Class of 2012 Abstract / Specific Aims: The incidence of non-response, recurrence, relapse, and rate of complications of Clostridium difficile infections treated with combination of metronidazole and vancomycin versus vancomycin or metronidazole alone over a one-year period by treatment and strain type (i.e. NAP1/BI/027) were evaluated. The incidence of mortality in patients with moderate to severe Clostridium difficile associated diarrhea prescribed metronidazole, vancomycin, or combination metronidazole plus vancomycin as initial therapy was also determined. Additionally, significant factors associated with the use of combination vancomycin-metronidazole as initial therapy for moderate to severe CDAD were characterized. Methods: T This retrospective medical record review has been approved by the Institutional Review Board. Adult patients with stool specimens tested for detection of Clostridium difficile toxin B by PCR between April 2010 and March 2011 at a tertiary care, academic medical center were evaluated. Patients were included in the study if diagnosed with moderate to severe disease and received either monotherapy with metronidazole, monotherapy with oral vancomycin, or combination therapy with metronidazole and oral vancomycin for at least 80% of the first 10 days of treatment. Patients who are discharged alive within 72 hours of admission or who received therapy for less than 48 hours were excluded. Main Results: All patients (N=411) with laboratory evidence of Clostridium difficile during the study time period were evaluated. A total of 26 subjects who received oral vancomycin monotherapy and 56 subjects who received oral vancomycin along with metronidazole for at least 80% of the first 10 days of treatment were identified. Of the subjects who received oral vancomycin monotherapy during the first ten days of therapy, 5 (19%) were classified has a treatment failure or died within the first 21 days of therapy and 5 (19%) had either a recurrence or reappearance of Clostridium difficile associated diarrhea between 22 and 65 days post start of therapy. Of the subjects who received a combination of oral vancomycin and metronidazole during the first 10 days of therapy, 14 (25%) were classified has a treatment failure or died within the first 21 days of therapy and 22 (39%) had either a recurrence or reappearance of Clostridium difficile associated diarrhea between 22 and 65 days post start of therapy. In the combination therapy group, 5 (9%) were reported to have an ileus, toxic megacolon, or necrotic bowel during the first 10 days of therapy. Conclusions: In this study, the subjects who received a combination of oral vancomycin and metronidazole had higher rates of clinical failure, death, and recurrence than subjects who received monotherapy. Current guideline statements recommend combination therapy only in patients with an ileus with Clostridium difficile-associated diarrhea.

Clostridium difficile infection (CDI) has proven to be a constantly evolving disease periodically posing new diagnostic and clinical dilemmas. Different regions of the world have reported specific local genomic characteristics of the infecting strains, which may be related to variation in disease presentation and outcome. This study was performed to determine the clinical and molecular features of severe, recurrent and community-associated disease in the Lothian region of Scotland, UK among patients diagnosed from August 2010-July 2011. Three hundred and thirty-five patients with laboratory confirmed CDI were studied for epidemiological features, clinical presentation, and laboratory markers. They were followed up for one year to determine recurrence and mortality. Four hundred and thirty-two episodes were recorded. Ribotypes, presence of toxin genes and MLVA subtypes of isolates from these episodes were determined. During the course of the study, PCR ribotype 078 was identified as an important emerging type and concerns of “hypervirulence” were raised when an outbreak was recorded in 2012. This ribotype was studied to compare its clinical and molecular characteristics with other endemic ribotypes and between its own outbreak-related and endemic subtypes. Asymptomatic children were also sampled to determine their role as pools of potential pathogens. Severe episodes accounted for 40.4% of total and 29.3% patients had multiple episodes on record. One-year mortality was 32.8% of which CDI was listed on 25.5% death certificates. Ribotype 078 was confirmed in 6.8% episodes. Community-associated disease was identified in 25.3% patients, which differed significantly from hospital-associated disease in the number of antibiotics and gastrointestinal manipulation prior to CDI. Endemic PCR ribotype 078 caused significantly less recurrent disease and more community- associated disease when compared to the most prevalent ribotype 001. Patients who died from ribotype 078 within 30d had a lower Charlson comorbidity index than ribotype 001 counterparts suggesting that the former may infect healthier patients. MLVA subtyping of ribotype 078 proved useful in identifying epidemiological relationships during the outbreak. CDI had contributed to the death of 50% of all patients infected with the outbreak related ribotype 078 strain compared to 14.3% of those infected with the endemic strains. This study documents the changing epidemiology of CDI in the region and demonstrates differences in epidemic and endemic disease.

Class of 2014 Abstract / Specific Aims: The incidence of Clostridium difficile (C. Diff) infections in pediatric patients has continually risen, which could be caused by the emergence of a hyper virulent strain, specifically NAP1/B1/027. The objectives of the study were to evaluate the incidence of strain type, compare treatment(s) prescribed, treatment duration, rate of infection recurrence based on strain and severity, rates of re-infection or recurrence, and treatment failures for patients less than 6 months and up to 18 years of age. Methods: A retrospective study of patients admitted to an academic medical center with detection of C. diff toxin was performed. Data analyses included descriptive and inferential statistics to examine demographics, strain type, infection severity, and treatment failure. Main Results: Fourty-five patients with C. Diff toxin detection were included in study analyses and the median age was 6.2 [0.31- 17.9 years]. Oral or intravenous metronidazole was prescribed as initial therapy in 89% of the patients. Strain type was available in 77% of patients, with NAP1/B1/027 detected in 31% of stool samples tested. Within 21 days after initial toxin detection, there was a 13% rate of clinical failure or death, although none directly associated with C. Diff. Within days 22 - 65 after initial toxin detection, there was a 16% rate of recurrence or reinfection. Initial therapy selection, therapy duration, and rate of recurrence or reinfection were not significantly associated with NAP1/B1/027 strain type. Conclusion: Despite variability in severity of infection, the majority of pediatric patients with C. Diff were treated with metronidazole and were infected with a non-B1/NAP1/027 strain.

The challenge of combating Clostridium difficile infections (CDI) is a major problem within many health care organizations as CDI adds to the cost of care and is an uncomfortable and sometimes fatal complication of hospitalization for the patient. The practice-focused question for this doctoral project was targeted at patients in hospital settings on a medical surgical floor and asked if clostridium difficile preventive bundles reduce the incidence of CDI compared with nonstandardized preventative methods. Using the plan-do-study-act framework, the purpose of this DNP project was to use a clostridium difficile bundle approach to study the effects of clostridium difficile incidence (CDI) decrease on a medical-surgical unit with high CDI incidences. Standardized environmental cleaning practices resulted in improvement of the patient environment. High-touch cleaning improved from 43.7% to 83.3%. Time between CDI events lengthened from 19.9 days to 30.2, environmental cleaning with the use of Dazo auditing improved from 33.4% to 81.6%, isolation practices improved from 62.7% to 90%, and with the implementation of the nurse-driven CD testing protocol, unnecessary testing improved. Results showed that the CDI incidence on an acute care medical surgical unit was reduced through the use of a clostridium difficile preventive bundle in this DNP project. Reducing the incidence of CDI is a significant contribution to social change as this unwanted complication of hospitalization causes discomfort and pain and adds unnecessary cost to health care.

Class of 2006 Abstract / Background: The processes’ underlying a recent rise in the rate of Clostridium difficile associated diarrhea (CDAD) at the Southern Arizona Veterans Administration Health Care System (SAVAHS) is unclear. Past changes to formulary in workhorse oral flouroquinolone from levofloxacin to gatifloxacin are under scrutiny. An infection-control component was also possible. Methods: 142 patients suspected of having CDAD had stool specimens submitted for toxin assay from late July to late Oct of 2004. A retrospective chart review was performed using the Veterans Administration Computerized Patient Record System (CPRS) to examine total antibiotic use in the three months prior to having specimens submitted for laboratory toxin analysis. A subset-analysis was performed on 100 specimens submitted for toxin analysis. Parallel culture was performed and 9 isolates of C. difficile were obtained for molecular analysis and fingerprinting. Results: Of the 142 patients sampled, 20 tested positive for C. difficile toxin with the remaining 122 patients testing negative. Antibiotic usage was categorized by total antibiotic use and gatifloxacin use. 98 patients received at least 1 antibiotic within the preceding 3 months with 44 patients receiving no antibiotic therapy of any kind. Of the 98 patients that received antibiotic therapy, 44 received gatifloxacin, however, all of these patients also received at least one other antibiotic. Of the nine isolates fingerprinted, two distinct genetic clusters were identified.

Clostridium difficile infection (CDI) continues to possess a significant disease burden in the United States (US) as well as all over the world. Given the increase in severity and recurrence rate, the decrease in cure rate, and the fact that the virulent ribotype 027 strain remains one of the most commonly identified strains in the US, the Infectious Diseases Society of America (IDSA) published a clinical practice guideline in February 2018 moving away from metronidazole as the first-line treatment for initial CDI and recommending either oral vancomycin or fidaxomicin. The aim of this study is to evaluate the clinical data available comparing the efficacy of primary treatment of CDI between those two antibiotics. We performed a PubMed, PubMed Central, and ScienceDirect database search without restriction to regions, publication types, or languages. A comprehensive literature search was performed from January 1, 1980 up to March 20, 2018. We used the following keywords in different combinations: Clostridium difficile, Clostridium difficile infection, CDI, C. diff, C. difficile, fidaxomicin, vancomycin, pseudomembranous colitis, and antibiotic-associated colitis. The search was limited to human studies. Data were independently extracted by two reviewers with disagreements resolved by a third author. We pooled an odds ratio (OR) on two primary outcomes: Clinical cure rate and rate of recurrence during the follow-up period. The computer search was also supplemented with manual searches by the authors of the retrieved review articles and primary studies. The search phrase "((Clostridium difficile) AND vancomycin) AND fidaxomicin" had the highest yield results. We identified four observational studies with a total of 2,303 patients with CDI that met our inclusion criteria. Compared with vancomycin, fidaxomicin use was associated with a significantly lower recurrence of CDI with a pooled OR of 0.47 (95% confidence interval (CI), 0.37 - 0.60, I2 = 0). On the other hand, there was no significant association of fidaxomicin use with CDI cure rate compared to vancomycin with a pooled OR of 1.22 (95% CI, 0.93 - 1.60, I2 = 0). In light of the recently updated clinical practice guidelines by the IDSA, our review suggests that fidaxomicin has a more sustained clinical response with a statistically significant lower recurrence rate. Although fidaxomicin appears to be the better drug with statistical significance, its cost-effectiveness continues to be an ongoing controversy. More randomized clinical trials are needed to shed light on this matter to assess if there is any clinical significance in fidaxomicin superiority.

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