Stuart Johnson

Loyola University Chicago, Chicago, Illinois, United States

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Publications (109)821.65 Total impact

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    ABSTRACT: Antibiotics have been shown to influence the risk of infection with specific Clostridium difficile strains as well as the risk of C. difficile infection (CDI). We performed a retrospective case-control study of patients infected with the epidemic BI/NAP1/027 strain in a US hospital following recognition of increased CDI severity and culture of stools positive by C. difficile toxin immunoassay. Between 2005 and 2007, 72% (103/143) of patients with first episode CDIs were infected with the BI strain by REA typing. Most patients received multiple antibiotics within 6 weeks of CDI onset (median of 3 antibiotic classes). By multivariate analysis, fluoroquinolone and macrolide exposure was more frequent among BI cases compared to non-BI controls (OR for fluoroquinolones; 3.2; 95% CI 1.3, 7.5; p
    No preview · Article · Nov 2015 · Antimicrobial Agents and Chemotherapy
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    ABSTRACT: Angiostrongylus cantonensis is the most common infectious cause of eosinophilic meningitis. Timely diagnosis of these infections is difficult, partly because reliable laboratory diagnostic methods are unavailable. The aim of this study was to evaluate the usefulness of a real-time polymerase chain reaction (PCR) assay for the detection of A. cantonensis DNA in human cerebrospinal fluid (CSF) specimens. A total of 49 CSF specimens from 33 patients with eosinophilic meningitis were included: A. cantonensis DNA was detected in 32 CSF specimens, from 22 patients. Four patients had intermittently positive and negative real-time PCR results on subsequent samples, indicating that the level of A. cantonensis DNA present in CSF may fluctuate during the course of the illness. Immunodiagnosis and/or supplemental PCR testing supported the real-time PCR findings for 30 patients. On the basis of these observations, this real-time PCR assay can be useful to detect A. cantonensis in the CSF from patients with eosinophilic meningitis.
    No preview · Article · Nov 2015 · The American journal of tropical medicine and hygiene
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    ABSTRACT: Unlabelled: Clostridium difficile is a leading cause of antibiotic-associated diarrhea, a significant animal pathogen, and a worldwide public health burden. Most disease-causing strains secrete two exotoxins, TcdA and TcdB, which are considered to be the primary virulence factors. Understanding the role that these toxins play in disease is essential for the rational design of urgently needed new therapeutics. However, their relative contributions to disease remain contentious. Using three different animal models, we show that TcdA(+) TcdB(-) mutants are attenuated in virulence in comparison to the wild-type (TcdA(+) TcdB(+)) strain, whereas TcdA(-) TcdB(+) mutants are fully virulent. We also show for the first time that TcdB alone is associated with both severe localized intestinal damage and systemic organ damage, suggesting that this toxin might be responsible for the onset of multiple organ dysfunction syndrome (MODS), a poorly characterized but often fatal complication of C. difficile infection (CDI). Finally, we show that TcdB is the primary factor responsible for inducing the in vivo host innate immune and inflammatory responses. Surprisingly, the animal infection model used was found to profoundly influence disease outcomes, a finding which has important ramifications for the validation of new therapeutics and future disease pathogenesis studies. Overall, our results show unequivocally that TcdB is the major virulence factor of C. difficile and provide new insights into the host response to C. difficile during infection. The results also highlight the critical nature of using appropriate and, when possible, multiple animal infection models when studying bacterial virulence mechanisms. Importance: Clostridium difficile is a leading cause of antibiotic-associated diarrhea and an important hospital pathogen. TcdA and TcdB are thought to be the primary virulence factors responsible for disease symptoms of C. difficile infections (CDI). However, the individual contributions of these toxins to disease remain contentious. Using three different animal models of infection, we show for the first time that TcdB alone causes severe damage to the gut, as well as systemic organ damage, suggesting that this toxin might be responsible for MODS, a serious but poorly understood complication of CDI. These findings provide important new insights into the host response to C. difficile during infection and should guide the rational development of urgently required nonantibiotic therapeutics for the treatment of CDI.
    Full-text · Article · Jun 2015 · mBio
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    Charlesnika T Evans · Stuart Johnson
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    ABSTRACT: Despite advances in the diagnosis and treatment of Clostridium difficile infection (CDI) and prevention efforts to reduce the spread of C. difficile, CDI remains a significant challenge to healthcare systems worldwide. Further advances in prevention of CDI may need to focus on those who continue to be exposed to the organism and who are susceptible. Interventions directed toward this susceptible population, particularly hospitalized patients who receive antibiotics, may be effective. There is moderate evidence on the effectiveness of probiotics to prevent primary CDI, but there are few data to support use in secondary prevention of recurrent CDI. This review discusses the literature available on the use of probiotics to prevent primary and secondary CDI. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.
    Preview · Article · May 2015 · Clinical Infectious Diseases
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    ABSTRACT: To address the significant morbidity and mortality rates associated with nosocomial Clostridium difficile-associated diarrhea (CDAD), a series of recommendations and a pathway to prevention were developed. An expert panel of infectious disease (ID) specialists participated in a modified Delphi process with specific objectives: (1) conduct a review for CDAD and prevention; (2) develop statements based upon panel members' opinions; (3) hold a panel meeting during the 2012 IDWeek; and (4) review the final recommendations and prevention pathway prior to submission for publication. The panel voted on (1) antibiotic stewardship (7 of 8 panelists); (2) reduction of other potentially modifiable risk factors (variable); (3) utilization of specific probiotics to prevent C. difficile overgrowth (8/8); (4) staff education regarding CDAD preventive measures (8/8); (5) appropriate hand hygiene for everyone (7/8); (6) environmental cleaning (8/8); (7) medical equipment disinfection (7/8); (8) early detection of CDAD in symptomatic patients (7/8); (9) usage of protective clothing/gloves (8/8); (10) proper measures during outbreak (8/8); and (11) surveillance to monitor efficacy data of preventive measures (8/8). The panel members agreed with 11 of 17 recommendations presented. The additional recommendations by the panel were proton pump inhibitor use as a risk factor and the use of adjunctive therapy with specific probiotic, as it was approved by Health Canada for the risk reduction of CDAD in hospitalized patients. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
    Full-text · Article · May 2015 · Clinical Infectious Diseases
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    Melinda M Soriano · Stuart Johnson
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    ABSTRACT: Vancomycin and metronidazole were historically considered equivalent therapies for the management of Clostridium difficile infections (CDI); however, recent data confirm more favorable outcomes with vancomycin. Fidaxomicin is a narrow spectrum antibiotic that has an advantage in reducing recurrence rates compared with vancomycin, possibly owing to its sparing effect on normal colonic microbiota. Data are limited for guiding management of CDI recurrences, particularly multiple recurrences. Several empiric approaches to manage these cases are reviewed. Published by Elsevier Inc.
    Full-text · Article · Jan 2015 · Infectious Disease Clinics of North America
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    Full-text · Dataset · Nov 2014
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    ABSTRACT: Reports of fidaxomicin treatment for patients with multiple recurrent Clostridium difficile infections ([mrCDI] ie, more than 2 CDI episodes) indicate symptomatic response to this agent, but 50% have subsequent mrCDI episodes. In an effort to improve outcomes in patients with mrCDI we used novel regimens of fidaxomicin based on strategies used with vancomycin. Of 8 patients who received a 10-day chaser of fidaxomicin given twice daily after a course of vancomycin, 3 (38%) experienced a subsequent recurrence. Two (18%) of 11 patients who completed a 14- to 33-day course of fidaxomicin in a tapering dose experienced a recurrence, both of whom received additional antibiotics before that recurrence. The median symptom-free interval (SFI) after fidaxomicin taper was greater than the median SFI after the most effective prior regimen for those patients (257 days [interquartile range, 280] vs 25 days [interquartile range, 30], respectively; P = .003). A fidaxomicin chaser or taper regimen may be effective in patients with mrCDI, but the number of patients treated is small, and randomized comparative data are not available.
    Full-text · Article · Sep 2014 · Open Forum Infectious Diseases
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    ABSTRACT: We report the results of an international Clostridium difficile typing study to cross reference strain designations for seven typing methodologies and facilitate inter-laboratory communication. Four genotypic and three phenotypic methods were used to type 100 isolates and compare the results to 39 PCR ribotypes identified among the collection.
    No preview · Article · Aug 2014 · Anaerobe
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    ABSTRACT: Background: Clostridium difficile infection (CDI) is a common complication of antibiotic therapy that is treated with antibiotics, contributing to ongoing disruption of the colonic microbiota and CDI recurrence. Two multinational trials were conducted to compare the efficacy of tolevamer, a nonantibiotic, toxin-binding polymer, with vancomycin and metronidazole. Methods: Patients with CDI were randomly assigned in a 2:1:1 ratio to oral tolevamer 9 g (loading dose) followed by 3 g every 8 hours for 14 days, vancomycin 125 mg every 6 hours for 10 days, or metronidazole 375 mg every 6 hours for 10 days. The primary endpoint was clinical success, defined as resolution of diarrhea and absence of severe abdominal discomfort for more than 2 consecutive days including day 10. Results: In a pooled analysis, 563 patients received tolevamer, 289 received metronidazole, and 266 received vancomycin. Clinical success of tolevamer was inferior to both metronidazole and vancomycin (P < .001), and metronidazole was inferior to vancomycin (P = .02; 44.2% [n = 534], 72.7% [n = 278], and 81.1% [n = 259], respectively). Clinical success in patients with severe CDI who received metronidazole was 66.3% compared with vancomycin, which was 78.5%. (P = .059). A post-hoc multivariate analysis that excluded tolevamer found 3 factors that were strongly associated with clinical success: vancomycin treatment, treatment-naive status, and mild or moderate CDI severity. Adverse events were similar among the treatment groups. Conclusions: Tolevamer was inferior to antibiotic treatment of CDI, and metronidazole was inferior to vancomycin. Trial Registration. clinicaltrials.gov NCT00106509 and NCT00196794.
    No preview · Article · May 2014 · Clinical Infectious Diseases
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    ABSTRACT: Background Recurrent Clostridium difficile (CDI) infection is a growing concern; however, there are little data on impact of recurrent CDI on those with spinal cord injury and disorder (SCI/D). Therefore, the objective of this study was to identify risk factors associated with recurrence of CDI among Veterans with SCI/D. Methods This was a retrospective cohort study with data from outpatient, inpatient, and extended care settings at 83 Department of Veterans Affairs facilities from 2002 to 2009. Results Of 1,464 cases of CDI analyzed, 315 cases (21.5%) had a first recurrence of CDI. Multivariable regression demonstrated that risk factors significantly associated with increased recurrence were concomitant fluoroquinolone use (odds ratio [OR], 1.39; 95% confidence interval [CI]: 1.08-1.80), whereas concomitant tetracycline use (OR, 0.35; 95% CI: 0.14-0.90), and cerebrovascular accident (OR, 0.46; 95% CI: 0.25-0.85) were associated with decreased recurrence. A subanalysis in those with health care facility-onset CDI showed that increased length of stay postinitial CDI was a significant risk factor for recurrence as was concomitant use of fluoroquinolones and that tetracycline remained protective for recurrence. Conclusion Concomitant fluoroquinolone use was a risk factor for the recurrence of CDI. In contrast, tetracyclines and cerebrovascular accident were protective. Length of stay greater than 90 days from the initial CDI episode was also a risk factor for recurrence among those with health care facility-onset CDI. Future studies should focus on effective strategies to prevent these risk factors among the SCI/D population.
    No preview · Article · May 2014 · American journal of infection control
  • Michael Wang · Stuart Johnson
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    ABSTRACT: Cancer patients, particularly those with neutropenia, are at risk for enteric and intra-abdominal infections. Specific infections and infectious syndromes in this setting include neutropenic enterocolitis, bacterial infections such as Clostridium difficile infection (CDI), viral infections such as CMV colitis, and parasitic infections such as strongyloidiasis. Diagnosing and gauging the severity of CDI presents challenges, as chemotherapy may produce symptoms that mimic CDI and laboratory findings such as leukocytosis are not reliable in this population. Treatment for enteric infections should be pathogen specific, although broad-spectrum antibiotics are often required as initial empiric therapy in patients with neutropenia.
    No preview · Article · Apr 2014 · Cancer treatment and research
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    Stuart Johnson

    Preview · Article · Apr 2014 · Clinical Infectious Diseases
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    Dale N Gerding · Stuart Johnson · Maja Rupnik · Klaus Aktories
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    ABSTRACT: Binary toxin (CDT) is frequently observed in Clostridium difficile strains associated with increased severity of C. difficile infection (CDI). CDT belongs to the family of binary ADP-ribosylating toxins consisting of two separate toxin components: CDTa, the enzymatic ADP-ribosyltransferase which modifies actin, and CDTb which binds to host cells and translocates CDTa into the cytosol. CDTb is activated by serine proteases and binds to lipolysis stimulated lipoprotein receptor. ADP-ribosylation induces depolymerization of the actin cytoskeleton. Toxin-induced actin depolymerization also produces microtubule-based membrane protrusions which form a network on epithelial cells and increase bacterial adherence. Multiple clinical studies indicate an association between binary toxin genes in C. difficile and increased 30-d CDI mortality independent of PCR ribotype. Further studies including measures of binary toxin in stool, analyses of CDI mortality caused by CDT-producing strains, and examination of the relationship of CDT expression to TcdA and TcdB toxin variants and PCR ribotypes are needed.
    Full-text · Article · Oct 2013 · Gut Microbes
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    ABSTRACT: Clinical guidelines exist to promote antibiotic stewardship, particularly in ambulatory care settings such as the emergency department (ED). However, there is limited evidence on prescribing practice for persons with spinal cord injury and disorder (SCI/D). The goal of this study was to assess trends in antibiotic prescribing in the ED setting for persons with SCI/D. A retrospective dynamic cohort study design. ED visits that did not result in same day hospitalization over 6 years (fiscal year (FY) 2002-FY2007) in Department of Veterans Affairs (VA) facilities Participants Veterans with SCI/D. VA clinical and administrative databases were used to identify the cohort and to obtain demographics, diagnoses, and medications. The rate of antibiotic prescribing for ED visits was defined as the number of antibiotics/total ED visits. Veterans with SCI/D had 21 934 ED visits and 5887 antibiotics prescribed over the study period (rate of 268.4 prescriptions/1000 visits). The antibiotic prescribing rate increased from 238.8/1000 visits in FY2002 to 310.8/1000 visits in FY2007 (P < 0.0001). This increase in the rate of prescribing was seen across all patient demographics and factors assessed. Although clinical guidelines for judicious use of antibiotics in persons with SCI/D have been disseminated to providers, antibiotic prescribing in an ED setting is high and continuing to rise in this population.
    No preview · Article · Sep 2013 · The journal of spinal cord medicine
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    ABSTRACT: Nontoxigenic Clostridium difficile (NTCD) has been shown to prevent fatal C. difficile infection in the hamster model when hamsters are challenged with standard toxigenic C. difficile strains. The purpose of this study was to determine if NTCD can prevent C. difficile infection in the hamster model when hamsters are challenged with restriction endonuclease analysis group BI C. difficile strains. Groups of 10 hamsters were given oral clindamycin, followed on day 2 by 106 CFU of spores of NTCD strain M3 or T7, and were challenged on day 5 with 100 CFU of spores of BI1 or BI6. To conserve animals, results for control hamsters challenged with BI1 or BI6 from the present study and controls from previous identical experiments were combined for statistical comparisons. NTCD strains M3 and T7 achieved 100% colonization and were 100% protective against challenge with BI1 (P ≤ 0.001). M3 colonized 9/10 hamsters and protected against BI6 challenge in the colonized hamsters (P = 0.0003). T7 colonized 10/10 hamsters, but following BI6 challenge, cocolonization occurred in 5 hamsters, 4 of which died, for protection of 6/10 animals (P = 0.02). NTCD colonization provides protection against challenge with toxigenic BI group strains. M3 is more effective than T7 in preventing C. difficile infection caused by the BI6 epidemic strain. Prevention of C. difficile infection caused by the epidemic BI6 strain may be more challenging than that of infections caused by historic BI1 and non-BI C. difficile strains.
    Full-text · Article · Aug 2013 · Antimicrobial Agents and Chemotherapy
  • Gerald S Murphy · Stuart Johnson
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    ABSTRACT: Angiostrongylus Eosinophilic Meningitis is caused by human infection with larvae of the rat lungworm, Angiostrongylus cantonensis. The clinical presentation includes a spectrum of disease, from meningitis through radiculitis, cranial nerve abnormalities, ataxia, encephalitis, coma, and rarely death. The condition is diagnosed by recognizing the triad of: the clinical syndrome, eosinophils in the cerebrospinal fluid or blood, and exposure history. A history of eating raw or poorly cooked snails is classic, but ingestion of other intermediate hosts or unwashed produce (such as lettuce) harboring hosts is not uncommon. Several serologic tests exist but none has yet been fully validated. There is good evidence that a 2 week course of high dose corticosteroids shortens the duration and severity of symptoms. There is somewhat weaker evidence that albendazole reduces symptoms. The combination of prednisolone and albendazole is being used more commonly for treatment. Some suggestions for future research are given.
    No preview · Article · Jun 2013 · Hawai'i journal of medicine & public health : a journal of Asia Pacific Medicine & Public Health
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    Dale N Gerding · Stuart Johnson

    Full-text · Article · Mar 2013 · Clinical Infectious Diseases
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    ABSTRACT: This study determined whether surrogate organisms can predict activity against Clostridium difficile spores and compared the efficacy of hand hygiene preparations against C. difficile. Our data suggest that surrogate organisms were not predictive of C. difficile spore removal. Four preparations were significantly more effective than tap water at removing C. difficile.
    Full-text · Article · Mar 2013 · Infection Control and Hospital Epidemiology
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    ABSTRACT: Objective. To describe characteristics of Clostridium difficile infection (CDI) and markers of severe CDI among patients with hematologic malignancies. Design. Case-control study. Setting. Tertiary care teaching hospital. Patients and Methods. Inpatients with hematologic malignancies and CDI were age and time matched with 2 control inpatients without hematologic malignancies. Chart reviews were performed, and C. difficile isolates were strain typed. Results. Case patients ([Formula: see text]) and control patients ([Formula: see text]) patients were different in respect to receipt of immunosuppressive agents within 2 months (92.7% vs 25.6%; [Formula: see text]); neutropenia within 2 months (75.6% vs 3.7%; [Formula: see text]) and mean (± standard deviation) white blood cell (WBC) count at diagnosis ([Formula: see text] vs [Formula: see text] cells/mL; [Formula: see text]); baseline mean creatinine level ([Formula: see text] vs [Formula: see text] mg/dL; [Formula: see text]), mean creatinine level at diagnosis ([Formula: see text] vs [Formula: see text] mg/dL; [Formula: see text]), and creatinine increases of 1.5 times over baseline (2.4% vs 15.1%; [Formula: see text]). Immunosuppressive agents and creatinine level remained significant in multivariable analysis ([Formula: see text] for both variables). Severity correlated with mortality when measured by alternate severity criteria but not when measured by the Society for Healthcare Epidemiology of America/Infectious Diseases Society of America criteria, which are based solely on WBC count and creatinine elevation. The prevalence of the epidemic BI/NAP1/027 strain was similar in both groups. Conclusions. Patients with hematologic malignancies had lower creatinine levels at the time of CDI diagnosis compared with control patients. WBC counts also tended to be lower in case patients. CDI severity criteria based on WBC count and creatinine level may not be applicable to patients with hematologic malignancies.
    No preview · Article · Feb 2013 · Infection Control and Hospital Epidemiology

Publication Stats

8k Citations
821.65 Total Impact Points

Institutions

  • 2007-2015
    • Loyola University Chicago
      • • Stritch School of Medicine
      • • Division of Infectious Disease
      Chicago, Illinois, United States
  • 2003-2015
    • Edward Hines, Jr. VA Hospital
      Hines, Oregon, United States
  • 2014
    • Illinois College
      Maywood, Illinois, United States
  • 2003-2014
    • Loyola University
      New Orleans, Louisiana, United States
  • 1990-2013
    • Minneapolis Veterans Affairs Hospital
      Minneapolis, Minnesota, United States
  • 2012
    • The University of Calgary
      Calgary, Alberta, Canada
  • 2003-2012
    • Loyola University Medical Center
      • Department of Medicine
      Maywood, Illinois, United States
  • 2010
    • University of California, Davis
      • Division of Infectious and Immunologic Diseases
      Davis, California, United States
  • 2005
    • United States Department of Veterans Affairs
      Бедфорд, Massachusetts, United States
  • 1997-2003
    • Northwestern University
      • • Division of Gastroenterology and Hepatology
      • • Division of Hospital Medicine
      Evanston, Illinois, United States