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1.
Clin Infect Dis ; 76(5): 890-896, 2023 03 04.
Article in English | MEDLINE | ID: mdl-36208202

ABSTRACT

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 and 2017 through the Centers for Disease Control and Prevention's Emerging Infections Program. METHODS: MICs to 6 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. Whole genome sequencing 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 < .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.


Subject(s)
Clostridioides difficile , Clostridium Infections , Humans , United States/epidemiology , Vancomycin/pharmacology , Vancomycin/therapeutic use , Metronidazole/therapeutic use , Clindamycin/therapeutic use , Moxifloxacin/therapeutic use , Clostridioides/genetics , Clostridium Infections/epidemiology , Clostridium Infections/drug therapy , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Genomics , Microbial Sensitivity Tests , Ribotyping
2.
N Engl J Med ; 382(14): 1320-1330, 2020 04 02.
Article in English | MEDLINE | ID: mdl-32242357

ABSTRACT

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.).


Subject(s)
Clostridioides difficile , Clostridium Infections/epidemiology , Community-Acquired Infections/epidemiology , Cross Infection/epidemiology , Hospital Mortality/trends , Hospitalization/trends , Humans , Incidence , Population Surveillance , Recurrence , Treatment Outcome , United States/epidemiology
3.
J Infect Dis ; 225(1): 121-129, 2022 01 05.
Article in English | MEDLINE | ID: mdl-34107037

ABSTRACT

BACKGROUND: The distribution of Clostridioides difficile strains and transmission dynamics in the United States are not well defined. Whole-genome sequencing across 2 Centers for Disease Control and Prevention Emerging Infections Program C. difficile infection (CDI) surveillance regions (Minnesota and New York) was performed to identify predominant multilocus sequence types (MLSTs) in community-associated (CA) and healthcare-associated (HCA) disease and assess transmission. METHODS: Whole-genome sequencing was performed on C. difficile isolates from patients with CDI over 3 months between 2016 and 2017. Patients were residents of the catchment area without a positive C. difficile test in the preceding 8 weeks. CDI cases were epidemiologically classified as HCA or CA. RESULTS: Of 422 isolates, 212 (50.2%) were HCA and 203 (48.1%) were CA. Predominant MLSTs were sequence type (ST) 42 (9.3%), ST8 (7.8%), and ST2 (8.1%). MLSTs associated with HCA-CDI included ST1 (76%), ST53 (83.3%), and ST43 (80.0%), while those associated with CA-CDI included ST3 (76.9%) and ST41 (77.8%). ST1 was more frequent in New York than in Minnesota (10.8% vs 3.1%). Thirty-three pairs were closely related genomically, 14 of which had potential patient-to-patient transmission supported by record review. CONCLUSIONS: The genomic epidemiology of C. difficile across 2 regions of the United States indicates the presence of a diverse strain profile and limited direct transmission.


Subject(s)
Clostridioides difficile/genetics , Clostridium Infections/epidemiology , Clostridium Infections/transmission , Hospitalization/statistics & numerical data , Whole Genome Sequencing , Clostridioides , Clostridium Infections/microbiology , Cross Infection/epidemiology , Genome , Genomics , Humans , Infectious Disease Transmission, Patient-to-Professional , Infectious Disease Transmission, Professional-to-Patient , Minnesota/epidemiology , Multilocus Sequence Typing , New York/epidemiology , Population Surveillance , United States/epidemiology
4.
Clin Infect Dis ; 73(4): 722-725, 2021 08 16.
Article in English | MEDLINE | ID: mdl-33462596

ABSTRACT

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.


Subject(s)
Clostridioides difficile , Clostridium Infections , Clostridioides , Clostridium Infections/epidemiology , Humans , Incidence , Social Class , United States/epidemiology
5.
MMWR Morb Mortal Wkly Rep ; 70(17): 651-656, 2021 Apr 30.
Article in English | MEDLINE | ID: mdl-33914723

ABSTRACT

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.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , Drug Approval , Practice Guidelines as Topic , Thrombocytopenia/epidemiology , Thrombosis/epidemiology , Adolescent , Adult , Adverse Drug Reaction Reporting Systems , Advisory Committees , COVID-19/epidemiology , COVID-19/prevention & control , Centers for Disease Control and Prevention, U.S. , Drug Labeling , Female , Humans , Male , Middle Aged , Risk Assessment , Safety-Based Drug Withdrawals , United States/epidemiology , United States Food and Drug Administration , Young Adult
6.
Transpl Infect Dis ; 23(4): e13589, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33617680

ABSTRACT

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 to 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); Escherichia coli (68.8% fluoroquinolone non-susceptible and 44.7% extended spectrum cephalosporin [ESC] non-susceptible); and Klebsiella pneumoniae and K. oxytoca (39.4% fluoroquinolone non-susceptible and 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.


Subject(s)
Liver Transplantation , Surgical Wound Infection , Anti-Bacterial Agents/therapeutic use , Enterococcus faecalis , Humans , Klebsiella pneumoniae , Liver Transplantation/adverse effects , Staphylococcus , Surgical Wound Infection/drug therapy , Surgical Wound Infection/epidemiology
7.
JAMA ; 325(24): 2448-2456, 2021 06 22.
Article in English | MEDLINE | ID: mdl-33929487

ABSTRACT

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.


Subject(s)
COVID-19 Vaccines/adverse effects , Sinus Thrombosis, Intracranial/etiology , Thrombocytopenia/etiology , Adolescent , Adult , ChAdOx1 nCoV-19 , Critical Care , Fatal Outcome , Female , Headache/etiology , Humans , Middle Aged , Platelet Count , Sinus Thrombosis, Intracranial/therapy , Thrombocytopenia/therapy
8.
Clin Infect Dis ; 70(1): 11-18, 2020 01 01.
Article in English | MEDLINE | ID: mdl-30820545

ABSTRACT

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 US 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 was defined as a discharge with a secondary International Classification of Diseases, Ninth Revision, Clinical Modification code 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% confidence interval [CI], 7.1-7.5) and 811 days of therapy (DOT)/1000 PD (95% CI, 803-820), respectively. In the cross-sectional analysis, for every 50 DOT/1000 PD increase in total AU, there was a 4.4% increase in HO-CDI. For every 10 DOT/1000 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, .47-.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 use of third- and fourth-generation cephalosporins were each associated with decreased HO-CDI rates.


Subject(s)
Anti-Bacterial Agents/adverse effects , Clostridioides difficile , Clostridium Infections/epidemiology , Cross Infection/epidemiology , Drug Prescriptions/statistics & numerical data , Adult , Aged , Cephalosporins/therapeutic use , Clostridium Infections/chemically induced , Clostridium Infections/microbiology , Cross Infection/chemically induced , Cross Infection/microbiology , Cross-Sectional Studies , Ecological and Environmental Phenomena , Female , Fluoroquinolones/therapeutic use , Hospitalization/statistics & numerical data , Hospitals/statistics & numerical data , Humans , Interrupted Time Series Analysis , Male , Metronidazole/therapeutic use , Middle Aged , United States/epidemiology , Vancomycin/therapeutic use
9.
J Gen Intern Med ; 35(2): 412-419, 2020 02.
Article in English | MEDLINE | ID: mdl-31768906

ABSTRACT

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/µl. 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.


Subject(s)
Clostridioides difficile , Clostridium Infections , Adult , Aged , Clostridioides , Clostridium Infections/diagnosis , Clostridium Infections/drug therapy , Clostridium Infections/epidemiology , Humans , Retrospective Studies , Vancomycin/therapeutic use
10.
Clin Infect Dis ; 68(4): 676-679, 2019 02 01.
Article in English | MEDLINE | ID: mdl-30060067

ABSTRACT

Candidemia and Clostridium difficile infection (CDI) are important healthcare-associated infections that share certain risk factors. We sought to describe candidemia-CDI coinfection using population-based surveillance data. We found that nearly 1 in 10 patients with candidemia had CDI coinfection.


Subject(s)
Candidemia/complications , Candidemia/epidemiology , Clostridium Infections/complications , Clostridium Infections/epidemiology , Coinfection/epidemiology , Cross Infection/complications , Cross Infection/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Incidence , Male , Middle Aged , Risk Factors , Young Adult
11.
Clin Infect Dis ; 69(10): 1667-1674, 2019 10 30.
Article in English | MEDLINE | ID: mdl-30615074

ABSTRACT

BACKGROUND: Few data suggest that Clostridioides difficile infections (CDIs) detected by toxin enzyme immunoassay (EIA) are more severe and have worse outcomes than those detected by nucleic acid amplification tests (NAATs) 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 2014-2015 by a testing algorithm (specimens initially tested by glutamate dehydrogenase 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 2 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 < .0001), had ≥3 unformed stools for ≥1 day (43.9% vs 36.6%; P < .0001), and had white blood cell counts ≥15 000 cells/µL (31.4% vs 21.4%; P < .0001). In multivariable analysis, toxin positivity was associated with recurrence (adjusted odds ratio [aOR], 1.89; 95% confidence interval [CI], 1.61-2.23), but not with CDI-related complications (aOR, 0.91; 95% CI, .67-1.23) or 30-day mortality (aOR, 0.95; 95% CI, .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 glutamate dehydrogenase screening test.


Subject(s)
Bacterial Toxins/analysis , Clostridium Infections/diagnosis , Immunoenzyme Techniques , Adolescent , Adult , Aged , Algorithms , Bacterial Proteins/analysis , Child , Child, Preschool , Clinical Laboratory Techniques , Clostridioides difficile , Clostridium Infections/mortality , Feces/chemistry , Female , Humans , Infant , Logistic Models , Male , Middle Aged , Nucleic Acid Amplification Techniques , Young Adult
13.
Ann Intern Med ; 169(7): ITC49-ITC64, 2018 10 02.
Article in English | MEDLINE | ID: mdl-30285209

ABSTRACT

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.


Subject(s)
Clostridium Infections/prevention & control , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/therapeutic use , Clostridioides difficile , Clostridium Infections/diagnosis , Clostridium Infections/therapy , Gastrointestinal Microbiome/drug effects , Humans
15.
N Engl J Med ; 369(17): 1610-9, 2013 Oct 24.
Article in English | MEDLINE | ID: mdl-24152260

ABSTRACT

BACKGROUND: Since September 18, 2012, public health officials have been investigating a large outbreak of fungal meningitis and other infections in patients who received epidural, paraspinal, or joint injections with contaminated lots of methylprednisolone acetate. Little is known about infections caused by Exserohilum rostratum, the predominant outbreak-associated pathogen. We describe the early clinical course of outbreak-associated infections. METHODS: We reviewed medical records for outbreak cases reported to the Centers for Disease Control and Prevention before November 19, 2012, from the six states with the most reported cases (Florida, Indiana, Michigan, New Jersey, Tennessee, and Virginia). Polymerase-chain-reaction assays and immunohistochemical testing were performed on clinical isolates and tissue specimens for pathogen identification. RESULTS: Of 328 patients without peripheral-joint infection who were included in this investigation, 265 (81%) had central nervous system (CNS) infection and 63 (19%) had non-CNS infections only. Laboratory evidence of E. rostratum was found in 96 of 268 patients (36%) for whom samples were available. Among patients with CNS infections, strokes were associated with an increased severity of abnormalities in cerebrospinal fluid (P<0.001). Non-CNS infections were more frequent later in the course of the outbreak (median interval from last injection to diagnosis, 39 days for epidural abscess and 21 days for stroke; P<0.001), and such infections developed in patients with and in those without meningitis. CONCLUSIONS: The initial clinical findings from this outbreak suggest that fungal infections caused by epidural and paraspinal injection of a contaminated glucocorticoid product can result in a broad spectrum of clinical disease, reflecting possible variations in the pathogenic mechanism and in host and exposure risk factors. (Funded by the Centers for Disease Control and Prevention.).


Subject(s)
Arachnoiditis/epidemiology , Disease Outbreaks , Drug Contamination , Glucocorticoids , Meningitis, Fungal/epidemiology , Methylprednisolone , Stroke/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Antifungal Agents/adverse effects , Antifungal Agents/therapeutic use , Arachnoiditis/microbiology , Arachnoiditis/mortality , Ascomycota/genetics , Ascomycota/isolation & purification , Aspergillus fumigatus/isolation & purification , Drug Compounding , Female , Glucocorticoids/administration & dosage , Humans , Injections, Epidural , Injections, Spinal , Male , Meningitis, Fungal/microbiology , Meningitis, Fungal/mortality , Meningitis, Fungal/pathology , Methylprednisolone/administration & dosage , Middle Aged , Polymerase Chain Reaction , Stroke/microbiology , Stroke/mortality , United States/epidemiology , Young Adult
16.
Clin Infect Dis ; 60(1): 48-54, 2015 Jan 01.
Article in English | MEDLINE | ID: mdl-25216687

ABSTRACT

BACKGROUND: Herbaspirillum species are gram-negative Betaproteobacteria that inhabit the rhizosphere. We investigated a potential cluster of hospital-based Herbaspirillum species infections. METHODS: Cases were defined as Herbaspirillum species isolated from a patient in our comprehensive cancer center between 1 January 2006 and 15 October 2013. Case finding was performed by reviewing isolates initially identified as Burkholderia cepacia susceptible to all antibiotics tested, and 16S ribosomal DNA sequencing of available isolates to confirm their identity. Pulsed-field gel electrophoresis (PFGE) was performed to test genetic relatedness. Facility observations, infection prevention assessments, and environmental sampling were performed to investigate potential sources of Herbaspirillum species. RESULTS: Eight cases of Herbaspirillum species were identified. Isolates from the first 5 clustered cases were initially misidentified as B. cepacia, and available isolates from 4 of these cases were indistinguishable. The 3 subsequent cases were identified by prospective surveillance and had different PFGE patterns. All but 1 case-patient had bloodstream infections, and 6 presented with sepsis. Underlying diagnoses included solid tumors (3), leukemia (3), lymphoma (1), and aplastic anemia (1). Herbaspirillum species infections were hospital-onset in 5 patients and community-onset in 3. All symptomatic patients were treated with intravenous antibiotics, and their infections resolved. No environmental source or common mechanism of acquisition was identified. CONCLUSIONS: This is the first report of a hospital-based cluster of Herbaspirillum species infections. Herbaspirillum species are capable of causing bacteremia and sepsis in immunocompromised patients. Herbaspirillum species can be misidentified as Burkholderia cepacia by commercially available microbial identification systems.


Subject(s)
Cross Infection/epidemiology , Cross Infection/microbiology , Gram-Negative Bacterial Infections/epidemiology , Gram-Negative Bacterial Infections/microbiology , Herbaspirillum/classification , Herbaspirillum/isolation & purification , Neoplasms/complications , Adolescent , Aged , Betaproteobacteria , Burkholderia cepacia , Child, Preschool , Cluster Analysis , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , DNA, Ribosomal/chemistry , DNA, Ribosomal/genetics , Electrophoresis, Gel, Pulsed-Field , Female , Genotype , Herbaspirillum/genetics , Humans , Male , Middle Aged , Molecular Typing , RNA, Ribosomal, 16S/genetics , Retrospective Studies , Sequence Analysis, DNA
17.
Emerg Infect Dis ; 21(9): 1611-6, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26290955

ABSTRACT

Preventing transmission of carbapenemase-producing, carbapenem-resistant Enterobacteriaceae (CP-CRE) is a public health priority. A phenotype-based definition that reliably identifies CP-CRE while minimizing misclassification of non-CP-CRE could help prevention efforts. To assess possible definitions, we evaluated enterobacterial isolates that had been tested and deemed nonsusceptible to >1 carbapenem at US Emerging Infections Program sites. We determined the number of non-CP isolates that met (false positives) and CP isolates that did not meet (false negatives) the Centers for Disease Control and Prevention CRE definition in use during our study: 30% (94/312) of CRE had carbapenemase genes, and 21% (14/67) of Klebsiella pneumoniae carbapenemase-producing Klebsiella isolates had been misclassified as non-CP. A new definition requiring resistance to 1 carbapenem rarely missed CP strains, but 55% of results were false positive; adding the modified Hodge test to the definition decreased false positives to 12%. This definition should be considered for use in carbapenemase-producing CRE surveillance and prevention.


Subject(s)
Bacterial Proteins/genetics , Communicable Diseases, Emerging/microbiology , Drug Resistance, Bacterial , Enterobacteriaceae Infections/microbiology , Enterobacteriaceae/isolation & purification , beta-Lactamases/genetics , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/metabolism , Carbapenems/pharmacology , Communicable Disease Control/standards , Communicable Diseases, Emerging/epidemiology , Communicable Diseases, Emerging/prevention & control , Diagnostic Tests, Routine/standards , Enterobacteriaceae/drug effects , Enterobacteriaceae/enzymology , Enterobacteriaceae Infections/epidemiology , Enterobacteriaceae Infections/prevention & control , Humans , Phenotype , Public Health Surveillance , United States/epidemiology , beta-Lactamases/metabolism
19.
JAMA ; 314(14): 1479-87, 2015 Oct 13.
Article in English | MEDLINE | ID: mdl-26436831

ABSTRACT

IMPORTANCE: Carbapenem-resistant Enterobacteriaceae (CRE) are increasingly reported worldwide as a cause of infections with high-mortality rates. Assessment of the US epidemiology of CRE is needed to inform national prevention efforts. OBJECTIVE: To determine the population-based CRE incidence and describe the characteristics and resistance mechanism associated with isolates from 7 US geographical areas. DESIGN, SETTING, AND PARTICIPANTS: Population- and laboratory-based active surveillance of CRE conducted among individuals living in 1 of 7 US metropolitan areas in Colorado, Georgia, Maryland, Minnesota, New Mexico, New York, and Oregon. Cases of CRE were defined as carbapenem-nonsusceptible (excluding ertapenem) and extended-spectrum cephalosporin-resistant Escherichia coli, Enterobacter aerogenes, Enterobacter cloacae complex, Klebsiella pneumoniae, or Klebsiella oxytoca that were recovered from sterile-site or urine cultures during 2012-2013. Case records were reviewed and molecular typing for common carbapenemases was performed. EXPOSURES: Demographics, comorbidities, health care exposures, and culture source and location. MAIN OUTCOMES AND MEASURES: Population-based CRE incidence, site-specific standardized incidence ratios (adjusted for age and race), and clinical and microbiological characteristics. RESULTS: Among 599 CRE cases in 481 individuals, 520 (86.8%; 95% CI, 84.1%-89.5%) were isolated from urine and 68 (11.4%; 95% CI, 8.8%-13.9%) from blood. The median age was 66 years (95% CI, 62.1-65.4 years) and 284 (59.0%; 95% CI, 54.6%-63.5%) were female. The overall annual CRE incidence rate per 100<000 population was 2.93 (95% CI, 2.65-3.23). The CRE standardized incidence ratio was significantly higher than predicted for the sites in Georgia (1.65 [95% CI, 1.20-2.25]; P < .001), Maryland (1.44 [95% CI, 1.06-1.96]; P = .001), and New York (1.42 [95% CI, 1.05-1.92]; P = .048), and significantly lower than predicted for the sites in Colorado (0.53 [95% CI, 0.39-0.71]; P < .001), New Mexico (0.41 [95% CI, 0.30-0.55]; P = .01), and Oregon (0.28 [95% CI, 0.21-0.38]; P < .001). Most cases occurred in individuals with prior hospitalizations (399/531 [75.1%; 95% CI, 71.4%-78.8%]) or indwelling devices (382/525 [72.8%; 95% CI, 68.9%-76.6%]); 180 of 322 (55.9%; 95% CI, 50.0%-60.8%) admitted cases resulted in a discharge to a long-term care setting. Death occurred in 51 (9.0%; 95% CI, 6.6%-11.4%) cases, including in 25 of 91 cases (27.5%; 95% CI, 18.1%-36.8%) with CRE isolated from normally sterile sites. Of 188 isolates tested, 90 (47.9%; 95% CI, 40.6%-55.1%) produced a carbapenemase. CONCLUSIONS AND RELEVANCE: In this population- and laboratory-based active surveillance system in 7 states, the incidence of CRE was 2.93 per 100<000 population. Most CRE cases were isolated from a urine source, and were associated with high prevalence of prior hospitalizations or indwelling devices, and discharge to long-term care settings.


Subject(s)
Anti-Bacterial Agents/pharmacology , Carbapenems/pharmacology , Enterobacteriaceae Infections/drug therapy , Enterobacteriaceae/drug effects , beta-Lactam Resistance , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Bacterial Proteins/analysis , Child , Child, Preschool , Colorado/epidemiology , Enterobacteriaceae Infections/epidemiology , Enterobacteriaceae Infections/urine , Female , Georgia/epidemiology , Humans , Incidence , Infant , Male , Maryland/epidemiology , Middle Aged , Minnesota/epidemiology , New Mexico/epidemiology , New York/epidemiology , Oregon/epidemiology , Population Surveillance , Sex Distribution , beta-Lactamases/analysis
20.
JAMA ; 312(14): 1447-55, 2014 Oct 08.
Article in English | MEDLINE | ID: mdl-25291580

ABSTRACT

IMPORTANCE: Carbapenem-resistant Enterobacteriaceae (CRE) producing the New Delhi metallo-ß-lactamase (NDM) are rare in the United States, but have the potential to add to the increasing CRE burden. Previous NDM-producing CRE clusters have been attributed to person-to-person transmission in health care facilities. OBJECTIVE: To identify a source for, and interrupt transmission of, NDM-producing CRE in a northeastern Illinois hospital. DESIGN, SETTING, AND PARTICIPANTS: Outbreak investigation among 39 case patients at a tertiary care hospital in northeastern Illinois, including a case-control study, infection control assessment, and collection of environmental and device cultures; patient and environmental isolate relatedness was evaluated with pulsed-field gel electrophoresis (PFGE). Following identification of a likely source, targeted patient notification and CRE screening cultures were performed. MAIN OUTCOMES AND MEASURES: Association between exposure and acquisition of NDM-producing CRE; results of environmental cultures and organism typing. RESULTS: In total, 39 case patients were identified from January 2013 through December 2013, 35 with duodenoscope exposure in 1 hospital. No lapses in duodenoscope reprocessing were identified; however, NDM-producing Escherichia coli was recovered from a reprocessed duodenoscope and shared more than 92% similarity to all case patient isolates by PFGE. Based on the case-control study, case patients had significantly higher odds of being exposed to a duodenoscope (odds ratio [OR], 78 [95% CI, 6.0-1008], P < .001). After the hospital changed its reprocessing procedure from automated high-level disinfection with ortho-phthalaldehyde to gas sterilization with ethylene oxide, no additional case patients were identified. CONCLUSIONS AND RELEVANCE: In this investigation, exposure to duodenoscopes with bacterial contamination was associated with apparent transmission of NDM-producing E coli among patients at 1 hospital. Bacterial contamination of duodenoscopes appeared to persist despite the absence of recognized reprocessing lapses. Facilities should be aware of the potential for transmission of bacteria including antimicrobial-resistant organisms via this route and should conduct regular reviews of their duodenoscope reprocessing procedures to ensure optimal manual cleaning and disinfection.


Subject(s)
Carbapenems/pharmacology , Disinfection/methods , Duodenoscopes/microbiology , Enterobacteriaceae Infections/etiology , Equipment Contamination , Escherichia coli , Adult , Aged , Aged, 80 and over , Case-Control Studies , Cohort Studies , Cross Infection/epidemiology , Disease Outbreaks , Drug Resistance, Bacterial , Enterobacteriaceae Infections/epidemiology , Escherichia coli/enzymology , Escherichia coli/isolation & purification , Female , Hospitals , Humans , Illinois/epidemiology , Male , Middle Aged , beta-Lactamases
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