Severe Complicated Clostridium Difficile Infection Research Articles

Fecal Microbiota Transplant for Severe Complicated Clostridium difficile Infection via a Loop Ileostomy: A Novel Administration Route

Introduction: Clostridium difficile infection (CDI) is the most common cause of infectious diarrhea in healthcare settings. High cure rates of CDI with fecal microbiota transplantation (FMT) have been reported (88 to 100%). Successful delivery of donor fecal material has been described via nasogastric duodenal tube, colonoscopy, physician administered retention enemas and self-administered enemas. To our knowledge there has been no reported case of successful FMT for CDI via a loop ileostomy. Case Report: A 57-year-old women with past medical history of hypertension and type II diabetes mellitus developed diarrhea related to CDI after a hospitalization for pneumonia that had required antibiotics. She was successfully treated with oral vancomycin and intravenous flagyl. Two months later she re-developed diarrhea and was diagnosed with severe complicated CDI. On this second presentation her WBC count was 87 k/uL and a CT abdomen showed pan-colitis. She developed septic shock with multi-organ system failure. She required pressor support, mechanical ventilation and intermittent hemodialysis. She was treated with oral and rectal vancomycin, intravenous flagyl and oral pro-biotics. When she failed to respond, a laparoscopy was done to create a loop ileostomy. She was given vancomycin solution through the ileostomy for about 10 days. She showed some clinical response to this aggressive antibiotic therapy with declining leukocytosis and pressor requirement but remained critically ill and continued to have diarrhea. At this point it was decided to perform a FMT. All her antibiotics were stopped for a 24-hour period prior to instillation of 250 mL of open biome donor feces into her ileostomy. All antibiotics were held for another week after the FMT. Her diarrhea completely resolved. Her subsequent hospital course was complicated by candidal fungemia, multiple drug resistant Pseudomonas aeruginosa empyema and bilateral femoral deep venous thrombosis but she remained free from recurrence of CDI. Two repeat PCR's for C. difficile approximately one and two month after FMT via loop ileostomy remained negative. She has now been discharged from the hospital and is doing well. Conclusion: This is the first ever reported case of successful cure of recurrent severe complicated CDI with FMT through a loop ileostomy. This report demonstrates the versatility of routes through which a successful FMT can be performed.

Leaping Forward in the Treatment of Clostridium Difficile Infection: Update in 2015

In recent years, significant advances in the treatment of Clostridium difficile infection (CDI) have risen. We review the most relevant updated recommendations in the current standard of care of CDI and discuss emerging therapies, including antibiotic, alternative therapies (probiotics, toxin-binding resins, immunotherapy) and new data on fecal transplantation. Upcoming surgical options and other rescue therapies for severe refractory disease are also addressed.Although oral metronidazole is a first-line therapy for non-severe CDI, emerging data have demonstrated its inferiority relatively to vancomycin, particularly in the setting of recurrent and/or severe infection. After a CDI recurrence for the first time, fidaxomicin has been shown to be associated with lower likelihood of CDI recurrence compared to vancomycin. Fecal transplantation is now strongly recommended for multiple recurrent CDI and may have a role in refractory disease. Oral, frozen stool capsules may simplify fecal transplantation in the future, with preliminary promising results. Diverting loop ileostomy combined with colonic lavage is a potential alternative to colectomy in severe complicated CDI. Potential alternative therapies requiring further investigation include toxin-binding resins and immunotherapy.

Role of intravenous immune globulin in streptococcal toxic shock syndrome and Clostridium difficile infection.

The use of intravenous immune globulin (IVIG) in the management of streptococcal toxic shock syndrome (STSS) and Clostridium difficile infection (CDI) is reviewed. IVIG has a wide range of uses in clinical practice, including STSS and CDI. It is an attractive option for these two infections because both infections are toxin mediated, and IVIG may contain antibodies that neutralize these toxins. For STSS and CDI, IVIG is often considered for use in critically ill patients who are not responding to traditional therapies. Several encouraging case reports and retrospective chart reviews have been published, highlighting the potential benefit of IVIG in such patients. However, its definitive role remains unclear, mainly due to the lack of high-level evidence. Data supporting its use have been extrapolated from retrospective chart reviews and case reports in which profound heterogeneity in patient populations and treatment modalities exist. The use of IVIG must be weighed carefully because it is not a benign product. As with the use of IVIG for STSS, the role of IVIG for CDI is unclear. Nonetheless, IVIG may serve as a useful adjunct therapy for patients suffering from severe complicated CDI (shock, ileus, or megacolon) who do not respond to conventional treatment. Adverse reactions to IVIG are mild and transitory and occur during or immediately after drug infusion. Although randomized, controlled trials supporting the use of IVIG for STSS and CDI are lacking, IVIG may be considered a last-line adjunct therapy in those patients for whom the clinical benefit outweighs the potential adverse effects of therapy.

Mo1848 Factors Predicting Development of Severe-Complicated Clostridium difficile Infection in Hospitalized Patients

Mo1848 Factors Predicting Development of Severe-Complicated Clostridium difficile Infection in Hospitalized Patients

Concomitant Medical Conditions and Therapies Preclude Accurate Classification of Children With Severe or Severe Complicated Clostridium difficile Infection

Severe and severe complicated Clostridium difficile infections (SCDI/SCCDI) were retrospectively assessed in a pediatric cohort. Underlying medical conditions and concomitant medical therapy preclude accurate classification of children with SCDI/SCCDI, using current CDI severity definitions. Revised CDI definitions in children should focus on more objective, age-appropriate, and CDI-specific markers of severity.

Tigecycline for the Treatment of Severe and Severe Complicated Clostridium difficile Infection.

Introduction Clostridium difficile infection (CDI) is a common cause of nosocomial diarrhea. Metronidazole and vancomycin are the primary treatment options for CDI, but increasing rates of antimicrobial resistance and severe, refractory disease have prompted the need for alternative agents. Tigecycline has previously demonstrated favorable in vitro activity against C. difficile isolates, but clinical data on its use in the treatment of CDI are severely lacking. The objective of this study was to describe our experience using tigecycline in the treatment of severe and severe complicated CDI.MethodsThis was a retrospective case series of hospitalized patients with severe and severe complicated CDI who were treated with tigecycline. Disease severity assessments were determined according to current practice guidelines. Diagnosis of toxigenic CDI was confirmed by polymerase chain reaction and patients were excluded if they received tigecycline for <48 h. Data were collected by review of the electronic medical record. The primary outcome was clinical cure. Secondary outcomes were sustained response, hospital mortality, and 28-day all-cause mortality.ResultsA total of 7 cases of severe and complicated CDI were reviewed. Intravenous tigecycline administered as a 100-mg loading dose followed by 50 mg twice daily resulted in clinical cure in 85.7% (n = 6/7) of cases. The majority of patients (n = 4/5) were treated with the novel triple therapy combination of tigecycline, vancomycin, and metronidazole and resulted in clinical cure in 80% (n = 4/5) cases. Sustained response at 28 days was 100% among evaluable cases (n = 5/5). Hospital mortality did not occur in any patients, and 28-day all-cause mortality was 28.6% (n = 2/7).ConclusionTigecycline appears to be a reasonable addition to the therapeutic regimen in the treatment of severe or complicated CDI, including cases that are refractory to standard therapy. A prospective clinical trial confirming these observational findings is warranted.Electronic supplementary materialThe online version of this article (doi:10.1007/s40121-014-0050-x) contains supplementary material, which is available to authorized users.

Rescue Therapy With Fecal Microbiota Transplantation in Hospitalized Patients With Severe and Severe-Complicated Clostridium difficile Infection

Introduction: Severe Clostridium difficile infection (CDI) is often complicated by fulminant colitis and multiorgan failure. Urgent subtotal colectomy can be lifesaving, but it is associated with 50% mortality. Fecal microbiota transplantation (FMT) is widely used to treat recurrent CDI; however, only a few case reports describe its use in hospitalized patients who are critically ill. Methods: Patients with severe and severe/complicated CDI (defined as per 2013 ACG guidelines) who were considered for urgent subtotal colectomy between July 2013 and April 2014 were offered the option of FMT at our institution. Patient variables and outcomes were prospectively collected using an IRB study protocol. FMT was performed using a colonoscope and CO2 insufflation with delivery either proximal or distal to the splenic flexure at the discretion of the endoscopist. Fresh stool was obtained from either a patient-selected donor or universal donor for FMT. After initial FMT, oral vancomycin (125 mg q 6 hrs) was started within 24-72 hours and continued until second FMT (range: 5-14 days). If pseudomembranous colitis was present at the time of the second FMT, oral vancomycin was resumed and a third FMT was offered (range: 5-14 days). Results: Seventeen patients (8 with severe and 9 with severe-complicated CDI) with mean age of 68±14.74 years (53% were females; 100% were white; 12% on immunosuppression) underwent FMT. All patients had failed to respond to prior antibiotic therapy (vancomycin or fidaxomicin) and had pseudomembranous colitis on the first FMT. The mean serum albumin level was 2.4±0.42 g/dL and the mean WBC count was 17.4±19.1 k/mm3. Eleven (65%) patients underwent bowel preparation prior to FMT. Stool was delivered proximal to the splenic flexure in 60% and distal to the splenic flexure in the remaining. Ten patients (59%) received a second FMT with median time to repeat FMT of 7.5 days. Three (18%) patients received a third FMT. Fifteen patients (88%) were cured and avoided colectomy within 3 months of initial FMT. Of the 2 patients who died of multiorgan failure, one was under immunosuppression (recent liver transplantation) and the other had septic shock with a pH of 7.09 at the time of initial FMT. No SAEs related to colonoscopy or FMT were observed. Conclusion: Response-guided FMT in combination with vancomycin is a promising treatment alternative to surgery for severe and severe-complicated CDI, a condition that is typically associated with high mortality.

Outcomes for Severe Complicated Clostridium difficile Infection Treated with Vancomycin Enemas

Introduction: The prevalence of Clostridium difficile infection (CDI) is increasing. Serious, complicated infections have been linked to a virulent strain (BI/NAP1), which produces elevated levels of toxin and can lead to colectomy or death. For these infections, standard of care is now concomitant treatment with IV metronidazole (IVM) and per oral vancomycin (POV). Some institutions use add-on therapy with vancomycin per rectum (VPR) to increase colonic drug delivery when there is a concern about delayed transit. Our purpose was to look at clinical outcomes of consecutive patients with CDI treated with VPR at our hospital. Methods: Using pharmacy records and manual chart review, we identified inpatients prescribed VPR from 1/2003 to 12/2013. Included patients had diarrhea, a positive stool test for Clostridium difficile toxin by ELISA, and no alternative cause for symptoms. Patients were required to have been in the ICU at the initiation of treatment and to have received ≥4 doses of VPR. Patients were followed to discharge or death. Results: We identified 43 CDI patients who received VPR during the study period. We excluded 18 patients because they did not receive ≥4 doses of VPR and 1 patient who received VPR after colonic surgery. There were 11 males and 13 females, mean age was 61.8±15.9 years (range: 21-93). The dose of VPR (IV solution mixed in 100 cc of tap water) ranged from 125 to 250 mg Q 6-8 hrs. Most patients received concomitant therapy with POV (n=17) and/or IVM (n=20). Four patients (16.7%) underwent colectomy and 3 died post-op. Mortality was 11/24 (45.8%) including the 3 post-op deaths. The mean number of doses of VPR in those who survived versus died was 22.3±6.9 vs. 19.3±19.4 (P=0.62). Similarly, there were no significant differences (all P>0.05) in age (64.5±16.7 vs. 59.1±15.3 years), WBC (24.6±11.5 vs. 25.7±17.9K), or interval rise in creatinine (91.6% vs. 100%) between those who survived versus died or those who survived versus the combined endpoint of surgery/death. There was notably a shorter median time interval between initiation of CDI treatment and initiation of VPR for those who survived and avoided surgery (3.5 days; IQR 1-15.25 vs. 8.5 days; IQR 2-19.5), but this was not statistically significant (P=0.47). Conclusion: In our study, the largest case series reported to date on the use of VPR for severe, complicated CDI, 50.0% of patients ultimately died or had a colectomy. Based on our modest sample size and high rate of morbidity and mortality we cannot strongly advocate for the use of VPR at this time. It appeared that earlier initiation of VPR may be beneficial. Controlled trials are needed to better assess this therapy.

Outcomes from Rectal Vancomycin Therapy in Patients with Severe-Complicated Clostridium difficile Infection

Outcomes from Rectal Vancomycin Therapy in Patients with Severe-Complicated Clostridium difficile Infection

Clinical Factors Associated With Development of Severe-Complicated Clostridium difficile Infection

Clostridium difficile infection (CDI) can cause life-threatening complications. Severe-complicated CDI is characterized by hypotension, shock, sepsis, ileus, megacolon, and colon perforation. We created a model to identify clinical factors associated with severe-complicated CDI. We analyzed data from 1446 inpatient cases of CDI (48.6% female; median age, 62.5 years; range, 0.1-103.7 years) at the Mayo Clinic from June 28, 2007, to June 25, 2010. Patients with severe-complicated CDI (n= 487) were identified as those who required admission to the intensive care unit or colectomy, or died, within 30 days of CDI diagnosis. Logistic regression models were used to identify variables that were independently associated with the occurrence of severe-complicated CDI in 2 cohorts. One cohort comprised all hospitalized patients; the other comprised a subset of these inpatients who were residents of Olmsted County, Minnesota to assess the association of comorbid conditions with the development of severe-complicated infection in a population-based cohort. The linear combinations of variables identified by using logistic regression models provided scores to predict the risk of developing severe-complicated CDI. In a multivariable model that included all inpatients, increasing age, leukocyte count >15×10(9)/L, increase in serum level of creatinine >1.5-fold from baseline, and use of proton pump inhibitors or narcotic medications were independently associated with severe-complicated CDI. In the secondary analysis, which included only patients from Olmsted County, comorbid conditions were not significantly associated with severe-complicated CDI. Older age, high numbers of leukocytes in blood samples, an increased serum level of creatinine, gastric acid suppression, and use of narcotic medications were independently associated with development of severe-complicated CDI in hospitalized patients. Early aggressive monitoring and intervention could improve outcomes.

Sa1236 Effect of Statins on Clinical Characteristics and Treatment Outcome of Clostridium difficile-Associated Disease Among Inpatients Taking Proton Pump Inhibitors or Not

G A A b st ra ct s in an inpatient cohort from Olmsted County, MN. Information on maximum change in serum creatinine (highest value compared to baseline over the past year) and WBC within 7 days of CDI diagnosis was obtained for three groups: pediatrics ( ,18 yrs old), adults (18-65), and the elderly (.65). Sensitivity (Se) and specificity (Sp) of various levels of WBC and creatinine ratio were estimated for predicting severe-complicated CDI, defined as need for ICU admission, colectomy, or death. Analysis of creatinine ratio in the pediatric population was not done due to a high proportion of missing baseline creatinine values. The cohort included 1446 patients (48.6% female, median age 62.5 yrs [range, 0.1-103.7]); 487 (33.7%) had severe-complicated CDI. A WBC .15 x10^9/L (the cut-off recommended in expert guidelines) had a similar Se and Sp for predicting severe-complicated CDI in pediatrics (Se= 54.5, Sp=78.8), adults (Se=53.7, Sp=73.2), and the elderly (Se=56.3, Sp=63.5). A serum creatinine ratio of 1.5 had a similar ability to predict severe-complicated CDI in adults (Se= 59.2, Sp=59.5) and the elderly (Se=61.9, Sp=54.1). Lowering the thresholds of WBC and creatinine ratio increased the Se but decreased the Sp for predicting severe-complicated CDI in all age groups. For example, lowering the WBC threshold to 12.5 or decreasing the creatinine threshold to 1.4 increases the Se by 10-18% with a similar decrease in Sp (Table 1). No optimal WBC or creatinine rise cut-offs to predict severe-complicated CDI were defined in this investigation. The current cut-off values according to expert guidelines performed similarly across age groups, but had relatively low sensitivities and specificities. For all age groups and for both WBC and creatinine rise, decreasing the cut-off value increased the sensitivity while decreasing the specificity; these variables should be considered as continuous predictors of complicated CDI, with higher values indicating higher risk. Values below the threshold values defined in current guidelines do not reliably exclude a significant risk of complicated CDI. Given the poor outcomes in patients with severecomplicated CDI and the recommendation that treatment be stratified by severity, a more sensitive predictor (lower WBC or creatinine cut-offs) may be more appropriate. Table 1. Sensitivities and specificities of peripheral leukocyte count and serum creatinine rise in predicting severe-complicated Clostridium difficile infection.

Sa1237 Epidemiological Features and Risk Factors Affecting Outcomes of Clostridium difficile Infection Among Inpatients At an Urban Hospital

G A A b st ra ct s in an inpatient cohort from Olmsted County, MN. Information on maximum change in serum creatinine (highest value compared to baseline over the past year) and WBC within 7 days of CDI diagnosis was obtained for three groups: pediatrics ( ,18 yrs old), adults (18-65), and the elderly (.65). Sensitivity (Se) and specificity (Sp) of various levels of WBC and creatinine ratio were estimated for predicting severe-complicated CDI, defined as need for ICU admission, colectomy, or death. Analysis of creatinine ratio in the pediatric population was not done due to a high proportion of missing baseline creatinine values. The cohort included 1446 patients (48.6% female, median age 62.5 yrs [range, 0.1-103.7]); 487 (33.7%) had severe-complicated CDI. A WBC .15 x10^9/L (the cut-off recommended in expert guidelines) had a similar Se and Sp for predicting severe-complicated CDI in pediatrics (Se= 54.5, Sp=78.8), adults (Se=53.7, Sp=73.2), and the elderly (Se=56.3, Sp=63.5). A serum creatinine ratio of 1.5 had a similar ability to predict severe-complicated CDI in adults (Se= 59.2, Sp=59.5) and the elderly (Se=61.9, Sp=54.1). Lowering the thresholds of WBC and creatinine ratio increased the Se but decreased the Sp for predicting severe-complicated CDI in all age groups. For example, lowering the WBC threshold to 12.5 or decreasing the creatinine threshold to 1.4 increases the Se by 10-18% with a similar decrease in Sp (Table 1). No optimal WBC or creatinine rise cut-offs to predict severe-complicated CDI were defined in this investigation. The current cut-off values according to expert guidelines performed similarly across age groups, but had relatively low sensitivities and specificities. For all age groups and for both WBC and creatinine rise, decreasing the cut-off value increased the sensitivity while decreasing the specificity; these variables should be considered as continuous predictors of complicated CDI, with higher values indicating higher risk. Values below the threshold values defined in current guidelines do not reliably exclude a significant risk of complicated CDI. Given the poor outcomes in patients with severecomplicated CDI and the recommendation that treatment be stratified by severity, a more sensitive predictor (lower WBC or creatinine cut-offs) may be more appropriate. Table 1. Sensitivities and specificities of peripheral leukocyte count and serum creatinine rise in predicting severe-complicated Clostridium difficile infection.

Sa1235 Peripheral Leukocyte Count and Serum Creatinine As Predictors of Severe-Complicated Clostridium difficile Infection in Different Age Groups

Sa1235 Peripheral Leukocyte Count and Serum Creatinine As Predictors of Severe-Complicated Clostridium difficile Infection in Different Age Groups

The Epidemiology of Clostridium difficile Infection in Children: A Population-Based Study

The incidence of Clostridium difficile infection (CDI) is increasing, even in populations previously thought to be at low risk, including children. Most incidence studies have included only hospitalized patients and are thus potentially influenced by referral or hospitalization biases. We performed a population-based study of CDI in pediatric residents (aged 0-18 years) of Olmsted County, Minnesota, from 1991 through 2009 to assess the incidence, severity, treatment response, and outcomes of CDI. We identified 92 patients with CDI, with a median age of 2.3 years (range, 1 month-17.6 years). The majority of cases (75%) were community-acquired. The overall age- and sex-adjusted CDI incidence was 13.8 per 100 000 persons, which increased 12.5-fold, from 2.6 (1991-1997) to 32.6 per 100 000 (2004-2009), over the study period (P < .0001). The incidence of community-acquired CDI was 10.3 per 100 000 persons and increased 10.5-fold, from 2.2 (1991-1997) to 23.4 per 100 000 (2004-2009) (P < .0001). Severe, severe-complicated, and recurrent CDI occurred in 9%, 3%, and 20% of patients, respectively. The initial treatment in 82% of patients was metronidazole, and 18% experienced treatment failure. In contrast, the initial treatment in 8% of patients was vancomycin and none of them failed therapy. In this population-based cohort, CDI incidence in children increased significantly from 1991 through 2009. Given that the majority of cases were community-acquired, estimates of the incidence of CDI that include only hospitalized children may significantly underestimate the burden of disease in children.

Empirical Antimicrobial Prescriptions in Patients withClostridium difficileInfection at Hospital Admission and Impact on Clinical Outcome

To determine, among patients with Clostridium difficile infection (CDI) at hospital admission, the impact of concurrent use of systemic, non-CDI-related antimicrobials on clinical outcomes and the risk factors associated with unnecessary antimicrobial prescribing. Retrospective cohort study. University-affiliated community hospital. We reviewed computerized medical records for all patients with CDI at hospital admission during a 24-month period (January 1, 2008, through December 31, 2009). Colectomy, discharge to hospice, and in-hospital mortality were considered to be adverse outcomes. Antimicrobial use was considered unnecessary in the absence of physical signs and laboratory or radiological findings suggestive of an infection other than CDI or in the absence of antimicrobial activity against the organism(s) recovered from clinical cultures. Among the 94 patients with CDI at hospital admission, 62% received at least one non-CDI-related antimicrobial during their hospitalization for CDI. Severe complicated CDI (odds ratio [OR], 7.1 [95% confidence interval {CI}, 1.8-28.5]; [Formula: see text]), duration of non-CDI-related antimicrobial exposure (OR, 1.2 [95% CI, 1.03-1.36]; [Formula: see text]), and age (OR, 1.1 [95% CI, 1.0-1.1]; [Formula: see text]) were independent risk factors for adverse clinical outcomes. One-third of the patients received unnecessary antimicrobial therapy. Sepsis at hospital admission (OR, 5.3 [95% CI, 1.8-15.8]; [Formula: see text]) and clinical suspicion of urinary tract infection (OR, 9.7 [95% CI, 2.9-32.3]; [Formula: see text]) were independently associated with unnecessary antimicrobial prescriptions. Empirical use of non-CDI-related antimicrobials was common. Prolonged exposure to non-CDI-related antimicrobials was associated with adverse clinical outcomes, including increased in-hospital mortality. Minimizing non-CDI-related antimicrobial exposure in patients with CDI seems warranted.

Current State of Clostridium difficile Treatment Options

Recent reports of reduced response to standard therapies for Clostridium difficile infection (CDI) and the risk for recurrent CDI that is common with all currently available treatment agents have posed a significant challenge to clinicians. Current recommendations include metronidazole for treatment of mild to moderate CDI and vancomycin for severe CDI. Results from small clinical trials suggest that nitazoxanide and teicoplanin may be alternative options to standard therapies, whereas rifaximin has demonstrated success in uncontrolled trials for the management of multiple recurrences. Anecdotal reports have also suggested that tigecycline might be useful as an adjunctive agent for the treatment of severe complicated CDI. Reports of resistance will likely limit the clinical use of fusidic acid and bacitracin and, possibly, rifaximin if resistance to this agent becomes widespread. Treatment of patients with multiple CDI recurrences and those with severe complicated CDI is based on limited clinical evidence, and new treatments or strategies are needed.

Gastric Acid Suppression and Outcomes in Clostridium difficile Infection: A Population-Based Study

ObjectiveTo evaluate the association of gastric acid suppression medications, including proton pump inhibitors and histamine type 2 blockers, with outcomes in patients with Clostridium difficile infection (CDI) in a population-based cohort. Patients and MethodsTo understand the association between acid suppression and outcomes in patients with CDI, we conducted a population-based study in Olmsted County, Minnesota, from January 1, 1991, through December 31, 2005. We compared demographic data and outcomes, including severe, severe-complicated, and recurrent CDI and treatment failure, in a cohort of patients with CDI who were treated with acid suppression medications with these outcomes in a cohort with CDI that was not exposed to acid-suppressing agents. ResultsOf 385 patients with CDI, 36.4% were undergoing acid suppression (23.4% with proton pump inhibitors, 13.5% with histamine type 2 blockers, and 0.5% with both). On univariate analysis, patients taking acid suppression medications were significantly older (69 vs 56 years; P<.001) and more likely to have severe (34.2% vs 23.6%; P=.03) or severe-complicated (4.4% vs 2.6% CDI; P=.006) infection than patients not undergoing acid suppression. On multivariable analyses, after adjustment for age and comorbid conditions, acid suppression medication use was not associated with severe or severe-complicated CDI. In addition, no association between acid suppression and treatment failure or CDI recurrence was found. ConclusionIn this population-based study, after adjustment for age and comorbid conditions, patients with CDI who underwent acid suppression were not more likely to experience severe or severe-complicated CDI, treatment failure, or recurrent infection.

Clinical Predictors of Severe Complicated Clostridium Difficile Infection

Purpose:Clostridium Difficile infection (CDI) can be severe, and associated with complications and mortality. Treatment recommendations are stratified based on severity. However, there are no robust models to predict severe complicated CDI. The objective of this study was to create a clinically useful model to predict severe complicated CDI. Methods: The microbiology laboratory database and patient medical records were queried to identify cases of CDI from June 1, 2007 - May 31, 2010. Severe complicated CDI was defined as need for ICU admission or colectomy, or death within 30 days of CDI diagnosis. Variables including patient demographics, Charlson Co-morbidity index, temperature, peripheral leukocyte count, serum albumin, and change in serum creatinine were obtained. Univariate and multiple variable logistic regression models were used to assess the association of these variables with complications of CDI. Only patients who had data for each variable of interest were included in the multiple variable analyses. Results: The cohort included 1400 patients with CDI (50% female, median age at CDI diagnosis was 63.1 years [range 1.2-100.1]), and 357 (25.5%) were severe complicated CDI cases. The frequency of ICU admission, colectomy, and death within 30 days of diagnosis was 19.3%, 2.3%, and 7.3%, respectively. In univariate analysis, increasing age (OR 1.15, 95% CI 1.08-1.23, p<0.0001), increasing peripheral leukocyte count (OR 1.05, 95% CI 1.03-1.06, p<0.0001), change in serum creatinine >1.5 fold (OR 2.61, 95% CI 2.04-3.34, p<0.0001), serum albumin (OR 0.48, 95% CI 0.35-0.66, p<0.0001), temperature (OR 1.36, 95% CI 1.35-1.59, p=0.0002), and Charlson Co-morbidity index (OR 1.09, 95% CI 1.03-1.15, p=0.001) were associated with severe complicated CDI. Serum albumin and temperature were not included in the multiple variable model due to missing data. In the multiple variable model (adjusting for referral distance), increasing age (OR 1.1, 95% CI 1.03-1.18, p=0.0072), increasing peripheral leukocyte count (OR 1.04, 95% CI 1.03-1.05, p<0.0001) and change in serum creatinine greater than 1.5-fold (OR 2.3, 95% CI 1.75-2.98, p<0.0001) were independent predictors of severe complicated CDI, but Charlson Comorbidity index score was not. Conclusion: Older age, higher peripheral leukocyte count, and rising serum creatinine independently predicted severe complicated CDI. Temperature and low serum albumin were also associated with severe complicated CDI by univariate analysis. An appreciation of these variables could be pivotal in identifying patients at increased risk of CDI complications. It is conceivable that early aggressive monitoring and intervention in these patients could have beneficial effects.

Tigecycline for the Treatment of Severe Clostridium difficile Infection

To evaluate the evidence for the use of tigecycline in the treatment of Clostridium difficile infection (CDI). Searches were performed (2004 to June 2011), using the EMBASE and MEDLINE databases, with the terms tigecycline, Tygacil, Clostridium difficile, C. difficile, Clostridium difficile infection, and CDI. Six case reports that described the use of tigecycline for treatment of CDI were included for review. No clinical trials were identified. In all case reports except 1, tigecycline (alone or in combination with other CDI therapies) was used for the treatment of CDI that was refractory to metronidazole and/or vancomycin. In 6 of the cases, treatment success was reported following initiation of tigecycline therapy; 1 patient died following a complicated hospitalization. The treatment duration with tigecycline was 2-4 weeks. In the cases with successful outcomes, symptoms began to improve within 1 week. None of these patients experienced recurrence during follow-up of various lengths. In vitro studies demonstrated a 90% minimum inhibitory concentration range for tigecycline of 0.016-0.25 mg/L for all C. difficile isolates. Tigecycline exhibited good fecal penetration because of primary biliary excretion of unchanged drug. Up to 59% of the dose is recovered in feces following administration over 4 days in healthy volunteers. Case reports have suggested that tigecycline may be successful for treatment of severe or severe complicated CDI, when prior therapy has failed. Data demonstrating tigecycline use as initial therapy for CDI are limited; therefore, this option should be reserved for patients in whom other therapeutic options, including metronidazole and vancomycin, have failed. A randomized controlled trial is needed to assess the safety and efficacy of tigecycline in this patient population and better define the drug's role in the treatment of CDI.