Background. An epidemic strain of Clostridium difficile designated by restriction endonuclease analysis (REA) as group BI has caused multiple outbreaks of severe C. difficile infection (CDI). The ...treatment response of patients infected with this strain is uncertain. Methods. Clostridium difficile isolates were collected from 2 phase 3 clinical trials comparing fidaxomicin to vancomycin and typed using REA. Clinical cure and recurrence outcomes were analyzed by strain type of the infecting organism, BI and non-BI, using both univariate and multivariate analyses. Results. From 999 patients, 719 isolates were available for typing (356 fidaxomicin treated and 363 vancomycin treated). BI was the most common REA group (34% of isolates). Patients infected with BI had lower cure rates (86.6%; 214 of 247) than those infected with non-BI strains (94.3%; 445 of 472) (P < .001). The cure rate difference between the BI and non-BI patients was significant for both vancomycin (P = .02) and fidaxomicin (P = .007). BI patients had a recurrence rate of 27.4% (51 of 186), compared with a recurrence rate of 16.6% (66 of 397) in non-BI patients (P = .002). By multivariate analysis, BI infection was statistically significant as a risk factor for reduced cure (odds ratio OR, 0.48; 95% confidence interval CI, .27—.85; P = .030) and for increased recurrence (OR, 1.57; 95% CI, 1.01—2.45; P = .046). Conclusions. The clinical cure rate of patients infected with the epidemic BI C. difficile strain is lower than the cure rate of those infected with non-BI strains whether treated with fidaxomicin or vancomycin. Similarly, the CDI recurrence rate is increased in patients with the BI strain compared with patients with other C. difficile strains.
To test the hypothesis that long-term care facility (LTCF) residents with Clostridium difficile infection (CDI) or asymptomatic carriage of toxigenic strains are an important source of transmission ...in the LTCF and in the hospital during acute-care admissions.
A 6-month cohort study with identification of transmission events was conducted based on tracking of patient movement combined with restriction endonuclease analysis (REA) and whole-genome sequencing (WGS).
Veterans Affairs hospital and affiliated LTCF.ParticipantsThe study included 29 LTCF residents identified as asymptomatic carriers of toxigenic C. difficile based on every other week perirectal screening and 37 healthcare facility-associated CDI cases (ie, diagnosis >3 days after admission or within 4 weeks of discharge to the community), including 26 hospital-associated and 11 LTCF-associated cases.
Of the 37 CDI cases, 7 (18·9%) were linked to LTCF residents with LTCF-associated CDI or asymptomatic carriage, including 3 of 26 hospital-associated CDI cases (11·5%) and 4 of 11 LTCF-associated cases (36·4%). Of the 7 transmissions linked to LTCF residents, 5 (71·4%) were linked to asymptomatic carriers versus 2 (28·6%) to CDI cases, and all involved transmission of epidemic BI/NAP1/027 strains. No incident hospital-associated CDI cases were linked to other hospital-associated CDI cases.
Our findings suggest that LTCF residents with asymptomatic carriage of C. difficile or CDI contribute to transmission both in the LTCF and in the affiliated hospital during acute-care admissions. Greater emphasis on infection control measures and antimicrobial stewardship in LTCFs is needed, and these efforts should focus on LTCF residents during hospital admissions.
During a surveillance study of patients in a long-term care facility and the affiliated acute care hospital in the United States, we identified a Clostridioides difficile strain related to the ...epidemic PCR ribotype (RT) 027 strain associated with hospital outbreaks of severe disease. Fifteen patients were infected with this strain, characterized as restriction endonuclease analysis group DQ and RT591. Like RT027, DQ/RT591 contained genes for toxin B and binary toxin CDT and a tcdC gene of identical sequence. Whole-genome sequencing and multilocus sequence typing showed that DQ/RT591 is a member of the same multilocus sequence typing clade 2 as RT027 but in a separate cluster. DQ/RT591 produced a similar cytopathic effect as RT027 but showed delayed toxin production in vitro. DQ/RT591 was susceptible to moxifloxacin but highly resistant to clindamycin. Continued surveillance is warranted for this clindamycin-resistant strain that is related to the fluoroquinolone-resistant epidemic RT027 strain.
Objective. Describe the clinical and molecular epidemiology of incident Clostridium difficile infection (CDI) cases in Chicago area acute healthcare facilities (HCFs).
Design and Setting. Laboratory, ...clinical, and epidemiologic information was collected for patients with incident CDI who were admitted to acute HCFs in February 2009. Stool cultures and restriction endonuclease analysis typing of the recovered C. difficile isolates was performed.
Patients. Two hundred sixty-three patients from 25 acute HCFs.
Results. Acute HCF rates ranged from 2 to 7 patients with CDI per 10,000 patient-days. The crude mortality rate was 8%, with 20 deaths occurring in patients with CDI. Forty-two (16%) patients had complications from CDI, including 4 patients who required partial, subtotal, or total colectomy, 3 of whom died. C. difficile was isolated and typed from 129 of 178 available stool specimens. The BI strain was identified in 79 (61%) isolates. Of patients discharged to long-term care who had their isolate typed, 36 (67%) had BI-associated CDI.
Conclusions. Severe disease was common and crude mortality was substantial among patients with CDI in Chicago area acute HCFs in February 2009. The outbreak-associated BI strain was the predominant endemic strain identified, accounting for nearly two-thirds of cases. Focal HCF outbreaks were not reported, despite the presence of the BI strain. Transfer of patients between acute and long-term HCFs may have contributed to the high incidence of BI cases in this investigation.
Abstract
Background
Omadacycline was approved for the treatment of community acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) in 2018. Previous ...studies demonstrate that omadacycline has in vitro activity against Clostridioides difficile. We determined the in vitro activity of omadacycline and of comparator antimicrobials for the approved indications, CABP and ABSSSI, towards a contemporary and clinically relevant collection of C. difficile isolates.
Methods
Antimicrobial agar dilution was performed on 200 clinical C. difficile isolates collected from 2014 – 2021. Isolates were selected based on the most prevalent restriction endonuclease analysis (REA) groups locally and nationally. Omadacycline was compared to 8 standard of care antimicrobials for CABP and ABSSSI: amoxicillin-clavulanate, azithromycin, ceftriaxone, clindamycin, doxycycline, linezolid, moxifloxacin, and trimethoprim-sulfamethoxazole.
Results
Omadacycline demonstrated in vitro activity against all C. difficile isolates tested. The geometric mean MIC of omadacycline was 0.07 μg/ml and the MIC50 and MIC90 were 0.0625 μg/ml and 0.125 μg/ml, respectively. Among the comparator antibiotics, 52% of isolates were resistant to ceftriaxone and 37% of isolates were resistant to clindamycin. The majority of REA group BI isolates were resistant to clindamycin (77.7%, 28/36) and the clindamycin geometric mean MICs were higher for group BI compared to all other REA group strains (32 µg/ml and 5.33 µg/ml, respectively, p < 0.005). REA group BI also had elevated azithromycin and moxifloxacin geometric MICs (335.2 and 17.3 µg/ml, respectively). REA group DH isolates had higher trimethoprim-sulfamethoxazole geometric MICs compared to all other REA group strains (17.28 µg/ml and 8.14 µg/ml, respectively p >0.001). Nearly half of REA group BK isolates (47%) had MICs ≥2 µg/ml which did not correspond to elevated omadacycline MICs for the same isolates.
Conclusion
Omadacycline demonstrated consistently low MICs against C. difficile when compared to approved antimicrobials for CABP and ABSSI which varied in activity among particular C. difficile strains. Omadacycline may reduce the risk of developing a C. difficile infection and requires further study.
Disclosures
Stuart Johnson, M.D., Ferring Pharmaceuticals: Membership on Ferring Publication Steering Committee|Ferring Pharmaceuticals: Employee|Summit Plc: Advisor/Consultant.
Abstract
Background
In 2017, the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiologist of America (SHEA) updated the C. difficile (CD) treatment guidelines ...recommending vancomycin as the preferred therapy for C. difficile infections (CDI). We assessed the in vitro vancomycin minimum inhibitory concentration (MIC) against CD across three decades to determine if the vancomycin MIC had increased since these guidelines were published.
Methods
We performed antimicrobial agar dilution susceptibility testing on 89 clinically relevant CD isolates collected within Chicagoland area. These isolates were selected from 3 separate timeframes: 2005 – 2007, 2013 – 2015, and 2021. Isolates were selected based on the prevalence of restriction endonuclease analysis (REA) strain types within each time cohort. Treatment response to vancomycin was reviewed for patients from the 2021 cohort if CD isolates had a vancomycin MIC of ≥ 16 μg/ml.
Results
The in vitro vancomycin geometric mean MIC against all 89 CD isolates was 2.53 μg/ml with a MIC50 of 2 μg/ml and MIC90 of 4 μg/ml. Comparing the 3 timeframes, the geometric mean vancomycin MICs from 2005-2007, 2013-2015, and 2021 were 2.35, 2.27, and 2.91, respectively (p=0.11). Comparison of the isolates collected from 2005 – 2015 to 2021, the in vitro vancomycin geometric mean MICs were 2.31 and 2.91, respectively (p = 0.037). REA group BI was the most common strain group to have an increased in vitro vancomycin MIC within the 2021 cohort as 4 of the 5 isolates tested had a MIC of 16 μg/ml. All 4 of the patients infected with these strains with an elevated vancomycin MICs were treated vancomycin. All 4 patients had a resolution of symptoms on vancomycin and 2 suffered from a recurrent infection within ≤4 weeks of completing vancomycin.
Conclusion
The vancomycin MIC against CD has trended upwards slightly over the past 20 years. The most notable change occurred between 2015 and 2021. We hypothesize that this increase is due to increased use of oral vancomycin for the treatment of CDI. However, these data indicate that most isolates still have a MIC of ≤4 μg/ml and an elevated MIC does not appear to impact clinical outcomes. Further study is required to determine if this upward trend in vancomycin MIC continues and if this could have any potential clinical implications.
Disclosures
Stuart Johnson, M.D., Ferring Pharmaceuticals: Membership on Ferring Publication Steering Committee|Ferring Pharmaceuticals: Employee|Summit Plc: Advisor/Consultant.
Abstract
Background
Surveillance of C. difficile infection (CDI), one of the most common U.S. healthcare-associated infections, is essential to inform public health response, characterize strains ...causing disease, and describe changes in strain prevalence over time. The U.S. CDC’s Emerging Infections Program (EIP) has conducted active CDI surveillance, including culturing of C. difficile from a convenience sample of stool samples from cases, since 2009. Cary-Blair transport medium (CBTM) is used by some clinical laboratories for stool testing, but little is known about its impact on the recovery of C. difficile from culture.
Methods
We performed a cross-sectional study of the recovery of C. difficile isolates from C. difficile positive stools received 10/2021 – 10/2022 from Colorado and Georgia EIP sites. Stools were collected and stored within CBTM or within no transport medium per site protocols and subsequently frozen. Frozen samples were thawed and inoculated on taurocholate-cycloserine-cefoxitin-fructose agar plates (TCCFA) for recovery. Specimens from which C. difficile was not recovered on TCCFA plates were subjected to alcohol shock to enhance the recovery rates. We compared the recovery rates of C. difficile from stools in CBTM and stools in no transport medium.
Results
We cultured 825 stools from Colorado and Georgia, recovering C. difficile from 81.5% of stools. Overall, 412 (49.9%) stools were in CBTM and 413 (50.1%) were stools in no transport medium. Of those with known testing data, 410/410 (100%) CBTM stools vs 371/407 (91.2%) non-CBTM stools were C. difficile positive by PCR test (p< 0.01). Colorado stools accounted for 78% of the CBTM specimens. We recovered C. difficile on TCCFA plates from 59% (244/412) of stools in CBTM compared to 84% (348/413) in no transport medium (p< 0.01). After including alcohol shock results, C. difficile was recovered from 72% of CBTM stools, and 91% from stools in no medium (p< 0.01).
Conclusion
Cary-Blair transport medium may limit the recovery of C. difficile from culture and impact the ability to detect emerging strains. A large parallel study is needed to determine if these findings are reproducible and if stool collection methods should be standardized to maximize the recoverability of C. difficile by culture.
Disclosures
Andrew M. Skinner, MD, Academy for Continued Healthcare Learning: Honoraria|American Society of Healthcare Pharmacists: Honoraria|Ferring Pharmaceuticals: Honoraria|MJH Life Sciences: Honoraria Dale N. Gerding, MD, Destiny Pharma,: Advisor/Consultant|Sebela Pharma: Advisor/Consultant
The prevalence of C. difficile infection (CDI) and severe CDI are influenced by the prevalence of specific C. difficile strains, which are themselves influenced by antimicrobial susceptibility ...determinants as well as antimicrobial usage patterns. Restriction endonuclease analysis (REA) typing and antimicrobial susceptibility testing were used to characterize 1808 C. difficile isolates obtained from patients enrolled in four multicenter, multi-country, randomized CDI treatment trials conducted between 2006 and 2009 and between 2012 and 2015. By 2015, the epidemic REA group BI strain (RT027) had decreased in prevalence in North America (US: 43%–18%, Canada: 39%–24%, P < 0.001), but rates of moxifloxacin resistance remained high. In contrast, REA group Y (RT014/020) and DH (RT106) strains, both of which had low rates of moxifloxacin resistance, increased in prevalence (Y strain - US: 6%–17%, Canada: 11%–23%, P < 0.001; DH strain - US: 1%–11%, Canada: 0%–8%, P < 0.0001). In Europe, the BI strain (RT027) was highly prevalent in Eastern European countries in 2015, but was unchanged in other parts of Europe. As in North America, the Y strain (RT014/020) was prevalent in both time periods, but the DH strain was rarely identified. Continued international molecular surveillance of C. difficile will be important to track prevalence of known epidemic strains and detect emergence of new strains of potential epidemiologic significance.
•Epidemiology of C. difficile strains from multinational clinical trials is described.•Similar REA group strains were identified in North America and Europe.•REA group BI decreased in prevalence in North America between 2006 and 2015.•BI was prevalent in Eastern European Countries between 2012 and 2015.•An emerging strain, REA group DH, increased in North America between 2006 and 2015.
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