Clostridioides difficile infection in cancer patients receiving immune checkpoint inhibitors

Vasavada, Shaleen; Panneerselvam, Kavea; Amin, Rajan; Varatharajalu, Krishnavathana; Okhuysen, Pablo C.; Wang, Jianbo; Grivas, Petros; Thomas, Anusha Shirwaikar; Wang, Yinghong

doi:10.20524/aog.2022.0722

Cited by 4 publications

(4 citation statements)

References 28 publications

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“…A retrospective single-center study explored the attributes of CDI in patients undergoing therapy with ICI in the presence of IMDC. The study concluded that the concurrence of CDI and IMDC is associated with prolonged symptom duration (20 vs. 5 days, p=0.003) and a reported higher rate of grade 3-4 diarrhea (41% vs. 7%, p=0.033) [ 13 ]. Similarly, in our case, the patient was started on treatment for the suggested IMDC with high-dose steroids.…”

Section: Discussionmentioning

confidence: 99%

Checkpoint Inhibitor Colitis With Superimposed Clostridioides difficile Infection

Mohammad¹,

Kusnik²,

Mostafa³

et al. 2023

Cureus

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Immune checkpoint inhibitors (ICI) are commonly used for various malignancies. A particular checkpoint inhibitor is the anti-PD-1 antibody pembrolizumab. Immune-mediated diarrhea and colitis (IMDC) is the most frequently observed immune-related adverse event (irAE) involving the gastrointestinal system. Although immune-mediated colitis precipitated by pembrolizumab is rarely life-threatening, it often necessitates a detailed diagnostic workup, including stool studies, imaging, and colonoscopy, to establish an accurate diagnosis. The coexistence of IMDC and Clostridioides difficile infection is not well understood, but patients undergoing pembrolizumab treatment have comparable risk factors to those who develop C. difficile infection. We report a case of a 76-year-old female with nonmetastatic non-small cell lung cancer who was diagnosed with IMDC responsive to steroid treatment but later developed worsening diarrhea leading to a diagnosis of checkpoint inhibitor colitis with superimposed C. difficile infection.

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Section: Discussionmentioning

confidence: 99%

Checkpoint Inhibitor Colitis With Superimposed Clostridioides difficile Infection

Mohammad¹,

Kusnik²,

Mostafa³

et al. 2023

Cureus

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“…In a retrospective study, 27 among 345 patients who received 492 terms of chemotherapy regimens, 36 (7.3%) had grade 2 or higher diarrhea, and eight had CDI without prior exposure to antibiotics. In a prospective study, 27 five cases of CDI were diagnosed among 263 patients with lung In a recent retrospective study, 28 among 421 patients with cancer receiving immunotherapy including programmed death-1 or its ligand inhibitors or cytotoxic T-lymphocyte-associated antigen 4 inhibitors, 41 patients had CDI (9.7%). Prior use of antibiotics and PPIs were significantly more common among individuals who CDI after immune checkpoint inhibitors exposure.…”

Section: Discussionmentioning

confidence: 99%

“…In a recent retrospective study, 28 among 421 patients with cancer receiving immunotherapy including programmed death-1 or its ligand inhibitors or cytotoxic T-lymphocyte-associated antigen 4 inhibitors, 41 patients had CDI (9.7%). Prior use of antibiotics and PPIs were significantly more common among individuals who developed CDI after immune checkpoint inhibitors exposure.…”

Section: Discussionmentioning

confidence: 99%

Clinical Impact of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Associated Clostridioides difficile Infection Among Patients with Lung Cancer

Chung

Lin

Hung

et al. 2022

OTT

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Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs)-associated Clostridioides difficile infection (CDI) among lung cancer patients have been reported in case reports and adverse events reporting system databases in the United States and Japan, but clinical data remained insufficient. This study aims to evaluate CDI in lung cancer patients receiving EGFR-TKIs. Methods: We conducted a retrospective cohort study using multi-institutional electronic medical records database. We included patients aged older than 20 years diagnosed with lung cancer and treated with EGFR-TKIs (gefitinib, erlotinib, afatinib). We defined EGFR-TKI initiation date as the index date and occurrence of diarrhea with CDI or without CDI as the event date. We followed patients from the index date until the event date, ICU admission, death, or 12/31/2019. Results: We included 2242 diarrhea patients, 51 were EGFR-TKI with CDI cohort, and 2191 were diarrhea without CDI cohort. Patients who were concurrently taking antibiotics (hazard ratio [HR], 3.30; 95% CI, 1.67-6.5) and systemic steroids (HR, 4.9; 95% CI, 2.65-9.06) had an increased risk of CDI. First-generation EGFR-TKIs tended to be associated with an increased risk of CDI compared with afatinib (HR, 1.81, 95% CI, 0.94-3.47). EGFR-TKI with CDI had a higher ICU admission rate (HR, 3.42, 95% CI, and mortality rate (HR, 2.34, 95% CI,) than diarrhea without CDI. Conclusion: Patients with CDI had higher ICU admission rates and mortality rates than those without CDI. Concurrent use of antibiotics and systemic steroids were risk factors for CDI among patients with lung cancer receiving EGFR-TKIs. Afatinib was not associated with a higher risk of CDI than first-generation EGFR-TKIs.

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“… 1 , 2 Generally, ICI‐induced colitis is similar to ulcerative colitis (UC), and therefore, similar treatment strategies are followed for treating both of them. In addition, similar to the clinical course of UC, few studies have reported the resistance to treatment due to complications of Clostridioides difficile infection (CDI), 3 , 4 which may be severe and fatal at times, and thus, demands appropriate treatment.…”

Section: Introductionmentioning

confidence: 99%

A case of refractory immune checkpoint inhibitor‐induced colitis with Clostridioides difficile infection

et al. 2022

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The clinical symptoms of an immune checkpoint inhibitor (ICI)‐induced colitis are similar to those of ulcerative colitis. ICI‐induced colitis, like ulcerative colitis, may be complicated by other colitis, such as Clostridioides difficile infection (CDI). A 72‐year‐old man was admitted because of watery and bloody stools 10 times a day after three courses of nivolumab (antibodies against programmed death 1) and ipilimumab (cytotoxic T‐lymphocyte‐associated antigen‐4) for stage IV renal cell carcinoma. Colonoscopy revealed erythema and multiple erosions in the colon. Histopathological examination of colonic mucosa revealed diffuse inflammatory cell infiltration and apoptosis. The initial cytomegalovirus antigen test and C. difficile detection assay results were negative. Based on these findings, we diagnosed the patient with ICI‐induced colitis and discontinued ICI therapy. The symptoms did not improve despite the administration of Prednisolone and infliximab. A repeat colonoscopy revealed a new appearance of pseudomembranes from the sigmoid colon to the rectum one month after the start of these treatments. At this point, the patient tested positive for C. difficile . With treatment with vancomycin for CDI, the abdominal symptoms gradually decreased. Nivolumab alone was cautiously restarted. However, no colitis recurrence and further tumor reduction were observed. Here, we report our experience of a case of refractory ICI‐induced colitis complicated by CDI. ICI‐induced colitis may be complicated by CDI and should be carefully treated with repeated CDI testing if refractory to treatment. We believe that our observation will provide helpful information for determining an appropriate treatment strategy for ICI‐induced colitis.

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Clostridioides difficile infection in cancer patients receiving immune checkpoint inhibitors

Cited by 4 publications

References 28 publications

Checkpoint Inhibitor Colitis With Superimposed Clostridioides difficile Infection

Checkpoint Inhibitor Colitis With Superimposed Clostridioides difficile Infection

Clinical Impact of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Associated Clostridioides difficile Infection Among Patients with Lung Cancer

A case of refractory immune checkpoint inhibitor‐induced colitis with Clostridioides difficile infection

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