Severe Pseudomembranous Colitis Following Distal Femur Plating: A Case for Early Endoscopic Evaluation Despite Negative Clostridioides difficile Testing

Abstract

Pseudomembranous colitis is a serious complication typically linked to Clostridioides difficile following antibiotic use. Even when standard diagnostic tests are negative, persistent symptoms should warrant early endoscopic evaluation. This case highlights the diagnostic and therapeutic approach in an elderly postoperative patient.

An 88-year-old female underwent distal femur plating surgery complicated by postoperative septic shock, which was treated by broad-spectrum antibiotics. Subsequently, she developed high-volume diarrhea, abdominal pain, and leukocytosis. Initial C. difficile polymerase chain reaction testing was negative. Owing to unresolved gastrointestinal symptoms and strong clinical suspicion, colonoscopy was performed, revealing extensive pseudomembranous colitis. The patient received targeted antibiotic therapy and supportive care. Her symptoms resolved fully, and follow-up endoscopy confirmed mucosal healing. This case underscores the limitations of polymerase chain reaction for C. difficile, particularly in the context of strong clinical suspicion. Early endoscopic assessment should be considered in patients with persistent diarrhea despite negative laboratory findings. Moreover, this illustrates the critical role of antibiotic stewardship in preventing severe colitis.

 

Scroll to top

Keywords

colitis - Clostridioides difficile - endoscopy - polymerase chain reaction - diarrhea - antibiotic-associated

Introduction

Clostridioides difficile is an anaerobic bacterium responsible for most of the diarrheal cases in Europe and North America.[1] This toxigenic bacterium is estimated to have a 30-day mortality rate of 5.8% and an annual infection rate exceeding half a million.[1] [2] The incidence as well as severity of C. difficile infection (CDI) have significantly increased in the past two decades, making it the most common nosocomial infection.[1] [2] The most common cause of its infection is using antibiotics such as cephalosporins, clindamycin, penicillin, etc.[1] [3] Apart from this, chronic kidney disease, chronic liver illness, malnutrition, previous infection with C. difficile, and use of proton-pump inhibitors are some of the etiological factors.[1] [3] [4]

Antibiotic-associated CDI typically presents as acute watery diarrhea in more than 20% of patients.[1] [3] In advanced cases, complications such as fulminant colitis, sepsis, and toxic megacolon may occur, often with the formation of pseudomembranes in the intestine.[1] In rare instances, protein-losing enteropathy and reactive arthritis have been reported as complications.[1] Laboratory diagnostic methods include cytotoxic assay, enzyme-linked immunoassay (EIA), nucleic acid amplification test (NAAT), and toxigenic culture specific to C. difficile toxigenic strains. However, in some cases, despite negative test results for the bacterium, patients exhibit clinical symptoms resembling CDI.[1] Such patients need advanced investigations such as computed tomography (CT), colonoscopy, and magnetic resonance imaging to confirm the presence of active C. difficile colitis.

In the present case, we report a similar patient with postoperative septic shock with negative laboratory investigations for C. difficile but pseudomembranous colitis on colonoscopy. Though such cases are uncommon, they highlight the complexity of antibiotic-associated diarrhea (AAD), especially in elderly patients with multiple comorbidities. The screening investigations should be supplemented by a thorough clinical examination, with CDI considered as a differential diagnosis.

 

Scroll to top

Case Report

An 88-year-old female was transferred to a tertiary care facility on May 11, 2024, from an outside hospital for further management following a postoperative septic shock. She had undergone left distal femur plating under spinal anesthesia on May 9, 2024, after a fall at her home 2 weeks earlier, which resulted in a left distal femur periprosthetic fracture. In the immediate postoperative period, she developed high-grade fever, hypotension requiring vasopressor support, sweating, and dizziness. After transferring to the intensive care unit (ICU), her laboratory parameters showed mild anemia, normal white blood cell count with a neutrophilic predominance, elevated inflammatory markers, and mild electrolyte imbalance. Low procalcitonin indicated an absence of severe systemic bacterial infection ([Table 1]). Mildly elevated cardiac markers suggested myocardial stress likely secondary to hypotension rather than acute coronary syndrome, given normal serial cardiac enzymes and no fresh electrocardiogram (ECG) changes.

Table 1 Investigations table

	15/05	16/05	17/05	18/05	19/05	20/05	21/05	22/05	23/05	24/05	25/05	27/05
Hemoglobin (g/dL)	9.7	10.6	9.1	8.6	8.7	8.6	8.4	7.8	10.3	10.6	11	11
Leukocytes count (×103)	6.92	12.9	5.93	10	13	14	91	0	8	8	9	9
CRP	8.9	203	240	249	139	85.5	136	162	84.7	54.8		17.9
PCT		1.65		0.49		0.176						0.173
Sodium	134	135	133	131	135	133	131	136	138	136	132	133
Potassium	3.74	5.07	3.96	4.74	3.87	4.39	3.41	3.77	4.10	4.12	3.93	3.88
Creatinine	0.58	0.87		0.62		0.51		0.46		0.51		0.50
C. difficile testing			GE PCR panel negative	C. difficile toxin (real-time RT-PCR CB-NAAT) - not detected			C. difficile toxin (real-time RT-PCR CB-NAAT) - not detected	EGD scopy and colonoscopy

Abbreviations: CB-NAAT, cartridge-based nucleic acid amplification test; CRP, C-reactive protein; EGD, esophagogastroduodenoscopy; PCT, procalcitonin; RT-PCR, reverse transcription polymerase chain reaction.

She had background of ischemic heart disease (status post-percutaneous transluminal coronary angioplasty in 2016) with an ejection fraction (EF) of 40%, hypothyroidism, trigeminal neuralgia, bilateral total knee replacement, and cataract excision. Initial investigations showed a right bundle branch block and new anteroseptal T-wave inversion in anterior leads on ECG, though serial cardiac enzymes were normal. A two-dimensional echocardiogram indicated no change with an EF of 40% and no right ventricular dysfunction. Laboratory results revealed a drop in hemoglobin, leukocytosis, and elevated inflammatory markers. She was started on intravenous meropenem and teicoplanin and received one unit of packed cell volume along with intravenous iron supplementation (ferric carboxymaltose). She was shifted back to ward on hospital day 4.

On hospital day 5, the patient developed severe hypotension (blood pressure [BP]: 70/40 mm Hg), altered sensorium, and abdominal discomfort. She was resuscitated with 500 mL of crystalloid, improving her BP to 100/60 mm Hg, but she remained drowsy and complained of persistent abdominal discomfort. She was subsequently transferred back to the ICU for close monitoring and intravenous fluid management. Despite initial stability, she experienced recurrent episodes of hypotension and severe lower abdominal pain. Examination revealed hard, impacted stools, prompting manual evacuation, enema, and administration of laxatives.

Further laboratory workup showed mild abnormalities. Imaging studies, including chest X-ray and abdominal ultrasound, were unremarkable except for gaseous dilated bowel loops. A CT scan of the abdomen and pelvis revealed fecal-loaded colonic loops with a maximum diameter of 5.2 cm in the sigmoid colon and mild circumferential wall thickening in the descending colon ([Fig. 1A]).

Fig. 1 (A) A computed tomography (CT) scan revealing thickened colon wall. (B) Colonoscopy showing extensive pseudomembranous colitis in the rectum and sigmoid colon.

The patient developed frequent watery, foul-smelling diarrhea, with up to 15 episodes per day. A gastroenteritis polymerase chain reaction (PCR) panel (hospital day 7) and C. difficile toxin assay (hospital day 8) were negative ([Table 1]). However, because of the high clinical suspicion of colitis, endoscopic evaluation was performed. Esophagogastroduodenoscopy revealed a hiatus hernia and mottled erythematous mucosa in the gastric body and antrum. A colonoscopy on hospital day 12 showed extensive pseudomembranous colitis in the rectum and sigmoid colon with mucosal friability and erythema ([Fig. 1B]). A rectal biopsy confirmed pseudomembranous colitis. On histopathology of the rectum, multiple greyish, friable tissue bits aggregated to 0.7 cm gross and intact to ulcerated rectal mucosa were observed on microscopy ([Fig. 2]). The later was covered with acute inflammatory exudate. However, the lamina propria showed moderately increased inflammatory infiltrate.

Fig. 2 A histopathology of the rectum showing acute inflammatory exudate.(A) Crypt abscesses and acute inflammatory infilterates.(B) Dense neutrophilic infilteration of lamina propria.

The patient was managed in isolation with contact precautions and barrier nursing. Tablet vancomycin (250 mg four times a day), vancomycin retention enema, and injection metronidazole (500 mg three times a day) were initiated. She showed clinical improvement with reduced stool frequency and consistency, improved oral intake, and was gradually mobilized. She was shifted out of ICU. However, on hospital day 22, she became drowsy and was shifted back to the ICU. The evaluation showed hypoventilation secondary to drowsiness (SpO₂ 92–93% on room air) and a urine routine revealing 50 to 55 pus cells/hpf. Urine culture grew multidrug-resistant Klebsiella sensitive only to a combination of ceftazidime-avibactam and aztreonam. Hence, started on these medications. Despite initial improvement, she developed increased stool frequency, necessitating discontinuation of these antibiotics after 7 days.

Vancomycin was continued for 4 weeks, while metronidazole was given for 10 days. Repeat endoscopy (on June 10, 2024) was done, which showed remarkable improvement and she was shifted back to ward ([Fig. 3]). Patient's condition stabilized, with a reduced frequency of diarrhea and improved oral intake, and she was discharged on hospital day 42.

Fig. 3 Repeat colonoscopy showing improvement in large intestine.

On periodic follow-up after her discharge, patient has been doing very well clinically with improved oral intake.

 

Scroll to top

Discussion

The current case presented the diagnostic and therapeutic challenges of management of pseudomembranous colitis in an elderly patient following distal femur plating. It underscored early recognition, diagnostic diligence, and judicious antibiotic use in postoperative sepsis and AAD. Differential diagnosis could be AAD; noninfectious osmotic diarrhea due to cathartic agents like laxative, milk, and magnesium salts; chronic underlying condition—inflammatory bowel disease (IBD) and irritable bowel syndrome; and infectious diarrhea caused by Salmonella/Shigella/Vibrio/amoeba. Each condition may present with diarrhea, abdominal discomfort, and systemic signs of infection or inflammation, making it crucial to evaluate the likelihood of each based on clinical findings, diagnostic tests, and patient history.

The patient was on broad-spectrum antibiotics, which makes AAD a potential diagnosis. However, her symptoms worsened with abdominal pain, fever, and a marked increase in stool frequency, suggesting something more severe than AAD.[5]

C. difficile-associated diarrhea is a common cause of AAD, especially in elderly or immunocompromised patients exposed to broad-spectrum antibiotics.[6] CDI typically manifests with watery, foul-smelling diarrhea, abdominal cramping, fever, and leukocytosis.[6] In severe cases, it leads to pseudomembranous colitis, which was confirmed in this patient through endoscopy and rectal biopsy. Osmotic diarrhea due to cathartic agents (laxatives, milk, magnesium salts) occurs when substances in the intestine cause excess water retention. Cathartic agents, including laxatives (given for impacted stools in this case), milk, or magnesium salts, can lead to diarrhea by drawing water into the gut lumen. The patient was treated with enemas, manual evacuation, and laxatives, which could have temporarily contributed to her diarrhea.[7] The improvement of her symptoms after targeted antibiotic therapy (vancomycin and metronidazole) further supports an infectious origin rather than osmotic diarrhea.

CDI is a significant cause of nosocomial diarrhea, particularly in patients with recent antibiotic exposure, hospitalization, or advanced age. The pathogenesis of CDI involves disruption of normal gut flora, colonization by C. difficile, and subsequent production of exotoxins—primarily toxins A and B. These toxins inactivate Rho GTPases, leading to cytoskeletal disassembly, apoptosis of colonic epithelial cells, and formation of pseudomembranes, a hallmark of severe colitis.[8] [9]

Diagnosis of CDI should be considered in patients with unexplained, new-onset diarrhea (≥ 3 unformed stools in 24 hours) and risk factors such as antibiotic use.[10] Only liquid stool should be submitted for testing, as formed stools from asymptomatic individuals may reflect colonization rather than active infection and do not require treatment.[10] A key limitation in diagnosis is that C. difficile toxins degrade rapidly at room temperature and may become undetectable within 2 hours. Therefore, stool samples should be tested promptly or stored at 4°C if delays are expected.[10]

Laboratory diagnosis begins with either a single or multistep algorithm. Glutamate dehydrogenase (GDH) is a highly sensitive enzyme produced by both toxigenic and non-toxigenic strains of C. difficile, making it a useful screening tool with high negative predictive value. However, its lack of specificity necessitates further confirmatory testing.[11]

The most widely used confirmatory test is the EIA for toxins A and B. Though rapid and widely available, EIAs have variable sensitivity (75–85%) and excellent specificity (95–100%). Due to their limited sensitivity, EIAs alone may yield false-negative results, particularly in low-toxin producing strains.[12] [13]

To improve diagnostic accuracy, a two-step or three-step algorithm is recommended. The initial GDH screening is followed by toxin testing, and in cases of discordant results (e.g., GDH positive but toxin negative), a NAAT such as PCR is employed. NAAT detects the toxin genes (TcdA, TcdB) with high sensitivity (80–100%) and specificity (87–99%). However, since NAAT identifies the presence of genes rather than active toxin production, it cannot distinguish between colonization and infection, potentially leading to overdiagnosis.[14]

Stool culture, though considered a gold standard due to its high sensitivity, is time-consuming, labor-intensive, and lacks clinical practicality. Similarly, the cell culture cytotoxicity neutralization assay allows for direct detection of functional toxin activity and is highly specific but is also resource-intensive and not routinely available in most clinical settings.[10]

In complex cases—especially where noninfectious etiologies such as IBD are suspected, or in the presence of atypical symptoms—further evaluation with colonoscopy may be warranted. Colonoscopy is typically reserved for patients with persistent or severe symptoms despite negative stool tests or when toxic megacolon or pseudomembranous colitis is suspected. Endoscopic findings may reveal pseudomembranes, confirming the diagnosis.[10]

In summary, timely diagnosis of CDI relies on a rational sequence of testing—starting with GDH and toxin EIAs and, if needed, confirmed by NAAT. Test results should always be interpreted in conjunction with clinical findings to guide appropriate management and avoid overtreatment of asymptomatic carriers

In our institute, GDH testing is not available; hence, NAAT for C. difficile was performed directly. Despite testing the patient with a comprehensive gastroenteritis PCR panel once and C. difficile-specific NAAT twice, all results were negative. Given the persistence of symptoms and high clinical suspicion, we proceeded with colonoscopy, which provided crucial diagnostic insights and guided further management.

In cases of AAD being unresponsive to initial management, a low threshold for endoscopic evaluation should be maintained, as early diagnosis and targeted therapy can significantly improve patient outcomes. Though a rarely reported case, it also reinforced the need for strict antibiotic stewardship and infection control measures in high-risk populations.

 

Scroll to top

 

Scroll to top

Conflict of Interest

None declared.

Acknowledgments

None.

Ethical Statement

Written informed consent was obtained from the patient for the publication of this case report and any accompanying images.

Authors' Contributions

A.J. drafted the initial manuscript and conducted the literature review; B.S. contributed to the manuscript revision; and P.D. performed the endoscopy and help with clinical images.

• References

• 1 Bassi R, Prakash P, Oyetoran A, Elsadek R, Loseke I, Leibach JR. A Review on Clostridioides Difficile Testing and How to Approach Patients With Multiple Negative Tests: A Case Report. Cureus [Internet]. January 27, 2023 . Accessed October 3, 2024 at: https://www.cureus.com/articles/132210-a-review-on-clostridioides-difficile-testing-and-how-to-approach-patients-with-multiple-negative-tests-a-case-report
• 2 Mada PK, Alam MU. Clostridioides difficile infection. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2024
• 3 Khanafer N, Vanhems P, Barbut F. et al; CDI01 Study group, Teams of. Factors associated with Clostridium difficile infection: a nested case-control study in a three year prospective cohort. Anaerobe 2017; 44: 117-123
• 4 Arriola V, Tischendorf J, Musuuza J, Barker A, Rozelle JW, Safdar N. Assessing the risk of hospital-acquired Clostridium difficile infection with proton pump inhibitor use: a meta-analysis. Infect Control Hosp Epidemiol 2016; 37 (12) 1408-1417
• 5 Coté GA, Buchman AL. Antibiotic-associated diarrhoea. Expert Opin Drug Saf 2006; 5 (03) 361-372
• 6 Oldfield III EC. Clostridium difficile-associated diarrhea: risk factors, diagnostic methods, and treatment. Rev Gastroenterol Disord 2004; 4 (04) 186-195
• 7 Roerig JL, Steffen KJ, Mitchell JE, Zunker C. Laxative abuse: epidemiology, diagnosis and management. Drugs 2010; 70 (12) 1487-1503
• 8 Eaton SR, Mazuski JE. Overview of severe Clostridium difficile infection. Crit Care Clin 2013; 29 (04) 827-839
• 9 Kelly CP, LaMont JT. Clostridium difficile–more difficult than ever. N Engl J Med 2008; 359 (18) 1932-1940
• 10 McDonald LC, Gerding DN, Johnson S. et al. Clinical practice guidelines for clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis 2018; 66 (07) e1-e48
• 11 Kukla M, Adrych K, Dobrowolska A, Mach T, Reguła J, Rydzewska G. Guidelines for Clostridium difficile infection in adults. Prz Gastroenterol 2020; 15 (01) 1-21
• 12 Albrecht P, Pituch H. Clostridium difficile–narastający problem diagnostyczny i terapeutyczny. Onkol Prakt Klin 2013; 9: 22-31
• 13 Jones BL, Wiuff C, Coia JE. UK laboratory diagnosis of Clostridium difficile infection: in a state of transition, confusion, or both?. J Hosp Infect 2012; 81 (03) 216
• 14 Planche T, Aghaizu A, Holliman R. et al. Diagnosis of Clostridium difficile infection by toxin detection kits: a systematic review. Lancet Infect Dis 2008; 8 (12) 777-784

Publication History

Received: 12 March 2025

Accepted: 07 August 2025

Article published online:
09 October 2025