A case report of severe Fusobacterium nucleatum sepsis secondary to nephrectomy
BMC Infectious Diseases volume 22, Article number: 309 (2022)
Fusobacterium nucleatum (F. nucleatum) is a resident anaerobic bacterium, which in rare cases may invade blood from the head and neck or the digestive tract to cause bacteremia and induce venous thrombosis. F. nucleatum is closely related to abdominal tumors, but it has not been reported in relation to renal tumors. We report herein a possible case.
This patient had kidney cancer with thrombosis in the right renal vein but had no sign of infection. After radical nephrectomy, thrombi formed in his left renal vein, and when removed, severe sepsis occurred. He did not respond to treatment with antibiotics and died, but the blood culture done confirmed that he had F. nucleatum bacteremia.
F. nucleatum may also be associated with kidney cancer, and could cause post-operative renal vein thrombosis, and sepsis or septic shock after thrombectomy.
Fusobacterium nucleatum (F. nucleatum) is a gram-negative anaerobe that exists in the upper respiratory tract, gastrointestinal tract, and female urogenital tract . It is an opportunistic pathogen. The first case reported with bacteremia followed suppurative thrombophlebitis of the internal jugular vein associated with oropharyngeal infection . This suggested that thrombosis may be a complication of bacterial infection. Subsequently, thrombosis was reported in other veins, such as portal vein , hepatic vein , inferior vena cava , and dural venous sinus , but renal vein thrombosis (RVT) has been reported in only one case . F. nucleatum is often associated with abdominal tumors, such as rectal and ovarian cancers , but there is no report of its association with kidney cancers. We report the case of a patient who had RVT after radical nephrectomy and developed severe sepsis due to the spread of F. nucleatum following thrombectomy. Whether kidney cancer is also associated with F. nucleatum infection, thereby increasing the risk of thrombectomy, is an issue that clinicians, particularly surgeons, would need to be aware of.
This Chinese patient was 59 years old. He was healthy before, without history of thrombosis. When he was admitted to our hospital, CT examination showed a mass in the right kidney, and there was no sign of infection. However, the subsequent CT angiography showed that the mass in the right kidney had abundant blood supply, and there was thrombosis in the right renal vein. Near the left renal vein there was another mass, but there were no thrombi in the left renal vein and portal vein (Figs. 1 and 2). The entire right kidney and the mass in the left kidney were excised by surgeons, and histological examination suggested WHO/ISUP grade-3 clear cell carcinoma. Post-operatively, he developed acute kidney injury (AKI) as evidenced by decreased urine volume (0.27 ml/h/kg for 3 h) and increased serum creatinine (75 mol/l higher than the preoperative level), and selective left renal venography showed a 2 cm filling defect in the left renal vein, suggesting thrombosis (Fig. 3). After the thrombus was removed, we performed continuous venovenous hemodiafiltration (CVVHDF) on the patient. Within the first 12 h, the patient was conscious, with stable vital signs. In addition, he had no fever, and the urine volume exceeded 40 ml/h, indicating that AKI was prerenal AKI caused by the thrombus in his left renal vein. Thus, he improved quickly after thrombectomy.
However, in the following 12 h, the patient showed signs of infection. His consciousness became poor, while body temperature and heart rate increased, and blood pressure, urine volume and oxygenation index decreased. The high CRP (71.82 mg/l) and PCT (22.82 ng/ml) levels also suggested that the patient might be infected. Based on the 2016 SSC guidelines, the patient had septic shock. In addition, SOFA score and laboratory test results were deteriorating (Table 1). Therefore, we immediately started fluid resuscitation, drew the patient's blood for culture, and empirically commenced meropenem and teicoplanin for treatment of the suspected sepsis.
Unfortunately, he continued to deteriorate such that by the second day his respiratory and circulatory systems collapsed and he required ventilation with almost pure oxygen. He died on the third day of respiratory and circulatory failure, and the result of the blood culture, which was received two days later, showed that he had F. nucleatum bacteremia, sensitive to penicillin, cefoxitin, piperacillin/tazobactam, cefoperazone/sulbactam, imipenem/cilastatin, meropenem, clindamycin and metronidazole, intermediate to ceftriaxone, and resistant to none.
Discussion and conclusion
This was a rapidly progressive case of septic shock due to F. nucleatum. The patient had no signs of infection before the operation, and full aseptic precautions were observed in all the operations. Therefore, we speculate that the F. nucleatum infection was associated with the patient's kidney cancer, as suggested by thrombosis in the right renal vein. The subsequent sepsis and thrombosis in the left renal vein were accompanied by F. nucleatum bacteremia.
The original source of the infection is unknown, but the reported sources are mainly concentrated in the head and neck and the abdominal cavity , although the bacteria from these sources have not been reported to cause RVT. Forming venous thrombosis after blood stream invasion is the prerequisite for F. nucleatum to disseminate septic emboli, because it promotes the aggregation of platelets .
Each year, only 5.5 to 7.6 people out of 1,000,000 develop F. nucleatum bacteremia, but the mortality rate is as high as 10–15% [6, 11]. Compared with women, men are more prone to F. nucleatum bacteremia, and the mortality rate of patients above 40 years old is much higher [12, 13]. Tumors also increase the risk of infection . The main cause of death is the dissemination of septic emboli and the formation of abscesses in special parts .
Our patient was male and over 40 years old. The kidney cancer may have compromised his local immunity, and subsequently F. nucleatum invaded the blood to form a thrombus in the renal vein. There is no evidence that the bacterium is from the head and neck or the abdominal cavity, but the thrombus in the renal vein suggests that the bacterium might have originated from the urinary tract.
F. nucleatum is closely related to abdominal tumors and its detection rate is highest in patients with colorectal cancer . However, the mechanism by which it induces tumor formation is unknown . There are no reports about the association of F. nucleatum with kidney cancer (Table 2), but we speculate that the bacterium could also be associated with the occurrence of renal tumors. Combining the 13 cases in Table 2 and the 22 cases collected by Yusuf et al. , we summarize the characteristics of the 35 cases reported so far in Table 3.
There have so far been no specific recommendations on the antibiotic therapy of infections due to F. nucleatum. Three case reports put forward that F. nucleatum is resistant to penicillin, amoxicillin, amox-clav , and metronidazole , but there is no evidence for the 2–6-week treatment  recommended by most doctors.
We treated our patient empirically in accordance with the 2016 SSC guidelines, and the subsequent in vitro susceptibility test of the isolate showed that meropenem was effective. Our patient might have died from the complications associated with the infection rather than from failure of antibiotic therapy.
We conclude that as with other abdominal tumors, F. nucleatum may also be associated with kidney tumors, and that septic thrombo-embolization and severe sepsis could complicate the post-operative management of such cases.
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All procedures carried out in this study were in accordance with the ethical standards of the institutional and national responsible committee on human experimentation and the Helsinki Declaration of 1964 and its later amendments or equivalents. This study was approved by the Ethics Committee of Affiliated Tumor Hospital of Zhengzhou University. Informed consent was obtained from the patient included in the study.
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Liu, C., Jia, Q., Wang, L. et al. A case report of severe Fusobacterium nucleatum sepsis secondary to nephrectomy. BMC Infect Dis 22, 309 (2022). https://doi.org/10.1186/s12879-022-07294-6