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1.
JAMA Netw Open ; 7(7): e2422281, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-39012634

ABSTRACT

Importance: Acute urinary retention (UR) is common, yet variations in diagnosis and management can lead to inappropriate catheterization and harm. Objective: To develop an algorithm for screening and management of UR among adult inpatients. Design, Setting, and Participants: In this mixed-methods study using the RAND/UCLA Appropriateness Method and qualitative interviews, an 11-member multidisciplinary expert panel of nurses and physicians from across the US used a formal multi-round process from March to May 2015 to rate 107 clinical scenarios involving diagnosis and management of adult UR in postoperative and medical inpatients. The panel ratings informed the first algorithm draft. Semistructured interviews were conducted from October 2020 to May 2021 with 33 frontline clinicians-nurses and surgeons from 5 Michigan hospitals-to gather feedback and inform algorithm refinements. Main Outcomes and Measures: Panelists categorized scenarios assessing when to use bladder scanners, catheterization at various scanned bladder volumes, and choice of catheterization modalities as appropriate, inappropriate, or uncertain. Next, qualitative methods were used to understand the perceived need, usability, and potential algorithm uses. Results: The 11-member expert panel (10 men and 1 woman) used the RAND/UCLA Appropriateness Method to develop a UR algorithm including the following: (1) bladder scanners were preferred over catheterization for UR diagnosis in symptomatic patients or starting as soon as 3 hours since last void if asymptomatic, (2) bladder scanner volumes appropriate to prompt catheterization were 300 mL or greater in symptomatic patients and 500 mL or greater in asymptomatic patients, and (3) intermittent was preferred to indwelling catheterization for managing lower bladder volumes. Interview findings were organized into 3 domains (perceived need, feedback on algorithm, and implementation suggestions). The 33 frontline clinicians (9 men and 24 women) who reviewed the algorithm reported that an evidence-based protocol (1) was needed and could be helpful to clinicians, (2) should be simple and graphically appealing to improve rapid clinician review, and (3) should be integrated within the electronic medical record and prominently displayed in hospital units to increase awareness. The draft algorithm was iteratively refined based on stakeholder feedback. Conclusions and Relevance: In this study using a systematic, multidisciplinary, evidence- and expert opinion-based approach, a UR evaluation and catheterization algorithm was developed to improve patient safety by increasing appropriate use of bladder scanners and catheterization. This algorithm addresses the need for practical guidance to manage UR among adult inpatients.


Subject(s)
Algorithms , Urinary Catheterization , Urinary Retention , Humans , Urinary Retention/therapy , Urinary Catheterization/methods , Male , Female , Adult , Inpatients/statistics & numerical data , Middle Aged , Qualitative Research
2.
Open Forum Infect Dis ; 11(6): ofae311, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38933739

ABSTRACT

Background: Early identification of newborns with congenital cytomegalovirus (CMV) is necessary to provide antiviral therapy and other interventions that can improve outcomes. Prior research demonstrates that universal newborn CMV screening would be the most cost-effective approach to identifying newborns who are infected. CMV is not uniformly prevalent, and it is uncertain whether universal screening would remain cost-effective in lower-prevalence neighborhoods. Our aim was to identify geographic heterogeneity in the cost-effectiveness of universal newborn CMV screening by combining a geospatial analysis with a preexisting cost-effectiveness analysis. Methods: This study used the CMV testing results and zip code location data of 96 785 newborns in 7 metropolitan areas who had been tested for CMV as part of the CMV and Hearing Multicenter Screening study. A hierarchical bayesian generalized additive model was constructed to evaluate geographic variability in the odds of CMV. The zip code-level odds of CMV were then used to weight the results of a previously published model evaluating universal CMV screening vs symptom-targeted screening. Results: The odds of CMV were heterogeneous over large geographic scales, with the highest odds in the southeastern United States. Universal screening was more cost-effective and afforded more averted cases of severe hearing loss than targeted testing. Universal screening remained the most cost-effective option even in areas with the lowest CMV prevalence. Conclusions: Universal newborn CMV screening is cost-effective regardless of underlying CMV prevalence and is the preferred strategy to reduce morbidity from congenital CMV.

4.
Infect Control Hosp Epidemiol ; : 1-5, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38654493

ABSTRACT

OBJECTIVE: To determine prevalence of technical and behavioral interventions aimed at preventing central line-associated bloodstream infection (CLABSI) following the COVID19 pandemic. DESIGN: Cross-sectional survey. SETTING: US acute care hospitals. PARTICIPANTS: Infection preventionists at participating hospitals. METHODS: Surveys were sent to infection preventionists from a national random sample of 881 US acute care hospitals. Questions covered use of technical interventions to prevent CLABSI (eg, alcohol-containing chlorhexidine gluconate [CHG] for skin antisepsis, use of coated catheters), socio-adaptive interventions (eg, feedback of CLABSI rates, use of appropriateness criteria), and leadership support for CLABSI prevention. RESULTS: Survey response rate was 47% (415/881). Technical interventions such as maximal sterile barriers (99%) or CHG-impregnated dressings (92%) were highly prevalent, but routine use of CHG bathing was less common (68% indicated regular use in intensive care unit [ICU] vs 18% in non-ICU settings). Although 97% of respondents indicated use of systems to monitor CLABSI, feedback to providers on CLABSI events was reported by 89%. Only 53% of respondents indicated regular use of tools to determine appropriateness of central venous catheters (CVC). Three-quarters of respondents indicated their hospital assessed CVC necessity daily, but only 23% reported strategies to reduce routine blood cultures. CLABSI prevention was extremely important to hospital leadership at 82% of responding hospitals. CONCLUSIONS: Most US hospitals continue to use evidence-based methods to prevent CLABSI as recommended by leading organizations. Opportunities to focus on socio-adaptive interventions such as feedback of infection rates, use of appropriateness criteria for CVC placement, and improving the "culture of pan-culturing" remain.

5.
Article in English | MEDLINE | ID: mdl-38415096

ABSTRACT

In a national survey of lead infection preventionists in Thai hospitals, spiritual and religious importance were associated with increased odds of career satisfaction. Cultivating environments for spiritual, religious, and self-care practices within the clinical setting may help facilitate emotional well-being-and prevent burnout-among Thai healthcare workers.

6.
Disabil Rehabil ; : 1-13, 2024 Jan 24.
Article in English | MEDLINE | ID: mdl-38265039

ABSTRACT

PURPOSE: Understanding navigational barriers and facilitators has the potential to advance equitable stroke care delivery. The aim of this study was to explore, using a qualitative study, the experiences of stroke survivors and their families as they journey through the stroke care system, both before and during the COVID-19 pandemic. METHODS: In-depth semi-structured interviews were conducted with 18 stroke survivors and 12 family members during 2021 and 2022. Participants were recruited through voluntary organisations, social media, and stroke support groups. Data analysis followed a systematic process guided by the framework method with steps including familiarisation, coding, framework development, and charting and interpretation. RESULTS: The experiences of navigating stroke care were particularly challenging following discharge from hospital into the community. Barriers to stroke care continuity included insufficient appropriate services and information, unsatisfactory relationships with healthcare professionals and distressed mental health. There were particular navigational challenges for survivors with aphasia. Facilitators to effective navigation included having prior knowledge of the health system, harnessing support for care co-ordination, and being persistent. CONCLUSION: Greater support for patient navigation, and person-centred referral pathways, particularly during times of increased pressure on the system, have the potential to improve access to services and wellbeing among stroke survivors.


Interactions between practitioners and stroke survivors need to be simple, empathetic, and transparent, using communication tools when needed for older stroke survivors or those with a communication or cognitive disabilityNavigation of the care system is a significant challenge and source of emotional distress for stroke survivors and their families, likely leading to foregone care and inequity in access to services. This indicates a need for both clearer, more standard stroke care pathways that are easier to navigate, and evidence-based patient navigation support programmes.The development of navigational interventions and stroke care pathways would benefit from co-design with motivated and knowledgeable stroke survivors.Taking advantage of the wealth of lived experience, and stroke survivors' capacity and passion for advocacy, has the potential to empower the wider stroke community.

7.
Open Forum Infect Dis ; 11(1): ofad620, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38213633

ABSTRACT

In a cross-sectional survey of US acute care hospitals, antimicrobial stewardship programs were present in most Veterans Affairs and nonfederal hospitals but varied in team composition, scope, and impact. Diagnostic stewardship was common across hospitals. Veterans Affairs hospitals had increased reach in outpatient settings. Telestewardship remains an opportunity in all hospital systems.

8.
PLoS One ; 19(1): e0297072, 2024.
Article in English | MEDLINE | ID: mdl-38241235

ABSTRACT

INTRODUCTION: Increasing numbers of people are living with stroke, due to population ageing and improved survival, leading to a need for evidence to inform future policy decision-making. This study aimed to engage with stakeholders in Ireland to identify priorities for stroke services development. METHODS: A sequential mixed methods design was used. Phase 1 (qualitative) was exploratory, involving initial priority gathering via an online qualitative survey and interviews, with stroke survivors, family/main carers, and professionals working in stroke care. Framework analysis was used to generate a long-list of improvements to stroke services. Phase 2 involved a quantitative survey, where stakeholders selected five priority improvements from the long-list. Results were discussed in a stakeholder meeting. RESULTS: In-depth interviews were completed with 18 survivors, 13 carers and 8 professionals, while 80 professionals took part in a qualitative survey (phase 1). Priority areas of care were identified and a long-list of 45 priority improvements was generated. In phase 2, 34 survivors, 19 family carers and 42 professionals completed a survey. The highest priority improvements (selected by >20% of respondents) were access to specialist neuro-rehabilitation, ongoing support for life after stroke, recruitment/retention of specialist staff, improved information and support for health system navigation, and access to specialist acute care. Stroke survivors/carers prioritised exploring ways to improve access for strokes with atypical presentation, while professionals prioritised specialist inpatient rehabilitation and early supported discharge. Neither group prioritised stroke prevention. Based on discussions in the stakeholder meeting (n = 12), it was decided that support for mental health should also be included as a priority. DISCUSSION: The development of stroke services benefits from exploring the priorities of those receiving and delivering stroke care. Findings emphasise the need for equitable access to high quality adequately-staffed services, particularly post-discharge, that are easy to navigate, with good communication, and effective information provision.


Subject(s)
Stroke Rehabilitation , Stroke , Humans , Caregivers/psychology , Ireland , Aftercare , Qualitative Research , Patient Discharge , Stroke/therapy , Stroke/psychology , Survivors/psychology
9.
Am J Infect Control ; 52(2): 191-194, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37295675

ABSTRACT

BACKGROUND: Antimicrobial stewardship in Thailand has made major progress backed by a national strategic plan. The current study aimed to assess the antimicrobial stewardship program (ASP) composition, reach, and breadth, as well as urine culture stewardship in Thai hospitals. METHODS: We sent an electronic survey to 100 Thai hospitals between February 1, 2021 and August 31, 2021. This hospital sample represented 20 hospitals in each of Thailand's 5 geographical regions. RESULTS: The response rate was 100%. A total of 86 of 100 hospitals had an ASP. These were often multi-disciplinary in nature, with half including infectious disease-trained physicians and pharmacists, infection preventionists, and nursing staff. Urine culture stewardship protocols existed in 51% of hospitals. CONCLUSIONS: The national strategic plan in Thailand has allowed the country to stand up robust ASPs. Further research should examine the effectiveness of such programs and ways to expand them into other medical settings, like nursing homes, urgent care, and outpatient while continuing to grow telehealth and urine culture stewardship.


Subject(s)
Anti-Infective Agents , Antimicrobial Stewardship , Humans , Thailand , Antimicrobial Stewardship/methods , Hospitals , Surveys and Questionnaires , Anti-Bacterial Agents/therapeutic use
10.
Infect Control Hosp Epidemiol ; 45(3): 310-315, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37702064

ABSTRACT

OBJECTIVE: To explore infection preventionists' perceptions of hospital leadership support for infection prevention and control programs during the coronavirus disease 2019 (COVID-19) pandemic and relationships with individual perceptions of burnout, psychological safety, and safety climate. DESIGN: Cross-sectional survey, administered April through December 2021. SETTING: Random sample of non-federal acute-care hospitals in the United States. PARTICIPANTS: Lead infection preventionists. RESULTS: We received responses from 415 of 881 infection preventionists, representing a response rate of 47%. Among respondents, 64% reported very good to excellent hospital leadership support for their infection prevention and control program. However, 49% reported feeling burned out from their work. Also, ∼30% responded positively for all 7 psychological safety questions and were deemed to have "high psychological safety," and 76% responded positively to the 2 safety climate questions and were deemed to have a "high safety climate." Our results indicate an association between strong hospital leadership support and lower burnout (IRR, 0.61; 95% CI, 0.50-0.74), higher perceptions of psychological safety (IRR, 3.20; 95% CI, 2.00-5.10), and a corresponding 1.2 increase in safety climate on an ascending Likert scale from 1 to 10 (ß, 1.21; 95% CI, 0.93-1.49). CONCLUSIONS: Our national survey provides evidence that hospital leadership support may have helped infection preventionists avoid burnout and increase perceptions of psychological safety and safety climate during the COVID-19 pandemic. These findings aid in identifying factors that promote the well-being of infection preventionists and enhance the quality and safety of patient care.


Subject(s)
Burnout, Professional , COVID-19 , Humans , United States/epidemiology , COVID-19/prevention & control , Leadership , Pandemics/prevention & control , Organizational Culture , Cross-Sectional Studies , Psychological Safety , Burnout, Professional/epidemiology , Burnout, Professional/prevention & control , Burnout, Professional/psychology , Hospitals , Surveys and Questionnaires
11.
Am J Infect Control ; 52(4): 495-497, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37944756

ABSTRACT

Our national cross-sectional survey of United States hospitals found greater implementation of contact precautions for multidrug-resistant organisms and a higher percentage reporting the use of supplemental no-touch disinfection devices among Veterans Affairs (VA) versus non-VA hospitals. Nationally coordinated infection prevention initiatives within the VA could account for these practice differences.


Subject(s)
Communicable Diseases , Veterans , Humans , United States , Cross-Sectional Studies , Infection Control/methods , Hospitals , United States Department of Veterans Affairs , Hospitals, Veterans
12.
Am J Infect Control ; 52(6): 726-730, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38122935

ABSTRACT

BACKGROUND: The degree to which religiosity, spirituality, and self-care practices can improve well-being among infection preventionists is not well understood. METHODS: We surveyed infection preventionists from a random sample of United States hospitals in 2021. Multivariable logistic regression models were used to examine the associations between measures of spirituality, religiosity, and self-care and well-being. RESULTS: Our response rate was 47% (415/881). A total of 49% of respondents reported burnout, 17% reported increased feelings of uncaring, and 69% would choose to become an infection preventionist again. Most respondents found importance in spiritual well-being (88%), religious beliefs (82%), and self-care practices (87%). Spiritual well-being was associated with increased odds of choosing to become an infection preventionist again (odds ratio = 2.32, 95% confidence interval = 1.19-4.53, P = .01). DISCUSSION: Our national survey provides evidence that spiritual importance is associated with career satisfaction among infection preventionists. Our findings contribute to a general body of evidence suggesting spiritual importance may translate to higher flourishing and well-being via serving a higher purpose. CONCLUSIONS: Promoting spiritual well-being may positively influence career satisfaction and overall well-being among infection preventionists.


Subject(s)
Self Care , Spirituality , Humans , United States , Male , Female , Surveys and Questionnaires , Self Care/psychology , Adult , Middle Aged , Infection Control Practitioners/psychology , Infection Control/methods
13.
Vaccine ; 41 Suppl 2: S53-S75, 2023 11 03.
Article in English | MEDLINE | ID: mdl-37806805

ABSTRACT

Cytomegalovirus (CMV) is the most common infectious cause of congenital malformation and a leading cause of developmental disabilities such as sensorineural hearing loss (SNHL), motor and cognitive deficits. The significant disease burden from congenital CMV infection (cCMV) led the US National Institute of Medicine to rank CMV vaccine development as the highest priority. An average of 6.7/1000 live births are affected by cCMV, but the prevalence varies across and within countries. In contrast to other congenital infections such as rubella and toxoplasmosis, the prevalence of cCMV increases with CMV seroprevalence rates in the population. The true global burden of cCMV disease is likely underestimated because most infected infants (85-90 %) have asymptomatic infection and are not identified. However, about 7-11 % of those with asymptomatic infection will develop SNHL throughout early childhood. Although no licensed CMV vaccine exists, several candidate vaccines are in development, including one currently in phase 3 trials. Licensure of one or more vaccine candidates is feasible within the next five years. Various models of CMV vaccine strategies employing different target populations have shown to provide substantial benefit in reducing cCMV. Although CMV can cause end-organ disease with significant morbidity and mortality in immunocompromised individuals, the focus of this vaccine value profile (VVP) is on preventing or reducing the cCMV disease burden. This CMV VVP provides a high-level, comprehensive assessment of the currently available data to inform the potential public health, economic, and societal value of CMV vaccines. The CMV VVP was developed by a working group of subject matter experts from academia, public health groups, policy organizations, and non-profit organizations. All contributors have extensive expertise on various elements of the CMV VVP and have described the state of knowledge and identified the current gaps. The VVP was developed using only existing and publicly available information.


Subject(s)
Cytomegalovirus Infections , Cytomegalovirus Vaccines , Hearing Loss, Sensorineural , Infant , Humans , Child, Preschool , Cytomegalovirus , Asymptomatic Infections , Seroepidemiologic Studies , Cytomegalovirus Infections/epidemiology , Cytomegalovirus Infections/prevention & control , Hearing Loss, Sensorineural/congenital , Hearing Loss, Sensorineural/epidemiology
14.
J Patient Saf ; 19(7): 447-452, 2023 10 01.
Article in English | MEDLINE | ID: mdl-37729642

ABSTRACT

OBJECTIVES: Hospitalized patients are at risk for diagnostic errors. Hospitalists caring for these patients are often multitasking when overseeing patient care. We aimed to measure hospitalist workload and understand its influences on diagnostic performance in a real-world clinical setting. METHODS: We conducted a single-center, prospective, pilot observational study of hospitalists admitting new patients to the hospital. Hospitalists completed an abridged Mindful Attention Awareness Tool and a survey about diagnostic confidence at shift completion. Data on differential diagnoses and resource utilization (e.g., laboratory, imaging tests ordered, and consultations) were collected from the medical record. The number of admissions and paging volume per shift were used as separate proxies for shift busyness. Data were analyzed using linear mixed effects models (continuous outcomes) or mixed effects logistic regression (dichotomous outcomes). RESULTS: Of the 53 hospitalists approached, 47 (89%) agreed to participate; complete data were available for 37 unique hospitalists who admitted 160 unique patients. Increases in admissions (odds ratio, 1.99; 95% confidence interval [CI], 1.04 to 3.82; P = 0.04) and pages (odds ratio, 1.11; 95% CI, 1.02 to 1.21; P = 0.01) were associated with increased odds of hospitalists finding it "difficult to focus on what is happening in the present." Increased pages was associated with a decrease in the number of listed differential diagnoses (coefficient, -0.02; 95% CI, -0.04 to -0.003; P = 0.02). CONCLUSIONS: Evaluation of hospitalist busyness and its associations with factors that may influence diagnosis in a real-world environment was feasible and demonstrated important implications on physician focus and differential diagnosis.


Subject(s)
Hospitalists , Humans , Pilot Projects , Prospective Studies , Hospitalization , Diagnostic Errors
15.
Infect Control Hosp Epidemiol ; 44(12): 1913-1919, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37259703

ABSTRACT

OBJECTIVE: The ways that device-associated infection prevention practices changed during the coronavirus disease 2019 (COVID-19) pandemic remain unknown. We collected data mid-pandemic to assess the use of several infection prevention practices and for comparison with historical data. DESIGN: Repeated cross-sectional survey. SETTING: US acute-care hospitals. PARTICIPANTS: Infection preventionists. METHODS: We surveyed infection preventionists from a national random sample of 881 US acute-care hospitals in 2021 to estimate the current use of practices to prevent catheter-associated urinary tract infection (CAUTI), central line-associated bloodstream infection (CLABSI), and ventilator-associated events (VAE). We compared the 2021 results with those from surveys occurring every 4 years since 2005. RESULTS: The 2021 survey response rate was 47%; previous survey response rates ranged from 59% to 72%. Regular use of most practices to prevent CLABSI (chlorhexidine gluconate for site antisepsis, 99.0%, and maximum sterile barrier precautions, 98.7%) and VAE (semirecumbent positioning, 93.4%, and sedation vacation, 85.8%) continued to increase or plateaued in 2021. Conversely, use of several CAUTI prevention practices (portable bladder ultrasound scanner, 65.6%; catheter reminders or nurse-initiated discontinuation, 66.3%; and intermittent catheterization, 37.3%) was lower in 2021, with a significant decrease for some practices compared to 2017 (P ≤ .02 for all comparisons). In 2021, 42.1% of hospitals reported regular use of the newer external urinary collection devices for women. CONCLUSIONS: Although regular use of CLABSI and VAE preventive practices continued to increase (or plateaued), use of several CAUTI preventive practices decreased during the COVID-19 pandemic. Structural issues relating to care during the pandemic may have contributed to a decrease in device-associated infection prevention practices.


Subject(s)
COVID-19 , Catheter-Related Infections , Cross Infection , Pneumonia, Ventilator-Associated , Urinary Tract Infections , United States/epidemiology , Humans , Female , Cross Infection/epidemiology , Cross Infection/prevention & control , Infection Control/methods , Catheter-Related Infections/epidemiology , Catheter-Related Infections/prevention & control , Pandemics/prevention & control , Cross-Sectional Studies , Health Care Surveys , COVID-19/epidemiology , COVID-19/prevention & control , Hospitals , Urinary Tract Infections/epidemiology , Urinary Tract Infections/prevention & control , Pneumonia, Ventilator-Associated/epidemiology
16.
Teach Learn Nurs ; 18(3): e89-e93, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37360267

ABSTRACT

With the urgent need to increase the number of diverse nurses in the healthcare system, it is more necessary than ever to explore and discuss solutions that help students succeed in the extremely stressful nursing school environment. COVID-19 has exacerbated stress for nursing students nationwide. Additionally, high ACE scores and living on the US-Mexico border put certain students in "triple-jeopardy" for failing. Trauma-informed pedagogy mitigates this danger by creating a secure and productive learning environment.

17.
18.
J Pediatric Infect Dis Soc ; 12(4): 230-233, 2023 Apr 28.
Article in English | MEDLINE | ID: mdl-36879401

ABSTRACT

Viral load in infant saliva and urine was assessed to predict sensorineural hearing loss (SNHL) in children with congenital cytomegalovirus infection. Viral load was higher in symptomatic infants. Viral load in asymptomatic children with and without SNHL did not differ. Congenital cytomegalovirus infection viral load in urine and saliva does not predict hearing loss.


Subject(s)
Cytomegalovirus Infections , Hearing Loss, Sensorineural , Infant , Humans , Child , Saliva , Cytomegalovirus , Viral Load
19.
Nurse Educ Today ; 124: 105776, 2023 May.
Article in English | MEDLINE | ID: mdl-36893614

ABSTRACT

Changes in the educational landscape and evolving parameters from academic accreditation partners require an evaluation of current pedagogical practices in graduate nursing education. Online educational platforms have grown in popularity, with 71 % of post-baccalaureate students reporting one or more online courses (NCES, 2022). Preparing nurses at the graduate level, proficient, and work-ready at an advanced level is a goal for graduate education. Accomplishing this goal requires increased faculty and student engagement levels in the online environment. In April 2021, the American Association of Colleges of Nursing (AACN) approved new nursing education standards requiring nursing schools to adopt a competency-based framework. The requirements are the same for online and face-to-face course designs. Therefore, intentionally designed online courses with activities and assignments that meet the criteria for competency-based outcome criteria must be developed. Passive learning activities, including exams, reading assignments, formal/information papers, and even discussion boards, will require adjustments to meet the requirements of a competency-based outcome framework.


Subject(s)
Education, Distance , Education, Nursing, Graduate , Students, Nursing , Humans , Motivation , Students , Learning
20.
mBio ; 14(1): e0354522, 2023 02 28.
Article in English | MEDLINE | ID: mdl-36728431

ABSTRACT

There is a limited understanding of host defense mechanisms targeting intracellular pathogens that proliferate in a lysosome. Coxiella burnetii is a model bacterial pathogen capable of replicating in the hydrolytic and acidic environment of the lysosome. It has been shown that gamma interferon (IFNγ)-stimulated host cells restrict C. burnetii replication by a mechanism that involves host IDO1 depletion of tryptophan. Host cells deficient in IDO1 activity, however, retain the ability to restrict C. burnetii replication when stimulated with IFNγ, which suggests additional mechanisms of host defense. This study identified syntaxin 11 (STX11) as a host protein that contributes to IFNγ-mediated suppression of C. burnetii replication. STX11 is a SNARE protein; SNARE proteins are proteins that mediate fusion of host vesicles with specific subcellular organelles. Depletion of STX11 using either small interfering RNA (siRNA)- or CRISPR-based approaches enhanced C. burnetii replication intracellularly. Stable expression of STX11 reduced C. burnetii replication in epithelial cells and macrophages, which indicates that this STX11-dependent cell-autonomous response is operational in multiple cell types and can function independently of other IFNγ-induced factors. Fluorescently tagged STX11 localized to the Coxiella-containing vacuole (CCV), and STX11 restriction was found to involve an interaction with STX8. Thus, STX11 regulates a vesicle fusion pathway that limits replication of this intracellular pathogen in a lysosome-derived organelle. IMPORTANCE Cell intrinsic defense mechanisms are used by eukaryotic cells to restrict the replication and dissemination of pathogens. This study identified a human protein called syntaxin 11 (STX11) as a host restriction factor that inhibits the intracellular replication of Coxiella burnetii. Syntaxins regulate the delivery of cargo inside vesicles by promoting specific membrane fusion events between donor and acceptor vesicles. Data presented here demonstrate that STX11 regulates an immunological defense pathway that controls replication of pathogens in lysosome-derived organelles, which provides new insight into the function of this SNARE protein.


Subject(s)
Coxiella burnetii , Q Fever , Humans , Host-Pathogen Interactions/physiology , Interferon-gamma/metabolism , Interferons/metabolism , Q Fever/metabolism , Qa-SNARE Proteins/genetics , Qa-SNARE Proteins/metabolism , RNA, Small Interfering/metabolism , Vacuoles/metabolism
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