CASE-LETTER
Fusobacterium nucleatum Endocarditis Presenting as Liver and Brain Abscesses in an Immunocompetent Patient
A
48-year-old African American male with a medical history of hypertensive cardiomyopathy and hypertension presented to the emergency department with a 4-day history of diarrhea with watery stools, right upper quadrant abdominal pain, low-grade fever and chills. He denied any bloody stools and described the diarrhea as occurring 5 times a day. He denied any history of alcohol or intravenous drug use. On admission, his temperature was 97.9°F, respiratory rate 25 bpm, blood pressure 113/71 mm Hg and pulse 72 bpm. Physical examination revealed a well-nourished man who appeared to be in mild acute distress. Examination of the oral cavity showed severe periodontal disease, and on further questioning, the patient stated that he had seen his dentist recently who informed him that all of his teeth needed to be pulled because of his extensive disease. Abdominal examination demonstrated moderate tenderness in the right upper quadrant with no radiation and no palpable masses. There was no hepatosplenomegaly present and no signs of hepatic insufficiency. Lungs were clear to auscultation, and heart examination was unremarkable. The patient’s white blood cell count was 35.2 3 103 cells per microliter with an absolute neutrophil count of 3,309 cells per cubic millimeter. Renal test showed creatinine of 1.2 mg/dL and blood urea nitrogen of 29 mg/dL. Liver function tests showed aspartate aminotransferase of 74 U/L, alanine transaminase of 99 U/L, alkaline phosphatase of 204 U/L and total bilirubin of 2.0 mg/dL with a direct bilirubin of 0.7 mg/dL. C-reactive protein level was elevated at 21.52 mg/dL. Two anaerobic and aerobic blood culture bottles drawn on admission showed no growth for 6 days. Computed tomography scan of the abdomen revealed a large poorly defined complex region at the right liver lobe measuring 7.9 cm 3 6.8 cm, which likely represented a hepatic abscess, and computed tomography–guided aspiration was ordered for further investigation. The patient was then placed on intravenous ceftriaxone 2 g daily and intravenous metronidazole 500 mg every 8 hours. Two hundred milliliters of foul smelling purulent fluid was drained from the abscess, and it was sent to pathology for culture and gram stain. The culture revealed gram-negative anaerobic species that eventually came back as Fusobacterium nucleatum. As the patient recovered from the procedure, he was continued on the regimen of ceftriaxone and metronidazole. Three days after the procedure, the patient began to complain of severe throbbing headaches that were pulsatile in nature. He also complained of left upper and lower-extremity numbness and tingling with mild weakness. Magnetic resonance imaging with contrast was ordered, which revealed numerous ring-enhancing intracranial lesions scattered throughout the infra- and supratentorial compartment suspicious for abscess (Figure 1). With these findings, the decision was made to have the patient undergo a transesophageal echocardiogram to rule out endocarditis being the primary source of the multiple abscesses. Transesophageal echocardiogram revealed a mobile 0.3 cm 3 0.4 cm vegetation on the ventricular surface of the noncoronary cusp of the aortic valve and showed mild-to-moderate aortic
284
FIGURE 1. Magnetic resonance imaging with contrast revealing numerous ring-enhancing intracranial lesions scattered throughout the infra- and supratentorial compartment suspicious for abscess. White arrows signify the ring enhancing lesions.
regurgitation. With this diagnosis of aortic valve endocarditis, the ceftriaxone was discontinued and replaced with intravenous penicillin G 4 million units every 4 hours. The patient continued to improve clinically and responded well to his antibiotic regimen of penicillin G and metronidazole. His white blood count decreased to 7.8 3 103 cells per microliter, liver enzymes trended downward to normal range and neurologic symptoms resolved during his 2-week hospital stay. The patient was discharged with a peripherally inserted central catheter line for an additional 8 weeks of intravenous antibiotics to complete a full 10-week course. Fusobacterium nucleatum and Fusobacterium necrophorum are gram-negative anaerobic bacilli and the most pathological species of the genera Fusobacterium but are rarely associated with endocarditis. These organisms are normal flora of mucomembraneous surfaces such as the oral cavity, respiratory tract, gastrointestinal tract and genitourinary tract.1 However, the typical presentation for Fusobacterium spp. septicemia includes pharyngitis, high fever and submandibular lymphadenopathy. Cases of oropharyngeal abscesses, septic jugular venous thrombophlebitis (Lemierre’s syndrome), intraabdominal infections, septic arthritis and, as in this case, infective endocarditis have been reported in the literature.2 A recent study showed that 2% to 16% of all endocarditis cases are caused by anaerobic bacteria. Of these cases, 77% of Fusobacterium spp. seeded from the head or neck.3 In our patient, severe periodontal disease was present, but there was no history of intravenous drug abuse and no signs or symptoms of acute pharyngitis. It is possible that the patient may have had some mild pharyngitis secondary to his poor oral hygiene; however, because this was not the patient’s main concern, our initial efforts included an abdominal workup. His primary complaint was the acute history of watery diarrhea. A case described by Handler et al4 of F necrophorum endocarditis presented with 1 week of watery diarrhea also had invasive disease at presentation including liver abscesses. That patient also had a concomitant acute pharyngitis and multiple splenic abscesses. Throughout the literature, Fusobacterium is known for its embolic characteristics;5 however, this is the first case to have hepatic and brain abscesses. Pre-existing valvular disease is not required for F nucleatum infective endocarditis;6 however, our patient did have underlying hypertensive cardiomyopathy. Shammas et al describe a case series that showed F nucleatum and F necrophorum infections in
The American Journal of the Medical Sciences
Volume 349, Number 3, March 2015
Case-Letter
both normal and abnormal heart valves, with involvement of aortic, mitral and/or tricuspid valves. Organ emboli are the common complication with the left heart infective endocarditis. With involvement of the right heart in cases likely due to intravenous drug abuse, pulmonary embolism has been reported as the major complication, which parallels infective endocarditis pathogens other than Fusobacterium.6 Our patient initially received ceftriaxone and metronidazole, but when the diagnosis of Fusobacterium was made, he was switched to penicillin G and metronidazole. Both penicillin G and metronidazole have been well documented to be effective treatments for Fusobacterium septicemia and endocarditis;4,6,7 however, recent literature also supports the use of alternative antimicrobials. Moore et al5 described a case that shows the importance of multiple antibiotic therapies as their patient was fatally infected by metronidazole-resistant F necrophorum infective endocarditis.
*Vishal Dahya, Jaymin Patel, Mark Wheeler, Gizatchew Ketsela,
MD MD MD MD
Department of Internal Medicine, Florida State University College of Medicine Tallahassee, Florida *E-mail: [email protected]
The authors have no financial or other conflicts of interest to disclose. REFERENCES 1. Gorbach SL, Bartlett JG. Anaerobic infections. N Engl J Med 1974; 290:1177–84. 2. Huggan PJ, Murdoch DR. Fusobacterial infections: clinical spectrum and incidence of invasive disease. J Infect 2008;57: 283–9. 3. Brook I. Infective endocarditis caused by anaerobic bacteria. Arch Cardiovasc Dis 2008;101:665–76. 4. Handler MZ, Miriovsky B, Gendelman HE, et al. Fusobacterium necrophorum causing infective endocarditis and liver and splenic abscesses. Rev Inst Med Trop Sao Paulo 2011;53:169–72. 5. Moore C, Addison D, Wilson JM, et al. First case of Fusobacterium necrophorum endocarditis to have presented after the 2nd decade of life. Tex Heart Inst J 2013;40:449–52. 6. Shammas NW, Murphy GW, Eichelberger J, et al. Infective endocarditis due to Fusobacterium nucleatum: case report and review of the literature. Clin Cardiol 1993;16:72–5. 7. Vedire S, Alpert MA, Ren J, et al. Fusobacterium necrophorum endocarditis in a previously healthy young adult. Am J Med Sci 2007;334: 125–7.
ERRATUM Deficiency of IRE1 and PERK Signal Pathways in Systemic Lupus Erythematosus: Erratum In the article that appeared on page 348 of Volume 348, Number 6, Qiyao Cheng’s affiliation was listed incorrectly. He is affiliated with the School of Pharmacy, Anhui Medical University. REFERENCE Wang J, Cheng Q, Wang X, et al. Deficiency of IRE1 and PERK signal pathways in systemic lupus erythematosus. Am J Med Sci. 2014;348(6):465–73.
Copyright © 2014 by the Southern Society for Clinical Investigation.
285
Fusobacterium nucleatum Endocarditis Presenting as Liver and Brain Abscesses in an Immunocompetent Patient
A
48-year-old African American male with a medical history of hypertensive cardiomyopathy and hypertension presented to the emergency department with a 4-day history of diarrhea with watery stools, right upper quadrant abdominal pain, low-grade fever and chills. He denied any bloody stools and described the diarrhea as occurring 5 times a day. He denied any history of alcohol or intravenous drug use. On admission, his temperature was 97.9°F, respiratory rate 25 bpm, blood pressure 113/71 mm Hg and pulse 72 bpm. Physical examination revealed a well-nourished man who appeared to be in mild acute distress. Examination of the oral cavity showed severe periodontal disease, and on further questioning, the patient stated that he had seen his dentist recently who informed him that all of his teeth needed to be pulled because of his extensive disease. Abdominal examination demonstrated moderate tenderness in the right upper quadrant with no radiation and no palpable masses. There was no hepatosplenomegaly present and no signs of hepatic insufficiency. Lungs were clear to auscultation, and heart examination was unremarkable. The patient’s white blood cell count was 35.2 3 103 cells per microliter with an absolute neutrophil count of 3,309 cells per cubic millimeter. Renal test showed creatinine of 1.2 mg/dL and blood urea nitrogen of 29 mg/dL. Liver function tests showed aspartate aminotransferase of 74 U/L, alanine transaminase of 99 U/L, alkaline phosphatase of 204 U/L and total bilirubin of 2.0 mg/dL with a direct bilirubin of 0.7 mg/dL. C-reactive protein level was elevated at 21.52 mg/dL. Two anaerobic and aerobic blood culture bottles drawn on admission showed no growth for 6 days. Computed tomography scan of the abdomen revealed a large poorly defined complex region at the right liver lobe measuring 7.9 cm 3 6.8 cm, which likely represented a hepatic abscess, and computed tomography–guided aspiration was ordered for further investigation. The patient was then placed on intravenous ceftriaxone 2 g daily and intravenous metronidazole 500 mg every 8 hours. Two hundred milliliters of foul smelling purulent fluid was drained from the abscess, and it was sent to pathology for culture and gram stain. The culture revealed gram-negative anaerobic species that eventually came back as Fusobacterium nucleatum. As the patient recovered from the procedure, he was continued on the regimen of ceftriaxone and metronidazole. Three days after the procedure, the patient began to complain of severe throbbing headaches that were pulsatile in nature. He also complained of left upper and lower-extremity numbness and tingling with mild weakness. Magnetic resonance imaging with contrast was ordered, which revealed numerous ring-enhancing intracranial lesions scattered throughout the infra- and supratentorial compartment suspicious for abscess (Figure 1). With these findings, the decision was made to have the patient undergo a transesophageal echocardiogram to rule out endocarditis being the primary source of the multiple abscesses. Transesophageal echocardiogram revealed a mobile 0.3 cm 3 0.4 cm vegetation on the ventricular surface of the noncoronary cusp of the aortic valve and showed mild-to-moderate aortic
284
FIGURE 1. Magnetic resonance imaging with contrast revealing numerous ring-enhancing intracranial lesions scattered throughout the infra- and supratentorial compartment suspicious for abscess. White arrows signify the ring enhancing lesions.
regurgitation. With this diagnosis of aortic valve endocarditis, the ceftriaxone was discontinued and replaced with intravenous penicillin G 4 million units every 4 hours. The patient continued to improve clinically and responded well to his antibiotic regimen of penicillin G and metronidazole. His white blood count decreased to 7.8 3 103 cells per microliter, liver enzymes trended downward to normal range and neurologic symptoms resolved during his 2-week hospital stay. The patient was discharged with a peripherally inserted central catheter line for an additional 8 weeks of intravenous antibiotics to complete a full 10-week course. Fusobacterium nucleatum and Fusobacterium necrophorum are gram-negative anaerobic bacilli and the most pathological species of the genera Fusobacterium but are rarely associated with endocarditis. These organisms are normal flora of mucomembraneous surfaces such as the oral cavity, respiratory tract, gastrointestinal tract and genitourinary tract.1 However, the typical presentation for Fusobacterium spp. septicemia includes pharyngitis, high fever and submandibular lymphadenopathy. Cases of oropharyngeal abscesses, septic jugular venous thrombophlebitis (Lemierre’s syndrome), intraabdominal infections, septic arthritis and, as in this case, infective endocarditis have been reported in the literature.2 A recent study showed that 2% to 16% of all endocarditis cases are caused by anaerobic bacteria. Of these cases, 77% of Fusobacterium spp. seeded from the head or neck.3 In our patient, severe periodontal disease was present, but there was no history of intravenous drug abuse and no signs or symptoms of acute pharyngitis. It is possible that the patient may have had some mild pharyngitis secondary to his poor oral hygiene; however, because this was not the patient’s main concern, our initial efforts included an abdominal workup. His primary complaint was the acute history of watery diarrhea. A case described by Handler et al4 of F necrophorum endocarditis presented with 1 week of watery diarrhea also had invasive disease at presentation including liver abscesses. That patient also had a concomitant acute pharyngitis and multiple splenic abscesses. Throughout the literature, Fusobacterium is known for its embolic characteristics;5 however, this is the first case to have hepatic and brain abscesses. Pre-existing valvular disease is not required for F nucleatum infective endocarditis;6 however, our patient did have underlying hypertensive cardiomyopathy. Shammas et al describe a case series that showed F nucleatum and F necrophorum infections in
The American Journal of the Medical Sciences
Volume 349, Number 3, March 2015
Case-Letter
both normal and abnormal heart valves, with involvement of aortic, mitral and/or tricuspid valves. Organ emboli are the common complication with the left heart infective endocarditis. With involvement of the right heart in cases likely due to intravenous drug abuse, pulmonary embolism has been reported as the major complication, which parallels infective endocarditis pathogens other than Fusobacterium.6 Our patient initially received ceftriaxone and metronidazole, but when the diagnosis of Fusobacterium was made, he was switched to penicillin G and metronidazole. Both penicillin G and metronidazole have been well documented to be effective treatments for Fusobacterium septicemia and endocarditis;4,6,7 however, recent literature also supports the use of alternative antimicrobials. Moore et al5 described a case that shows the importance of multiple antibiotic therapies as their patient was fatally infected by metronidazole-resistant F necrophorum infective endocarditis.
*Vishal Dahya, Jaymin Patel, Mark Wheeler, Gizatchew Ketsela,
MD MD MD MD
Department of Internal Medicine, Florida State University College of Medicine Tallahassee, Florida *E-mail: [email protected]
The authors have no financial or other conflicts of interest to disclose. REFERENCES 1. Gorbach SL, Bartlett JG. Anaerobic infections. N Engl J Med 1974; 290:1177–84. 2. Huggan PJ, Murdoch DR. Fusobacterial infections: clinical spectrum and incidence of invasive disease. J Infect 2008;57: 283–9. 3. Brook I. Infective endocarditis caused by anaerobic bacteria. Arch Cardiovasc Dis 2008;101:665–76. 4. Handler MZ, Miriovsky B, Gendelman HE, et al. Fusobacterium necrophorum causing infective endocarditis and liver and splenic abscesses. Rev Inst Med Trop Sao Paulo 2011;53:169–72. 5. Moore C, Addison D, Wilson JM, et al. First case of Fusobacterium necrophorum endocarditis to have presented after the 2nd decade of life. Tex Heart Inst J 2013;40:449–52. 6. Shammas NW, Murphy GW, Eichelberger J, et al. Infective endocarditis due to Fusobacterium nucleatum: case report and review of the literature. Clin Cardiol 1993;16:72–5. 7. Vedire S, Alpert MA, Ren J, et al. Fusobacterium necrophorum endocarditis in a previously healthy young adult. Am J Med Sci 2007;334: 125–7.
ERRATUM Deficiency of IRE1 and PERK Signal Pathways in Systemic Lupus Erythematosus: Erratum In the article that appeared on page 348 of Volume 348, Number 6, Qiyao Cheng’s affiliation was listed incorrectly. He is affiliated with the School of Pharmacy, Anhui Medical University. REFERENCE Wang J, Cheng Q, Wang X, et al. Deficiency of IRE1 and PERK signal pathways in systemic lupus erythematosus. Am J Med Sci. 2014;348(6):465–73.
Copyright © 2014 by the Southern Society for Clinical Investigation.
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