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A 28-year-old woman employed as a dog groomer in a veterinary practice was bitten on the forearm by a clinically normal 2-year-old male Cocker Spaniel. The puncture wounds were cleansed with povidone-iodine solution and a dressing was applied. Three days later, the woman left work complaining of chills, malaise, weakness, and increasing pain at the bite site. During the next 12 hours, she became progressively depressed and was taken to an emergency room in a state of collapse after 2 grand mal seizures.

The woman's oral temperature was 38.4 C, her blood pressure was 85/50 mm of Hg, her heart rate was 62 beats/min, and her respiration rate was 17 breaths/min. Necrotizing cellulitis was evident at the bite site. Petechial and ecchymotic hemorrhages were noticed on the face, extremities, and trunk. A scar was observed in the area of the upper abdomen. Upon questioning, the woman's husband informed the physician that his wife had undergone splenectomy 2 years earlier for refractory idiopathic thrombocytopenic purpura.

A CBC revealed leukocytosis. Serum biochemical abnormalities were indicative of acute renal failure. Disseminated intravascular coagulation was diagnosed. Higher than normal numbers of neutrophils were observed in a specimen of CSF. Many neutrophils containing long intracytoplasmic bacilli were observed in Wright-stained blood smears. Examination of gram-stained buffy coat smears revealed these bacilli to be beaded gram-negative rods. Intravenous penicillin treatment was started after samples of blood and CSF were obtained for bacterial culture. Five days later, all specimens contained a slow-growing gram-negative rod that was eventually identified as dysgonic fermenter-2 (DF-2). After completion of antimicrobial therapy and treatment for acute oliguric renal failure and disseminated intravascular coagulation, the woman was discharged from the hospital and recovered without further complication.

While visiting his employee in the hospital, the veterinarian directed the following questions to her attending physician.^a

Q: What kind of bacterium is DF-2?

A: Dysgonic fermenter-2 is a fastidious, gram-negative, opportunistic pathogen that can cause multiorgan disease in human beings.¹ The first case of DF-2 infection was reported in 1976, when the organism was isolated from the blood and CSF of a patient who had been bitten by 2 dogs.² Dysgonic fermenter-2 is an organism of low virulence, usually causing serious illness only in people with impaired defense mechanisms against infection.³ The organism has a tropism for the endocardium and vascular endothelium,⁴ and can maintain a continuous bacteremia.³

The alphanumeric name of the organism, assigned by the Centers for Disease Control, results from its unusual growth characteristics and biochemical profile.⁵ Dysgonic fermenter-2 is a filamentous, non-spore-forming facultative aerobe.¹ The organism fails to grow on MacConkey agar and most other solid media. Growth is slow on chocolate agar,⁵ but rapid on heart infusion agar with 5% rabbit blood. On this medium, the colonies are punctate and have a purplish cast.⁶ Growth of DF-2 is enhanced by an atmosphere enriched by 5 to 10% carbon dioxide at 35 to 37 C,⁶ and by the addition of a streak of Staphylococcus aureus.^7,8 The organism is positive for oxidase and catalase, and negative for indole, nitrate reduction, and urease.⁹ Dysgonic fermenter-2 weakly produces acids from mannitol, sucrose, and xylose.¹⁰

Q: What is the source of DF-2 and how is it transmitted?

A: In one study,¹ DF-2 was isolated from the oronasal fluids of 8% of clinically normal dogs. The organism has been recovered from the oral cavity of dogs^12,13 and cats⁸ that bit persons who later developed DF-2 infection. Most human patients with DF-2 infection report a history of a recent dog bite.(14) Many of the remaining patients mention a history of animal exposure.

Q: Are any groups of people at risk for DF-2 infection?

A: Life-threatening infections with DF-2 are more likely to develop in people who have undergone splenectomy, who suffer from alcoholism, or who have chronic pulmonary disease.¹⁴ Advanced hepatic disease, which may accompany alcoholism, may cause impaired neutrophil function and an increased susceptibility to bacteremia.¹⁵

Infection with DF-2 was diagnosed in a patient with chronic lymphocytic leukemia who was receiving a moderately high dose of prednisone.¹⁶ The DF-2 organism was associated with corneal perforation in a patient who was not from a high-risk group, but was receiving corticosteroid ophthalmic drops after ocular surgery for a dog scratch wound.¹⁰

Life-threatening DF-2 infection developed in an immunologically intact infant after a severe bite wound, suggesting that infants may be at risk if the organism is inoculated into a large area of traumatized soft tissue.⁶

Q: Why does splenectomy predispose human beings to DF-2 infection?

A: It is estimated that splenectomized people are 30 to 200 times more likely to suffer fatal bacterial infections than the general population, the risk being highest in the first 2 years after surgery.¹⁷ The risks for postsplenectomy sepsis never disappear completely, and serious infections may develop many years after surgery.¹⁸ People who undergo splenectomy because of underlying medical disorders such as thalassemia or lymphoreticular malignancies are more likely to developserious infections than people whose spleens were removed as a result of trauma.¹⁷

Organisms that are most likely to cause postsplenectomy sepsis include Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, group A Streptococcus spp, Staphylococcus spp, Escherichia coli, Pseudomonas spp, and Babesia spp.¹⁷

The spleen plays an important role in clearing particulate antigens, especially encapsulated microorganisms, from blood of the nonimmune host.^4,17 Splenectomized people have impaired production of IgM and IgG-2, and delayed macrophage mobilization. In addition, defective clearance of bacteria results from decreased production of tuftsin, a molecule that is released from IgG and stimulates phagocytosis.¹⁹

Q: What are the typical symptoms of DF-2 infection?

A: The severity of clinical symptoms in DF-2 infections varies from signs of fulminant postsplenectomy sepsis, as seen in the dog groomer, to a milder disease in patients with intact spleens,¹⁵ in which fever and cellulitis are the most common signs. Localizing signs in severely affected patients include endocarditis, purulent meningitis, and septic arthritis.³ Symmetric peripheral gangrene may develop,⁴ and a necrotizing eschar may form at the bite site.⁵

Q: Does DF-2 infection resemble any other diseases?

A: Dysgonic fermenter-2 infection must be differentiated from diseases causing fulminant postsplenectomy sepsis, diseases causing petechial and ecchymotic hemorrhages, such as Rocky Mountain spotted fever,²⁰ and bacteremias caused by other fastidious gram-negative bacteria, including H aphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Campylobacterfetus, and Brucella spp.³

Q: How do physicians confirm a diagnosis of DF-2 infection?

A: A diagnosis of DF-2 infection is supported when severe sepsis develops after a dog or cat bite in a person with defective defense mechanisms against infection, when stained smears of blood or buffy coat reveal gram-negative bacilli within neutrophils (bacteria are more likely to be seen in asplenic patients with DF-2 infection in whom high-grade bacteremia is common),¹⁵ and when bacterial culture of body fluids yields growth of DF-2.¹⁵

Q: Why is DF-2 infection rarely diagnosed?

A: Dysgonic fermenter-2 is an organism of low virulence for people with intact defense mechanisms because it is lysed by normal human serum.¹⁵ In most instances, dog and cat bites cause DF-2 infection only in people in high-risk groups.

The slow growth of DF-2 in blood culture and its fastidious growth on solid media may result in it being missed, or identification of the organism being delayed.⁵

After wound cleansing and debridement, many emergency room physicians empirically prescribe penicillin to prevent wound infection with Pasteurella multocida or Eikenella corrodens.¹ Because most strains of DF-2 are susceptible to penicillin, many early undetected infections may be cured before severe sepsis develops.

Q: What is the treatment for DF-2 infection?

A: On the basis of in vitro antimicrobial susceptibility testing and clinical response to treatment, penicillin G is the antibiotic of choice for DF-2 infection.¹⁴ However, the first case of penicillin resistance recently was reported.²⁰ The author of that report recommended that when DF-2 infection is suspected, treatment should be started with penicillin and a third-generation cephalosporin pending the results of bacterial culture and antimicrobial susceptibility tests.

Q: How can DF-2 infections be prevented?

A: People in high-risk groups, especially asplenic individuals, should be aware of the dangers of being bitten by dogs and cats and should seek prompt medical attention if bitten. Asplenic people should consider wearing a bracelet to inform health care personnel of their condition in case of emergency.¹⁷

One author²¹ has recommended that "given the frequency with which DF-2 is found in the oral microflora of dogs and cats, asplenic individuals should be advised not to keep dogs and cats as pets." Although this advice may be controversial, it would be prudent for asplenic individuals to minimize the chances for dog or cat bites at work or at home.

Footnote

(a) The following questions and answers posed to a physician are offered to JAVMA readers for their own information, but are not intended as a source of information from which a veterinarian would offer advice on human medical matters.

References

1. Archer SL. Dysgonic fermenter-2 infection resulting in chronic glomerulonephntis. Can Med Assoc J 1985; 132:657-660.

2. Bobo RA, Newton EJ. A previously undescribed gram-negative bacillus causing septicemia and meningitis. Am J Clin Pathol 1976; 65:564-569.

3. Butler T, Weaver RE, Ramani TKV, et al. Unidentified gram-negative rod infection. A new disease of man. Ann Intern Med 1977; 86:1-5.

4. Case records of the Massachusetts General Hospital. Case 29--1986. N Engl J Med 1986; 315:241-249.

5. Kalb R, Kaplan MH, Tenenbaum MJ. Cutaneous infection at dog bite wounds associated with fulminant DF-2 sepocemia. Am J Med 1985; 78:687-690.

6. Dankner WM, Davis CE, Thompson MA. DF-2 bacteremia following a dog bite in a 4-month-old child. Pediatr Infect Dis J 1987; 7:695-696.

7. Tison DL, Latimer JM. Lysis-centrifugation-direct plating technique for isolation of group DF-2 from the blood of a dog bite victim. J Infect Dis 1986; 153:1001-1002.

8. Carpenter PD, Heppner BT, Gnann JW. DF-2 bacteremia following cat bites. Report of 2 cases. Am J Med 1987; 82:621-623.

9. Butler T, Johnston KH, Gutierrez Y, et al. Enhancement of experimental bacteremia and endocarditis caused by dysgonic fermenter (DF-2) bacterium after treatment with methylprednisolone and after splenectomy. Infect Immun 1985; 47:294-300.

10. Kiel RJ, Crane LR, Aguilar J, et al. Corneal perforation caused by dysgonic fermenter-2. JAMA 1987; 257:3269-3270.

11. Bailie WE, Stowe EC, Schmitt AM. Aerobic bacterial flora of oral and nasal fluids of canines with reference to bacteria associated with bites. J Clin Microbiol 1978; 7:223-231.

12. Chan PCY, Fonseca K. Septicaemia and meningitis caused by dysgonic fermenter-2 (DF-2). J Clin Pathol 1986; 39:1021-1024.

13. Martone WJ, Zuehl RW, Minson GE, et al. Postsplenectomy sepsis with DF-2: report of a case with isolation of the organism from the patients dog. Ann Intern Med 1980; 93:457-458.

14. Fibbe W, Ligthart G, van den Broek P, et al. Septicemia with a dysgonic fermenter-2 (DF-2) bacterium in a compromised host. Infection 1985; 13:286-287.

15. Hicklin H, Verghese A, Alvarez S. Dysgonic fermenter-2 septicemia. Rev Infect Dis 1987; 9:884-890.

16. Worthington M, Gleason T, Pandian NG, et al. Tricuspid valve myxoma infected with dysgonic fermenter-2. South Med J 1984; 77:241-242.

17. Case records of the Massachusetts General Hospital. Case 20--1983. N Engl J Med 1983; 308:1212-1218.

18. Evans D. Postsplenectomy sepsis 10 years or more after operation. J Clin Pathol 1985; 38:309-311.

19. Likhite VV. Immunological impairment and susceptibility to infection after splenectomy. JAMA 1976; 236:1376-1377.

20. Perez RE. Dysgonic fermenter-2 infections. West J Med 1988; 148:90-92.

21. Kerr KG. Dysgonic fermenter organisms and post-splenectomy risks (letter). Lancet 1987; 2:1473.

Addendum

To determine the carriage rate of dysgonic fermenter-2 (DF-2) and the DF-2-like organism in domestic species, swabs were used to collect specimens from the incisor teeth and gingival margins of 180 dogs, 249 cats, 12 sheep, and 15 cattle.¹ Dysgonic fermenter-2-like organism is closely related to DF-2, causes localized infections following bite wounds, and is incapable of causing septicemia. Dysgonic fermenter-2 and DF-2-like organism were isolated from 24% and 11% of the dogs, respectively, and from 17% and 8% of the cats, respectively. Dysgonic fermenter-2 was isolated from 25% and 33% of the sheep and cattle, respectively. In the same study, DF-2 could not be isolated from human oral flora.

Recently, it has been proposed that DF-2 and DF-2-like organism be renamed Capnocytophaga canimorsus sp nov. and C cynodegmi sp nov., respectively, because of several characteristics that they share with Capnocytophaga spp.² Capnocytophaga spp are part of the normal oral flora of human beings and may cause certain types of periodontal disease. The organism has been associated with infections in immunocompromised and immunocompetent human beings.³

References

1. Westwell AJ, Kerr K, Spencer MB, et al. DF-2 infection. Br Med J 1989; 298:116-117.

2. Brenner DJ, Hollis DG, Fanning GR, et al. 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 1989; 27:231-235.

3. Bremmelgaard A, Pers C, Kristiansen JE, et al. Susceptibility testing of Danish isolates of Capnocytophaga and CDC group DF-2 bacteria. APMIS 1989; 97:43-48.