U.S.-Based National Sentinel Surveillance Study for the Epidemiology of Clostridium difficile-Associated Diarrheal Isolates and Their Susceptibility to Fidaxomicin

Snydman, David R.; McDermott, L. A.; Jacobus, Nilda V.; Thorpe, Cheleste M.; Stone, Sheldon; Jenkins, Stephen G.; Goldstein, Ellie J. C.; Patel, Robin; Forbes, Betty A.; Mirrett, Stanley; Johnson, Stuart; Gerding, Dale N.

doi:10.1128/aac.00845-15

Cited by 60 publications

(52 citation statements)

References 29 publications

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“…Although access to C. difficile isolates obtained from an adult cohort in the same year (i.e., 2013) and geographical location (i.e., the Chicago area) as the pediatric cohort was a strength of this study, this convenience sample of isolates from adults at a VA hospital may not necessarily reflect the general adult population in the Chicago area. However, in a multicenter study of adult CDI that included 925 isolates (all of which underwent antibiotic susceptibility testing and 322 [35%] of which underwent REA) collected from patients at 7 geographically diverse U.S. medical centers in 2011 to 2012 (including Hines VA Hospital), the proportion of isolates identified as belonging to REA group BI (26%) and the proportions of isolates resistant to clindamycin and moxifloxacin (24% and 34%, respectively) were similar to those identified in the 2013 Hines VA Hospital adult cohort in the present study (29). More-recent data from this same multicenter cohort from 2013 suggest that, while there is significant variability among U.S. medical centers, CDI isolates at Hines VA Hospital are similar to those collected at many other hospitals in the United States.…”

Section: Discussionsupporting

confidence: 55%

“…In this multicenter cohort, the proportions of isolates that were of REA group BI, clindamycin resistant, and moxifloxacin resistant were 20%, 21%, and 27%, respectively. The proportions of isolates identified as belonging to REA group BI at Hines VA Hospital in 2013 were very similar to those identified at Tufts Medical Center and Virginia Medical College (27% and 33%), respectively, which are medical centers that include more generalizable adult populations (30).…”

Section: Discussionmentioning

confidence: 54%

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Differences in the Molecular Epidemiology and Antibiotic Susceptibility of Clostridium difficile Isolates in Pediatric and Adult Patients

Kociolek

Gerding

Osmolski

et al. 2016

Antimicrob Agents Chemother

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fThe rising incidence of Clostridium difficile infections (CDIs) in adults is partly related to the global spread of fluoroquinoloneresistant strains, namely, BI/NAP1/027. Although CDIs are also increasingly diagnosed in children, BI/NAP1/027 is relatively uncommon in children. Little is known about the antibiotic susceptibility of pediatric CDI isolates. C. difficile was cultured from tcdB-positive stools collected from children diagnosed with CDI between December 2012 and December 2013 at an academic children's hospital. CDI isolates were grouped by restriction endonuclease analysis (REA). MICs were measured by agar dilution method for 7 antibiotics. Susceptibility breakpoints were based on guidelines from CLSI and/or the European Committee on Antimicrobial Susceptibility Testing (EUCAST). MICs and REA groupings of C. difficile isolates from 74 adult patients (29 isolates underwent REA) from a temporally and geographically similar adult cohort were compared to those of pediatric isolates. Among 122 pediatric and 74 adult isolates, respectively, the rates of resistance were as follows: metronidazole, 0% and 0%; vancomycin, 0% and 8% (P ‫؍‬ 0.003); rifaximin, 1.6% and 6.7% (P ‫؍‬ 0.11); clindamycin, 18.9% and 25.3% (P ‫؍‬ 0.29); and moxifloxacin, 2.5% and 36% (P ‫؍‬ <0.0001). Only 1 of 122 (0.8%) BI/NAP1/027 isolates was identified among the children, compared to 9 of 29 (31%) isolates identified among the adults (P ‫؍‬ <0.0001). The 3 moxifloxacin-resistant pediatric isolates were of REA groups BI and CF and a nonspecific group. The 2 rifaximin-resistant pediatric isolates were of REA groups DH and Y. The 21 clindamycin-resistant pediatric isolates were distributed among 9 REA groups (groups A, CF, DH, G, L, M, and Y and 2 unique nonspecific REA groups). These data suggest that a diverse array of relatively antibiotic-susceptible C. difficile strains predominate in a cohort of children with CDI compared to adults. T he increased frequency, morbidity, and mortality of Clostridium difficile infections (CDI) in adults over the past 2 decades are primarily attributable to the emergence and global spread of a fluoroquinolone-resistant strain known as BI/NAP1/027 (1, 2). CDI is now the most frequently encountered health care-associated infection in the United States (3), causing nearly 500,000 infections and 30,000 deaths each year (4). These troubling trends in the clinical and molecular epidemiology of CDI recently prompted the Centers for Disease Control and Prevention (CDC) to classify CDI among the most serious immediate antibiotic-resistant diseases representing "public health threats that require urgent and aggressive action" (5).The molecular epidemiology (6-8) and antibiotic resistance (7-9) patterns of CDI in adults over the past 3 decades have been well described. Although the prevalence of BI/NAP1/027 is declining, recent data from the United States (4) and the United Kingdom (10) indicate that BI/NAP1/027 is still an important cause of CDI in adults. Limited investigation of the molecular epidemiology of...

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 54%

Differences in the Molecular Epidemiology and Antibiotic Susceptibility of Clostridium difficile Isolates in Pediatric and Adult Patients

Kociolek

Gerding

Osmolski

et al. 2016

Antimicrob Agents Chemother

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“…Infection with C. difficile, a major focus for hospitalized patients in the general population (24)(25)(26), was also specifically examined in the Peer report (12). Admissions for C. difficile infections among dialysis patients within the first 12 months of initiation increased nearly 44% between 2004 and 2012, from approximately 1.6 (95% CI, 1.5 to 1.7) to 2.3 (95% CI, 2.1 to 2.4) admissions per 100 patient-years.…”

Section: Novel Disease Findingsmentioning

confidence: 99%

Improving Outcomes in Patients Receiving Dialysis: The Peer Kidney Care Initiative

Wetmore

Gilbertson

Liu

et al. 2016

CJASN

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The past decade has witnessed a marked reduction in mortality rates among patients receiving maintenance dialysis. However, the reasons for this welcome development are uncertain, and greater understanding is needed to translate advances in care into additional survival gains. To fill important knowledge gaps and to enable dialysis provider organizations to learn from one another, with the aim of advancing patient care, the Peer Kidney Care Initiative (Peer) was created in 2014 by the chief medical officers of 14 United States dialysis provider organizations and the Chronic Disease Research Group. Areas of particular clinical importance were targeted to help shape the public health agenda in CKD and ESRD. Peer focuses on the effect of geographic variation on outcomes, the implications of seasonality for morbidity and mortality, the clinical significance of understudied disorders affecting dialysis patients, and the debate about how best to monitor and evaluate progress in care. In the realm of geovariation, Peer has provided key observations on regional variation in the rates of ESRD incidence, hospitalization, and pre-ESRD care. Regarding seasonality, Peer has reported on variation in both infectionrelated and non-infection-related hospitalizations, suggesting that ambient environmental conditions may affect a range of health outcomes in dialysis patients. Specific medical conditions that Peer highlights include Clostridium difficile infection, which has become strikingly more common in patients in the year after dialysis initiation, and chronic obstructive pulmonary disease, the treatments for which have the potential to contribute to sudden cardiac death. Finally, Peer challenges the nephrology community to consider alternatives to standardized mortality ratios in assessing progress in care, positing that close scrutiny of trends over time may be the most effective way to drive improvements in patient care.

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“…C. difficile is not significantly resistant to drugs currently used to treat the disease; however some concerns about antibiotic resistance exist. Hypervirulent BI/NAP1/027 strains that emerged in the early 2000s are associated with fluoroquinolone resistance, 5–9 and more recently the European EUCAST epidemiological marker of resistance for metronidazole and vancomycin has increased for C. difficile isolates in the U.S. 10 Even more concerning is the prophylactic use of vancomycin or metronidazole to prevent CDI; 11,12 oral administration of these drugs has been linked to a decline in intestinal microbiota colonization that imposes a greater risk for developing CDI. 13 Despite a lack of significant antibiotic resistance by C.difficile , the unique relationship of CDI with antibiotic treatment and escalating incidence and mortality rates have driven the Centers for Disease Control and Prevention (CDC) to classify C. difficile as an urgent public health threat requiring urgent and aggressive action 14 .…”

Section: Introductionmentioning

confidence: 99%

Probiotics as adjunctive therapy for preventing Clostridium difficile infection – What are we waiting for?

2016

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With the end of the golden era of antibiotic discovery, the emergence of a new post-antibiotic age threatens to thrust global health and modern medicine back to the pre-antibiotic era. Antibiotic overuse has resulted in the natural evolution and selection of multi-drug resistant bacteria. One major public health threat, Clostridium difficile, is now the single leading cause of hospital-acquired bacterial infections and is by far the most deadly enteric pathogen for the U.S. population. Due to the high morbidity and mortality and increasing incidence that coincides with antibiotic use, non-traditional therapeutics are ideal alternatives to current treatment methods and also provide an avenue towards prevention. Despite the need for alternative therapies to antibiotics and the safety of most probiotics on the market, researchers are inundated with regulatory issues that hinder the translational science required to push these therapies forward. This review discusses the regulatory challenges of probiotic research, expert opinion regarding the application of probiotics to C. difficile infection and the efficacy of probiotics in preventing this disease.

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U.S.-Based National Sentinel Surveillance Study for the Epidemiology of Clostridium difficile-Associated Diarrheal Isolates and Their Susceptibility to Fidaxomicin

Cited by 60 publications

References 29 publications

Differences in the Molecular Epidemiology and Antibiotic Susceptibility of Clostridium difficile Isolates in Pediatric and Adult Patients

Differences in the Molecular Epidemiology and Antibiotic Susceptibility of Clostridium difficile Isolates in Pediatric and Adult Patients

Improving Outcomes in Patients Receiving Dialysis: The Peer Kidney Care Initiative

Probiotics as adjunctive therapy for preventing Clostridium difficile infection – What are we waiting for?

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