Clostridium paraputrificum in a Middle-Aged Male With Liver Disease

Abstract

Clostridium paraputrificum is a gram-positive anaerobic spore-forming bacillus with a pathological prevalence of <1% among all Clostridium species. However, despite being a rare bacterium, there have been reported cases of C paraputrificum causing a wide range of varying pathologies. Herein presented is a case of cirrhosis secondary to alcoholism complicated by developing C paraputrificum bacteremia suspected due to gastrointestinal mucosal damage. There is literature demonstrating certain comorbid conditions having an impact on the overall prognosis of patients with C paraputrificum bacteremia.

Introduction

Clostridium paraputrificum (C paraputrificum) is an early colonizer bacteria that is naturally present in the human gastrointestinal (GI) flora. ¹ It is generally detected in the feces within the first week of birth, along with Clostridium butyricum and Clostridium difficile. ² Although it is generally present from birth up until the first year of being formula fed, C paraputrificum tends to be present thereafter. Breastfed infants are noted to lack this bacterium after weaning. ² What is interesting is that this bacterium is associated with various pathologies including necrotizing enterocolitis in preterm neonates and adults.^1,3,4 With the gut microbiota being an active area of research, it is pertinent to discuss the various bacterial pathologies that can disrupt it. ²

Clostridium infections are associated with varying species namely Clostridium perfringes at 42%, Clostridium septicum at 14%, Clostridium ramosum 9%, Clostridium clostridiiforme 6%, Clostridium difficile 5%, and Clostridium paraputrificum <1%. ⁵ Despite C paraputrificum causing less than 1% of pathologies, what is known is that medical conditions such as colonic malignancy,^6,7 acquired deficiency syndrome (AIDS), ⁶ hemodialysis, ⁸ inflammatory bowel disease (IBD), ⁸ and so on tend to increase the risk of systemic C paraputrificum infections. Liver disease also is known to be an independent risk factor for mortality in anaerobic bacteremia. A suspected pathway by which this bacteria could translocate to the liver would be due to the breakdown of the mucosal barrier of the intestines.^6,7,9 As such we are presenting a case of C paraputrificum bacteremia in a cirrhotic patient.

Case Presentation

A 46-year-old man with a history of alcohol dependence by drinking 750 mL of liquor daily for 10 years presented with a 2-week history of progressively worsening, constant abdominal pain. Four days prior to presentation, he developed squirts of bright red blood per rectum occurring every 3 hours.

In route to the hospital via emergency medical services, the patient was noted to have systolic blood pressure in the 60s and was given 500 cc of normal saline. Upon arrival to the emergency department, the patient was found to be extremely jaundiced with scleral icterus and noted to have a severely distended abdomen. Initial vitals were significant for blood pressure 83/50 mmHg, heart rate 87 beats per minute, respiratory rate 30 breaths per minute, saturating at 99% on room air and afebrile. The abdominal examination revealed a positive fluid wave, dull to percussion with moderate tenderness to palpation in all 4 quadrants without rebound tenderness or guarding.

Despite 3 liters of normal saline administration, no significant improvement in his blood pressure was noted. He was subsequently initiated on septic shock protocol with norepinephrine drip and broad-spectrum antibiotics with ceftriaxone 2 g intravenously. Computed tomography of the abdomen and pelvis was also obtained which revealed free fluid (Image 1). Paracentesis was then performed which resulted in removal of 600 cc of straw fluid. Fluid analysis revealed 325 nucleated cells and 375 red blood cells (RBC), with neutrophils at 18% and macrophages at 74%. Due to the neutrophils being 67.5 of nucleated cells, a diagnosis of spontaneous bacterial peritonitis was not made. Regardless, there were still concerns of an underlying infection. Initial blood work was done which portrays an elevated white blood count with bandemia and due to the patient’s lactic acidosis along with the vitals, the patient was noted to be in septic shock (Table 1). The patient was also noted to have low hemoglobin due to the rectal bleed. Bilirubin was also noted to be elevated as well as prolong creatinine, AST, and prothrombin time (Table 1). Two out of four blood cultures from different body sites on day 1 grew gram-positive rods (Images 2 and 3), which were further analyzed using VIiTEK 2 by bioMerieux with a confidence interval of 80.0 to 99.9 of bacterial strains. ¹⁰

Image 1.

CT scan of abdomen showing free fluid and moderate amount of ascites. Paracentesis fluid analysis did not find evidence of spontaneous bacterial peritonitis.

Table 1.

Blood Work on Presentation.

Parameter	Value	Reference range
Sodium (Na)	131 mmol/L	136 mmol/L– 145 mmol/L
Potassium (K)	4.4 mmol/L	3.5 mmol/L– 5.1 mmol/L
Chloride (Cl)	98 mmol/L	98 mmol/L– 107 mmol/L
Corrected calcium (Ca)	9 mg/dL	8.5 mg/dL – 10.1 mg/dL
Magnesium (Mg)	1.5 mg/dL	1.8 mg/dL – 2.4 mg/dL
Phosphorus (P)	4.6 mg/dL	2.5 mg/dL – 4.9 mg/dL
Creatinine	3.29 mg/dL	0.51 mg/dL – 0.95 mg/dL
Blood urea nitrogen (BUN)	39 mg/dL	7 mg/dL – 18 mg/dL
Lactic acid	4.4 mmol/L	0.4 mmol/L – 2 mmol/L
Direct bilirubin	20.1 mg/dL	0 mg/dL – 0.2 mg/dL
Total bilirubin	23.1 mg/dL	0 mg/dL – 1 mg/dL
Aspartate aminotransferase (AST)	127 unit/L	15 unit/L – 37 unit/L
Alanine aminotransferase (ALT)	24 unit/L	13 unit/L – 61 unit/L
White blood count (WBC)	21x10^3/mcL	4.5x10^3/ mcL – 11x10^3/ mcL
Hemoglobin	7 g/dL	11.1 g/dL – 15.4 g/dL
Hematocrit	21 %	38.9 - 51 %
Mean corpuscular volume (MCV)	109 μm3	75.7 μm3 – 97.6 μm3
Platelet	183 000/mcL	150 000/mcL – 450 000/mcL
Band %	31 %	<10%
Prothrombin time (PT)	26.2 seconds	10 – 13 seconds
Partial thromboplastin time (PTT)	26 seconds	25 – 35 seconds
International normalized ratio (INR)	2.48	<1.1

Image 2.

Blood culture gram stain showing gram positive rods as indicated by the yellow arrow.

Image 3.

Anaerobic culture media showing colony morphology of Clostridium paraputrificum (ViTek2, bioMérieux).

Patient’s blood pressure showed improvement and the patient was eventually weaned off the norepinephrine drip with lactic acid improving to 1.8. The shock had resolved with systolic blood pressure in the 90s to low 100s with diastolic in the 50s and mean arterial pressure in the high 60s to 70s. However, the patient was noted to have worsening creatinine function slowly increasing from 3.29 up to 5.93. Urine studies were unremarkable and computed tomography of the abdomen and pelvis only showed hepatosplenomegaly with fatty infiltration of liver with ascites present as well as enlarged veins in the upper quadrant suggesting underlying cirrhosis as well as portal hypertension. Albeit there was no evidence of obstruction leading to post renal acute kidney injury was noted in CT scan. Ultrasound of the abdomen also showed normal renal cortical echogenicity without shadowing calculus or hydronephrosis. No nephrotoxic agents were also used throughout admission. Patient was then started on albumin and vasoactive medication for concerns of suspicion of hepatorenal syndrome type 1. Patient was also noted to be oliguric with an up trending blood urea nitrogen from 39 up to 67, with mild symptoms of encephalopathy. As such hemodialysis was done without fluid removal to prevent hypotension. Fresh frozen plasma was administered for coagulopathy, and packed RBC’s each time the patient’s hemoglobin dropped to less than 7. Esophagogastroduodenoscopy and colonoscopy were done once the patient was more stable which revealed large internal hemorrhoids associated with rectal varices. Blood Culture revealed that the patient had a bacterimic infection composed of C paraputrificum and metronidiazole was added. Sensitivities portrayed that the bacterium was sensitive to metronidiazole and the antibiotic was continued (Table 2).

Table 2.

Clostridium paraputrificum Sensitivities.

Antibiotic	Mean inhibitory concentration
Ampicillin/Sulbactam Clindamycin Imipenem Meropenem Metronidazole Penicillin	0.25 Sensitive 8 Resistant 1 Sensitive 0.5 Sensitive 0.5 Sensitive 0.5 Sensitive

Repeat blood cultures were negative but unfortunately, the patient continued to decompensate despite all measures. Surgical intervention was heavily considered, but NISQIP showed that the patient was a poor surgical candidate. Ultimately, the patient and family agreed with hospice care, and the patient was discharged shortly after.

Discussion

Throughout literature, there have only been a few cases of C paraputrificum, some of which show a very severe pathogenesis, causing colon necrosis, ⁸ bacteremia,^6,8,11,12 and liver abscesses. ¹³ Although in those cases the patients had severe comorbidities, in others, the patient’s only risk factor was old age. ¹² Yet, prior cases have shown that patients with significant medical comorbidities tend to develop a poor prognosis (Table 3).^6,14

Table 3.

Patients With Prior Clostridium paraputrificum Infections.

Age/sex/demographic	Comorbidities	Isolate	Antibiotic treatment	Outcome
47 y/o African Male 15	Sickle cell disease Thalassemia COVID-19 pneumonia Pulmonary embolism	Clostridium paraputrificum	Vancomycin Metronidazole	The patient’s pain drastically improved with an increasing range of motion of right shoulder and her fever had resided.
65 y/o Male 8	AIDS Ischemic Cardiomyopathy Atrial fibrillation Chronic Orthostatic Hypotension Diabetes mellitus Hepatitis B Hepatitis C End-stage renal disease	Clostridium paraputrificum	Vancomycin Piperacillin with Tazobactam Metronidazole	Transferred to rehab 15 days after admission
32 y/o Male 6	AIDS (CD4 8 mm^3) Duodenal mass revealing Kaposi Sarcoma	Clostridium paraputrificum	Vancomycin Metronidazole	August 27 patient expired due to sepsis caused by Staphylococcus epidermidis
88 y/o Male 11	Hypertension Heart block on prior electrocardiogram (EKG) Benign prostatic hyperplasia Coma Blindness Dementia Former tobacco smoker	Clostridium paraputrificum	Metronidazole	Doing well at 2 week follow-up
88 y/o Male 12	Hypertension Prior diagnosis of pyogenic spondylitis treated 8 months prior	Clostridium paraputrificum	Ampicillin with Sulbactam	Antibiotic therapy alleviated the fever, and subsequent blood cultures conducted after 2 weeks of treatment yielded negative results. He was investigated for other comorbidity but didn’t have any unless stated above and didn’t have relapse 6 months after discharge.
23 y/o Female 13	Obesity (BMI 37) Polycystic Ovarian Syndrome	Clostridium paraputrificum	Vancomycin Levofloxacin Metronidazole	Patient discharged and on 2 week follow showed reduction of abscess cavity. She most likely survived based on last lab values
74 y/o Male 14	Hypertension Iron deficiency Anemia Recent history of Community Acquired pneumonia	Clostridium paraputrificum	Vancomycin Metronidazole Meropenem	Palliative team was consulted and patient eventually expired
58 y/o Female 16	Covid-19 Diabetes Mellitus Type 2 Hypertension Acid Reflux	Clostridium paraputrificum	Piperacillin with Tazobactam Clindamycin (Zoysn was switched to Meropenam)	N/A
86 y/o Female 17	Bilateral Total Knee Arthroplasties Degenerative Joint Arthritis	Clostridium paraputrificum	Vancomycin Cefepime Metronidazole	Patient was cleared of any infection and doing well
64 y/o Female 18	Colon Cancer Crohn’s disease	Clostridium paraputrificum	Metronidazole	N/A
59 y/o Male 19	Human Immunodeficiency Virus (HIV) Hepatitis C (HCV) Type 2 Diabetes Mellitus Hypertension Smoking Active drug abuse (Heroin and Alcohol) Chronic Kidney Disease III Cervical Spine Abscess	Clostridium paraputrificum	Vancomycin Meropenem	Patient experienced sudden cardiac arrest due to reflex arrhythmia and unfortunately passed away
78 y/o Caucasian Male 7	Intestinal Carcinoma Liver Neoplastic Lesions	Clostridium paraputrificum	Metronidazole	Patient was discharged from the hospital and doing well

Our patient had decompensated alcoholic cirrhosis with lower GI bleed, hepatorenal syndrome, coagulopathy, and ascites. His GI tract was likely already colonized with C paraputrificum, which translocated to blood stream and eventually his liver during the GI bleed. ²⁰ This was also supported by the fact that his esophagogastroduodenoscopy (EGD) found moderate portal hypertensive gastropathy in the gastric cardia and fundus with colonoscopy revealing large internal hemorrhoids with inflammatory changes and associated rectal varices. The patient’s liver decompensation was also most likely caused by the bacterium since he developed worsening symptoms a few days after his bloody stools. The fact that this bacterium has been known to cause liver damage in other case reports also supports this hypothesis. ¹³

Fortunately, empiric Ceftriaxone was given in the ED along with IV fluids and vasopressors, which improved his septic shock, and once the bacterium was identified as C paraputrificum the patient was put on anaerobic coverage particularly metronidazole with further sensitivities pending (Table 2). Fortunately the bacterium was sensitive to metronidazole and the antibiotic was continued. Yet, the patient was not able to show signs of improvement overall regarding his other medical issues such as the hepatorenal syndrome, the progressing liver decompensation, and so on. Despite weeks of medical management, and although repeat blood cultures were negative, liver failure continued to be prominent. This as a result can show how patients who grow C paraputrificum usually have severe comorbidities and the bacterium itself can worsen such medical comorbidities leading to a poor prognosis.

Conclusion

It can be concluded that most Clostridium species have varying modes of virulence (Table 3). Patients with many comorbidities tend to have an overall poor prognosis (Table 3)^6,14; however, our patient with decompensated cirrhosis and anaerobic bacteremia showed an even worse prognosis. It was hypothesized that the patient was susceptible to this bacterium due to mucosal breakdowns and GI bleeding. ⁷ As such, in situations where blood cultures do grow C paraputrificum, the ideal approach is to add anaerobic coverage with metronidazole, until sensitivities (Table 2) result for further specific coverage (Table 3). However, once sensitivities are identified, the antibiotic of choice should be started immediately with discontinuation of other unnecessary antibiotics alongside proper clinical judgment. It should also be crucial that stabilizing the patient’s other medical issues should be prompt since patients that grow this bacterium tend to have various medical issues.