Last data update: Dec 02, 2024. (Total: 48272 publications since 2009)
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Informing estimates of probability of Clostridioides difficile infection for testing and treatment: expert consensus from a modified-Delphi procedure
Baghdadi JD , Wessel M , Dubberke ER , Lydecker A , Claeys KC , Alonso C , Coffey KC , Durkin M , Gonzales-Luna AJ , Guh AY , Kwon JH , Martin E , Mehrotra P , Polage CR , Pulia MS , Rock C , Skinner AM , Vaughn VM , Vijayan T , Yarrington ME , Morgan DJ . Antimicrob Steward Healthc Epidemiol 2024 4 (1) e168 BACKGROUND: Clostridioides difficile infection (CDI) may be misdiagnosed if testing is performed in the absence of signs or symptoms of disease. This study sought to support appropriate testing by estimating the impact of signs, symptoms, and healthcare exposures on pre-test likelihood of CDI. METHODS: A panel of fifteen experts in infectious diseases participated in a modified UCLA/RAND Delphi study to estimate likelihood of CDI. Consensus, defined as agreement by >70% of panelists, was assessed via a REDCap survey. Items without consensus were discussed in a virtual meeting followed by a second survey. RESULTS: All fifteen panelists completed both surveys (100% response rate). In the initial survey, consensus was present on 6 of 15 (40%) items related to risk of CDI. After panel discussion and clarification of questions, consensus (>70% agreement) was reached on all remaining items in the second survey. Antibiotics were identified as the primary risk factor for CDI and grouped into three categories: high-risk (likelihood ratio [LR] 7, 93% agreement among panelists in first survey), low-risk (LR 3, 87% agreement in first survey), and minimal-risk (LR 1, 71% agreement in first survey). Other major factors included new or unexplained severe diarrhea (e.g., ≥ 10 liquid bowel movements per day; LR 5, 100% agreement in second survey) and severe immunosuppression (LR 5, 87% agreement in second survey). CONCLUSION: Infectious disease experts concurred on the importance of signs, symptoms, and healthcare exposures for diagnosing CDI. The resulting risk estimates can be used by clinicians to optimize CDI testing and treatment. |
Carbapenem-resistant and extended-spectrum β-Lactamase-producing enterobacterales in children, United States, 2016-2020
Grome HN , Grass JE , Duffy N , Bulens SN , Ansari U , Campbell D , Lutgring JD , Gargis AS , Masters T , Kent AG , McKay SL , Smith G , Wilson LE , Vaeth E , Evenson B , Dumyati G , Tsay R , Phipps E , Flores K , Wilson CD , Czaja CA , Johnston H , Janelle SJ , Lynfield R , O'Malley S , Vagnone PS , Maloney M , Nadle J , Guh AY . Emerg Infect Dis 2024 30 (6) 1104-1114 |
Complete genome sequences of Clostridioides difficile surveillance isolates representing the top 10 ribotypes from the Emerging Infections Program, United States, 2016
Adamczyk M , Vlachos N , Breaker E , Orazi G , Paulick AL , Rowe LA , McAllister G , Machado MJ , Korhonen L , Guh AY , Rasheed JK , Karlsson M , McKay SL , Lutgring JD , Gargis AS . Microbiol Resour Announc 2024 e0112823 Ten Clostridioides difficile isolates representing the top 10 ribotypes collected in 2016 through the Emerging Infections Program underwent long-read sequencing to obtain high-quality reference genome assemblies. These isolates are publicly available through the CDC & FDA Antibiotic Resistance Isolate Bank. |
Carbapenem-resistant Acinetobacter baumannii complex in the United States - an epidemiological and molecular description of isolates collected through the Emerging Infections Program, 2019
Bulens SN , Campbell D , McKay SL , Vlachos N , Burgin A , Burroughs M , Padila J , Grass JE , Jacob JT , Smith G , Muleta DB , Maloney M , Macierowski B , Wilson LE , Vaeth E , Lynfield R , O'Malley S , Snippes Vagnone PM , Dale J , Janelle SJ , Czaja CA , Johnson H , Phipps EC , Flores KG , Dumyati G , Tsay R , Beldavs ZG , Maureen Cassidy P , Hall A , Walters MS , Guh AY , Magill SS , Lutgring JD . Am J Infect Control 2024 BACKGROUND: Understanding the epidemiology of carbapenem-resistant A. baumannii complex (CRAB) and the patients impacted is an important step towards informing better infection prevention and control practices and improving public health response. METHODS: Active, population-based surveillance was conducted for CRAB in 9 U.S. sites from January 1-December 31, 2019. Medical records were reviewed, isolates were collected and characterized including antimicrobial susceptibility testing and whole genome sequencing. RESULTS: Among 136 incident cases in 2019, 66 isolates were collected and characterized; 56.5% were from cases who were male, 54.5% were from persons of Black or African American race with non-Hispanic ethnicity, and the median age was 63.5 years. Most isolates, 77.2%, were isolated from urine, and 50.0% were collected in the outpatient setting; 72.7% of isolates harbored an acquired carbapenemase gene (aCP), predominantly bla(OXA-23) or bla(OXA-24/40); however, an isolate with bla(NDM) was identified. The antimicrobial agent with the most in vitro activity was cefiderocol (96.9% of isolates were susceptible). CONCLUSIONS: Our surveillance found that CRAB isolates in the U.S. commonly harbor an aCP, have an antimicrobial susceptibility profile that is defined as difficult-to-treat resistance, and epidemiologically are similar regardless of the presence of an aCP. |
Characteristics of patients with initial clostridioides difficile infection (CDI) that are associated with increased risk of multiple CDI recurrences
Guh AY , Li R , Korhonen L , Winston LG , Parker E , Czaja CA , Johnston H , Basiliere E , Meek J , Olson D , Fridkin SK , Wilson LE , Perlmutter R , Holzbauer SM , D'Heilly P , Phipps EC , Flores KG , Dumyati GK , Pierce R , Ocampo VLS , Wilson CD , Watkins JJ , Gerding DN , McDonald LC . Open Forum Infect Dis 2024 11 (4) ofae127 BACKGROUND: Because interventions are available to prevent further recurrence in patients with recurrent Clostridioides difficile infection (rCDI), we identified predictors of multiple rCDI (mrCDI) in adults at the time of presentation with initial CDI (iCDI). METHODS: iCDI was defined as a positive C difficile test in any clinical setting during January 2018-August 2019 in a person aged ≥18 years with no known prior positive test. rCDI was defined as a positive test ≥14 days from the previous positive test within 180 days after iCDI; mrCDI was defined as ≥2 rCDI. We performed multivariable logistic regression analysis. RESULTS: Of 18 829 patients with iCDI, 882 (4.7%) had mrCDI; 437 with mrCDI and 7484 without mrCDI had full chart reviews. A higher proportion of patients with mrCDI than without mrCDI were aged ≥65 years (57.2% vs 40.7%; P < .0001) and had healthcare (59.1% vs 46.9%; P < .0001) and antibiotic (77.3% vs 67.3%; P < .0001) exposures in the 12 weeks preceding iCDI. In multivariable analysis, age ≥65 years (adjusted odds ratio [aOR], 1.91; 95% confidence interval [CI], 1.55-2.35), chronic hemodialysis (aOR, 2.28; 95% CI, 1.48-3.51), hospitalization (aOR, 1.64; 95% CI, 1.33-2.01), and nitrofurantoin use (aOR, 1.95; 95% CI, 1.18-3.23) in the 12 weeks preceding iCDI were associated with mrCDI. CONCLUSIONS: Patients with iCDI who are older, on hemodialysis, or had recent hospitalization or nitrofurantoin use had increased risk of mrCDI and may benefit from early use of adjunctive therapy to prevent mrCDI. If confirmed, these findings could aid in clinical decision making and interventional study designs. |
Potential underreporting of treated patients using a Clostridioides difficile testing algorithm that screens with a nucleic acid amplification test
Guh AY , Fridkin S , Goodenough D , Winston LG , Johnston H , Basiliere E , Olson D , Wilson CD , Watkins JJ , Korhonen L , Gerding DN . Infect Control Hosp Epidemiol 2024 1-9 OBJECTIVE: Patients tested for Clostridioides difficile infection (CDI) using a 2-step algorithm with a nucleic acid amplification test (NAAT) followed by toxin assay are not reported to the National Healthcare Safety Network as a laboratory-identified CDI event if they are NAAT positive (+)/toxin negative (-). We compared NAAT+/toxin- and NAAT+/toxin+ patients and identified factors associated with CDI treatment among NAAT+/toxin- patients. DESIGN: Retrospective observational study. SETTING: The study was conducted across 36 laboratories at 5 Emerging Infections Program sites. PATIENTS: We defined a CDI case as a positive test detected by this 2-step algorithm during 2018-2020 in a patient aged ≥1 year with no positive test in the previous 8 weeks. METHODS: We used multivariable logistic regression to compare CDI-related complications and recurrence between NAAT+/toxin- and NAAT+/toxin+ cases. We used a mixed-effects logistic model to identify factors associated with treatment in NAAT+/toxin- cases. RESULTS: Of 1,801 cases, 1,252 were NAAT+/toxin-, and 549 were NAAT+/toxin+. CDI treatment was given to 866 (71.5%) of 1,212 NAAT+/toxin- cases versus 510 (95.9%) of 532 NAAT+/toxin+ cases (P < .0001). NAAT+/toxin- status was protective for recurrence (adjusted odds ratio [aOR], 0.65; 95% CI, 0.55-0.77) but not CDI-related complications (aOR, 1.05; 95% CI, 0.87-1.28). Among NAAT+/toxin- cases, white blood cell count ≥15,000/µL (aOR, 1.87; 95% CI, 1.28-2.74), ≥3 unformed stools for ≥1 day (aOR, 1.90; 95% CI, 1.40-2.59), and diagnosis by a laboratory that provided no or neutral interpretive comments (aOR, 3.23; 95% CI, 2.23-4.68) were predictors of CDI treatment. CONCLUSION: Use of this 2-step algorithm likely results in underreporting of some NAAT+/toxin- cases with clinically relevant CDI. Disease severity and laboratory interpretive comments influence treatment decisions for NAAT+/toxin- cases. |
Trends in incidence of carbapenem-resistant enterobacterales in 7 US sites, 2016─2020
Duffy N , Li R , Czaja CA , Johnston H , Janelle SJ , Jacob JT , Smith G , Wilson LE , Vaeth E , Lynfield R , O'Malley S , Vagnone PS , Dumyati G , Tsay R , Bulens SN , Grass JE , Pierce R , Cassidy PM , Hertzel H , Wilson C , Muleta D , Taylor J , Guh AY . Open Forum Infect Dis 2023 10 (12) ofad609 BACKGROUND: We described changes in 2016─2020 carbapenem-resistant Enterobacterales (CRE) incidence rates in 7 US sites that conduct population-based CRE surveillance. METHODS: An incident CRE case was defined as the first isolation of Escherichia coli, Klebsiella spp., or Enterobacter spp. resistant to ≥1 carbapenem from a sterile site or urine in a surveillance area resident in a 30-day period. We reviewed medical records and classified cases as hospital-onset (HO), healthcare-associated community-onset (HACO), or community-associated (CA) CRE based on healthcare exposures and location of disease onset. We calculated incidence rates using census data. We used Poisson mixed effects regression models to perform 2016─2020 trend analyses, adjusting for sex, race/ethnicity, and age. We compared adjusted incidence rates between 2016 and subsequent years using incidence rate ratios (RRs) and 95% confidence intervals (CIs). RESULTS: Of 4996 CRE cases, 62% were HACO, 21% CA, and 14% HO. The crude CRE incidence rate per 100 000 was 7.51 in 2016 and 6.08 in 2020 and was highest for HACO, followed by CA and HO. From 2016 to 2020, the adjusted overall CRE incidence rate decreased by 24% (RR, 0.76 [95% CI, .70-.83]). Significant decreases in incidence rates in 2020 were seen for HACO (RR, 0.75 [95% CI, .67-.84]) and CA (0.75 [.61-.92]) but not for HO CRE. CONCLUSIONS: Adjusted CRE incidence rates declined from 2016 to 2020, but changes over time varied by epidemiologic class. Continued surveillance and effective control strategies are needed to prevent CRE in all settings. |
Reply to Gonzales-Luna et al
Gargis AS , Karlsson M , Kamile Rasheed J , Kent AG , McKay SL , Paulick AL , Anderson KF , Adamczyk M , Campbell D , Korhonen LC , McAllister G , Vlachos N , Halpin AL , Lutgring JD , Guh AY , Clifford McDonald L , Elkins CA . Clin Infect Dis 2023 76 (11) 2039-2041 We thank Gonzales-Luna and colleagues [1] for their comments. We agree that laboratories must have access to accurate and standardized methods for antimicrobial susceptibility testing (AST) results to be clinically meaningful. The reference method for performing Clostridioides difficile AST is agar dilution according to Clinical and Laboratory Standards Institute (CLSI) guidelines [2]. The CLSI method for performing AST for anaerobic bacteria recommends that 5 μg/mL of hemin be incorporated into agar dilution plates and that the hemin stock solution should be protected from light and stored at 4°C–8°C for no longer than 1 month [2]. The susceptibility testing done by Gargis et al [3] was performed according to these guidelines, and the hemin stock solution was protected from light. | | Nevertheless, we read with interest the research in recent years [4–6] related to heme-dependent metronidazole resistance, including the reported association between isolates characterized as heme dependent and metronidazole resistant and the presence of a T to G mutation (PnimBG) in the −10 promoter region of the nitroimidazole reductase gene, nimB [5]. While Olaitan et al [5] found that not all heme-dependent metronidazole-resistant isolates contained the PnimBG mutation, Olaitan et al [5] indicate that most do; therefore, the presence of PnimBG may be predictive of resistance. We determined that the nimB mutation was present in 20% of our study isolates (116 of 593), of which 99% (115 of 116) belonged to RT027 (Table 1). The remaining isolate was RT014, the only RT014 isolate containing the PnimBG mutation among the 65 evaluated. |
Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) Aged 12-20 Years in the United States Who Received COVID-19 Vaccine, December 2020 through August 2021 (preprint)
Yousaf AR , Cortese MM , Taylor AW , Broder KR , Oster ME , Wong JM , Guh AY , McCormick DW , Kamidani S , Schlaudecker EP , Edwards K , Creech CB , Staat MA , Belay ED , Marquez P , Su JR , Salzman MB , Thompson D , Campbell AP , Museru O , Howard LM , Parise M , Finn LE , Kim M , Raman KV , Komatsu KK , Spiker BL , Burkholder CP , Lang SM , Soslow JH . medRxiv 2022 05 Background: Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory condition associated with antecedent SARS-CoV-2 infection. In the United States, reporting of MIS-C after vaccination is required under COVID-19 vaccine emergency use authorizations. This case series describes persons aged 12-20 years with MIS-C following COVID-19 vaccination reported to passive surveillance systems or through clinician outreach to CDC. Method(s): We investigated potential cases of MIS-C after COVID-19 vaccination reported to CDC's health department-based national MIS-C surveillance, the Vaccine Adverse Event Reporting System (VAERS, co-administered by CDC and the U.S. FDA), and CDC's Clinical Immunization Safety Assessment Project (CISA) from December 14, 2020, to August 31, 2021. We describe cases meeting the CDC MIS-C case definition. Any positive SARS-CoV-2 serology test satisfied the case criteria although anti-nucleocapsid antibody indicates SARS-CoV-2 infection, while anti-spike protein antibody indicates either infection or COVID-19 vaccination. Finding(s): We identified 21 persons with MIS-C after COVID-19 vaccination. Of these 21 persons, median age was 16 years (range, 12-20 years); 13 (62%) were male. All were hospitalized; 12 (57%) had intensive care unit admission, and all were discharged home. Fifteen (71%) of the 21 had laboratory evidence of past or recent SARS-CoV-2 infection, and six (29%) did not. Through August 2021, 21,335,331 persons aged 12-20 years had received >=1 dose of COVID-19 vaccine, making the overall reporting rate for MIS-C following vaccination 1.0 case per million persons receiving >=1 vaccine dose in this age group. The reporting rate for those without evidence of SARS-CoV-2 infection was 0.3 cases per million vaccinated persons. Interpretation(s): In our case series, we describe a small number of persons with MIS-C who had received >=1 COVID-19 vaccine dose before illness onset. Continued reporting of potential cases and surveillance for MIS-C illnesses after COVID-19 vaccination is warranted. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Development of a broth microdilution method to characterize chlorhexidine mics among bacteria collected from 2005 to 2019 at three U.S. Sites
Lutgring JD , Grass JE , Lonsway D , Yoo BB , Epson E , Crumpler M , Galliher K , O'Donnell K , Zahn M , Evans E , Jacob JT , Page A , Satola SW , Smith G , Kainer M , Muleta D , Wilson CD , Hayden MK , Reddy S , Elkins CA , Rasheed JK , Karlsson M , Magill SS , Guh AY . Microbiol Spectr 2023 11 (3) e0413422 Chlorhexidine bathing to prevent transmission of multidrug-resistant organisms has been adopted by many U.S. hospitals, but increasing chlorhexidine use has raised concerns about possible emergence of resistance. We sought to establish a broth microdilution method for determining chlorhexidine MICs and then used the method to evaluate chlorhexidine MICs for bacteria that can cause health care-associated infections. We adapted a broth microdilution method for determining chlorhexidine MICs, poured panels, established quality control ranges, and tested Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae complex isolates collected at three U.S. sites. Chlorhexidine MICs were determined for 535 isolates including 129 S. aureus, 156 E. coli, 142 K. pneumoniae, and 108 E. cloacae complex isolates. The respective MIC distributions for each species ranged from 1 to 8 mg/L (MIC(50) = 2 mg/L and MIC(90) = 4 mg/L), 1 to 64 mg/L (MIC(50) = 2 mg/L and MIC(90) = 4 mg/L), 4 to 64 mg/L (MIC(50) = 16 mg/L and MIC(90) = 32 mg/L), and 1 to >64 mg/L (MIC(50) = 16 mg/L and MIC(90) = 64 mg/L). We successfully adapted a broth microdilution procedure that several laboratories were able to use to determine the chlorhexidine MICs of bacterial isolates. This method could be used to investigate whether chlorhexidine MICs are increasing. IMPORTANCE Chlorhexidine bathing to prevent transmission of multidrug-resistant organisms and reduce health care-associated infections has been adopted by many hospitals. There is concern about the possible unintended consequences of using this agent widely. One possible unintended consequence is decreased susceptibility to chlorhexidine, but there are not readily available methods to perform this evaluation. We developed a method for chlorhexidine MIC testing that can be used to evaluate for possible unintended consequences. |
Reference Susceptibility Testing and Genomic Surveillance of Clostridioides difficile, United States, 2012-17.
Gargis AS , Karlsson M , Paulick AL , Anderson KF , Adamczyk M , Vlachos N , Kent AG , McAllister GA , McKay SL , Halpin AL , Albrecht V , Campbell D , Korhonen L , Elkins CA , Rasheed JK , Guh AY , McDonald LC , Lutgring JD . Clin Infect Dis 2022 76 (5) 890-896 BACKGROUND: Antimicrobial susceptibility testing (AST) is not routinely performed for Clostridioides difficile and data evaluating minimum inhibitory concentrations (MICs) are limited. We performed AST and whole genome sequencing (WGS) for 593 C. difficile isolates collected between 2012-2017 through the Centers for Disease Control and Prevention's Emerging Infections Program. METHODS: MICs to six antimicrobial agents (ceftriaxone, clindamycin, meropenem, metronidazole, moxifloxacin, and vancomycin) were determined using the reference agar dilution method according to Clinical and Laboratory Standards Institute guidelines. WGS was performed on all isolates to detect the presence of genes or mutations previously associated with resistance. RESULTS: Among all isolates, 98.5% displayed a vancomycin MIC ≤ 2 μg/mL and 97.3% displayed a metronidazole MIC ≤ 2 μg/mL. Ribotype 027 (RT027) isolates displayed higher vancomycin MICs (MIC50: 2 μg/mL; MIC90: 2 μg/mL) than non-RT027 isolates (MIC50: 0.5 μg/mL; MIC90: 1 μg/mL) (P < 0.01). No vanA/B genes were detected. RT027 isolates also showed higher MICs to clindamycin and moxifloxacin and were more likely to harbor associated resistance genes or mutations. CONCLUSIONS: Elevated MICs to antibiotics used for treatment of C. difficile infection were rare and there was no increase in MICs over time. The lack of vanA/B genes or mutations consistently associated with elevated vancomycin MICs suggests there are multifactorial mechanisms of resistance. Ongoing surveillance of C. difficile using reference AST and WGS to monitor MIC trends and the presence of antibiotic resistance mechanisms is essential. |
Comparison of the risk of recurrent Clostridioides difficile infections among patients in 2018 versus 2013
Guh AY , Yi SH , Baggs J , Winston L , Parker E , Johnston H , Basiliere E , Olson D , Fridkin SK , Mehta N , Wilson L , Perlmutter R , Holzbauer SM , D'Heilly P , Phipps EC , Flores KG , Dumyati GK , Hatwar T , Pierce R , Ocampo VLS , Wilson CD , Watkins JJ , Korhonen L , Paulick A , Adamczyk M , Gerding DN , Reddy SC . Open Forum Infect Dis 2022 9 (9) ofac422 Among persons with an initial Clostridioides difficile infection (CDI) across 10 US sites in 2018 compared with 2013, 18.3% versus 21.1% had 1 recurrent CDI (rCDI) within 180 days. We observed a 16% lower adjusted risk of rCDI in 2018 versus 2013 (P<.0001). |
Trends in facility-level rates of Clostridioides difficile infections in US hospitals, 2019-2020
Rose AN , Baggs J , Kazakova SV , Guh AY , Yi SH , McCarthy NL , Jernigan JA , Reddy SC . Infect Control Hosp Epidemiol 2022 44 (2) 1-8 OBJECTIVES: The coronavirus disease 2019 pandemic caused substantial changes to healthcare delivery and antibiotic prescribing beginning in March 2020. To assess pandemic impact on Clostridioides difficile infection (CDI) rates, we described patients and trends in facility-level incidence, testing rates, and percent positivity during 2019-2020 in a large cohort of US hospitals. METHODS: We estimated and compared rates of community-onset CDI (CO-CDI) per 10,000 discharges, hospital-onset CDI (HO-CDI) per 10,000 patient days, and C. difficile testing rates per 10,000 discharges in 2019 and 2020. We calculated percent positivity as the number of inpatients diagnosed with CDI over the total number of discharges with a test for C. difficile. We used an interrupted time series (ITS) design with negative binomial and logistic regression models to describe level and trend changes in rates and percent positivity before and after March 2020. RESULTS: In pairwise comparisons, overall CO-CDI rates decreased from 20.0 to 15.8 between 2019 and 2020 (P < .0001). HO-CDI rates did not change. Using ITS, we detected decreasing monthly trends in CO-CDI (-1% per month, P = .0036) and HO-CDI incidence (-1% per month, P < .0001) during the baseline period, prior to the COVID-19 pandemic declaration. We detected no change in monthly trends for CO-CDI or HO-CDI incidence or percent positivity after March 2020 compared with the baseline period. CONCLUSIONS: While there was a slight downward trajectory in CDI trends prior to March 2020, no significant change in CDI trends occurred during the COVID-19 pandemic despite changes in infection control practices, antibiotic use, and healthcare delivery. |
Reported cases of multisystem inflammatory syndrome in children aged 12-20 years in the USA who received a COVID-19 vaccine, December, 2020, through August, 2021: a surveillance investigation.
Yousaf AR , Cortese MM , Taylor AW , Broder KR , Oster ME , Wong JM , Guh AY , McCormick DW , Kamidani S , Schlaudecker EP , Edwards KM , Creech CB , Staat MA , Belay ED , Marquez P , Su JR , Salzman MB , Thompson D , Campbell AP , Museru O , Howard LM , Parise M , Finn LE , Kim M , Raman KV , Komatsu KK , Spiker BL , Burkholder CP , Lang SM , Soslow JH . Lancet Child Adolesc Health 2022 6 (5) 303-312 BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory condition associated with antecedent SARS-CoV-2 infection. In the USA, reporting of MIS-C after vaccination is required under COVID-19 vaccine emergency use authorisations. We aimed to investigate reports of individuals aged 12-20 years with MIS-C after COVID-19 vaccination reported to passive surveillance systems or through clinician outreach to the US Centers for Disease Control and Prevention (CDC). METHODS: In this surveillance activity, we investigated potential cases of MIS-C after COVID-19 vaccination reported to CDC's MIS-C national surveillance system, the Vaccine Adverse Event Reporting System (co-administered by CDC and the US Food and Drug Administration), and CDC's Clinical Immunization Safety Assessment Project. A multidisciplinary team adjudicated cases by use of the CDC MIS-C definition. Any positive SARS-CoV-2 serology test satisfied case criteria; although anti-nucleocapsid antibodies indicate previous SARS-CoV-2 infection, anti-spike protein antibodies indicate either past or recent infection or COVID-19 vaccination. We describe the demographic and clinical features of cases, stratified by laboratory evidence of SARS-CoV-2 infection. To calculate the reporting rate of MIS-C, we divided the count of all individuals meeting the MIS-C case definition, and of those without evidence of SARS-CoV-2 infection, by the number of individuals aged 12-20 years in the USA who received one or more COVID-19 vaccine doses up to Aug 31, 2021, obtained from CDC national vaccine surveillance data. FINDINGS: Using surveillance results from Dec 14, 2020, to Aug 31, 2021, we identified 21 individuals with MIS-C after COVID-19 vaccination. Of these 21 individuals, median age was 16 years (range 12-20); 13 (62%) were male and eight (38%) were female. All 21 were hospitalised: 12 (57%) were admitted to an intensive care unit and all were discharged home. 15 (71%) of 21 individuals had laboratory evidence of past or recent SARS-CoV-2 infection, and six (29%) did not. As of Aug 31, 2021, 21 335 331 individuals aged 12-20 years had received one or more doses of a COVID-19 vaccine, making the overall reporting rate for MIS-C after vaccination 1·0 case per million individuals receiving one or more doses in this age group. The reporting rate in only those without evidence of SARS-CoV-2 infection was 0·3 cases per million vaccinated individuals. INTERPRETATION: Here, we describe a small number of individuals with MIS-C who had received one or more doses of a COVID-19 vaccine before illness onset; the contribution of vaccination to these illnesses is unknown. Our findings suggest that MIS-C after COVID-19 vaccination is rare. Continued reporting of potential cases and surveillance for MIS-C illnesses after COVID-19 vaccination is warranted. FUNDING: US Centers for Disease Control and Prevention. |
Genomic analysis of Clostridioides difficile in two regions of the United States reveals a diversity of strains and limited transmission.
Pecora N , Holzbauer S , Wang X , Gu Y , Taffner S , Hatwar T , Hardy D , Dziejman M , D'Heilly P , Pung K , Guh A , Qiu X , Gill S , Dumyati G . J Infect Dis 2021 225 (1) 121-129 BACKGROUND: The distribution of Clostridioides difficile strains and transmission dynamics in the United States are not well defined. Whole genome sequencing (WGS) across two CDC Emerging Infections Program C. difficile infection (CDI) surveillance regions (Minnesota and New York) was performed to identify predominant multilocus sequence types (MLSTs) in community and healthcare-associated disease and assess transmission. METHODS: C. difficile isolates from CDI cases over three months between 2016 and 2017 underwent WGS. Cases were residents of the catchment area without a positive C. difficile test in the preceding 8 weeks. Cases were epidemiologically classified as healthcare (HCA) or community (CA) associated. RESULTS: Of 422 isolates, 212 (50.2%) were HCA and 203 (48.1%) were CA. Predominant MLSTs were ST42 (9.3%), ST8 (7.8%), and ST2 (8.1%). MLSTs associated with HCA-CDI included ST1 (76%), ST53 (83.3%), ST43 (80.0%), while those associated with CA-CDI included ST3 (76.9%), and ST41 (77.8%). ST1 was more frequent in NY than MN (10.8% vs 3.1%). Thirty three pairs were closely related genomically, 14 of which had potential patient-patient transmission supported by chart review. DISCUSSION: The genomic epidemiology of C. difficile across two regions of the US indicates the presence of a diverse strain profile and limited direct transmission. |
Associations of facility-level antibiotic use and hospital-onset Clostridioides difficile infection in US acute-care hospitals, 2012-2018
Kazakova SV , Baggs J , Yi SH , Reddy SC , Hatfield KM , Guh AY , Jernigan JA , McDonald LC . Infect Control Hosp Epidemiol 2021 43 (8) 1-3 Previously reported associations between hospital-level antibiotic use and hospital-onset Clostridioides difficile infection (HO-CDI) were reexamined using 2012-2018 data from a new cohort of US acute-care hospitals. This analysis revealed significant positive associations between total, third-generation, and fourth-generation cephalosporin, fluoroquinolone, carbapenem, and piperacillin-tazobactam use and HO-CDI rates, confirming previous findings. |
US Case Reports of Cerebral Venous Sinus Thrombosis With Thrombocytopenia After Ad26.COV2.S Vaccination, March 2 to April 21, 2021.
See I , Su JR , Lale A , Woo EJ , Guh AY , Shimabukuro TT , Streiff MB , Rao AK , Wheeler AP , Beavers SF , Durbin AP , Edwards K , Miller E , Harrington TA , Mba-Jonas A , Nair N , Nguyen DT , Talaat KR , Urrutia VC , Walker SC , Creech CB , Clark TA , DeStefano F , Broder KR . JAMA 2021 325 (24) 2448-2456 IMPORTANCE: Cerebral venous sinus thrombosis (CVST) with thrombocytopenia, a rare and serious condition, has been described in Europe following receipt of the ChAdOx1 nCoV-19 vaccine (Oxford/AstraZeneca), which uses a chimpanzee adenoviral vector. A mechanism similar to autoimmune heparin-induced thrombocytopenia (HIT) has been proposed. In the US, the Ad26.COV2.S COVID-19 vaccine (Janssen/Johnson & Johnson), which uses a human adenoviral vector, received Emergency Use Authorization (EUA) on February 27, 2021. By April 12, 2021, approximately 7 million Ad26.COV2.S vaccine doses had been given in the US, and 6 cases of CVST with thrombocytopenia had been identified among the recipients, resulting in a temporary national pause in vaccination with this product on April 13, 2021. OBJECTIVE: To describe reports of CVST with thrombocytopenia following Ad26.COV2.S vaccine receipt. DESIGN, SETTING, AND PARTICIPANTS: Case series of 12 US patients with CVST and thrombocytopenia following use of Ad26.COV2.S vaccine under EUA reported to the Vaccine Adverse Event Reporting System (VAERS) from March 2 to April 21, 2021 (with follow-up reported through April 21, 2021). EXPOSURES: Receipt of Ad26.COV2.S vaccine. MAIN OUTCOMES AND MEASURES: Clinical course, imaging, laboratory tests, and outcomes after CVST diagnosis obtained from VAERS reports, medical record review, and discussion with clinicians. RESULTS: Patients' ages ranged from 18 to younger than 60 years; all were White women, reported from 11 states. Seven patients had at least 1 CVST risk factor, including obesity (n = 6), hypothyroidism (n = 1), and oral contraceptive use (n = 1); none had documented prior heparin exposure. Time from Ad26.COV2.S vaccination to symptom onset ranged from 6 to 15 days. Eleven patients initially presented with headache; 1 patient initially presented with back pain and later developed headache. Of the 12 patients with CVST, 7 also had intracerebral hemorrhage; 8 had non-CVST thromboses. After diagnosis of CVST, 6 patients initially received heparin treatment. Platelet nadir ranged from 9 ×103/µL to 127 ×103/µL. All 11 patients tested for the heparin-platelet factor 4 HIT antibody by enzyme-linked immunosorbent assay (ELISA) screening had positive results. All patients were hospitalized (10 in an intensive care unit [ICU]). As of April 21, 2021, outcomes were death (n = 3), continued ICU care (n = 3), continued non-ICU hospitalization (n = 2), and discharged home (n = 4). CONCLUSIONS AND RELEVANCE: The initial 12 US cases of CVST with thrombocytopenia after Ad26.COV2.S vaccination represent serious events. This case series may inform clinical guidance as Ad26.COV2.S vaccination resumes in the US as well as investigations into the potential relationship between Ad26.COV2.S vaccine and CVST with thrombocytopenia. |
Updated Recommendations from the Advisory Committee on Immunization Practices for Use of the Janssen (Johnson & Johnson) COVID-19 Vaccine After Reports of Thrombosis with Thrombocytopenia Syndrome Among Vaccine Recipients - United States, April 2021.
MacNeil JR , Su JR , Broder KR , Guh AY , Gargano JW , Wallace M , Hadler SC , Scobie HM , Blain AE , Moulia D , Daley MF , McNally VV , Romero JR , Talbot HK , Lee GM , Bell BP , Oliver SE . MMWR Morb Mortal Wkly Rep 2021 70 (17) 651-656 On February 27, 2021, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the Janssen COVID-19 (Ad.26.COV2.S) vaccine (Janssen Biotech, Inc., a Janssen Pharmaceutical company, Johnson & Johnson; New Brunswick, New Jersey), and on February 28, 2021, the Advisory Committee on Immunization Practices (ACIP) issued interim recommendations for its use in persons aged ≥18 years (1,2). On April 13, 2021, CDC and FDA recommended a pause in the use of the Janssen COVID-19 vaccine after reports of six U.S. cases of cerebral venous sinus thrombosis (CVST) with thrombocytopenia, a rare thromboembolic syndrome, among Janssen COVID-19 vaccine recipients (3). Two emergency ACIP meetings were rapidly convened to review reported cases of thrombosis with thrombocytopenia syndrome (TTS) and to consider updated recommendations for use of the Janssen COVID-19 vaccine in the United States. On April 23, 2021, after a discussion of the benefits and risks of resuming vaccination, ACIP reaffirmed its interim recommendation for use of the Janssen COVID-19 vaccine in all persons aged ≥18 years under the FDA's EUA, which now includes a warning that rare clotting events might occur after vaccination, primarily among women aged 18-49 years. Patient and provider education about the risk for TTS with the Janssen COVID-19 vaccine, especially among women aged <50 years, as well as the availability of alternative COVID-19 vaccines, is required to guide vaccine decision-making and ensure early recognition and clinical management of TTS. |
Rates and causative pathogens of surgical site infections attributed to liver transplant procedures and other hepatic, biliary or pancreatic procedures, 2015-2018
Chea N , Sapiano MRP , Zhou L , Epstein L , Guh A , Edwards JR , Allen-Bridson K , Russo V , Watkins J , Pouch SM , Magill SS . Transpl Infect Dis 2021 23 (4) e13589 Liver transplant recipients are at high risk for surgical site infections (SSIs). Limited data are available on SSI epidemiology following liver transplant procedures (LTPs). We analyzed data on SSIs from 2015-2018 reported to CDC's National Healthcare Safety Network to determine rates, pathogen distribution, and antimicrobial resistance after LTPs and other hepatic, biliary, or pancreatic procedures (BILIs). LTP and BILI SSI rates were 5.7% and 5.9%, respectively. The odds of SSI after LTP were lower than after BILI (adjusted odds ratio = 0.70, 95% confidence interval 0.57-0.85). Among LTP SSIs, 43.1% were caused by Enterococcus spp., 17.2% by Candida spp., and 15.0% by coagulase-negative Staphylococcus spp. (CNS). Percentages of SSIs caused by Enterococcus faecium or CNS were higher after LTPs than BILIs, whereas percentages of SSIs caused by Enterobacteriaceae, Enterococcus faecalis, or viridans streptococci were higher after BILIs. Antimicrobial resistance was common in LTP SSI pathogens, including E. faecium (69.4% vancomycin-resistant); E. coli (68.8% fluoroquinolone-non-susceptible, 44.7% extended spectrum cephalosporin [ESC]-non-susceptible); and K. pneumoniae and K. oxytoca (39.4% fluoroquinolone-non-susceptible, 54.5% ESC-non-susceptible). National LTP SSI pathogen and resistance data can help prioritize studies to determine effective interventions to prevent SSIs and reduce antimicrobial resistance in liver transplant recipients. |
Association between socioeconomic status and incidence of community-associated Clostridioides difficile infection - United States, 2014-2015
Skrobarcek KA , Mu Y , Ahern J , Basiliere E , Beldavs ZG , Brousseau G , Dumyati G , Fridkin S , Holzbauer SM , Johnston H , Kainer MA , Meek J , Ocampo VLS , Parker E , Perlmutter R , Phipps EC , Winston L , Guh A . Clin Infect Dis 2021 73 (4) 722-725 We evaluated the association between socioeconomic status (SES) and community-associated Clostridioides difficile infection (CA-CDI) incidence across 2474 census tracts in 10 states. Highly correlated community-level SES variables were transformed into distinct factors using factor analysis. We found low SES communities were associated with higher CA-CDI incidence. |
Characterization of Clostridioides difficile Isolates Available through the CDC & FDA Antibiotic Resistance Isolate Bank.
Paulick A , Adamczyk M , Anderson K , Vlachos N , Machado MJ , McAllister G , Korhonen L , Guh AY , Halpin AL , Rasheed JK , Karlsson M , Lutgring JD , Gargis AS . Microbiol Resour Announc 2021 10 (1) Thirty Clostridioides difficile isolates collected in 2016 through the Centers for Disease Control and Prevention Emerging Infections Program were selected for reference antimicrobial susceptibility testing and whole-genome sequencing. Here, we present the genetic characteristics of these isolates and announce their availability in the CDC & FDA Antibiotic Resistance Isolate Bank. |
Evaluation of viral co-infections among patients with community-associated Clostridioides difficile infection
Korhonen L , Cohen J , Gregoricus N , Farley MM , Perlmutter R , Holzbauer SM , Dumyati G , Beldavs Z , Paulick A , Vinjé J , Limbago BM , Lessa FC , Guh AY . PLoS One 2020 15 (10) e0240549 We assessed viral co-infections in 155 patients with community-associated Clostridioides difficile infection in five U.S. sites during December 2012-February 2013. Eighteen patients (12%) tested positive for norovirus (n = 10), adenovirus (n = 4), rotavirus (n = 3), or sapovirus (n = 1). Co-infected patients were more likely than non-co-infected patients to have nausea or vomiting (56% vs 31%; p = 0.04), suggesting that viral co-pathogens contributed to symptoms in some patients. There were no significant differences in prior healthcare or medication exposures or in CDI complications. |
Prescriber perceptions of fluoroquinolones, extended-spectrum cephalosporins, and Clostridioides difficile infection
Szymczak JE , Muller BM , Shakamuri NS , Hamilton KW , Gerber JS , Laguio-Vila M , Dumyati GK , Fridkin SK , Guh AY , Reddy SC , Lautenbach E . Infect Control Hosp Epidemiol 2020 41 (8) 1-7 BACKGROUND: Fluoroquinolones (FQs) and extended-spectrum cephalosporins (ESCs) are associated with higher risk of Clostridioides difficile infection (CDI). Decreasing the unnecessary use of FQs and ESCs is a goal of antimicrobial stewardship. Understanding how prescribers perceive the risks and benefits of FQs and ESCs is needed. METHODS: We conducted interviews with clinicians from 4 hospitals. Interviews elicited respondent perceptions about the risk of ESCs, FQs, and CDI. Interviews were audio recorded, transcribed, and analyzed using a flexible coding approach. RESULTS: Interviews were conducted with 64 respondents (38 physicians, 7 nurses, 6 advance practice providers, and 13 pharmacists). ESCs and FQs were perceived to have many benefits, including infrequent dosing, breadth of coverage, and greater patient adherence after hospital discharge. Prescribers stated that it was easy to make decisions about these drugs, so they were especially appealing to use in the context of time pressures. They described having difficulty discontinuing these drugs when prescribed by others due to inertia and fear. Prescribers were skeptical about targeting specific drugs as a stewardship approach and felt that the risk of a negative outcome from under treatment of a suspected bacterial infection was a higher priority than the prevention of CDI. CONCLUSIONS: Prescribers in this study perceived many advantages to using ESCs and FQs, especially under conditions of time pressure and uncertainty. In making decisions about these drugs, prescribers balance risk and benefit, and they believed that the risk of CDI was acceptable in compared with the risk of undertreatment. |
Trends in U.S. burden of Clostridioides difficile infection and outcomes
Guh AY , Mu Y , Winston LG , Johnston H , Olson D , Farley MM , Wilson LE , Holzbauer SM , Phipps EC , Dumyati GK , Beldavs ZG , Kainer MA , Karlsson M , Gerding DN , McDonald LC . N Engl J Med 2020 382 (14) 1320-1330 BACKGROUND: Efforts to prevent Clostridioides difficile infection continue to expand across the health care spectrum in the United States. Whether these efforts are reducing the national burden of C. difficile infection is unclear. METHODS: The Emerging Infections Program identified cases of C. difficile infection (stool specimens positive for C. difficile in a person >/=1 year of age with no positive test in the previous 8 weeks) in 10 U.S. sites. We used case and census sampling weights to estimate the national burden of C. difficile infection, first recurrences, hospitalizations, and in-hospital deaths from 2011 through 2017. Health care-associated infections were defined as those with onset in a health care facility or associated with recent admission to a health care facility; all others were classified as community-associated infections. For trend analyses, we used weighted random-intercept models with negative binomial distribution and logistic-regression models to adjust for the higher sensitivity of nucleic acid amplification tests (NAATs) as compared with other test types. RESULTS: The number of cases of C. difficile infection in the 10 U.S. sites was 15,461 in 2011 (10,177 health care-associated and 5284 community-associated cases) and 15,512 in 2017 (7973 health care-associated and 7539 community-associated cases). The estimated national burden of C. difficile infection was 476,400 cases (95% confidence interval [CI], 419,900 to 532,900) in 2011 and 462,100 cases (95% CI, 428,600 to 495,600) in 2017. With accounting for NAAT use, the adjusted estimate of the total burden of C. difficile infection decreased by 24% (95% CI, 6 to 36) from 2011 through 2017; the adjusted estimate of the national burden of health care-associated C. difficile infection decreased by 36% (95% CI, 24 to 54), whereas the adjusted estimate of the national burden of community-associated C. difficile infection was unchanged. The adjusted estimate of the burden of hospitalizations for C. difficile infection decreased by 24% (95% CI, 0 to 48), whereas the adjusted estimates of the burden of first recurrences and in-hospital deaths did not change significantly. CONCLUSIONS: The estimated national burden of C. difficile infection and associated hospitalizations decreased from 2011 through 2017, owing to a decline in health care-associated infections. (Funded by the Centers for Disease Control and Prevention.). |
Treatment of Clostridioides difficile infection and non-compliance with treatment guidelines in adults in 10 US geographical locations, 2013-2015
Novosad SA , Mu Y , Winston LG , Johnston H , Basiliere E , Olson DM , Farley MM , Revis A , Wilson L , Perlmutter R , Holzbauer SM , Whitten T , Phipps EC , Dumyati GK , Beldavs ZG , Ocampo VLS , Davis CM , Kainer M , Gerding DN , Guh AY . J Gen Intern Med 2019 35 (2) 412-419 BACKGROUND: Infectious Diseases Society of America/Society for Healthcare Epidemiology of America (IDSA/SHEA) guidelines describe recommended therapy for Clostridioides difficile infection (CDI). OBJECTIVE: To describe CDI treatment and, among those with severe CDI, determine predictors of adherence to the 2010 IDSA/SHEA treatment guidelines. DESIGN: We analyzed 2013-2015 CDI treatment data collected through the Centers for Disease Control and Prevention's Emerging Infections Program. Generalized linear mixed models were used to identify predictors of guideline-adherent therapy. PATIENTS: A CDI case was defined as a positive stool specimen in a person aged >/= 18 years without a positive test in the prior 8 weeks; severe CDI cases were defined as having a white blood cell count >/= 15,000 cells/mul. MAIN MEASURES: Prescribing and predictors of guideline-adherent CDI therapy for severe disease. KEY RESULTS: Of 18,243 cases, 14,257 (78%) were treated with metronidazole, 7683 (42%) with vancomycin, and 313 (2%) with fidaxomicin. The median duration of therapy was 14 (interquartile range, 11-15) days. Severe CDI was identified in 3250 (18%) cases; of 3121 with treatment data available, 1480 (47%) were prescribed guideline-adherent therapy. Among severe CDI cases, hospital admission (adjusted odds ratio [aOR] 2.48; 95% confidence interval [CI] 1.90, 3.24), age >/= 65 years (aOR 1.37; 95% CI 1.10, 1.71), Charlson comorbidity index >/= 3 (aOR 1.27; 95% CI 1.04, 1.55), immunosuppressive therapy (aOR 1.21; 95% CI 1.02, 1.42), and inflammatory bowel disease (aOR 1.56; 95% CI 1.13, 2.17) were associated with being prescribed guideline-adherent therapy. CONCLUSIONS: Provider adherence to the 2010 treatment guidelines for severe CDI was low. Although the updated 2017 CDI guidelines, which expand the use of oral vancomycin for all CDI, might improve adherence by removing the need to apply severity criteria, other efforts to improve adherence are likely needed, including educating providers and addressing barriers to prescribing guideline-adherent therapy, particularly in outpatient settings. |
Risk factors for community-associated Clostridioides difficile infection in young children
Weng MK , Adkins SH , Bamberg W , Farley MM , Espinosa CC , Wilson L , Perlmutter R , Holzbauer S , Whitten T , Phipps EC , Hancock EB , Dumyati G , Nelson DS , Beldavs ZG , Ocampo V , Davis CM , Rue B , Korhonen L , McDonald LC , Guh AY . Epidemiol Infect 2019 147 e172 The majority of paediatric Clostridioides difficile infections (CDI) are community-associated (CA), but few data exist regarding associated risk factors. We conducted a case-control study to evaluate CA-CDI risk factors in young children. Participants were enrolled from eight US sites during October 2014-February 2016. Case-patients were defined as children aged 1-5 years with a positive C. difficile specimen collected as an outpatient or 3 days of hospital admission, who had no healthcare facility admission in the prior 12 weeks and no history of CDI. Each case-patient was matched to one control. Caregivers were interviewed regarding relevant exposures. Multivariable conditional logistic regression was performed. Of 68 pairs, 44.1% were female. More case-patients than controls had a comorbidity (33.3% vs. 12.1%; P = 0.01); recent higher-risk outpatient exposures (34.9% vs. 17.7%; P = 0.03); recent antibiotic use (54.4% vs. 19.4%; P < 0.0001); or recent exposure to a household member with diarrhoea (41.3% vs. 21.5%; P = 0.04). In multivariable analysis, antibiotic exposure in the preceding 12 weeks was significantly associated with CA-CDI (adjusted matched odds ratio, 6.25; 95% CI 2.18-17.96). Improved antibiotic prescribing might reduce CA-CDI in this population. Further evaluation of the potential role of outpatient healthcare and household exposures in C. difficile transmission is needed. |
Association between antibiotic use and hospital-onset Clostridioides difficile infection in U.S. acute care hospitals, 2006-2012: an ecologic analysis
Kazakova SV , Baggs J , McDonald LC , Yi SH , Hatfield KM , Guh A , Reddy SC , Jernigan JA . Clin Infect Dis 2019 70 (1) 11-18 BACKGROUND: Unnecessary antibiotic use (AU) contributes to increased rates of Clostridioides difficile Infection (CDI). The impact of antibiotic restriction on hospital-onset CDI (HO-CDI) has not been assessed in a large group of U.S. acute care hospitals (ACHs). METHODS: We examined cross-sectional and temporal associations between rates of hospital-level AU and HO-CDI using data from 549 ACHs. HO-CDI, a discharge with a secondary ICD-9-CM for CDI (008.45) and treatment with metronidazole or oral vancomycin >/= 3 days after admission. Analyses were performed using multivariable generalized estimating equation models adjusting for patient and hospital characteristics. RESULTS: During 2006-2012, the unadjusted annual rates of HO-CDI and total AU were 7.3 per 10,000 patient-days (PD) (95% CI: 7.1-7.5) and 811 days of therapy (DOT)/1,000 PD (95% CI: 803-820), respectively. In the cross-sectional analysis, for every 50 DOT/1,000 PD increase in total AU, there was a 4.4% increase in HO-CDI. For every 10 DOT/1,000 PD increase in use of third- and fourth-generation cephalosporins or carbapenems there was a 2.1% and 2.9% increase in HO-CDI, respectively. In the time-series analysis, the 6 ACHs with a >/= 30% decrease in total AU had a 33% decrease in HO-CDI (rate ratio, 0.67; 95% CI, 0.47-0.96); ACHs with a >/= 20% decrease in fluoroquinolone or third- and fourth-generation cephalosporin use had a corresponding decrease in HO-CDI of 8% and 13%, respectively. CONCLUSIONS: At an ecologic level, reductions in total AU, use of fluoroquinolones and third- and fourth-generation cephalosporins were each associated with decreased HO-CDI rates. |
Toxin enzyme immunoassays detect Clostridioides difficile infection with greater severity and higher recurrence rates
Guh AY , Hatfield KM , Winston LG , Martin B , Johnston H , Brousseau G , Farley MM , Wilson L , Perlmutter R , Phipps EC , Dumyati GK , Nelson D , Hatwar T , Kainer MA , Paulick AL , Karlsson M , Gerding DN , McDonald LC . Clin Infect Dis 2019 69 (10) 1667-1674 Background: Few data suggest Clostridioides difficile infections (CDI) detected by toxin enzyme immunoassays (EIA) are more severe and have worse outcomes than those detected by nucleic acid amplification tests (NAAT) only. We compared toxin-positive and NAAT-positive only CDI across geographically-diverse sites. Methods: A case was defined as a positive C. difficile test in a person >/=1 year old with no positive tests in the prior 8 weeks. Cases were detected during 2014-15 by a testing algorithm (specimens initially tested by glutamate dehydrogenase [GDH] and toxin EIA; if discordant results, specimens were reflexed to NAAT) and classified as toxin-positive or NAAT-positive only. Medical charts were reviewed. Multivariable logistic regression models were used to compare CDI-related complications, recurrence, and 30-day mortality between the two groups. Results: Of 4878 cases, 2160 (44.3%) were toxin-positive and 2718 (55.7%) were NAAT-positive only. More toxin-positive than NAAT-positive only cases were aged >/=65 years (48.2% vs 38.0%; P<0.0001), had >/=3 unformed stool for >/=1 day (43.9% vs 36.6%; P<0.0001), and had white blood cells >/=15,000/microl (31.4% versus 21.4%; P<0.0001). In multivariable analysis, toxin-positivity was associated with recurrence (adjusted odds ratio [aOR]: 1.89, 95% CI: 1.61-2.23), but not with CDI-related complications (aOR: 0.91, 95% CI: 0.67-1.23) or 30-day mortality (aOR: 0.95; 95% CI: 0.73-1.24). Conclusions: Toxin-positive CDI is more severe, but there were no differences in adjusted CDI-related complication and mortality rates between toxin-positive and NAAT-positive only CDI that were detected by an algorithm that utilized an initial GDH screening test. |
Web Exclusive. Annals On Call - C difficile: The Most Common Health Care-Associated Infection in the United States
Centor RM , Guh AY , Kutty PK . Ann Intern Med 2019 170 (8) Oc1 In this episode of Annals On Call, Dr. Centor discusses the prevention, diagnosis, and treatment of infection with C difficile with Drs. Allison Guh and Preeta Kutty, both of whom work at the U.S. Centers for Disease Control and Prevention. |
Clostridioides difficile Infection
Guh AY , Kutty PK . Ann Intern Med 2018 169 (7) Itc49-itc64 Clostridioides difficile (formerly Clostridium difficile) infection is the most frequently identified health care-associated infection in the United States. C difficile has also emerged as a cause of community-associated diarrhea, resulting in increased incidence of community-associated infection. Clinical illness ranges in severity from mild diarrhea to fulminant colitis and death. Appropriate management of infection requires understanding of the various diagnostic assays and therapeutic options as well as relevant measures to infection prevention. This article provides updated recommendations regarding the prevention, diagnosis, and treatment of incident and recurrent C difficile infection. |
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