denmark, 1982-1995:review of 39 cases. Clin Infect Dis 23(1): 71-75.
• Blanche P, Bloch E, Sicard D. 1998. Capnocytophaga canimorsus in the oral flora of dogs and cats. J Infect 36(1): 134.
• Ngaage DL, Kotidis KN, Sandoe JA, Unnikrishnan Nair R. 1999. Do not snog the dog: infective endocarditis due to Capnocytophaga canimorsus. Eur J Cardiothorac Surg. 16(3): 362-3.
• Jolivet-Gougeon A, Buffet A, Dupuy C, Sixou JL, et al. 2000. In vitro susceptibilities of Capnocytophagia isolates to beta-lactam antibiotics and beta-lactamase inhibitors. 44(11): 3186-8.
• Bilgrami S, Berstrom SK, Peterson DE, et al. 1992. Capnocytophaga bacteremia in a patient with Hodgkin's disease following bone marrow transplantation: case report and review. Clin Infect Dis. 14(5): 1045-1049.