A case of community-acquired Clostridioides difficile infection causing intussusception, severe pneumonia, and severe hypokalemia

Abstract

Background

Clostridioides difficile infection is associated with antibiotic use and manifests as diarrhea; however, emerging cases of fulminant diarrhea caused by binary toxin-producing C. difficile unrelated to prior antibiotic exposure have been reported. Although fulminant colitis caused by C. difficile has been documented, instances of intussusception remain scarce. Here, we present a case of adult intussusception with severe hypokalemia and pneumonia resulting from a community-acquired C. difficile infection in Japan.

Case presentation

An 82-year-old male presented with dizziness, progressive weakness, and diarrhea. Initial vital signs indicated severe respiratory and circulatory distress, and laboratory findings revealed hypokalemia, pneumonia, and septic shock. Imaging confirmed intussusception of the ascending colon. Although colonoscopy suggested a potential tumor, no malignancy was found. The C. difficile rapid test result was positive, indicating community-acquired C. difficile infection. Treatment with vancomycin was initiated; however, intussusception relapsed. Surgical intervention was successful and led to clinical improvement.

The patient's complex pathophysiology involved community-acquired C. difficile-induced severe diarrhea, hypokalemia, hypermetabolic alkalosis, and subsequent intussusception. Although adult intussusception is uncommon, this case was uniquely linked to binary toxin-producing C. difficile. The identified strain, SUH1, belonged to a novel sequence type (ST1105) and clade 3, suggesting a highly virulent clone. Resistome analysis aligned with phenotypic susceptibility to metronidazole and vancomycin, confirming their treatment efficacy.

Conclusion

This case report highlights a binary toxin-producing C. difficile that caused intussusception. The consideration of community-acquired C. difficile in the differential diagnosis of severe enteritis is necessary, even in Japan.

Background

Clostridioides difficile is a bacterium that causes intestinal infection resulting in diarrhea; it is usually associated with the use of antibiotics. Recently, fulminant diarrhea caused by binary toxin-producing C. difficile that may not be associated with prior use of antibiotics has been reported [1]. Some reports have described fulminant colitis, such as toxic megacolon or ileus, requiring surgical intervention due to C. difficile infection (CDI) [2, 3]. However, there are few reports of intussusception caused by community-acquired CDI. The prevalence of community-acquired CDI varies by country, and is rare in Japan [4]. Here, we present a case of adult intussusception accompanied by severe hypokalemia and pneumonia caused by community-acquired CDI in Japan. We also conducted molecular and genomic analyses, including whole-genome sequencing, to characterize the isolated C. difficile strain.

Case presentation

An 82-year-old male presented with a chief complaint of dizziness. He lived with his wife who required nursing care. He reported feeling unwell and had had diarrhea for several days before visiting our hospital. On the day of the visit, his symptoms worsened and he had difficulty walking; thus, he called for an ambulance. Past medical history included the presence of hypertension.

In the emergency room evaluation, his airway was patent with a respiratory rate of 30 breaths/min; SpO₂ could not be measured, his blood pressure was 60/25, his heart rate was 67 bpm, he had a Glasgow Coma Scale (GCS) of 4–2-6, and his body temperature was 37.2 °C. Arterial gas showed a pH of 7.557, PCO₂ of 47.9 mmHg, PO₂ of 47.4 mmHg, HCO₃ at 42.5 mmol/L, BE at 17.4, Na at 134 mEq/L, K at 1.2 mEq/L, and lactate at 49 mg/dL. Blood tests showed a WBC of 2900 cells/μL, CRP at 8.9 mg/dL, procalcitonin at 20.9 mg/dL, BUN at 45.3 mg/dL, Crea at 2.53 mg/dL, AST at 66, ALT at 45, and T-bil at 2.1. Chest radiography revealed a right lobular infiltrate and suspected ileus (Fig. 1). The patient was intubated, and fluid resuscitation, catecholamine support, high-dose potassium correction, and meropenem were administered. Computed tomography (CT) confirmed pneumonia in the right lower lobe and ileus caused by an intussusception of the ascending colon (Fig. 2).

Fig. 1

Chest X-ray. Chest X-ray showed diffuse consolidation in the right lung. Additionally, incidental finding suggests intestinal obstruction in the abdomen

Fig. 2

CT scan of the abdomen. CT image showed a dilatated colon and the intussusception in the ascending colon

After initiating intense respiratory and circulatory support, the patient’s blood pressure increased to 124/60 mmHg. Colonoscopy was performed to treat the intussusception. A colonoscopy revealed an elevated lesion (Fig. 3); the patient was diagnosed with probable colon cancer which caused the intussusception and subsequent ileus. The ileus induced vomiting, resulting in aspiration pneumonia with septic shock; however, we believed that it did not explain the diarrhea and hypokalemia. Because of this, we also performed a stool culture and the C. difficile rapid test, and the commercial testing kit CD GDH/TOX (Shimadzu Diagnostics) yielded positive results. We then initiated vancomycin treatment using a nasogastric tube. We still believed the primary diagnosis is colon cancer and it is accompanied with CDI.

Fig. 3

Colonoscopy. A raised lesion was observed in the ascending colon. A biopsy was performed

After hospitalization, the patient’s circulatory status stabilized, and inflammatory data improved, however, severe hypokalemia persisted on day 5 with > 100 mEq/day potassium infusion, and no stool was observed during this period. Because of this, we suspected a relapse of the intussusception, and the CT scan was repeated. The scan revealed a relapse or worsened intussusception and ileus. Biopsy report of the colonoscopy was below: There were two specimens from ileum and the finding was necrotizing tissue with inflammatory cells and bleeding. There was no evidence of malignant cells. Xpert C. difficile (Beckman Coulter, Tokyo, Japan) returned positive results (Toxin B ( +) PCR cycle threshold (Ct) value of 27.2, binary toxin ( +) Ct value of 26.9, and Tcdc(-)), confirming that the intussusception was caused by CDI enteritis. We decided to treat the intussusception surgically, and an ileocecectomy was performed by acute-care surgeons (Fig. 4). Following surgery, the patient’s diarrhea and electrolyte disorders improved. The patient was transferred to another hospital for rehabilitation 56 days after admission. The resected specimen did not show the mass seen on colonoscopy and there was no malignant initial finding on pathology.

Fig. 4

Resection specimen. The portion of the ileocecal lesion exhibiting ischemia was excised

To further characterize the C. difficile isolate, we determined the minimum inhibitory concentrations (MICs) of metronidazole and vancomycin using Etest (bioMérieux, Marcy-l’Etoile, France), as described previously [5]. The strain, identified as SUH1, was susceptible to metronidazole (MIC = 0.047 mg/L) and vancomycin (MIC = 0.75 mg/L). We then conducted whole-genome sequencing, followed by in silico analyses of multilocus sequence typing, phylogenetic analysis, genotypical toxin profiles, and detection of antibiotic resistance determinants (ARDs) following previously described methods [5,6,7]. The genome of SUH1 was assigned to novel sequence type (ST) 1105 among strains deposited in the PubMLST C. difficile genome database (accessed on January 10, 2024) [8] and belonged to clade 3 as determined by maximum-likelihood phylogenetic analysis based on C. difficile core genomes (Fig. 5). In addition, SUH1 possessed tcdA, tcdB, cdtA, and cdtB, supporting the results from the commercial CD GDH/TOX and Xpert C. difficile testing kits. Although no ARD was detected in SUH1 with 100% identity by CARD, CCD-1-like β-lactamase (responsible for carbapenem resistance) was detected with high amino acid identity (99.68%), as well as QacG (responsible for multidrug resistance; 40.2%), and VanY (responsible for glycopeptide resistance; 38.62%).

Fig. 5

Maximum-likelihood phylogenetic analysis based on C. difficile core-genomes. The tree includes 16 reference genomes reported in previous studies [6, 9], and was constructed using IqTree ver. 2.2.0.3 [10]. Clades are indicated by their designated number

Discussion and conclusion

We encountered a case of adult intussusception with severe hypokalemia and pneumonia caused by binary toxin-producing C. difficile. The pathophysiology of this case was complex and difficult to ascertain. We believe that the patient initially developed severe diarrhea due to community-onset CDI; consequently, severe hypokalemia and hypermetabolic alkalosis developed. The patient subsequently developed intussusception because of severe intestinal hyperperistalsis. Intestinal obstruction due to intestinal accumulation can result in vomiting and aspiration pneumonia. Severe dehydration due to diarrhea and sepsis caused by severe pneumonia causes hypotension, resulting in elevated lactate levels. A colonoscopy performed to treat the patient for intussusception revealed some findings that initially appeared to be a tumor; however, the results were later thought to show an inverted intestinal mucosa. The key factor in understanding the pathophysiology of this case was the C. difficile toxin test, which was performed to identify the cause of the diarrhea that caused the severe hypokalemia.

Intussusception is defined as a condition in which one segment of the intestinal tract is stuck within another segment. Intestinal intussusception mainly occurs in children and is seen rarely in adults. Adult intussusception is often caused by colorectal cancer, which affects the advanced part of the colon. There are limited reports on intussusception caused by CDI [11,12,13,14], and none reported the type of toxin or ribotype (RT) of C. difficile. Our case of intussusception may have been caused by a highly toxic strain of CDI which produces binary toxin. To our knowledge, this is the first case report of binary toxin-producing C. difficile causing intussusception.

To date, C. difficile hypervirulent lineages–clade 2 dominated by RT027/ST1, and clade 5 dominated by RT078/ST11–are a global public threat, but are not commonly seen in Japan [5, 6, 15, 16]. Recently, clade 3 (dominated by RT023) was reported to be a highly virulent lineage involved in CDI relapse, especially in Europe [9]. Our case showed severe diarrhea caused by a binary toxin-producing C. difficile isolate, SUH1, which belongs to novel ST1105. This isolate was genotypically characterized as clade 3 in Japan for the first time, suggesting that it is a highly virulent clone, however, further investigation is required to quantify the production of each toxin will be needed to confirm this. Our findings from the resistome analysis coincided with the phenotypic results of metronidazole and vancomycin MICs, suggesting that these two antibiotics were effective in the treatment of this strain.

We encountered a case of binary toxin-producing community-acquired CDI in Japan. The diagnosis was based on the severity of diarrhea, which caused severe hypokalemia. The distribution of bacterial epidemiology changes over time, and though it has been rare to date, community-acquired CDI should be included in the differential diagnosis of patients with severe enteritis in Japan.