An Immunosuppression Hidden Malignancy: Case Report of An Unexpected Clostridium Septicum Infection and Its Fatal Consequence

Clostridium septicum (CS) belongs to the gas-producing bacterium and occurs naturally in the soil as well as the intestinal flora. They are toxin-producing, gram-positive, obligatory anaerobic and form spores under certain conditions. Only 1% of all blood culture samples are positive for Clostridia and among them CS makes up to 1.3% of the total [1]. Proven CS in blood cultures is associated with gastrointestinal and hematological malignancy, immunosuppression and diabetes mellitus [2-4]. Related infection mortalities appear to be over 50 % [4,5]. Cases are reported highlighting the correlation between immunosuppression and CS as well as CS and colon cancer. We present a rare clinical case in which an unexpected colon cancer was detected alongside a CS infection in an immunocompromised patient.

A 67-year-old man was referred to our department by his general practitioner for clarifying the cause of anaemia, fatigue and inappetence. The patient was in a moderate condition and complained of an unexpected weight loss of 7kg in 3 months. He revealed a 40 pack-year smoking history and admitted to eating meat daily. Pre-existing illnesses were lupus erythematosus (treated with 10mg prednisolone, 400mg hydroxychloroquine and 100 mg azathioprine), arterial hypertension and coronary artery disease treated with atorvastatin, aspirin and clopidogrel. His physical examination was normal, but the laboratory results showed a reduced haemoglobin concentration of 9.5g/dl (norm.: 14-18mg/ dl), elevated CRP of 140mg/l (norm.: <5mg/l), raised procalcitonin of 0.26 ng/ml (norm.: <0.005ng/ml) and a high ESR over 120mm/ hr (norm.: 15mm/hr). Blood cultures were sent immediately. Sonography and x-ray examination did not reveal any relevant findings. The decision was taken to commence antibiotic therapy with piperacillin / tazobactam after further elevations of CRP (321mg/l) and procalcitonin (0.65ng/ml). The following day, blood cultures showed evidence of Staphylococcus saccharloyticus and Clostridium septicum. We added clindamycin whilst infection parameters decreased and proceeded with gastrointestinal endoscopy. A biopsy was taken which revealed adenocarcinoma stage T4a (infiltration of the serosa) N0 M0 G2 V0 L0 and UICC stadium IVa (Figure 1). The decision to commence surgery was made after treating the infection. On the same night the patient lost blood, developed peritonitis and became hemodynamically unstable with a blood pressure of 60/40mmHg. An emergency laparoscopy and right-sided hemicolectomy was performed. Intraoperatively, the tumor demonstrated infiltration of the mesenteric root with formation of an abscess cavity. A bacterial smear was taken and lavage and hemicolectomy with double ileostomy were performed. E. coli and Bac. fragilis were found on the smear and identified as being sensible to piperacillin/tazobactam. The patient made a full surgical recovery after receiving a continued antibiotic course. Additional outpatient chemotherapy was recommended.

Figure 1:Results of the coloscopy (A, B) with circular growing tumor and histology (C) with atypical glandular cell infiltration from the right colon.

The clinical manifestation of Clostridium septicum infections can vary. The patient in our hospital showed anaemia, inappetence and fatigue. Further cases have described associations with aortic aneurysm 6, the formation of gas gangrene [7] and even pneumocephalus [8]. As a result, diagnosis, treatment and complications may vary and the detection of CS can be forgotten. Early antibiotic treatment has been shown to improve outcomes. The most effective antibiotics are clindamycin, penicillin, metronidazole and moxalactam [1]. We chose clindamycin and the infection parameters decreased. However, the patient became haemodynamic unstable, after blood loss and the onset of peritonitis, before we could completely cure the bacteremia. E. coli and Bac. fragilis were found intraoperatively. Some cases have shown a correlation between CS, perforation and multipathogenic infection with bacteria including Streptococcus bovis, Fusobacterium spp. as well as E. coli and Bac. fragilis [9-11]. The patient we present has a history of systemic lupus erythematosus and takes prednisolone, hydroxychloroquine and azathioprine. The drugs intervene with the immune system in different ways in order to achieve effective immunosuppression [12]. Cellular and humoral immune response are reduced with prednisolone by inhibiting intracellular NF-pathways [13]. Hydroxychloroquine affects toll like receptor-mediated activation of the innate immune response [14] and azathioprine belongs to the group of purine analogues which reduce DNS replication and proliferation of CD3+T cells. Therefore TNF-α release is decreased [15]. A correlation between immunosuppression and bacteraemia with CS has been described [3,4]. That may have increased the risk of asymptomatic CS appearance in this case. The detection of CS has great clinical significance. It demonstrates a symptomatic course, is associated with gastrointestinal and hematological malignancy and has been shown to have high mortality rates. An early diagnosis and treatment of the bacteremia could improve patient outcomes. Infection in immunocompromised patients may however be clinical inapparent. Therefore, the diagnosis of this bacteria and associated malignancy and complications can be difficult or even fail.

Learning points

1. Clostridum septicum is strongly associated with malignancy. Colonoscopy is therefore indicated

2. Immunusuppression may hide infection due to Clostridium septicum and therefore the associated malignancy. Missing the microbiological diagnosis may lead to the misinterpretation of malignant tumors.

The authors declare that they have no conflicts of interests.

M. Grade and E. Welk contributed equally to this article.

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