An Unusual Presentation of Clostridioides Difficile Colitis in a Patient on Opioids

Clostridioides difficile colitis is an inflammation of the colon due to toxins produced by a gram-positive bacterium called Clostridioides difficile (also known as Clostridium difficile). Clostridioides difficile colitis is associated with an increased risk of morbidity and mortality in elderly patients. The infection develops because of the disruption of the microbiome that usually suppresses the overgrowth of Clostridioides difficile. Testing for Clostridium difficile infection is routinely recommended in patients with at least three loose bowel movements in a day. We present an unusual case of a 74-year-old woman on chronic opioids who presented with a three-day history of lower abdominal pain, constipation, hematochezia, with no diarrhea. Radiologic imaging showed evidence of colitis, and the patient was found to have Clostridium difficile colitis.


Introduction
Clostridioides difficile colitis is caused by toxins produced by Clostridioides difficile (also known as Clostridium difficile or C. difficile), a gram-positive, spore-forming, obligate anaerobic rod bacterium [1]. According to the Centers for Disease Control and Prevention (CDC), C. difficile causes almost 500,000 infections in the United States each year [2]. The infection is typically related to antibiotic use, usually misuse and overuse, which often characterize antimicrobial resistance [3]. The current recommendations by the American College of Gastroenterology, the Infectious Diseases Society of America, and our local health institution support testing for C. difficile only in patients having diarrhea (defined as three or more loose stools within 24 hours) and after holding off laxative medications [4,5]. We present an unusual case of C. difficile colitis in a patient on opioids with no diarrhea.

Case Presentation
A 74-year-old woman presented to the emergency department with a three-day history of lower abdominal pain, constipation, and blood in the stool (hematochezia) four days after a recent hospitalization for community-acquired pneumonia. She has a past medical history of anxiety, depression, chronic obstructive pulmonary disease, hypertension, hyperlipidemia, coronary artery disease, gastroesophageal reflux disease, mild-moderate mitral regurgitation, hypothyroidism, systemic lupus erythematosus, substance use disorder on methadone maintenance, and constipation. Before her recent discharge from the hospital, she was treated with ceftriaxone and azithromycin. On admission, she had a low-grade temperature of 99.4°F, blood pressure of 137/73 mmHg, respiratory rate of 20/minute, heart rate of 70 beats per minute, and oxygen saturation of 100% on room air. Physical examination was remarkable for dry mucous membranes and abdominal tenderness in the left upper and lower quadrants. Rectal examination showed a normal tone with frank blood. Laboratory studies revealed leukocytosis with absolute neutrophilia, normal hemoglobin level, thrombocytosis, elevated blood urea nitrogen and creatinine, hyponatremia, hypokalemia, and normal serum lactic acid levels ( Table 1).   While in the emergency department, the patient had a single loose stool with brown and bloody components. She was started on intravenous fluids and broad-spectrum antibiotics, namely ceftriaxone and metronidazole. Due to recent antibiotic exposure and evidence of colitis on the CT scan, the patient was tested for C. difficile. Both C. difficile DNA PCR and toxin were positive. The patient was then placed on contact precautions, parenteral antibiotics were discontinued, and she was started on oral vancomycin. On day 5 of hospitalization, an abdominal X-ray was performed to evaluate abdominal distension, which showed no evidence of free intraperitoneal air, dilated colon, or obstruction ( Figure 2).

FIGURE 2: Abdominal X-ray showing no evidence of free intraperitoneal air, dilated colon, or obstruction.
She was treated for methadone-induced constipation with methylnaltrexone bromide. Subsequently, her abdominal pain, leukocytosis, and renal failure improved, and hematochezia resolved. The patient was discharged home on day 8 in stable condition.

Discussion
Clostridioides difficile has a wide range of clinical manifestations, from asymptomatic colonization to fulminant disease with toxic megacolon. Clostridioides difficile infection is associated with an increased risk of morbidity and mortality in the elderly (aged 65 years and older) [2]. Besides, around 9% of the elderly who have been diagnosed with healthcare-associated C. difficile infection die within one month [2]. In addition to pneumonia and surgical site infections, C. difficile infection is a leading cause of nosocomial infection in the United States [6][7][8]. In 2017, hospitalized patients accounted for around 223,900 cases of nosocomial C. difficile and around 12,800 deaths in the United States [9].
The normal microbiota of healthy intestines often suppresses the growth of C. difficile, and disruption of the microbiome can lead to the overgrowth of the bacteria [10,11]. The C. difficile bacterium produces toxins A and B that disrupt the cytoskeleton of the colon, hence leading to pseudomembranous colitis [11]. Risk factors for C. difficile infection include exposure to antibiotics, age 65 years and older, recent hospitalization or nursing home stay, immunosuppression (including HIV/AIDS, cancer, and organ transplantation), immunosuppressive therapies, hypoalbuminemia, and previous C. difficile infection [2,11]. Symptoms include diarrhea (defined as at least three loose bowel movements in a day), fever, abdominal pain, nausea, and loss of appetite.
The American College of Gastroenterology, the Infectious Diseases Society of America, and our institutional guidelines recommend only testing for C. difficile in patients with diarrhea [4,5]. In our case, the patient did not present with diarrhea and did not meet the criteria for testing based on the current guidelines. It is important to note that the patient was on methadone maintenance, a long-acting opioid with constipation as one of its major side effects. In addition, elderly individuals are also at an increased risk of constipation due to decreased gastrointestinal motility. The side effect of this medication and the patient's age likely masked the usual symptoms of C. difficile colitis, specifically diarrhea. Although the patient did not meet the criteria for testing based on stool frequency, she warranted testing given other consistent symptoms, recent antibiotic exposure, markedly elevated white blood cell count, and evidence of colitis on the abdominal CT scan.

Conclusions
Clostridioides difficile infection is associated with significant morbidity and mortality in individuals aged 65 years and older. The early diagnosis of C. difficile colitis can decrease the risk of transmission, length of hospital stays, and mortality. Although the current recommendations do not support testing patients who present without diarrhea, suspicion for C. difficile infection should still be maintained in patients on antimotility agents who have other clinical signs and symptoms consistent with C. difficile colitis.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.