Renal failure due to Capnocytophaga canimorsus generalized Shwartzman reaction from a dog bite (DF-2 nephropathy) Valerie Tan, MD, and John C. Schwartz, MD
We report a case of a 54-year-old man who developed gram-negative sepsis with multiorgan failure and generalized Shwartzman reaction after sustaining a dog bite. The causative organism was the fastidious gramnegative rod Capnocytophaga canimorsus, which is a commensal organism found in the oral flora of dogs and cats. More than 30 years after it was first described and despite technological advances in identification techniques, proper identification of this organism remains a challenge. In light of the increase in pet ownership as well as the increase in the different immunocompromised populations of the 21st century, we decided to revisit the case and reignite awareness of physicians caring for patients with recent dog or cat bites presenting with fulminant sepsis.
apnocytophaga canimorsus is a fastidious microaerophilic, non–spore-forming gram-negative rod that is 1 to 3 μm long, is oxidase and catalase positive, and is capable of gliding motility under the microscope. The first strain was received by the Centers for Disease Control and Prevention (CDC) in 1961 and was assigned the name CDC Group DF-2 (dysgonic fermenter-2). It first came to be recognized as a pathogen in 1976 when Bobo and Newton reported a case of an unidentified gram-negative rod isolated in the blood and cerebrospinal fluid of their patient with septicemia and meningitis who sustained a dog bite. It was not until 1989 when Brenner et al studied 150 strains of the organism sent to the CDC that the formal name of Capnocytophaga canimorsus was proposed (1).
C
CASE REPORT A 54-year-old white man with previously good health was admitted with septic shock. A dog had bitten his left thumb 3 days earlier. The wound was cleaned and nothing unusual happened over the next 2 days. Fever, chills, and myalgias then appeared. He was admitted through the emergency room with dyspnea and changes in skin color. His temperature was 103.4°F; blood pressure, 70/45 mm Hg; respiratory rate, 30 breaths/min; and heart rate, 120 beats/ min. He had diffuse dermal purpura with ecchymoses as well as distal gangrene of the fingers, toes, ear tips, and nose. The puncture site on the left thumb had some surrounding necrosis. He was emergently intubated and received vigorous fluids Proc (Bayl Univ Med Cent) 2014;27(2):139–140
Table 1. Admitting laboratory results Day 1 White blood cells (K/uL) Neutrophils (%)
41
Bands (%)
43
Metamyelocytes (%)
3
Platelet count (K/uL)
115
Prothrombin time (seconds)
50
Partial thromboplastin time (seconds)
Day 2
3.9
15
>200
Blood urea nitrogen (mg/dL)
20
38
Creatinine (mg/dL)
1.5
4.3
Lactate dehydrogenase (IU/L)
14,000
and dopamine. He was started on ceftriaxone and tobramycin. Penicillin was later added. Admission laboratory data (Table 1) revealed leukopenia with a left shift, worsening thrombocytopenia, prolonged coagulation times, worsening renal function tests, and a marked elevation in lactate dehydrogenase level. Bacillary organisms were seen on peripheral blood smear. He rapidly developed multiorgan failure, including disseminated sepsis with shock, respiratory failure with acute respiratory distress syndrome, disseminated intravascular coagulation, and oligoanuric acute renal failure. He received anti–lipid A monoclonal antibody (Centoxin). Ampicillin-sulbactam was added to his regimen. His hemodynamics stabilized, but he developed worsening intradermal hemorrhage with diffuse distal blistering, with toes and fingertips becoming necrotic. Initial blood cultures and repeat blood cultures were negative at day 4, even though persistent bacteria were seen on his peripheral blood smear. Blood cultures at day 8 revealed a slow-growing gram-negative rod. The specimen was sent to the State Laboratory of Hygiene for definitive identification. Blood From the Division of Nephrology, Department of Internal Medicine, Baylor University Medical Center at Dallas. Corresponding author: Valerie Tan, MD, 3600 Gaston Avenue, Barnett Tower, Suite 904, Dallas, TX 75246 (e-mail: [email protected]). 139
Table 2. Renal function tests over time Day 4 Day 14 Day 44 Day 55 Day 79 Blood urea nitrogen (mg/dL)
96
129
50
52
28
Creatinine (mg/dL)
8.0
10.5
5.4
5.3
2.1
cultures, approximately a month following admission, were confirmed as Capnocytophaga canimorsus (DF-2). Hemodialysis was initiated on day 4. The patient remained virtually anuric. Residual renal function by creatinine clearance was zero. He underwent dialysis 4 times per week. He was extremely catabolic, with a urea nitrogen generation rate of 20 g per day. He was treated with oral and parenteral nutrition to achieve a protein intake of 120 g per day (1.8 g/kg per day). He was extubated on day 6. His blood pressure was stable off dopamine at that time. Antibiotics were continued for 2 weeks. A mercaptoacetyltriglycine (MAG3) scan on day 20 revealed clear evidence of radionuclide uptake without renal excretion, suggesting reversible renal disease. Hemodialysis was decreased to 3 times per week. He underwent amputation of all 10 toes on day 24, with split-thickness skin grafting to both arms and legs at the same time. He underwent repeat skin grafting 1 week later. Residual renal function measured by creatinine clearance was 2 mL/min on day 31. At that time, his urine output was rising. He underwent his last hemodialysis treatment on day 40 after 21 treatments. Residual renal function measured by creatinine clearance on day 44 was 7 mL/min. The patient was subsequently discharged on day 48. He experienced continued improvement in his renal function in the outpatient setting over the next month (Table 2). Dialysis was never again needed. DISCUSSION Capnocytophaga canimorsus (formerly CDC Group DF-2) has been rarely but regularly isolated from dog or cat bite infections since its discovery in 1976. It is a commensal organism of the canine oral flora and can be isolated from mouths of healthy dogs and cats (2, 3). Zoonotic infectious manifestations range from local cellulitis to fulminant gram-negative sepsis with multiorgan failure, disseminated intravascular coagulation, and peripheral gangrene. The portal of entry is usually the skin after having been bitten by a dog or cat, but there have also been reports of infection from ordinary exposure, licks, and scratches (3–7). The organism spreads hematogenously to the meninges, endocardium, and synovium, causing infection in those sites. The reported mortality rate is 30% to 36%, and implicated risk factors are a history of splenectomy, alcohol abuse, lung disease, and an immunocompromised state. Infection, however, is not limited to that population, with as many as 40% of cases having no obvious risk factor (2, 4, 5). Association of a generalized Shwartzman reaction after a dog bite was first reported in 1970, when Capnocytophaga canimorsus was still unrecognized as a significant pathogen in dog bites. The generalized Shwartzman reaction has been well described in fulminant gram-negative septicemia in pregnancy and meningococcemia. It is characterized by thrombohemorrhagic skin necrosis and 140
disseminated intravascular coagulation from endotoxins causing deposition of fibrin thrombi in small vessels (mainly renal glomerular capillaries and adrenals), which is considered the hallmark of the disease. The deposition of fibrin thrombi usually results in varying degrees of necrosis and hemorrhage, which accounts for the renal failure from bilateral renal cortical necrosis and peripheral gangrene associated with the generalized Shwartzman reaction (8, 9). Subsequent case reports of Capnocytophaga canimorsus infections, including our case, made it clear, however, that infection with the organism can be associated with renal failure apart from or as part of the full spectrum of the generalized Shwartzman reaction (4–6, 10, 11). For this reason, we would like to coin the term DF-2 nephropathy to describe reversible or nonreversible oligoanuric renal failure in Capnocytophaga canimorsus (DF-2) sepsis with or without association with a generalized Shwartzman reaction. Capnocytophaga canimorsus is susceptible to penicillins, imipenem, erythromycin, vancomycin, clindamycin, third-generation cephalosporins, chloramphenicol, rifampicin, doxycycline, and fluoroquinolones. It is resistant to aztreonam and aminoglycosides and has variable resistance to trimethoprim-sulfamethoxazole. As such, penicillin had long been the initial empiric drug of choice. A recent report of a beta-lactamase–resistant strain has made a thirdgeneration cephalosporin or combination beta-lactam antibiotic/ beta-lactamase inhibitor better empiric coverage. The organism can be identified by conventional microbiologic identification, polymerase chain reaction, or DNA sequencing (1, 7, 12, 13). 1.
2.
3. 4.
5.
6. 7. 8.
9. 10.
11. 12.
13.
Brenner DJ, Hollis DG, Fanning GR, Weaver RE. 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(2):231–235. Mally M, Shin H, Paroz C, Landmann R, Cornelis GR. Capnocytophaga canimorsus: a human pathogen feeding at the surface of epithelial cells and phagocytes. PLoS Pathog 2008;4(9):e1000164. Carpenter PD, Heppner BT, Gnann JW Jr. DF-2 bacteremia following cat bites. Report of two cases. Am J Med 1987;82(3 Spec No):621–623. Butler T, Weaver RE, Ramani TK, Uyeda CT, Bobo RA, Ryu JS, Kohler RB. Unidentified gram-negative rod infection. A new disease of man. Ann Intern Med 1977;86(1):1–5. Kalb R, Kaplan MH, Tenenbaum MJ, Joachim GR, Samuels S. Cutaneous infection at dog bite wounds associated with fulminant DF-2 septicemia. Am J Med 1985;78(4):687–690. Zeier MG. A lick may be as bad as a bite: irreversible acute renal failure. Nephrol Dial Transplant 2000;15(11):1883–1884. Low SC, Greenwood JE. Capnocytophaga canimorsus: infection, septicaemia, recovery and reconstruction. J Med Microbiol 2008;57(Pt 7):901–903. Meyers BR, Hirschman SZ, Sloan W. Generalized Shwartzman reaction in man after a dog bite. Consumption coagulopathy, symmetrical peripheral gangrene, and renal cortical necrosis. Ann Intern Med 1970;73(3):433–438. Hjort P, Rapaport S. The Shwartzman reaction: pathogenetic mechanisms and clinical manifestations. Annu Rev Med 1965;16:135–168. Findling JW, Pohlmann GP, Rose HD. Fulminant gram-negative bacillemia (DF-2) following a dog bite in an asplenic woman. Am J Med 1980;68(1):154–156. Hinrichs JH, Dunkelberg WE. DF-2 septicemia after splenectomy: epidemiology and immunologic response. South Med J 1980;73(12):1638–1640. Velculescu V, Velji AM. Capnocytophaga canimorsus (DF-2) infection: a continuing challenge for clinicians and microbiologists. Microb Ecol Health Dis 1998;10(3–4):155–157. Janda JM, Graves MH, Lindquist D, Probert WS. Diagnosing Capnocytophaga canimorsus infections. Emerg Infect Dis 2006;12(2):340–342.
Baylor University Medical Center Proceedings
Volume 27, Number 2
We report a case of a 54-year-old man who developed gram-negative sepsis with multiorgan failure and generalized Shwartzman reaction after sustaining a dog bite. The causative organism was the fastidious gramnegative rod Capnocytophaga canimorsus, which is a commensal organism found in the oral flora of dogs and cats. More than 30 years after it was first described and despite technological advances in identification techniques, proper identification of this organism remains a challenge. In light of the increase in pet ownership as well as the increase in the different immunocompromised populations of the 21st century, we decided to revisit the case and reignite awareness of physicians caring for patients with recent dog or cat bites presenting with fulminant sepsis.
apnocytophaga canimorsus is a fastidious microaerophilic, non–spore-forming gram-negative rod that is 1 to 3 μm long, is oxidase and catalase positive, and is capable of gliding motility under the microscope. The first strain was received by the Centers for Disease Control and Prevention (CDC) in 1961 and was assigned the name CDC Group DF-2 (dysgonic fermenter-2). It first came to be recognized as a pathogen in 1976 when Bobo and Newton reported a case of an unidentified gram-negative rod isolated in the blood and cerebrospinal fluid of their patient with septicemia and meningitis who sustained a dog bite. It was not until 1989 when Brenner et al studied 150 strains of the organism sent to the CDC that the formal name of Capnocytophaga canimorsus was proposed (1).
C
CASE REPORT A 54-year-old white man with previously good health was admitted with septic shock. A dog had bitten his left thumb 3 days earlier. The wound was cleaned and nothing unusual happened over the next 2 days. Fever, chills, and myalgias then appeared. He was admitted through the emergency room with dyspnea and changes in skin color. His temperature was 103.4°F; blood pressure, 70/45 mm Hg; respiratory rate, 30 breaths/min; and heart rate, 120 beats/ min. He had diffuse dermal purpura with ecchymoses as well as distal gangrene of the fingers, toes, ear tips, and nose. The puncture site on the left thumb had some surrounding necrosis. He was emergently intubated and received vigorous fluids Proc (Bayl Univ Med Cent) 2014;27(2):139–140
Table 1. Admitting laboratory results Day 1 White blood cells (K/uL) Neutrophils (%)
41
Bands (%)
43
Metamyelocytes (%)
3
Platelet count (K/uL)
115
Prothrombin time (seconds)
50
Partial thromboplastin time (seconds)
Day 2
3.9
15
>200
Blood urea nitrogen (mg/dL)
20
38
Creatinine (mg/dL)
1.5
4.3
Lactate dehydrogenase (IU/L)
14,000
and dopamine. He was started on ceftriaxone and tobramycin. Penicillin was later added. Admission laboratory data (Table 1) revealed leukopenia with a left shift, worsening thrombocytopenia, prolonged coagulation times, worsening renal function tests, and a marked elevation in lactate dehydrogenase level. Bacillary organisms were seen on peripheral blood smear. He rapidly developed multiorgan failure, including disseminated sepsis with shock, respiratory failure with acute respiratory distress syndrome, disseminated intravascular coagulation, and oligoanuric acute renal failure. He received anti–lipid A monoclonal antibody (Centoxin). Ampicillin-sulbactam was added to his regimen. His hemodynamics stabilized, but he developed worsening intradermal hemorrhage with diffuse distal blistering, with toes and fingertips becoming necrotic. Initial blood cultures and repeat blood cultures were negative at day 4, even though persistent bacteria were seen on his peripheral blood smear. Blood cultures at day 8 revealed a slow-growing gram-negative rod. The specimen was sent to the State Laboratory of Hygiene for definitive identification. Blood From the Division of Nephrology, Department of Internal Medicine, Baylor University Medical Center at Dallas. Corresponding author: Valerie Tan, MD, 3600 Gaston Avenue, Barnett Tower, Suite 904, Dallas, TX 75246 (e-mail: [email protected]). 139
Table 2. Renal function tests over time Day 4 Day 14 Day 44 Day 55 Day 79 Blood urea nitrogen (mg/dL)
96
129
50
52
28
Creatinine (mg/dL)
8.0
10.5
5.4
5.3
2.1
cultures, approximately a month following admission, were confirmed as Capnocytophaga canimorsus (DF-2). Hemodialysis was initiated on day 4. The patient remained virtually anuric. Residual renal function by creatinine clearance was zero. He underwent dialysis 4 times per week. He was extremely catabolic, with a urea nitrogen generation rate of 20 g per day. He was treated with oral and parenteral nutrition to achieve a protein intake of 120 g per day (1.8 g/kg per day). He was extubated on day 6. His blood pressure was stable off dopamine at that time. Antibiotics were continued for 2 weeks. A mercaptoacetyltriglycine (MAG3) scan on day 20 revealed clear evidence of radionuclide uptake without renal excretion, suggesting reversible renal disease. Hemodialysis was decreased to 3 times per week. He underwent amputation of all 10 toes on day 24, with split-thickness skin grafting to both arms and legs at the same time. He underwent repeat skin grafting 1 week later. Residual renal function measured by creatinine clearance was 2 mL/min on day 31. At that time, his urine output was rising. He underwent his last hemodialysis treatment on day 40 after 21 treatments. Residual renal function measured by creatinine clearance on day 44 was 7 mL/min. The patient was subsequently discharged on day 48. He experienced continued improvement in his renal function in the outpatient setting over the next month (Table 2). Dialysis was never again needed. DISCUSSION Capnocytophaga canimorsus (formerly CDC Group DF-2) has been rarely but regularly isolated from dog or cat bite infections since its discovery in 1976. It is a commensal organism of the canine oral flora and can be isolated from mouths of healthy dogs and cats (2, 3). Zoonotic infectious manifestations range from local cellulitis to fulminant gram-negative sepsis with multiorgan failure, disseminated intravascular coagulation, and peripheral gangrene. The portal of entry is usually the skin after having been bitten by a dog or cat, but there have also been reports of infection from ordinary exposure, licks, and scratches (3–7). The organism spreads hematogenously to the meninges, endocardium, and synovium, causing infection in those sites. The reported mortality rate is 30% to 36%, and implicated risk factors are a history of splenectomy, alcohol abuse, lung disease, and an immunocompromised state. Infection, however, is not limited to that population, with as many as 40% of cases having no obvious risk factor (2, 4, 5). Association of a generalized Shwartzman reaction after a dog bite was first reported in 1970, when Capnocytophaga canimorsus was still unrecognized as a significant pathogen in dog bites. The generalized Shwartzman reaction has been well described in fulminant gram-negative septicemia in pregnancy and meningococcemia. It is characterized by thrombohemorrhagic skin necrosis and 140
disseminated intravascular coagulation from endotoxins causing deposition of fibrin thrombi in small vessels (mainly renal glomerular capillaries and adrenals), which is considered the hallmark of the disease. The deposition of fibrin thrombi usually results in varying degrees of necrosis and hemorrhage, which accounts for the renal failure from bilateral renal cortical necrosis and peripheral gangrene associated with the generalized Shwartzman reaction (8, 9). Subsequent case reports of Capnocytophaga canimorsus infections, including our case, made it clear, however, that infection with the organism can be associated with renal failure apart from or as part of the full spectrum of the generalized Shwartzman reaction (4–6, 10, 11). For this reason, we would like to coin the term DF-2 nephropathy to describe reversible or nonreversible oligoanuric renal failure in Capnocytophaga canimorsus (DF-2) sepsis with or without association with a generalized Shwartzman reaction. Capnocytophaga canimorsus is susceptible to penicillins, imipenem, erythromycin, vancomycin, clindamycin, third-generation cephalosporins, chloramphenicol, rifampicin, doxycycline, and fluoroquinolones. It is resistant to aztreonam and aminoglycosides and has variable resistance to trimethoprim-sulfamethoxazole. As such, penicillin had long been the initial empiric drug of choice. A recent report of a beta-lactamase–resistant strain has made a thirdgeneration cephalosporin or combination beta-lactam antibiotic/ beta-lactamase inhibitor better empiric coverage. The organism can be identified by conventional microbiologic identification, polymerase chain reaction, or DNA sequencing (1, 7, 12, 13). 1.
2.
3. 4.
5.
6. 7. 8.
9. 10.
11. 12.
13.
Brenner DJ, Hollis DG, Fanning GR, Weaver RE. 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(2):231–235. Mally M, Shin H, Paroz C, Landmann R, Cornelis GR. Capnocytophaga canimorsus: a human pathogen feeding at the surface of epithelial cells and phagocytes. PLoS Pathog 2008;4(9):e1000164. Carpenter PD, Heppner BT, Gnann JW Jr. DF-2 bacteremia following cat bites. Report of two cases. Am J Med 1987;82(3 Spec No):621–623. Butler T, Weaver RE, Ramani TK, Uyeda CT, Bobo RA, Ryu JS, Kohler RB. Unidentified gram-negative rod infection. A new disease of man. Ann Intern Med 1977;86(1):1–5. Kalb R, Kaplan MH, Tenenbaum MJ, Joachim GR, Samuels S. Cutaneous infection at dog bite wounds associated with fulminant DF-2 septicemia. Am J Med 1985;78(4):687–690. Zeier MG. A lick may be as bad as a bite: irreversible acute renal failure. Nephrol Dial Transplant 2000;15(11):1883–1884. Low SC, Greenwood JE. Capnocytophaga canimorsus: infection, septicaemia, recovery and reconstruction. J Med Microbiol 2008;57(Pt 7):901–903. Meyers BR, Hirschman SZ, Sloan W. Generalized Shwartzman reaction in man after a dog bite. Consumption coagulopathy, symmetrical peripheral gangrene, and renal cortical necrosis. Ann Intern Med 1970;73(3):433–438. Hjort P, Rapaport S. The Shwartzman reaction: pathogenetic mechanisms and clinical manifestations. Annu Rev Med 1965;16:135–168. Findling JW, Pohlmann GP, Rose HD. Fulminant gram-negative bacillemia (DF-2) following a dog bite in an asplenic woman. Am J Med 1980;68(1):154–156. Hinrichs JH, Dunkelberg WE. DF-2 septicemia after splenectomy: epidemiology and immunologic response. South Med J 1980;73(12):1638–1640. Velculescu V, Velji AM. Capnocytophaga canimorsus (DF-2) infection: a continuing challenge for clinicians and microbiologists. Microb Ecol Health Dis 1998;10(3–4):155–157. Janda JM, Graves MH, Lindquist D, Probert WS. Diagnosing Capnocytophaga canimorsus infections. Emerg Infect Dis 2006;12(2):340–342.
Baylor University Medical Center Proceedings
Volume 27, Number 2
