Clostridium difficile infection following colon subtotal resection in a patient with gallstones: A case report and review of literature

Abstract

BACKGROUND

Clostridium difficile (C. difficile) infection (CDI) is a rare clinical disease caused by changes in the intestinal microenvironment, which has a variety of causes and a poor prognosis, and for which there is no standardized clinical treatment.

CASE SUMMARY

A patient experienced recurrent difficulty in bowel movements over the past decade. Recently, symptoms worsened within the last ten days, leading to a clinic visit due to constipation. The patient was subsequently referred to our department. Preoperatively, the patient was diagnosed with obstructed colon accompanied by gallstones. Empirical antibiotics were administered both before and after surgery to prevent infection. On the fourth day post-surgery, symptoms of CDI emerged. Stool cultures confirmed the presence of C. difficile DNA. Treatment involved a combination of vancomycin and linezolid, resulting in the patient's successful recovery upon discharge. However, the patient failed to adhere to the prescribed medication after discharge and was discovered deceased during a follow-up two months later.

CONCLUSION

CDI is the leading cause of nosocomial post-operative care, with limited clinical cases and poor patient prognosis, and comprehensive clinical treatment guidelines are still lacking. This infection can be triggered by a variety of factors, including intestinal hypoxia, inappropriate antibiotic use, and bile acid circulation disorders. In patients with chronic bowel disease and related etiologies, prompt preoperative attention to possible CDI and preoperative bowel preparation is critical. Adequate and prolonged medication should be maintained in the treatment of CDI to prevent recurrence of the disease.

Key Words: Cholecystolithiasis; Clostridium difficile; Bile acid circulation; Intestinal microenvironment; Case report

Core Tip: Clostridium difficile infection, a rare and serious condition, often lacks standardized treatment. A case involved obstructed colon and subsequent infection post-surgery, successfully treated with vancomycin and linezolid. However, non-adherence to medication led to patient fatality. Timely preoperative assessment and prolonged treatment are crucial for chronic bowel disease patients. More comprehensive clinical guidelines are needed.

INTRODUCTION

Clostridium difficile (C. difficile), a bacterium predominantly found in soil and the intestinal environment, was initially isolated from the feces of newborns and termed "C. difficile" by Hall and O'Toole[1]. This bacterium constitutes a part of the normal gut microbiota, which accounts for 70% of the total microbial population in the human body. Alterations in the gut microbiota, triggered by factors such as the use of antibiotics, disruptions in the bile acid cycle, and chronic intestinal hypoxia, can lead to the development of C. difficile infection (CDI)[2]. In clinical settings, CDI often manifest with multidrug resistance. Currently, the primary diagnostic approach involves confirming the presence of toxigenic strains or toxins in fecal samples based on clinical symptoms and laboratory test results[3]. While relatively rare in clinical practice, we now present a case of a cholecystolithiasis patient from the First Hospital of Jilin University, who developed a CDI following a colon subtotal resection. In this report, the patient has given written consent, all identifiable information has been removed to protect privacy, and the use of clinical data and images has been done with the patient's consent and in compliance with the data use policy of the relevant healthcare institution, we collected various data since his onset, as described below.

CASE PRESENTATION

Chief complaints

A 58-year-old male patient presented with a history of constipation that commenced a decade ago. He experienced infrequent bowel movements occurring every 3 to 4 days, without accompanying abdominal pain or distention.

History of present illness

Over the years, he resorted to self-administered laxatives, which provided temporary relief. However, in the past ten days, the patient's condition deteriorated, and he ceased to pass stools, coupled with progressive abdominal distension.

History of past illness

Seeking further medical intervention, the patient sought outpatient care at our institution and was admitted to our department on October 8, 2022, with a primary diagnosis of "constipation".

Personal and family history

The patient denied any family history of malignant tumours.

Physical examination

The physical examination found no positive signs.

Laboratory examinations

No significant abnormal results were found in laboratory tests.

Imaging examinations

An abdominal contrast-enhanced computed tomography (CT) scan revealed the presence of gallstones and a substantial amount of colonic content. Colonic transit studies demonstrated a pronounced reduction in colonic transit speed (refer to Figure 1). Physical examination revealed a flat abdominal contour without significant tenderness or rebound tenderness.

Figure 1 Illustrates two distinct medical conditions diagnosed in October 2022. A: The patient exhibited gallbladder calculi (cholelithiasis) alongside gallbladder wall thickening; B: Observed on October 15, the presence of small intestine gas and fluid accumulation (intestinal gas and fluid retention) was noted.

MULTIDISCIPLINARY EXPERT CONSULTATION

Gallstones can be treated conservatively.

FINAL DIAGNOSIS

Combined with the patient’s medical history, the final diagnosis was CDI.

TREATMENT

Prior to surgery, the patient received a cefazolin (2 g) prophylactic treatment on October 9^th and orally administered a compound polyethylene glycol electrolyte solution. Subsequently, on October 10^th, the patient underwent laparoscopic subtotal colectomy, appendectomy, ascending colon-rectal end-to-end anastomosis, and adhesiolysis. During the procedure, slight dilation of the proximal rectal segment, as well as the absence of cecal pouches in the ascending colon, transverse colon, descending colon, and sigmoid colon, was observed. Combining the patient's medical history and preoperative examination, intraoperative diagnosis was adhesive small bowel obstruction. Postoperatively, the patient received empiric antimicrobial therapy with cefepime.

OUTCOME AND FOLLOW-UP

During the first and second days of postoperative rehabilitation and care, the results of a complete blood count showed a gradual increase in white blood cell count. Although the patient did not exhibit obvious discomfort, considering the physiologic stress response induced by the surgery, we conducted dynamic monitoring. However, on the fourth postoperative day, the patient suddenly developed high fever accompanied by watery diarrhea, with more than 10 bowel movements on that day, presenting with pronounced foul odor. The nursing team informed the doctor in charge of the situation in time, and the doctor in charge adjusted the medication plan in time after checking the patient's situation. Meanwhile, the nursing team carried out the nursing task more strictly and recorded the patient's subsequent defecation frequency and fecal characteristics in detail. Concurrently, the white blood cell count continued to decrease. Two abdominal CT scans reported fluid and gas accumulation within the small intestine, though no significant intestinal constriction was evident, raising the possibility of intestinal infection (Figure 2). The patient received oral montmorillonite and symptomatic supportive therapy to stabilize the internal environment. Furthermore, stool and blood samples were collected for culture, including both aerobic and anaerobic bacteria.

Figure 2 Illustrates two significant observations in the patient's medical records. A: Dated October 15, 2022, we observe evidence of pelvic small bowel constriction; B: Recorded on October 17, 2022, there is a notable presence of intestinal fluid accumulation and gas retention within the small intestine.

Figure 2 illustrates two significant observations in the patient's medical records. In Figure 2A, dated October 15, 2022, we observe evidence of pelvic small bowel constriction. Subsequently, in Figure 2B, recorded on October 17, 2022, there is a notable presence of intestinal fluid accumulation and gas retention within the small intestine.

Postoperative day 5-6: The patient experienced intermittent fever, with temperatures reaching up to 38.5 degrees celsius, and worsening diarrhea, leading to frequent bowel movements. Symptomatic treatment was administered, involving ibuprofen and fluid replacement therapy.

Postoperative Day 7: Results of the bowel culture indicated the presence of C. difficile DNA, specifically the non-toxigenic 027 strain, while blood cultures remained negative. These findings confirmed the diagnosis of "postoperative CDI." Following a consultation with the pharmacy department, the patient received vancomycin (0.5 g vancomycin + 50 mL warm water via nasogastric tube, every 6 hours) and intravenous metronidazole (600 mL, every 12 hours) as part of the antimicrobial treatment. Additionally, a probiotic supplement containing bifidobacterium quadruple live bacteria tablets (0.5 g, three times a day) was incorporated into the treatment regimen.

Subsequently: The patient's symptoms, clinical signs, and laboratory results gradually improved during the treatment period. Key indicators such as high-sensitivity C-reactive protein (CRP), white blood cell count, and total bile acid exhibited changes, as depicted in Figure 3. CRP reached its peak on the 8^th postoperative day, gradually decreasing and approaching normal levels. White blood cell count increased on the 2^nd postoperative day, subsequently decreasing, with a brief increase on the 5^th day, and continued elevation from the 11^th day, stabilizing around the 13^th day. Total bile acid levels began to rise on the 2^nd day, peaked on the 8^th day, and then gradually decreased.

Figure 3 Indicators and medication regimens upon patient admission. CRP: C-reactive protein.

On October 23, 2022, the patient was discharged with instructions to continue oral vancomycin for two additional weeks. However, during a follow-up two months after discharge, it was noted that the patient, due to non-compliance with the prescribed antibiotic regimen, experienced a recurrence of symptoms, including high fever, diarrhea, and vomiting related to gastrointestinal infection. The patient sought care at a local hospital, but the symptoms progressed, ultimately leading to multi-organ failure and an unfortunate demise.

DISCUSSION

In this case, the use of cefoperazone (2 g) prior to surgery and ertapenem following it emerged as significant risk factors for the challenging CDI. Furthermore, the patient had a long history of constipation, which may have contributed to a chronically anaerobic intestinal environment and potentially altered the composition of the gut microbiota, leading to an increased proportion of anaerobic bacteria, thus creating a favorable postoperative environment for CDI to some extent.

Additionally, under normal circumstances, cholesterol in the human body undergoes metabolism to synthesize primary bile acids, which are then excreted into the intestines with bile. These primary bile acids are further transformed into secondary bile acids through the action of the gut microbiota. For patients with a history of gallstones, this could signify the presence of bile stasis and impaired excretion, resulting in reduced primary bile acids in the intestines. Moreover, antibiotic usage may alter the gut microbiota, leading to decreased synthesis of secondary bile acids. Consequently, the relative abundance of primary bile acids may increase. Primary bile acids stimulate the growth of C. difficile, while secondary bile acids inhibit C. difficile production[4]. Therefore, it is of particular importance to focus on protecting the liver and promoting bile acid circulation in patients with gallstones to maintain a normal bile acid composition ratio.

As the use of antibiotics continues to advance, the incidence of CDI has been steadily increasing. This increase is primarily associated with alterations in the gut microbiota balance resulting from antibiotic use[5]. CDI typically has an incubation period of 2-3 days, and patients with gallstones often experience disturbances in the bile acid cycle[6]. Some gallstone patients who undergo gastrointestinal surgery during their hospitalization may subsequently develop CDI, and there is even a school of thought suggesting that patients may already carry latent infections upon admission[7].

In the conventional antibiotic treatment of patients following CDI, there is a need to reestablish a healthy gut microbiota[8], which typically requires 2-3 years. If C. difficile continues to maintain dominance in the intestinal microbiome after the microbiota reconstitution, it can potentially lead to the recurrence of CDI[9]. The potential mechanisms for this phenomenon are illustrated in Figure 4.

Figure 4  Potential mechanisms of Clostridium difficile infection caused by gallstones.

The primary cause of post-operative care within hospitals is CDI, commonly found in intensive care units or critically ill patients. Clinical manifestations of CDI typically include mild to moderate diarrhea, which can be watery, bloody, or accompanied by mucous and pus in the stool; characteristic patches or filamentous pseudomembranes might be visible in the stool[10]. Presently, detecting C. difficile toxin B remains the most specific method for CDI diagnosis[11]. The usage of different antibiotics, especially clindamycin, second and third-generation cephalosporins, fluoroquinolones, and macrolides, can alter the proportions of various microbial communities, disrupt the intestinal microbiota balance, and increase the risk of CDI. Furthermore, research indicates that mechanical bowel preparation before surgery and the addition of oral antibiotics during this preparation do not increase the risk of post-colon surgery CDI, emphasizing the importance of proactive preoperative preparation[12]. However, studies also suggest cautious use of laxatives, first and second-generation narrow-spectrum cephalosporins, or metronidazole, as they may have protective effects against CDI[13].

Patients often experience symptoms such as fever, lower abdominal pain, tenderness, and bloating. Therefore, we recommend routine examinations for patients exhibiting these symptoms postoperatively to exclude CDI. Early detection and implementation of preventive and therapeutic measures are crucial to preventing outbreaks of nosocomial CDI. Moreover, most patients infected with C. difficile usually exhibit an elevated white blood cell count. However, in this case, the patient's white blood cell count decreased to a critical level after reaching its peak, possibly related to C. difficile-induced bone marrow suppression, although the specific mechanism remains unclear. During follow-ups after surgery, patients might face the risk of death, including recurrence of CDI due to inadequate use of vancomycin. Hence, healthcare professionals should actively explain the necessity of complete antibiotic usage to patients, aiming to improve patient compliance and consequently enhance the prognosis of patients after colon surgery.

Previous reports have documented cases of difficult CDI occurring after total colectomy[14], total hip arthroplasty[15], and ileal pouch-anal anastomosis surgery[16]. As a result, there is a need to standardize the treatment approaches for CDI. Currently, recommended treatments for CDI include oral metronidazole (for milder cases) and oral vancomycin or fidaxomicin (for more severe cases), typically administered for a 10-day course per dose. Severe CDI cases often necessitate colectomy. For the treatment of the first recurrence, the same medication used for the initial episode is typically employed. In cases of a second recurrence, medication dosages are usually tapered or prolonged courses of vancomycin are considered to facilitate gut microbiota restoration, or alternative medications like fidaxomicin may be explored. There have also been reports of successful treatment of patients with nonmotile intestinal obstruction and concurrent CDI using intracolonic vancomycin[17].

In contrast to antibiotic therapy, ileostomy or colon irrigation serves as an alternative to colectomy for the treatment of severe and complicated CDI, aiming to preserve the colon[18]. Additionally, intestinal oxygen therapy has been successfully employed in the treatment of pediatric C. difficile colitis[19]. Bacterial therapy through fecal microbiota transplantation is also considered an emerging approach for the management of recurrent cases[20].

Linazolid may potentially offer protective effects against CDI and can be considered for selective use. But the drug is generally more effective at preventing CDI, and vancomycin is still the treatment of choice after an infection has already occurred[21]. The antibacterial effect of Tidazoid in vitro has been proven[22], and it can also become a new drug for clinical treatment after clinical trials in the future. In the event of a CDI, healthcare personnel should pay special attention to surgical hygiene to prevent cross-infections. Patients should be isolated individually and provided with dedicated restroom facilities to minimize the risk of C. difficile transmission. Additionally, pulsed xenon ultraviolet disinfection can be effectively employed to address surface contamination by C. difficile.

C. difficile primarily spreads the disease through spore transmission, leading to a recurrence rate as high as 30%[23]. Its primary mechanism may be related to alterations in fecal bile acids induced by the antibiotics used in treatment, resulting in a reduction in primary bile acids and an increase in secondary bile acids[24]. Primary bile acids promote the germination of C. difficile spores, while secondary bile acids have the opposite effect[25]. Recurrent patients often experience disruptions in bile acid circulation; thus, post CDI, regulating the patient's bile acid circulation is necessary to prevent disease recurrence.

In the study conducted by Maseda et al[26] initial CDI was primarily associated with the use of two broad-spectrum antibiotics, cephalosporins, and clindamycin. Other research indicates that proton pump inhibitors, nonsteroidal anti-inflammatory drugs, and the laxative polyethylene glycol solution may also increase the incidence of C. difficile by damaging the gastrointestinal mucosa and altering intestinal colonization resistance[27-29].

As research delves deeper, preventing CDI in the intestinal tract appears to be more intricate than safeguarding against the spore-forming CDI. Owing to the diversity in clinical presentations, the severity of symptoms can vary greatly; milder cases may manifest with abdominal pain and diarrhea, while more severe cases may involve severe diarrhea, toxic megacolon, intestinal obstruction, and colonic dilation. In the case of initial CDI, where the intestinal mucosa is mildly damaged, probiotics are commonly employed to expedite the restoration of intestinal microbiota[30]. Initial cases of CDI are typically treated with a combination of vancomycin and other high-level antibiotics, which has shown effective outcomes. However, due to the broad-spectrum nature of these antibiotics, they have a widespread impact on the intestinal microbiota. Therefore, current research is gradually expanding to investigate the use of narrow-spectrum antibiotics such as fidaxomicin[31,32]. Failure of patients to adhere to the prescribed antibiotic course could lead to a fatal outcome, increasing the likelihood of recurrent CDI. Hence, healthcare professionals should actively emphasize the necessity of completing the full course of antibiotics to improve patient compliance and subsequently enhance the prognosis of CDI patients following colon surgery.

In cases of recurrent and refractory CDI, the intestinal mucosa and normal intestinal microbiota typically endure more severe damage. The natural recovery of intestinal microbiota is relatively slow in such situations. In these instances, fecal microbiota transplantation with a success rate ranging from 85% to 95%[33-35] is a viable option. Compared to natural recovery, exogenous microbiota can expedite the restoration of intestinal microbiota balance, inhibit the growth of refractory C. difficile, and thereby achieve therapeutic effectiveness[27].

Post-gastrointestinal surgery CDI invariably arises from C. difficile becoming the dominant microbial community within the intestinal tract, often presenting as pseudomembranous enteritis. If left untreated, pseudomembranous colitis can lead to severe diarrhea, hypovolemic shock, toxic colonic dilatation, cecal perforation, bleeding, and death. Consequently, in patients with concurrent intestinal obstruction, severe abdominal pain, noticeable tenderness, immunosuppression, advanced age, high white blood cell count, acute renal dysfunction, altered mental status, or cardiopulmonary impairment, an early surgical consultation should be considered, with emergency surgical intervention if necessary[36].

For patients with vancomycin-resistant clostridium difficile infection, nursing care should include the following meticulous measures: (1) Strictly implement isolation measures to ensure that patients are isolated individually and, if necessary, transferred to the intensive care unit for treatment, and that healthcare workers wear the appropriate level of protective gear; (2) Pay close attention to the patient's condition, and record and report any symptomatic changes in a timely manner. In addition, keep the environment in which the patient is living clean, emphasizing regular disinfection and cleaning of contaminated items such as those in the ward[37]; and (3) Patient care should be combined with medical measures, medication should be administered according to prescribed protocols, and doctors should be cooperated in monitoring and evaluating the condition and making timely adjustments to the treatment program[38]. These nursing measures should be implemented according to the specific conditions of the patient and under the guidance of the doctor to ensure that the patient receives scientific and effective care and treatment.

CDI post colon subtotal resection: Case review limitations of this study mainly include the small number of patients, which may have some individual variability, and the fact that patient deaths occurred out-of-hospital, which may have some confounding factors. In the future, with CDI, they should be examined for the presence of specific complications similar to methicillin-resistant staphylococcus aureus pneumonia, which may be an influential factor in the prognosis of infected patients. We may need prospective studies on the etiology of CDI to further explore the mechanism of CDI.

CONCLUSION

In conclusion, this case highlights the importance of being vigilant for CDI in patients undergoing gastrointestinal surgery, especially those with risk factors such as antibiotic use and a history of constipation. Early diagnosis and prompt treatment are crucial in managing C. difficile infections post-surgery. Healthcare providers should focus on preventive measures, routine monitoring, and patient adherence to treatment regimens to improve outcomes and minimize the risk of recurrent infections. Further research is needed to explore effective strategies for preventing and treating C. difficile infections in surgical patients.

ACKNOWLEDGEMENTS

Thank for all the patients in this research, thank for all the scholars in this article. Thank for all the teammates for supporting this research. We are also particularly grateful to our colleagues in The First Affiliated Hospital of Jilin University for their contributions.