Features of Clostridioides difficile infection (CDI) in patients with cancer: A seven-year study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13606-e13606
Author(s):  
Inmaculada Gallego ◽  
Miguel Rodriguez-Fernandez ◽  
Marta Trigo Rodriguez ◽  
Rocio Herrero ◽  
Nicolás Merchante

e13606 Background: Clostridioides difficile infection (CDI) is frequently seen in patients with cancer. However, information of the features and clinical course of CDI in this specific setting is lacking. Our objective was to describe the clinical picture of CDI in patients with cancer and to compare it with that observed in patients without cancer. Methods: This was an observational cohort study which included all consecutive patients diagnosed of CDI at the Hospital Universitario de Valme (Sevilla, Spain) between January 2014 and October 2020. Recurrence was defined as the reappearance of symptoms of CDI with microbiologic confirmation of toxigenic Clostridioides difficile in the first 8 weeks after the end of CDI treatment according to the Infectious Diseases Society of America criteria. Results: 481 patients had a first episode of CDI during the study period, 102 (21%) had an active neoplasm at CDI diagnosis and 379 (79%) did not had history of active cancer. The proportion of CDI cases in patients with cancer among the total cases of CDI per year was: 2014: 10/70 (17%); 2015: 10/47 (21%); 2016: 17/59 (29%); 2017: 12/80 (15%); 2018: 23/82 (28%); 2019: 16/80 (20%); 2020: 14/73 (19%); p=0.3). When compared with patients without cancer, those with cancer showed differences in: age (68 [58-79] vs 77 [61-84] years; p=0.002); male sex (68 [58-79] vs 77 [61-84]; p=0.002); Charlson comorbidity index > 2 (93 [92%] vs 234 [63%]; p<0.001); nosocomial or healthcare related CDI (90 [88%] vs 275 [72%]; p<0.001); immunosuppression (72 [70%] vs 52 [14%]; p<0.001); hospitalization during the last year (78 [76%] vs 224 [59%]; p=0.001); concomitant use of proton bomb inhibitors (89 [87%] vs 265 [70%]; p=0.001) and concomitant use of antibiotics (45 [45%] vs 125 [33%]; p<0.03). Regarding CDI treatment, 64 (69%), 25 (27%) and 2 (2%) patients in the cancer-group were treated with metronidazole, vancomycin and fidaxomicin, respectively, whereas the corresponding figures in non-cancer patients were 228 (67%), 102 (30%) and 5 (1.5%) (p=0.8). The proportion of oncologic patients receiving vancomycin increased after implementing an antimicrobial stewardship program focused on CDI management during 2017 (2014-2017: 2 [4%]; 2018: 3 (17%); 2019: 11 (73%); 2020: 10 (83%); p<0.001). CDI recurrence could not be assessed in 23 (5%) patients who died during the first 8 weeks of follow-up for reasons other than CDI, including 8 patients with CDI and cancer. Among evaluable patients, 16 (17%) of those with cancer and 61 (17%) of those without cancer had a first CDI recurrence (p=0.9). Conclusions: CDI recurrence rates in cancer patients are similar to that observed in non-cancer patients in spite of a higher frequency of risk factors for recurrence. Appropriate CDI therapy could have counterbalanced this worse profile during recent years. Our study shows that CDI should be included among the scenarios covered by antimicrobial stewardship programs in oncologic patients.

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S163-S164
Author(s):  
Tiffany Wu ◽  
Susan L Davis ◽  
Susan L Davis ◽  
Brian Church ◽  
George J Alangaden ◽  
...  

Abstract Background Our antimicrobial stewardship program identified high rates of suboptimal metronidazole prescribing for Clostridioides difficile infection (CDI) within ambulatory clinics. An outpatient best practice advisory (BPA) was implemented to notify prescribers “Vancomycin or fidaxomicin are preferred over metronidazole for C.difficile infection” when metronidazole was prescribed to a patient with CDI. Methods We conducted an IRB approved quasi-experiment before and after implementation of the BPA on June 3, 2020. Inclusion: Adult patients diagnosed with and treated for a first episode of symptomatic CDI at an ambulatory clinic between 11/1/2019 and 11/30/2020. Exclusion: fulminant CDI. Primary endpoint: guideline-concordant CDI therapy, defined as oral vancomycin or fidaxomicin. Oral metronidazole was considered guideline-concordant if prescribed due to cost barrier. Secondary endpoints: reasons for alternative CDI therapy, patient outcomes, prescriber response to the BPA. Descriptive and bivariate analyses were completed. Results 189 patients were included in the study, 92 before and 97 after the BPA. Median age: 59 years, 31% male, 75% Caucasian, 30% with CDI-related comorbidities, 35% with healthcare exposure, 65% with antibiotic exposure, 44% with gastric acid suppression therapy within 90 days of CDI diagnosis. The BPA was accepted 23 out of 26 times and optimized the therapy of 16 patients in six months. Guideline-concordant therapy increased after implementation of the BPA (72% vs. 91%, p=0.001) (Figure 1). Vancomycin prescribing increased and metronidazole prescribing decreased after the BPA (Figure 2). Reasons for alternative CDI therapy included medication cost, lack of insurance coverage, and non-CDI infection. There was no difference in clinical response or unplanned encounter within 14 days after treatment initiation. Fewer patients after the BPA had CDI recurrence within 14-56 days of the initial episode (27% vs. 7%, p&lt; 0.001). Figure 1. Guideline-concordant CDI therapy Figure 2. Specific CDI therapy Conclusion Clinical decision support increased prescribing of guideline-concordant CDI therapy in the outpatient setting. A targeted BPA is an effective stewardship intervention and may be especially useful in settings with limited antimicrobial stewardship resources. Disclosures Susan L. Davis, PharmD, Nothing to disclose Rachel Kenney, PharmD, Medtronic, Inc. (Other Financial or Material Support, spouse is an employee and shareholder)


Author(s):  
Eduardo A Yepez Guevara ◽  
Samuel L Aitken ◽  
Adilene V Olvera ◽  
Lily Carlin ◽  
Kerri E Fernandes ◽  
...  

Abstract Background Patients with cancer are particularly vulnerable to Clostridioides difficile infection (CDI). Guidelines recommend a two-step diagnostic algorithm to differentiate carriers from CDI; however, there are limited data for this approach while including other confounding risk factors for diarrhea such as radiation, cytotoxic chemotherapy, and adoptive cell based therapies. Methods We conducted a prospective, non-interventional, single center, cohort study of cancer patients with acute diarrhea and C. difficile, identified in stools by nucleic acid amplification tests (NAAT) and culture. Fecal toxin A/B was detected by enzyme immunoassay (EIA) and isolates were ribotyped using 16s rRNA fluorescent sequencing. Patients were followed for 90 days to compare outcomes according to malignancy type, infecting ribotype, and EIA status. Results We followed 227 patients with a positive NAAT. Of these, 87% were hospitalized and 83% had an active malignancy. EIA was confirmed positive in 80/227 (35%) of patients. Those with EIA+ were older (60 ± 18 years vs 54 ± 19 years., P = .01), more likely to fail therapy [24/80 (30%) vs 26/147 (18%), P = .04] and experience recurrence [20/80 (25%) vs 21/147(14%), P &lt; .05]. We found a low prevalence (22%) of ribotypes historically associated with poor outcomes (002, 018, 027, 56, F078-126, 244) but their presence were associated with treatment failure [17/50 (34%) vs 33/177 (19%), P = .02]. Conclusions When compared to cancer patients with fecal NAAT+/EIA−, patients with NAAT+/EIA+ CDI are less likely to respond to therapy and more likely to experience recurrence, particularly when due to ribotypes associated with poor outcomes.


2020 ◽  
Vol 10 (1) ◽  
pp. 2
Author(s):  
Rosa Escudero-Sánchez ◽  
María Ruíz-Ruizgómez ◽  
Jorge Fernández-Fradejas ◽  
Sergio García Fernández ◽  
María Olmedo Samperio ◽  
...  

Bezlotoxumab is marketed for the prevention of recurrent Clostridioides difficile infection (rCDI). Its high cost could be determining its prescription to a different population than that represented in clinical trials. The objective of the study was to verify the effectiveness and safety of bezlotoxumab in preventing rCDI and to investigate factors related to bezlotoxumab failure in the real world. A retrospective, multicentre cohort study of patients treated with bezlotoxumab in Spain was conducted. We compared the characteristics of cohort patients with those of patients treated with bezlotoxumab in the pivotal MODIFY trials. We assessed recurrence rates 12 weeks after completion of treatment against C. difficile, and we analysed the factors associated with bezlotoxumab failure. Ninety-one patients were included in the study. The cohort presented with more risk factors for rCDI than the patients included in the MODIFY trials. Thirteen (14.2%) developed rCDI at 12 weeks of follow-up, and rCDI rates were numerically higher in patients with two or more previous episodes (25%) than in those who had fewer than two previous episodes of C. difficile infection (CDI) (10.4%); p = 0.09. There were no adverse effects attributable to bezlotoxumab. Despite being used in a more compromised population than that represented in clinical trials, we confirm the effectiveness of bezlotoxumab for the prevention of rCDI.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S441-S442
Author(s):  
Xing Tan ◽  
Andrew M Skinner ◽  
Benjamin Sirbu ◽  
Larry H Danziger ◽  
Dale N Gerding ◽  
...  

Abstract Background There is a paucity of data assessing outcomes of alternate fidaxomicin strategies in patients with recurrent Clostridioides difficile infection (rCDI). The objective of our study is to evaluate a tapered-pulsed (T-P) fidaxomicin regimen that was administered immediately following a course of CDI treatment with initial symptom resolution in patients with multiple rCDI. Methods We reviewed the characteristics and outcomes of 46 consecutive patients who received T-P fidaxomicin between January 1, 2014-June 30, 2019 in a specialty CDI clinic. The first episode in which fidaxomicin T-P was administered was analyzed. Failure was defined as the persistence of diarrhea and/or the need for additional CDI treatment at any time on T-P fidaxomicin. Sustained clinical cure (SCC) was defined as resolution of diarrhea without recurrence. Recurrence was defined as the return of diarrhea requiring retreatment with CDI therapy after completion of T-P fidaxomicin. Both SCC and recurrence were evaluated at 30 and 90 days after completion of T-P fidaxomicin. Results The mean±SD age of the 46 patients was 63.2±19.9 years, 71.7% were female, and the mean±SD CDI episodes within the past year was 3±1.4 . Most patients (73.9%) had previously failed a vancomycin tapered and/or pulsed regimen. Prior to administering T-P fidaxomicin, a treatment regimen was given to ensure resolution of symptoms. The CDI treatment most commonly used (58.7%) was vancomycin. The T-P fidaxomicin regimen used consisted of 200 mg given once daily for 7 days followed by 200 mg every other day for a median (min-max) duration of 33 (6-120) days. Two patients (4%) failed to respond to T-P fidaxomicin; 34 (74%) and 28 (61%) achieved SCC at 30 and 90 days, respectively. Among the 44 patients that successfully completed the T-P fidaxomicin regimen, recurrence developed in 10 (22.7%) and 16 (36.4%) of patients at 30 and 90 days, respectively, with a median (min-max) time to recurrence of 20 (3-87) days (Figure 1). Four patients with recurrence had received subsequent systemic antibiotics. Figure 1. Course of CDI therapy and follow-up Conclusion A tapered-pulsed fidaxomicin strategy may be effective in patients with multiply rCDI who are refractory to other treatments, including a vancomycin tapered and pulsed regimen. Disclosures Larry H. Danziger, PharmD, Merck (Speaker’s Bureau)


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S687-S687
Author(s):  
Philip Chung ◽  
Kate Tyner ◽  
Scott Bergman ◽  
Teresa Micheels ◽  
Mark E Rupp ◽  
...  

Abstract Background Long-term care facilities (LTCF) often struggle with implementation of antimicrobial stewardship programs (ASP) that meet all CDC core elements (CE). The CDC recommends partnership with infectious diseases (ID)/ASP experts to guide ASP implementation. The Nebraska Antimicrobial Stewardship Assessment and Promotion Program (ASAP) is an initiative funded by NE DHHS via a CDC grant to assist healthcare facilities with ASP implementation. Methods ASAP performed on-site baseline evaluation of ASP in 5 LTCF (42–293 beds) in the spring of 2017 using a 64-item questionnaire based on CDC CE. After interviewing ASP members, ASAP provided prioritized facility-specific recommendations for ASP implementation. LTCF were periodically contacted in the next 12 months to provide implementation support and evaluate progress. The number of CE met, recommendations implemented, antibiotic starts (AS) and days of therapy (DOT)/1000 resident-days (RD), and incidence of facility-onset Clostridioides difficile infections (FO-CDI) were compared 6 to 12 months before and after on-site visits. Paired t-test and Wilcoxon signed rank test were used for statistical analyses. Results Multidisciplinary ASP existed in all 5 facilities at baseline with medical directors (n = 2) or directors of nursing (n = 3) designated as team leads. Median CE implemented increased from 3 at baseline to 6 at the end of follow-up (P = 0.06). No LTCF had all 7 CE at baseline. By the end of one year, 2 facilities implemented all 7 CE with the remaining implementing 6 CE. LTCF not meeting all CE were only deficient in reporting ASP metrics to providers and staff. Among the 38 recommendations provided by ASAP, 82% were partially or fully implemented. Mean AS/1000 RD reduced by 19% from 10.1 at baseline to 8.2 post-intervention (P = 0.37) and DOT/1000 RD decreased by 21% from 91.7 to 72.5 (P = 0.20). The average incidence of FO-CDI decreased by 75% from 0.53 to 0.13 cases/10,000 RD (P = 0.25). Conclusion Assessment of LTCF ASP along with feedback for improvement by ID/ASP experts resulted in more programs meeting all 7 CE. Favorable reductions in antimicrobial use and CDI rates were also observed. Moving forward, the availability of these services should be expanded to all LTCFs struggling with ASP implementation. Disclosures All authors: No reported disclosures.


2021 ◽  
Vol 1 (S1) ◽  
pp. s41-s41
Author(s):  
Kinta Alexander ◽  
Frances Petersen ◽  
Sean Brown

Background:Clostridioides difficile is a gram-positive bacteria that is the most common cause of hospital-associated infectious diarrhea among traditional and nontraditional high-risk populations. Excess healthcare costs associate with C. difficile infection (CDI) prevalence, morbidity, and mortality is shown to economically impact the US healthcare system with at least an additional $1 billion in annual cost. Exposure to antimicrobial agents resulted in increased risk for hospital-onset CDI (HO-CDI) at an inner-city hospital during 2010 and 2011. Methods: A retrospective case-control study of all persons with HO-CDI in the MICU was conducted at an inner-city hospital between January 1, 2010, and December 31, 2011. A patient was considered to have developed HO-CDI if diarrhea developed after 72 hours of admission into the MICU and a confirmed laboratory stool specimen for Clostridioides difficile infection (CDI) was obtained. A non–HO-CDI person was randomly selected using “risk set sampling.” After the application of inclusion and exclusion criteria, 88 cases were eligible for the study. Of these cases, 29 met the definition for HO-CDI, and 59 met the definition for non–HO-CDI. The relationship between antimicrobial use and the development of HO-CDI in patients in the MICU at an inner-city hospital was investigated using a logistic regression model in which the variable of total antibiotics was used as a possible predictor for predicting a positive HO-CDI. Results: Logistic regression was utilized to determine the relationships between selected study variables and presence or absence of HO-CDI. Total antibiotics was significantly related to HO-CDI. The results of this analysis showed that total antibiotics was a significant predictor for HO-CDI. The total value of the coefficient B for this predictor was 0.47, and the exponentiated value (exp[B]) of this coefficient was 1.60 (95% CI, 1.08–2.35). In this sample, patients who had 1 or more antibiotics were at a 60% greater risk of having a positive HO-CDI culture. There was a significant association between the use of metronidazole and HO-CDI (p < .001). Conclusions: Antimicrobial stewardship is an integral part of patient safety. The findings from this study were instrumental in the implementation of a fledging antimicrobial stewardship program and the use of evidence-based practices at this inner-city hospital.Funding: NoDisclosures: None


2021 ◽  
Author(s):  
Christopher A. Okeahialam ◽  
Ali A. Rabaan ◽  
Albert Bolhuis

AbstractBackgroundAntimicrobial stewardship has been associated with a reduction in the incidence of health care associated Clostridium difficile infection (HA-CDI). However, CDI remains under-recognized in many low and middle-income countries where clinical and surveillance resources required to identify HA-CDI are often lacking. The rate of toxigenic C. difficile stool positivity in the stool of hospitalized patients may offer an alternative metric for these settings, but its utlity remains largely untested.Aim/ObjectiveTo examine the impact of an antimicrobial stewardship on the rate of toxigenic C. difficile positivity among hospitalized patients presenting with diarrhoeaMethodsA 12-year retrospective review of laboratory data was conducted to compare the rates of toxigenic C. difficile in diarrhoea stool of patients in a hospital in Saudi Arabia, before and after implementation of an antimicrobial stewardship programResultThere was a significant decline in the rate of toxigenic C difficile positivity from 9.8 to 7.4% following the implementation of the antimicrobial stewardship program, and a reversal of a rising trend.DiscussionThe rate of toxigenic C. difficile positivity may be a useful patient outcome metric for evaluating the long term impact of antimicrobial stewardship on CDI, especially in settings with limited surveillance resources. The accuracy of this metric is however dependent on the avoidance of arbitrary repeated testing of a patient for cure, and testing only unformed or diarrhoea stool specimens. Further studies are required within and beyond Saudi Arabia to examine the utility of this metric.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S234-S235
Author(s):  
Alvaro J Martinez-Valencia ◽  
Brian J Gomez Martinez ◽  
Anita Montañez Ayala ◽  
Katherine Garcia ◽  
Ricardo Sánchez Pedraza ◽  
...  

Abstract Background Cancer patients are susceptible to infections due to immunodeficiency, frequent invasive interventions-devices, chemotherapy and antibiotics exposure. Infections caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae increase morbidity and mortality. The objective was to identify clinical factors associated with ESBL in infected patients with cancer at the Instituto Nacional de Cancerología. Methods A case–control study was conducted from 2013 to 2015. Cases were infected patients with ESBL-producer Enterobacteriaceae. Controls (matched for date and ward) with non-ESBL-producer Enterobacteriaceae were included. Data were extracted from electronic medical records at index culture: clinical and admission data, Charlson index, immunosuppressive, radio and chemotherapy, neutropenia, invasive devices, surgical procedures and antimicrobial therapy. Microorganisms were identified by the automatized system. Conditional logistic regression and backward stepwise was used to identify predictors of ESBL isolation. Results A total of 265 patients with ESBL producer Enterobacteriaceae and 445 non-ESBL producers were identified, mean age 59, 61% male, 48% admitted as outpatients, 73% with solid tumors, 38% with Charlson index ≥4. E.coli and Klebsiella spp. represented 90% of microorganisms. Factor associated with ESBL producer Enterobacteriaceae were hospitalization ≥7 days (OR: 1,59; CI 1.11–2,29), hospitalization the previous year (OR: 4.02; CI 2,68–6,02), immunosuppressive therapy (OR: 2.07; CI 1,05–4.05), Β-lactam therapy the last month (OR: 1.54; CI 1.05–2.26), invasive devices (OR: 1.58; CI 1.10–2.27), active neoplasia (OR: 2,22; CI1.05–4.68), neutropenia (OR: 2.03; CI:1.26–3.27) and absence of chemotherapy during last 3 months (OR: 1.91; CI1.29–2.82). Discriminatory capacity was acceptable (AUC: 0.71). Conclusion The presence of ESBL-producer Enterobacteriaceae in oncologic patients is associated with health care, hospital admission and length of stay, invasive devices and exposure to antibiotics. The magnitude of associated factors are weak and do not completely allow the identification of cancer patients infected with ESBL-producer Enterobacteriaceae. Disclosures All authors: No reported disclosures.


2020 ◽  
Vol 68 (4) ◽  
pp. 888-892 ◽  
Author(s):  
Paige A Bishop ◽  
Carmen Isache ◽  
Yvette S McCarter ◽  
Carmen Smotherman ◽  
Shiva Gautam ◽  
...  

Clostridioides difficile is the most common cause of healthcare-associated infection and gastroenteritis-associated death in the USA. Adherence to guideline recommendations for treatment of severe C. difficile infection (CDI) is associated with improved clinical success and reduced mortality. The purpose of this study was to determine whether implementation of a pharmacist-led antimicrobial stewardship program (ASP) CDI initiative improved adherence to CDI treatment guidelines and clinical outcomes. This was a single-center, retrospective, quasi-experimental study evaluating patients with CDI before and after implementation of an ASP initiative involving prospective audit and feedback in which guideline-driven treatment recommendations were communicated to treatment teams and documented in the electronic health record via pharmacy progress notes for all patients diagnosed with CDI. The primary endpoint was the proportion of patients treated with guideline adherent definitive regimens within 72 hours of CDI diagnosis. Secondary objectives were to evaluate the impact on clinical outcomes, including length of stay (LOS), infection-related LOS, 30-day readmission rates, and all-cause, in-hospital mortality. A total of 233 patients were evaluated. The proportion of patients on guideline adherent definitive CDI treatment regimen within 72 hours of diagnosis was significantly higher in the post-interventional group (pre: 42% vs post: 58%, p=0.02). No differences were observed in clinical outcomes or proportions of patients receiving laxatives, promotility agents, or proton pump inhibitors within 72 hours of diagnosis. Our findings demonstrate that a pharmacist-led stewardship initiative improved adherence to evidence-based practice guidelines for CDI treatment.


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