Clostridium difficile infection in orthopaedic patients

In a review of the results of toxin assays, twenty-five orthopaedic patients who had a Clostridium difficile infection and associated diarrhea were identified. The infection was due to the use of antibiotics in all but one patient. Seventeen patients had received the antibiotics prophylactically. The two most commonly implicated antibiotics were cefazolin and clindamycin, because those drugs had been commonly used for prophylaxis at the study institutions. However, other antibiotics were implicated. There was a positive correlation between the delay in diagnosis and the severity of the illness. A white blood-cell count of more than 20 x 10(9) per liter indicated severe disease in our survey. The possibility of Clostridium difficile infection should be considered in patients who have signs and symptoms that mimic those of intestinal obstruction. Patients who have an unexplained fever or high white blood-cell count and in whom diarrhea develops in the postoperative period should be treated immediately with metronidazole, and a specimen of stool should be obtained for an assay for Clostridium difficile toxin. If the diagnosis of Clostridium difficile infection is confirmed by the presence of toxin in the stool and the patient has persistent, severe diarrhea, oral administration of vancomycin should be added to the regimen. The duration of antibiotic prophylaxis should be minimized to decrease the risk of Clostridium difficile colitis.     

Clostridium difficile colitis in surgical patients

The clinical course of 75 patients with diarrhea and positive C. difficile toxin stool assays has been examined. The mean age of the patients was 68 years. Five of 25 surgical nursing units accounted for two thirds of the cases. Many patients were immuno-suppressed with cancer, sepsis, or diabetes mellitus. The median onset of diarrhea was 2.7 days after initial administration of antibiotics. Fever and leukocytosis were frequently seen. Diarrhea ceased in 30 percent of the patients after withdrawal of the offending antibiotics. The remainder required specific therapy with vancomycin, bacitracin, or metronidazole. Two deaths were directly attributable to C. difficile colitis. The hospital stay was prolonged in many patients. C. difficile colitis should be suspected in any patient in whom diarrhea develops during or after a course of antibiotics. Enteric precautions may prevent clustering in these cases and colonization in other susceptible patients.     

Clostridium difficile-associated colitis in uremic patients

Five uremic patients managed in a renal unit developed Clostridium difficile-associated colitis. Four cases occurred in a cluster at about the same time. All patients had previously received or were on antibiotic therapy at the onset of diarrhea and one patient was also on oral steroid therapy. Cefotaxime, a third generation cephalosporin was involved in all five cases. All patients had severe diseases with explosive diarrhea and systemic toxicity. The diagnosis was confirmed in all cases by culture of C. difficile and demonstration of high titers of C. difficile cytotoxin in the stool. Histology from rectal biopsy in one patient showed classical pseudomembranous colitis. Response to treatment with vancomycin was generally good though one patient had two relapses. Uremic patients have impaired immune response and intestinal motility and are predisposed to C. difficile infection. Cross-infection can occur and the isolation of affected patients seems prudent.     

Pseudomembranous colitis: a lethal complication of Hirschsprung's disease unrelated to antibiotic usage

Seventy-two new cases of Hirschsprung's disease were seen between 1980 and 1985. Twenty-six patients (36%) developed the clinical features of enterocolitis and, of nine patients who died, colitis was the immediate cause of death in six. Histologic material was available from 20 patients with colitis; this showed nonspecific inflammation typical of Hirschsprung's colitis in 13 cases but seven had pseudomembranous colitis (PMC). Five of the patients with PMC had not recently been exposed to antibiotics. PMC was responsible for three of the six deaths from colitis. All patients with Hirschsprung's disease who develop signs of colitis should have stool testing for Clostridium difficile toxin and should be treated with an antibiotic active against Clostridium difficile.     

Acute abdomen and Clostridium difficile colitis: still a lethal combination

BACKGROUND: With the steadily prevalent appropriate and inappropriate use of antimicrobial agents, Clostridium difficile colitis has continued to be noticed as a common problem in hospitalized patients. The aim of this communication is to highlight a subset of C. difficile colitis patients who presented with an acute abdomen. METHODS: This is a retrospective study of 10 patients who underwent laparotomy for an 'acute abdomen' with an intraoperative or postoperative diagnosis of C. difficile colitis. RESULTS: All patients received antibiotics (mean 9.5 days) for other illnesses. The mean APACHE II score was 18.8 (range 8-25) and the mortality rate was 80%. Two patients had colostomies created. One patient underwent a subtotal colectomy, and another underwent a Hartmann procedure; the rest had a nontherapeutic procedure. CONCLUSION: We conclude that C. difficile colitis presenting as an 'acute abdomen' still represents a lethal entity. Patients who present with an 'acute abdomen', with a history of recent or current antibiotic intake, and without findings which mandate an exploration should have C. difficile colitis urgently excluded. Timely diagnosis of C. difficile colitis through bedside sigmoidoscopy or a CT scan could spare the critically ill patient an unneccessary and risky operation. Furthermore, if laparotomy is subsequently needed then having a preoperative diagnosis of C. difficile colitis will allow appropriate surgical therapy to be implemented.     

Pseudomembranous colitis following resection for Hirschsprung's disease.

Enterocolitis is the most common cause of significant morbidity and death in Hirschsprung's disease. Although most cases respond to nasogastric decompression, antibiotics, and colonic evacuation, some children have an unusually fulminant or protracted clinical course. Four cases are reported of pseudomembranous colitis (PMC) that developed 1 to 18 months (mean, 8 months) after definitive surgery for Hirschsprung's disease (Soave endorectal pull-though, 2; Duhamel procedure, 2). While all children presented with fever, abdominal distention, and diarrhea, indistinguishable from typical Hirschsprung's enterocolitis, the clinical course was fulminant in two cases, both of whom died of septic shock. Postmortem examination in both showed extensive colonic pseudomembranes despite identification of Clostridium difficile toxin and subsequent vancomycin therapy (initiated late in the clinical course). Two children in the series had protracted hospitalizations and eventually required diverting enterostomy despite recognition of C difficile toxin and treatment with enteral vancomycin, in one child necessitating multiple courses of antibiotic therapy. Awareness of the virulence of PMC associated with Hirschsprung's disease (even after definitive resection) should prompt submission of stool specimens from any child who presents with enterocolitis for both C difficile culture and toxin levels. On the basis of our experience it is our policy to initiate a prompt course of vancomycin by rectal lavage or nasogastric tube in all children with Hirschsprung's enterocolitis, pending culture results, in view of the significant morbidity and mortality exemplified by cases in this review.     

Clostridium difficile colitis: an increasingly aggressive iatrogenic disease?

HYPOTHESIS: The diagnosis of Clostridium difficile colitis is increasing in frequency, with worsening patient outcomes. DESIGN: Retrospective cohort study. SETTING: University hospital. PATIENTS: One hundred fifty-seven patients diagnosed with C difficile colitis between 1994-2000. MAIN OUTCOME MEASURES: Resolution of disease, operative intervention, and death. RESULTS: Compared with our previous 10-year experience, overall cases of C difficile colitis have risen by more than 30%, and immunocompromised patients comprise a larger proportion of those affected. One third of patients were receiving posttransplantation medication, chemotherapy, or had human immunodeficiency virus. Of these, 2 (4%) of 51 required surgical intervention and 10 (20%) of 51 died. An additional 18.5% of patients had diabetes, renal failure, or both. Of these, 2 (7%) of 30 required surgery and 4 (13%) of 30 died. Only 9.5% of patients had prophylactic perioperative antibiotics as a sole risk factor; 2 (13%) of 15 required surgery and 3 (20%) of 15 died. The overall mortality rate was 15.3%, increased from 3.5% in our previous series. Neither need for surgery nor mortality differed among these patient groups. CONCLUSIONS: The frequency of C difficile colitis remains high and seems to be associated with increasing mortality. Among patients with positive C difficile toxin assay results, immunocompromise and delayed diagnosis no longer seem to be associated with higher risk for death. All patients taking antibiotics are at risk and require early recognition and aggressive medical intervention.     

Study on clostridium difficile-associated diarrhea suspected as nosocomial infection in urology ward

Between June 2000 and January 2001, 11 patients were diagnosed with Clostridium diffcile (C. difficile)-associated diarrhea in the ward of urology at the Kakegawa Municipal Hospital. Of these 11 patients, 10 had exposure to antimicrobial agents, before the onset of diarrhea. All patients' stools were positive for C. difficile toxin A. After discotinuing antimicrobial agents with or without administering Vancomycin, they recovered from C. difficile-associated diarrhea. Between January 2001 and September 2002, 17 patients who were diagnosed with C. difficile-associated diarrhea in our hospital were classified into two types by PCR ribotyping. Therefore, we suspected a nosocomial outbreak of diarrhea caused by C. difficile.     

Fulminant Clostridium difficile: an underappreciated and increasing cause of death and complications

OBJECTIVE: To review the epidemiology and characteristics of patients who died or underwent colectomy secondary to fulminant Clostridium difficile colitis. SUMMARY BACKGROUND DATA: In patients with C. difficile colitis, a progressive, systemic inflammatory state may develop that is unresponsive to medical therapy; it may progress to colectomy or death. METHODS: The authors reviewed 2,334 hospitalized patients with C. difficile colitis from January 1989 to December 2000. Sixty-four patients died or underwent colectomy for pathologically proven C. difficile colitis. RESULTS: In 2000, the incidence of C. difficile colitis in hospitalized patients increased from a baseline of 0.68% to 1.2%, and the incidence of patients with C. difficile colitis in whom life-threatening symptoms developed increased from 1.6% to 3.2%. Forty-four patients required a colectomy and 20 others died directly from C. difficile colitis. Twenty-two percent had a prior history of C. difficile colitis. A recent surgical procedure and immunosuppression were common predisposing conditions. Lung transplant patients were 46 times more likely to have C. difficile colitis and eight times more likely to have severe disease. Abdominal computed tomography scan correctly diagnosed all patients, whereas 12.5% of toxin assays and 10% of endoscopies were falsely negative. Patients undergoing colectomy for C. difficile colitis had an overall death rate of 57%. Significant predictors of death after colectomy were preoperative vasopressor requirements and age. CONCLUSIONS: C. difficile colitis is a significant and increasing cause of death. Surgical treatment of C. difficile colitis has a high death rate once the fulminant expression of the disease is present.     

Clostridium difficile in Crohn's disease

Clostridium difficile has been detected in the stools of some patients with relapse of Crohn's disease. The authors looked prospectively for present or previous exposure to C. difficile cytotoxin in 10 patients with mild to severe Crohn's disease. None of 25 stool samples from these 10 patients was positive for C. difficile cytotoxin. These negative stool ultrafiltrates had mild cytotoxin neutralizing activity, but this finding did not differ from that in 30 cytotoxin-negative stools from patients with other diarrheal diseases. Serum from these patients also showed no cytotoxin neutralizing activity. Review of the literature reveals that C. difficile can cause complications ranging from diarrhea to toxic megacolon in a small but variable proportion of patients with Crohn's disease. There is no evidence that C. difficile plays a part in the pathogenesis of the disease.     

Outcome of colectomy for Clostridium difficile colitis: a plea for early surgical management

BACKGROUND: Fulminant Clostridium difficile colitis is a common nosocomial infection that occurs with increasing frequency. METHODS: A total of 3,237 consecutive cases of C difficile cytotoxin-positive stool samples from 1998 to 2006 were reviewed. Commonly referenced indicators for surgical intervention were gathered on the day of surgery. The preoperative characteristics of patients surviving subtotal colectomy were compared with those who did not survive. RESULTS: Thirty-six patients underwent colectomy. Twenty-three patients (64%) were discharged from the hospital alive. Preoperative intubation and vasopressor requirement were risk factors for in-hospital mortality (odds ratio [OR], 7.15; 95% confidence interval [95% CI], 1.28-39.8 and OR, 6.0; CI, 1.08-33, respectively). Patients who had a recent surgical procedure had a lower in-hospital mortality rate (OR, .11; 95% CI, .02-.52). CONCLUSIONS: Fulminant C difficile colitis is associated with a high mortality rate. Development of a vasopressor requirement or need for intubation are ominous signs and should lead to rapid surgical intervention.     

Pneumatosis cystoides intestinalis in children beyond the first year of life: manifestations and management.

Beyond infancy, pneumatosis cystoides intestinalis (PCI) is rare. Data concerning pathogenesis and treatment are limited. Our experience with 12 children was examined to define predisposing factors, presentation, treatment, and outcome. Nine children were immunosuppressed, thus identifying an important etiologic subgroup. Presentation was variable but included abdominal pain, distention, diarrhea and hematochezia. Clostridium difficile was found in 3 patients and cytomegalovirus in 1. Radiographs showed free air in 3. Nine were treated with antibiotics and bowel rest, 1 with bowel rest alone, 1 with oral metronidazole, and 1 with observation. PCI resolved in 7 of 9 treated with antibiotics, although 1 child with leukemia had severe hematochezia secondary to colonic ulceration and required hemicolectomy. No other patient required laparotomy. The free air resolved in 2 of 3. There were 2 deaths, both from sepsis. One had free air on admission but no perforation was found at autopsy. Treatment recommendations remain unclear; however, C difficile and cytomegalovirus are important pathogens that should be identified and treated promptly. In symptomatic patients, bowel rest and antibiotics seem beneficial. Operative intervention should be reserved for patients with peritoneal signs, progressive deterioration, obstruction, or persistent, severe bleeding. Free air alone is not an indication for operative management in children with PCI.     

Preoperative oral antibiotics in colorectal surgery increase the rate of Clostridium difficile colitis

HYPOTHESIS: Bowel preparation traditionally consists of cathartics, oral antibiotics, and intravenous antibiotics. We hypothesize that the use of oral antibiotics in bowel preparation results in a higher rate of postoperative Clostridium difficile colitis. DESIGN: Retrospective case-controlled study of elective colon surgery patients; January 1997 to June 2003. SETTING: Tertiary care veterans administration hospital. PATIENTS: Records of patients who underwent elective colorectal surgery (n = 304) were reviewed. Patients with bowel obstruction or emergent operation were excluded. MAIN OUTCOME MEASURE: Detection of C difficile toxin A/B by enzyme-linked immunosorbent assay in a stool specimen within 30 days of surgery. RESULTS: All 304 patients received both cathartics and intravenous antibiotics. Of 304 patients, 107 (35.1%) received oral antibiotics. The rate of postoperative C difficile colitis was 4.2% in the entire study population. The rate of C difficile infection was higher in patients who received oral antibiotics (7.4%) compared with patients who did not receive oral antibiotics (2.6%; P = .03). There were no C difficile-related mortalities. CONCLUSION: Oral nonabsorbable antibiotics in bowel preparation resulted in a higher rate of C difficile infection. This may be due to the additional effect of oral antibiotics on normal bowel flora. We recommend that oral nonabsorbable antibiotics not be used in preoperative bowel preparation regimens since postoperative C difficile infection can lead to additional morbidity, length of stay, and hospital costs.     

Prevalence of clostridium difficile in excluded colons

Clostridium difficile infection is associated with substantial morbidity and mortality, increased duration of hospitalization, and a marked economic impact. Several case reports and case series have described C. difficile infection in excluded bowels or immediately after reversal of defunctioning ileostomy. The aim of this prospective study is to detect whether the excluded colon is associated with a higher rate of C. difficile colonization than the normal population, which may increase the risk of C. difficile infection. Patients with defunctioning loop ileostomy, undergoing closure of ileostomy to restore bowel continuity, were prospectively recruited. Two stool samples were collected from the ileostomy effluent before closure of ileostomy and two after the procedure including the first bowel movement. All samples were cultured for C. difficile and analyzed for toxins A and B by a Premier EIA test. Demographic data and possible confounding factors were observed and recorded. Twenty-fine adult patients were recruited to this study; five patients were subsequently excluded. Two patients had positive stool cultures for C. difficile in the postoperative samples and another patient developed clinical pseudomembranous colitis with positive toxin. This indicates a possible colonization rate of 3 to 38 per cent (95% confidence interval). Four observed cases out of the 20 subjects taking part in this study would confidently conclude that C. difficile colonization in the excluded colon is 6 to 44 per cent, i.e., higher than the incidence in the healthy adult population, which is 3 per cent. However, the findings of this study prompt larger and well-powered studies to confirm these findings.     

Surgical management of fulminant pseudomembranous colitis.

The presentation of pseudomembranous colitis ranges from mild self-limiting diarrhea to fulminant colitis with overwhelming sepsis. The management of the severe forms of this disease, including the role of surgical intervention, is poorly defined. To evaluate the management and outcome in severe cases, the authors reviewed the records of six patients (four women, two men) seen at The Toronto Hospital between 1985 and 1989 with pseudomembranous colitis manifesting as fulminant colitis. The patients ranged in age from 19 to 69 years (mean 52 years). All presented with nonbloody diarrhea, had peritoneal signs and were severely dehydrated, and all had received antibiotics between 4 days and 6 weeks before the onset of symptoms. The mean preoperative leukocyte count was 40.9 x 10(9)/L. Radiologically, the colon appeared to be dilated in three patients. Two patients were operated on immediately. The other four were treated medically, but three of them required surgery within 24 hours of presentation. Four (67%) of the six patients died. All four had been treated surgically. The mean age of the survivors was 28 years compared with 64 years for those who died. Pseudomembranous colitis can present as severe acute colitis and can carry a high mortality, especially in the aged. Surgical treatment may be required in those who fail to respond to medical management or have peritoneal signs.     

The outcome of surgery in fulminant Clostridium difficile colitis

BACKGROUND: The clinical presentation of Clostridium difficile infection ranges from asymptomatic carriage, colitis with or without pseudomembranes, to fulminant colitis. Although not common, fulminant C. difficile colitis can result in bowel perforation and peritonitis with a high mortality rate. Colectomy is often indicated in these cases. METHODS: We retrospectively analysed the outcome of 14 patients who underwent surgery for fulminant C. difficile colitis in the period 1996-2003 in our Unit. RESULTS: The indications for surgery were systemic toxicity and peritonitis (n = 10), radiological and clinical evidence of progressive toxic colonic dilatation (n = 3) and progressive colonic dilatation with bowel perforation (n = 1). C. difficile infection as the cause of colitis was diagnosed pre-operatively in seven (50%) patients, six of whom underwent a total colectomy and one a right hemicolectomy. Overall mortality in our series was 35.7%. Total colectomy was associated with a lower mortality rate of 11.1% (1/9) when compared with left hemicolectomy was 100% (4/4) (P = 0.01). One patient who underwent a right hemicolectomy (on the basis of deceptively normal external appearance of the rest of the colon intra-operatively) survived after a prolonged hospital stay. CONCLUSIONS: Early or pre-operative microbiological diagnosis of C. difficile infection can be difficult in patients with a fulminant presentation. Those patients with C. difficile colitis, who develop signs of toxicity, peritonitis or perforation, should undergo a total colectomy as the operation of choice.     

Treatment of orthopaedic infections complicated by an antibiotic-associated colitis

Summary Antibiotic treatment of orthopedic infections may result in the developement of Antibiotic-Associated colitis (AAC). Clinical symptoms such as colic tenesmus and diarrhoea are often associated with therapy-induced overgrowth of Clostridium difficile in the colon but clinically asymptomatic cases with only rising C-reactive protein values or increasing leucocyte counts are also reported. In a retrospective study we identified 34/603 patients (5,6%) with orthopedic infections complicated by an AAC who were treated at our departement between 1/90 and 2/95. Infections developed after orthopedic operations as early infections in 11 cases and as late infections in 5 patients. Eighteen patients suffered from bone-or soft tissue infections. Surgical intervention was carried out in 26 cases and all 34 patients were given intravenous antibiotics (29 cases with clindamycin as single therapy or in combination). First signs of AAC occured at an average of 16 days (range 3 to 37). Clinical symptoms developed in 27 patients, elevated temperature in 4 and a rise of C-reactive protein and leucocyte count without abdominal symptoms in 3 patients. Diagnosis of Clostridium difficile in the stool of patients was carried out using a latextest and stool cultures in parallel. Together with oral colitis therapy in 31 patients antibiotic therapy was stopped in 17 cases, changed in 11 and continued in the remaining 5. One patient died due to a myocardial infarct on the day of diagnosis — the remaining 33 patients were discharged after successful treatment of their primary disease and the colitis. As a result we recommend not using clindamycin in older patients or patients with a history of colitis.     

Decompressive colonoscopy with intracolonic vancomycin administration for the treatment of severe pseudomembranous colitis

Background: We explored the potential of early decompressive colonoscopy with intracolonic vancomycin administration as an adjunctive therapy for severe pseudomembranous Clostridium difficile colitis with ileus and toxic megacolon. Methods: We reviewed the symptoms, signs, laboratory tests, radiographic findings, and outcomes from the medical records of seven patients who experienced eight episodes of severe pseudomembranous colitis with ileus and toxic megacolon. All seven patients underwent decompressive colonoscopy with intracolonic perfusion of vancomycin. Results: Fever, abdominal pain, diarrhea, abdominal distention, and tenderness were present in all patients. Five of seven patients were comatose, obtunded, or confused, and six of the seven required ventilatory support. The white blood cell count was greater than 16,000 in seven cases (six patients). Colonoscopy showed left-side pseudomembranous colitis in one patient, right-side colitis in one patient, and diffuse pseudomembranous pancolitis in five patients. Two patients were discharged with improvement. Five patients had numerous medical problems leading to their death. Complete resolution of pseudomembranous colitis occurred in four patients. One patient had a partial response, and two patients failed therapy. Conclusion: Colonoscopic decompression and intracolonic vancomycin administration in the management of severe, acute, pseudomembranous colitis associated with ileus and toxic megacolon is feasible, safe, and effective in approximately 57% to 71% of cases. apd: 7 May 2001     

Increasing prevalence and severity of Clostridium difficile colitis in hospitalized patients in the United States

OBJECTIVE: To evaluate changes in the epidemiological features of Clostridium difficile colitis in hospitalized patients in the United States (C difficile is a common cause of nosocomial diarrhea that has been shown to be increasing in virulence in Canada and across Europe). DESIGN: Cohort analysis of all patients with C difficile colitis in the Nationwide Inpatient Sample. SETTING: Population-based data from the Nationwide Inpatient Sample, a 20% stratified random sample of US hospital discharge abstracts from January 1, 1993, through December 31, 2003. PATIENTS: Using standard International Classification of Diseases, Ninth Revision (ICD-9) diagnostic codes, we identified patients with C difficile colitis. We controlled for comorbid conditions by calculating the Deyo modification of the Charlson score. To determine the relationship of year of diagnosis on main outcome measures, we constructed multivariate models. MAIN OUTCOME MEASURES: The prevalence, case fatality, total mortality rate, and colectomy rate of C difficile colitis. RESULTS: We found that the prevalence, case fatality, total mortality rate, and colectomy rate of C difficile colitis increased from 1993 through 2003. In our regression analysis, the year of diagnosis predicted an increase in prevalence, case fatality, total mortality rate, and colectomy rate after adjusting for potential confounders. CONCLUSIONS: The prevalence, case fatality, total mortality rate, and colectomy rate of C difficile colitis significantly increased from 1993 to 2003. These findings provide compelling evidence of the changing epidemiological features of C difficile colitis.     

Detection of Clostridium difficile in stool samples from patients in the early period after liver transplantation

OBJECTIVE: We examined the frequency of detection of Clostridium difficile (CD) toxins compared with the recovery of C. difficile in stool specimen cultures among orthotopic liver transplant (OLT) patients with nosocomial diarrhea in the early period. MATERIALS AND METHODS: The study included stool samples obtained during the first 30 days after OLT in adults who were suspected of CD-associated diseases. The identification of cultured CD strains was performed by standard microbiological methods. The presence of CD toxins was assayed using a commercial immunoassay. RESULTS: All patients were followed prospectively for CD infections from the date of OLT for the first 4 weeks after surgery. Among 54 samples, 16.7% were culture-positive for CD. CD toxins were tested on 54 samples, yielding 63% toxin-positive samples and 30% toxin- and culture-negative results. In the first week after OLT, samples from 19 patients were subjected to CD investigation. Among 19 samples positive for toxin, 52.6% of all samples were culture-negative. We analyzed 35 samples from the second to the fourth week after OLT in 31 recipients. Among 35 samples, 68.6% and 25.7% were positive for CD toxin and for culture, while 20% of samples were negative for toxin and culture. CONCLUSION: In our study, 63% of samples were toxin-positive with 16.7% yielding growth of CD and 30% being negative for toxins and cultures.