INCIDENCE OF DIARRHEA BY Clostridium difficile IN HEMATOLOGIC PATIENTS AND HEMATOPOIETIC STEM CELL TRANSPLANTATION PATIENTS: RISK FACTORS FOR SEVERE FORMS AND DEATH

We describe the rate of incidence of Clostridium difficile-associated diarrhea (CDAD) in hematologic and patients undergone stem cell transplant (HSCT) at HC-FMUSP, from January 2007 to June 2011, using two denominators 1,000 patient and 1,000 days of neutropenia and the risk factors associated with the severe form of the disease and death. The ELISA method (Ridascreen-Biopharm, Germany) for the detections of toxins A/B was used to identify C. difficile. A multivariate analysis was performed to evaluate potential factors associated with severe CDAD and death within 14 days after the diagnosis of CDAD, using multiple logistic regression. Sixty-six episodes were identified in 64 patients among 439 patients with diarrhea during the study period. CDA rate of incidence varied from 0.78 to 5.45 per 1,000 days of neutropenia and from 0.65 to 5.45 per 1,000 patient-days. The most common underlying disease was acute myeloid leukemia 30/64 (44%), 32/64 (46%) patients were neutropenic, 31/64 (45%) undergone allogeneic HSCT, 61/64 (88%) had previously used antibiotics and 9/64 (13%) have severe CDAD. Most of the patients (89%) received treatment with oral metronidazole and 19/64 (26%) died. The independent risk factors associated with death were the severe form of CDAD, and use of linezolid.     

Risk Factors for Treatment Failure and Recurrence after Metronidazole Treatment for Clostridium difficile-associated Diarrhea

Background/Aims

The incidence of treatment failure or recurrence of Clostridium difficile-associated diarrhea (CDAD) following metronidazole treatment has increased recently. We studied the treatment failure, recurrence rate, and risk factors predictive of treatment failure and recurrence after metronidazole treatment for CDAD.

Methods

We retrospectively identified consecutive patients who were admitted and treated for CDAD at a single tertiary institution in Korea over a recent 10-year period (i.e., 1998-2008).

Results

Metronidazole was administered as the initial treatment to 111 of 117 patients (94.9%) with CDAD. Fourteen patients (12.6%) had no clinical response to the metronidazole treatment, and in 13 patients (13.4%) CDAD recurred after successful metronidazole treatment. Diabetes mellitus (p=0.014) and sepsis (p=0.002) were independent risk factors for metronidazole treatment failure. Patients who had received surgery within 1 month before CDAD developed were more likely to experience a recurrence after metronidazole treatment (p=0.032). Vancomycin exhibited a higher response rate after treatment failure, and metronidazole showed a reasonable response rate in the treatment of recurrence. Treatment failure and recurrence rates increased with time after metronidazole treatment for CDAD over the 10-year study period.

Conclusions

Our data suggest that diabetes mellitus and sepsis are independent risk factors for metronidazole treatment failure, and that operation history within 1 month of development of CDAD is a predictor of a recurrence after metronidazole treatment.     

Clostridium difficile-associated disease:Adherence with current guidelines at a tertiary medical center

AIM:To assess adherence with the the Society for Healthcare Epidemiology of America(SHEA)/the Infectious Diseases Society of America(IDSA)guidelines for management of Clostridium difficile(C.difficile)-associated disease(CDAD)at a tertiary medical center.METHODS:All positive C.difficile stool toxin assays in adults between May 2010 and May 2011 at the University of Maryland Medical Center were identified.CDAD episodes were classified as guideline adherent or nonadherent and these two groups were compared to determine demographic and clinical factors predictive of adherence.Logistic regression analysis was performed to assess the effect of multiple predictors on guideline adherence.RESULTS:320 positive C.difficile stool tests were identified in 290 patients.Stratified by disease severity criteria set forth by the SHEA/IDSA guidelines,42.2%of cases were mild-moderate,48.1%severe,and 9.7%severe-complicated.Full adherence with the guidelines was observed in only 43.4%of cases.Adherence was65.9%for mild-moderate CDAD,which was significantly better than in severe cases(25.3%)or severe-complicated cases(35.5%)(P<0.001).There was no difference in demographics,hospitalization,ICU exposure,recurrence or 30-d mortality between adherent and non-adherent groups.A multivariate model revealed significantly decreased adherence for severe or severecomplicated episodes(OR=0.18,95%CI:0.11-0.30)and recurrent episodes(OR=0.46,95%CI:0.23-0.95).CONCLUSION:Overall adherence with the SHEA/IDSA guidelines for management of CDAD at a tertiary medical center was poor;this was most pronounced in severe,severe-complicated and recurrent cases.Educational interventions aimed at improving guideline adherence are warranted.     

Probiotic use as prophylaxis for Clostridium difficile-associated diarrhea in a community hospital

This study was a retrospective chart review from January 1, 2015 through June 30, 2017, comparing the incidence of Clostridium difficile-associated diarrhea (CDAD) in patients taking select broad spectrum antibiotics with probiotics versus without probiotics. The purpose was to determine if probiotic use was associated with a reduction in the incidence of CDAD. A total of 5,574 hospital encounters were reviewed, showing a 0.96% incidence of CDAD in patients receiving a probiotic compared to a 2.19% incidence of CDAD in patients with no probiotic (risk ratio = 0.442; P = .00743). These findings show probiotic use was associated with a statistically significant lower incidence of positive C. difficile test results compared to no probiotic use.     

Clinical Predictors of Fulminant Colitis in Patients with Clostridium difficile Infection

Background/Aim:

Clostridium difficile infection (CDI) can affect up to 8% of hospitalized patients. Twenty-five percent CDI patients may develop C. difficile associated diarrhea (CDAD) and 1–3% may progress to fulminant C. difficile colitis (FCDC). Once developed, FCDC has higher rates of complications and mortality.

Patients and Methods:

A 10-year retrospective review of FCDC patients who underwent colectomy was performed and compared with randomly selected age- and sex-matched non-fulminant CDAD patients at our institution. FCDC (n=18) and CDAD (n=49) groups were defined clinically, radiologically, and pathologically. Univariate analysis was performed using Chi-square and Student''s t test followed by multivariate logistic regression to compute independent predictors.

Results:

FCDC patients were significantly older (77 ± 13 years), presented with triad of abdominal pain (89%), diarrhea (72%), and distention (39%); 28% had prior CDI and had greater hemodynamic instability. In contrast, CDAD patients were comparatively younger (65 ± 20 years), presented with only 1 or 2 of these 3 symptoms and only 5% had prior CDI. No significant difference was noted between the 2 groups in terms of comorbid conditions, use of antibiotics, or proton pump inhibitor. Leukocytosis was significantly higher in FCDC patients (18.6 ± 15.8/mm³ vs 10.7 ± 5.2/mm³; P=0.04) and further increased until the point of surgery. Use of antiperistaltic medications was higher in FCDC than CDAD group (56% vs 22%; P=0.01).

Conclusions:

Our data suggest several clinical and laboratory features in CDI patients, which may be indicative of FCDC. These include old age (>70 years), prior CDI, clinical triad of increasing abdominal pain, distention and diarrhea, profound leukocytosis (>18,000/mm³), hemodynamic instability, and use of antiperistaltic medications.     

Reducing the risk of severe complications among patients with Clostridium difficile infection

BACKGROUND:

The incidence and severity of Clostridium difficile infections are increasing, and there is a need to optimize the prevention of complicated disease.

OBJECTIVE:

To identify modifiable processes of care associated with an altered risk of C difficile complications.

METHODS:

A retrospective cohort study (with prospective case ascertainment) of all C difficile infections during 2007/2008 at a tertiary care hospital was conducted.

RESULTS:

Severe complications were frequent (occurring in 97 of 365 [27%] C difficile episodes), with rapid onset (median three days postdiagnosis). On multivariable analysis, nonmodifiable predictors of complications included repeat infection (OR 2.67), confusion (OR 2.01), hypotension (OR 0.97 per increased mmHg) and elevated white blood cell count (OR 1.04 per 10⁹ cells/L). Protection from complications was associated with initial use of vancomycin (OR 0.24); harm was associated with ongoing use of exacerbating antibiotics (OR 3.02).

CONCLUSION:

C difficile infections often occur early in the disease course and are associated with high complication rates. Clinical factors that predicted a higher risk of complications included confusion, hypotension and leukocytosis. The most effective ways to improve outcomes for patients with C difficile colitis are consideration of vancomycin as first-line treatment for moderate to severe cases, and the avoidance of unnecessary antibiotics.     

Clostridium difficile and inflammatory bowel disease: Role in pathogenesis and implications in treatment

Clostridium difficile(C.difficile)is the leading cause of antibiotic associated colitis and nosocomial diarrhea.Patients with inflammatory bowel disease(IBD)are at increased risk of developing C.difficile infection(CDI),have worse outcomes of CDI-including higher rates of colectomy and death,and experience higher rates of recurrence.However,it is still not clear whether C.difficile is a cause of IBD or a consequence of the inflammatory state in the intestinal environment.The burden of CDI has increased dramatically over the past decade,with severe outbreaks described in many countries,which have been attributed to a new and more virulent strain.A parallel rise in the incidence of CDI has been noted in patients with IBD.IBD patients with CDI tend be younger,have less prior antibiotic exposure,and most cases of CDI in these patients represent outpatient acquired infections.The clinical presentation of CDI in these patients can be unique-including diversion colitis,enteritis and pouchitis,and typical findings on colonoscopy are often absent.Due to the high prevalence of CDI in patients hospitalized with an IBD exacerbation,and the prognostic implications of CDI in these patients,it is recommended to test all IBD patients hospitalized with a disease flare for C.difficile.Treatment includes general measures such as supportive care and infection control measures.Antibiotic therapy with either oral metronidazole,vancomycin,or the novel antibiotic-fidaxomicin,should be initiated as soon as possible.Fecal macrobiota transplantation constitutes another optional treatment for severe/recurrent CDI.The aim of this paper is to review recent data on CDI in IBD:role in pathogenesis,diagnostic methods,optional treatments,and outcomes of these patients.     

Increasing incidence of Clostridium difficile-associated diarrhea in inflammatory bowel disease

Introduction and aimOver the last decade a rise in Clostridium difficile-associated diarrhea (CDAD) has been observed. A higher incidence of CDAD has also been suggested in patients with inflammatory bowel disease (IBD), and may be a challenging factor in the differential diagnosis of flares. It is unclear if the increase is caused by the enhanced use of immunosuppressive therapy in IBD. We investigated if CDAD infection is increasing in IBD patients and evaluated outcome and possible predisposing factors.MethodsThrough an electronic database of the Laboratory of Microbiology of our hospital (tertiary referral center), all stool samples from patients admitted for diarrhea and hospitalized on gastroenterology wards between January 2000 and January 2008 were reviewed for diagnosis of CDAD. For analysis, we compared two periods of equal duration.ResultsA total of 57 patients were diagnosed with CDAD, of whom 26.3% had concomitant IBD. A 3.75-fold increase in CDAD was observed between period 1 and period 2, irrespective of underlying IBD and with a comparable total number of analyzed stool samples between both periods. Non-IBD patients were significantly older. Antibiotic use three months prior to the infection was higher in non-IBD (29/42 or 69%) than in IBD patients (6/15 or 42%) (p = 0.047). Nine IBD patients were on concomitant immunomodulators, and this was not different between period 1 and period 2. Most patients had a successful outcome and only one patient with ulcerative colitis needed semi-urgent colectomy. Two patients died in the non-IBD group. The duration of hospital stay was significantly lower in IBD patients.ConclusionWe observed a significant rise in CDAD in both IBD and non-IBD. The clinical outcome was favorable with only one IBD patient needing semi-urgent colectomy. Because C. difficile can mimic an IBD flare, it is essential that clinicians are vigilant to this complication. The use of immunosuppressive drugs in IBD does not influence the risk.     

Clostridium difficile infection worsens the prognosis of ulcerative colitis

BACKGROUND:

The impact of Clostridium difficile infections among ulcerative colitis (UC) patients is well characterized. However, there is little knowledge regarding the association between C difficile infections and postoperative complications among UC patients.

OBJECTIVE:

To determine whether C difficile infection is associated with undergoing an emergent colectomy and experiencing postoperative complications.

METHODS:

The present population-based case-control study identified UC patients admitted to Calgary Health Zone hospitals for a flare between 2000 and 2009. C difficile toxin tests ordered in hospital or 90 days before hospital admission were provided by Calgary Laboratory Services (Calgary, Alberta). Hospital records were reviewed to confirm diagnoses and to extract clinical data. Multivariate logistic regression analyses were performed among individuals tested for C difficile to examine the association between C difficile infection and emergent colectomy and diagnosis of any postoperative complications and, secondarily, an infectious postoperative complication. Estimates were presented as adjusted ORs with 95% CIs.

RESULTS:

C difficile was tested in 278 (58%) UC patients and 6.1% were positive. C difficile infection was associated with an increased risk for emergent colectomy (adjusted OR 3.39 [95% CI 1.02 to 11.23]). Additionally, a preoperative diagnosis of C difficile was significantly associated with the development of postoperative infectious complications (OR 4.76 [95% CI 1.10 to 20.63]).

CONCLUSION:

C difficile diagnosis worsened the prognosis of UC by increasing the risk of colectomy and postoperative infectious complications following colectomy. Future studies are needed to explore whether early detection and aggressive management of C difficile infection will improve UC outcomes.     

From the Cover: Thuricin CD,a posttranslationally modified bacteriocin with a narrow spectrum of activity against Clostridium difficile

The last decade has seen numerous outbreaks of Clostridium difficile-associated disease (CDAD), which presented significant challenges for healthcare facilities worldwide. We have identified and purified thuricin CD, a two-component antimicrobial that shows activity against C. difficile in the nanomolar range. Thuricin CD is produced by Bacillus thuringiensis DPC 6431, a bacterial strain isolated from a human fecal sample, and it consists of two distinct peptides, Trn-α and Trn-β, that act synergistically to kill a wide range of clinical C. difficile isolates, including ribotypes commonly associated with CDAD (e.g., ribotype 027). However, this bacteriocin thuricin CD has little impact on most other genera, including many gastrointestinal commensals. Complete amino acid sequencing using infusion tandem mass spectrometry indicated that each peptide is posttranslationally modified at its respective 21st, 25th, and 28th residues. Solution NMR studies on [¹³C,¹⁵N] Trn-α and [¹³C,¹⁵N]Trn-β were used to characterize these modifications. Analysis of multidimensional NOESY data shows that specific cysteines are linked to the α-carbons of the modified residues, forming three sulfur to α-carbon bridges. Complete sequencing of the thuricin CD gene cluster revealed genes capable of encoding two S′-adenosylmethionine proteins that are characteristically associated with unusual posttranslational modifications. Thuricin CD is a two-component antimicrobial peptide system with sulfur to α-carbon linkages, and it may have potential as a targeted therapy in the treatment of CDAD while also reducing collateral impact on the commensal flora.     

Incidence and outcomes of Clostridium difficile-associated disease in hematopoietic cell transplant recipients

Hematopoietic stem cell transplant (HSCT) recipients are at a high risk of Clostridium difficile-associated disease (CDAD) given frequent hospitalizations, prolonged antibiotic usage and altered integrity of intestinal mucosa. The prevalence and trends of CDAD in HSCT patients have not been extensively studied. In this study, the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes were used to identify CDAD in HSCT patients using a nationwide inpatient sample in the United States from 2000 to 2009. The prevalence of CDAD and in-hospital mortality in HSCT were investigated and compared to those without any transplants. Multivariate analysis was performed to identify if BMT and graft versus host disease (GVHD) were independently associated with mortality in CDAD patients. Of the 344,507 HSCT discharges, 4.7 % had CDAD. This was about 5 times higher when compared to non-transplant discharges. During engraftment admission, rates of CDAD were higher in allogenic group (8.4 vs. 5.7 %, p < 0.001). In subsequent admissions, those with GVHD had higher rates of CDAD (5.7 vs. 3.2 %, p < 0.001). On adjusted analysis in patients with CDAD, during engraftment admission, allogenic group had significantly higher mortality when compared with non-transplants (OR 3.7). Notably, there was no significant difference in mortality between patients with and without CDAD during the engraftment period for the allogeneic group. In subsequent admissions, there was higher mortality in those with GVHD (OR 4.8). Though the prevalence of CDAD in non-transplant population doubled (from 0.44 % in 2000 to 0.99 % in 2008), it has remained stable in HSCT patients (from 4.8 % in 2000 to 5.6 % in 2008). HSCT and GVHD are independently associated with CDAD though its presence does not affect mortality.     

Epidemiology of Clostridium difficile-associated disease in internal medicine wards in northern Italy

Clostridium difficile-associated disease (CDAD) is a growing health care problem. Elderly patients with multiple comorbidities and repeated hospitalization are at high risk for developing the disease. Few data are available on epidemiology of CDAD in Italy and no studies have focused on CDAD burden in internal medicine wards. We retrospectively analysed all CDAD cases in four internal medicine wards of a city hospital in northern Italy and reviewed the medical records of patients who developed CDAD during hospitalization. We identified 146 newly acquired cases, yielding a cumulative incidence of 2.56 per 100 hospitalizations and an incidence rate of 23.3 per 10,000 patient-days. Main risk factors were advanced age and length of hospitalization. A high proportion of CDAD patients had several comorbidities and had been treated with more than one antibiotic. The incidence is among the highest previously reported, this may be due to the characteristics of patients admitted to internal medicine wards and to the wards per se. We conclude that efforts are needed to reduce CDAD’s burden in this setting, paying attention to logistics, patients care and antibiotic use.     

<Emphasis Type="Italic">Clostridium difficile</Emphasis> infection: clinical spectrum and approach to management

Clostridium difficile is recognized globally as an important enteric pathogen associated with considerable morbidity and mortality due to the widespread use of antibiotics. The overall incidence of C. difficile-associated diarrhea (CDAD) is increasing due to the emergence of a hypervirulent strain known as NAP1/BI/027. C. difficile acquisition by a host can result in a varied spectrum of clinical conditions inclusive of both colonic and extracolonic manifestations. Repeated occurrence of CDAD, manifested by the sudden re-appearance of diarrhea and other symptoms usually within a week of stopping treatment, makes it a difficult clinical problem. C. difficile infection has also been reported to be involved in exacerbation of inflammatory bowel diseases. The first step in the management of a suspected CDAD case is the withdrawal of the offending agent and changing the antibiotic regimens. Antimicrobial therapy directed against C. difficile viz. metronidazole for mild cases and vancomycin for severe cases is needed. For patients with ileus, oral vancomycin with simultaneous intravenous (IV) metronidazole and intracolonic vancomycin may be given. Depending on the severity of disease, the further line of management may include surgery, IV immunoglobulin treatment or high dose of vancomycin. Adjunctive measures used for CDAD are probiotics and prebiotics, fecotherapy, adsorbents and immunoglobulin therapy. Among the new therapies fidaxomicin has recently been approved by the American Food and Drugs Administration for treatment of CDAD.     

Clostridium difficile as a cause of acute diarrhea: a prospective study in a tertiary care center

Introduction

Clostridium difficile-associated diarrhea (CDAD) is an increasing problem. Recent reports suggest presence of community acquired CDAD (CA CDAD). Studies in India have shown varied results.

Aims

The following are the aims of this study: (a) the prevalence of CDAD and CA CDAD in patients with acute diarrhea; (b) the incremental yield of second stool sample for the diagnosis of C. difficile infection (CDI); and (c) the risk factors for CDI.

Patients and Methods

Patients with acute diarrhea (<4 weeks) between April 2009 and December 2010 had two stool sample tested for C. difficile toxin (CDT) by enzyme-linked immunofluorescent assay. Demographic, clinical data, risk factors, clinical course, complications, treatment, and response were noted.

Results

Of 150 patients (mean age, 47.3 years; 76 males), 12 (8 %) had their first stool sample positive for CDT. Two patients (1.3 %) had community acquired CDI. The study group was compared with 138 patients (“control group”, stool samples negative for CDT). Compared to the controls, the study group were more likely to have had intensive care unit (ICU) stay (p?=?0.018) and tube feeding (p?=?0.035). Eleven patients were treated with metronidazole. One patient did not respond to metronidazole and was treated with vancomycin. No patient developed complications of CDAD.

Conclusions

The prevalence of CDAD in our population was 8 % and of CA CDAD was 1.3 %. There was no advantage of testing two samples. ICU stay and tube feeding were major risk factors for the CDAD. Metronidazole was an effective first-line therapy.     

Effect of Treatment Variation on Outcomes in Patients with Clostridium difficile

Purpose

New guidelines for the treatment of Clostridium difficile-associated diarrhea were published by the Infectious Disease Society of America (IDSA) in 2010, however, there has been no literature evaluating the effectiveness of these guidelines. The purpose of this study was to examine the clinical outcomes of Clostridium difficile infection including death, C difficile infection recurrence, toxic megacolon, and surgery between patients who received guideline-concordant therapy vs guideline-discordant therapy.

Methods

Retrospective case-control study of hospitalized adults with C difficile infection presenting to a 420-bed tertiary care referral county teaching hospital. Patients were identified by International Classification of Diseases-9th Revision codes, and included if they were ≥18 years of age and treated for C difficile infection during their hospital visit. Complication rates (death, infection recurrence, toxic megacolon, and surgery) of patients with C difficile infection were measured to determine if following the IDSA guidelines improves outcomes.

Results

Only 51.7% of the patients' prescribers followed the 2010 IDSA guidelines. Patients whose prescribers followed the IDSA guidelines experienced fewer complications than patients whose prescribers strayed from the guidelines (17.2% vs 56.3%, P <.0001). This difference was mainly due to a reduction in mortality (5.4% vs 21.8%, P = .0012) and infection recurrence (14% vs 35.6%, P = .0007). Patients who presented with severe and complicated disease received guideline-based therapy significantly less often than patients with mild disease (19.7%, 35.3%, and 81.2%, respectively, P <.0001).

Conclusions

There was a significant reduction in C difficile infection recurrence and mortality when prescribers followed the IDSA/Society for Healthcare Epidemiology of America guidelines for treatment of C difficile infection.     

Proton pump inhibitors as a risk factor for recurrence of Clostridium-difficile-associated diarrhea

AIM:To investigate the risk factors for Clostridiumdifficile-associated diarrhea(CDAD)recurrence,and its relationship with proton pump inhibitors(PPIs). METHODS:Retrospective data of 125 consecutive hospitalized patients diagnosed with CDAD between January 2006 and December 2007 were collected by medical chart review.Collected data included patient characteristics at baseline,underlying medical disease, antibiotic history before receiving a diagnosis of CDAD, duration of hospital stay,severity of CDAD,concu...     

Multiple Interventions Used to Lower Clostridium difficile– Associated Diarrhea Rates in a Large Urban Hospital

BACKGROUND: Clostridium difficile–associated diarrhea (CDAD) is a common nosocomial infection. CDAD has been associated with prolonged use of antibiotics. C. difficile spores, which are present in stool, can live for up to 70 days and are often spread by the hands of healthcare professionals.METHODS: An increased rate of CDAD was noted in June and July 2002 at Barnes-Jewish Hospital, a 1442-bed tertiary care hospital in St. Louis, Missouri. The CDAD rate for the hospital in the first 5 months of 2002 was 2.8 cases/1000 patient-days. The rate in June and July was 6.2 cases/1000 patient-days (p<0.001). A computerized laboratory surveillance tool helped infection control specialists promptly identify the rise in CDAD rates. Unit-specific interventions were performed in two ICUs. The surgical ICU (SICU) (10.4 cases/1000 patient-days in July 2002) instituted enhanced environmental cleaning, including bleach, in rooms of CDAD patients. The medical ICU (MICU) (25 cases/1000 patient-days in June 2002) intensified active surveillance, including monthly reporting of CDAD rates to the ICU staff. Additionally in this unit, rooms of CDAD patients were bleached at discharge. A hospital-wide hand hygiene intervention was also implemented between January and April 2003.RESULTS: The hospital's overall CDAD rate decreased to 2.5 cases per 1000 patient-days in the last 5 months of 2002 (p<0.001). The CDAD rate in the SICU dropped to 4.8 cases/1000 patient-days (p=.20) after the start of the intervention. Since the implementation of the intervention in the MICU, the CDAD rate has decreased to 5.1 cases/1000 patient-days (p<0.001). The hospital CDAD rate dropped to 2.1 cases/1000 patient-days (p<0.001) in the months following the hand hygiene intervention.CONCLUSION: Early recognition allows prompt interventions to address infection control issues such as this increase in CDAD rates. The use of multidisciplinary interventions to reduce CDAD infection rates was a successful strategy in this case.     

Intrahospital mortality in patients with Clostridium difficile-associated diarrhea infection

BackgroundClostridium difficile (C. difficile) is a gram-positive anaerobic bacillus capable of producing diarrhea or colitis in the hospitalized patient, particularly in those exposed to the use of antibiotics, and 6% to 38% mortality in patients with C. difficile-associated diarrhea (CDAD) has been described.AimsTo determine the hospital death rate in patients presenting with CDAD. As a secondary aim, hospital stay and risk factors for unfavorable outcome were recorded.MethodsA retrospective cohort study was carried out. The case records of hospitalized patients presenting with diarrhea and that tested positive for C. difficile through toxin A and B assays were reviewed. The number of non-surviving patients that presented with CDAD during hospitalization was recorded along with the principal factors associated with the worst outcome.ResultsOf the 66 patients enrolled in the study, 6 (9,1%) died during their hospitalization. The median age was lower in the group of surviving patients than in the group of non-surviving patients, with 51,5 years (range 36 to 66,75) and 81,5 years (range 69,5 to 83,25), respectively (p=0,002). Hospital stay was 32,50 days (range 8,25 to 64,25) in the group of non-surviving patients and was 6,5 days (range 4 to 15,75) (p=0,045) in the group with no deaths.ConclusionsThe elevated mortality found in the hospitalized CDAD patients in the Intensive Care Unit makes the maintenance of strict surveillance in this population imperative so there can be opportune detection and treatment.     

The value of repeat Clostridium difficile toxin testing during and after an outbreak of C difficile-associated diarrhea

BACKGROUND:

The recent increase in Clostridium difficile-associated diarrhea (CDAD) has led to questions about the reproducibility and sensitivity of C difficile toxin testing (CDTT). While there have been recommendations to repeat CDTT following a negative result, previous studies have failed to show a benefit. However, no studies were performed during an outbreak of CDAD. The value of repeat CDTT after an initial negative result in patients tested during and after an outbreak of CDAD is reported in the present study, as well as the reproducibility of CDTT when multiple samples are received and tested on the same day.

METHODS:

The results of CDTT, performed using a cell cytotoxicity assay between April 1, 2001, and March 31, 2008, were retrieved and searched for patients who had repeat samples tested after an initial negative result. The result and the number of days after a negative result were determined using the date of the most recent negative test. The cumulative positivity rate was calculated by adding all of the repeat positive test results for the days in question and dividing by the total number of tests performed during that time.

RESULTS:

A total of 8661 patients submitted 14,991 stool specimens for CDTT during the study period. There were 3095 samples that tested positive (20.6%) for the toxin. The results were divided into two time periods to reflect the CDAD outbreak, which began in April 2002: period 1 (outbreak) was from April 1, 2002, to March 31, 2006, and period 2 was from April 1, 2006, to March 31, 2008. The rate of positivity was 24.2% during period 1, and 11.6% during period 2 (P<0.001). Repeat CDTT was performed 619 times on samples received on the same day as the initial specimen, and only three (0.5%) were discordant. A total of 1630 samples were retested within one to seven days of a negative result, and 103 (6.3%) tested positive (7.8% period 1 and 2.9% period 2; P=0.002). The likelihood of a positive result on repeat testing in the first three days after a negative result was low (0.9%, 7% and 4%, respectively). The cumulative positivity for repeat testing performed in the first three days was 0.9%, 3.3% and 3.5%, respectively, and did not differ significantly at day 3 during the period of high CDTT positivity (P=0.110).

CONCLUSIONS:

The value of repeat CDTT, performed using a cell cytotoxicity assay, was low in the first three days after an initial negative result and was unchanged during a CDAD outbreak.