A Data-Driven Framework for Identifying Intensive Care Unit Admissions Colonized With Multidrug-Resistant Organisms.

Background: The rising prevalence of multi-drug resistant organisms (MDROs), such as Methicillin-resistant Staphylococcus aureus (MRSA), Vancomycin-resistant Enterococci (VRE), and Carbapenem-resistant Enterobacteriaceae (CRE), is an increasing concern in healthcare settings. Materials and Methods: Leveraging data from electronic healthcare records and a unique MDRO universal screening program, we developed a data-driven modeling framework to predict MRSA, VRE, and CRE colonization upon intensive care unit (ICU) admission, and identified the associated socio-demographic and clinical factors using logistic regression (LR), random forest (RF), and XGBoost algorithms. We performed threshold optimization for converting predicted probabilities into binary predictions and identified the cut-off maximizing the sum of sensitivity and specificity. Results: Four thousand six hundred seventy ICU admissions (3,958 patients) were examined. MDRO colonization rate was 17.59% (13.03% VRE, 1.45% CRE, and 7.47% MRSA). Our study achieved the following sensitivity and specificity values with the best performing models, respectively: 80% and 66% for VRE with LR, 73% and 77% for CRE with XGBoost, 76% and 59% for MRSA with RF, and 82% and 83% for MDRO (i.e., VRE or CRE or MRSA) with RF. Further, we identified several predictors of MDRO colonization, including long-term care facility stay, current diagnosis of skin/subcutaneous tissue or infectious/parasitic disease, and recent isolation precaution procedures before ICU admission. Conclusion: Our data-driven modeling framework can be used as a clinical decision support tool for timely predictions, characterization and identification of high-risk patients, and selective and timely use of infection control measures in ICUs.

Assessment of Local Health Worker Attitudes toward International Medical Volunteers in Low- and Middle-income Countries: A Global Survey.

BACKGROUND: International Medical Volunteers (IMVs) positively and negatively impact host countries, and the goals of their trips may not always align with the interests of the hosts in Low- and Middle-Income Countries (LMICs). We sought to better understand local physicians' interest of hosting IMVs and what type of support they desired. METHODS: This study was a convenience sample survey-based needs assessment. The surveys were distributed to local physicians by 28 professional society groups in LMICs. FINDINGS: A total of 102 physicians from 51 countries completed the survey. Despite 61.8% participants having no experience with IMVs, 75% were interested in hosting them. Host physicians most desired clinical education (39%), research collaboration (18%), and Systems Development (11%). The most requested specialties were obstetrics and gynecology (25%) and emergency medicine (11%). Respondents considered public hospitals (62%) to be the most helpful clinical setting in which IMVs could work, and 3 months (47%) as the ideal length of stay.Respondents expressed interest in advertising the specific needs of the host country to potential IMVs (80%). Qualitative analyses suggested hosts wanted more training opportunities, inclusion of all stakeholders, culturally competent volunteers, and aid focused on subspecialty education, health policy, public health, and research. CONCLUSION: Hosts desire more bidirectional clinical education and research capacity building than just direct clinical care. Importantly, cultural competence is key to a successful host partnership, potentially improved through IMV preparation. Finally, respondents want IMVs to ensure that they stay within their scope of practice and training.

Critical care capacity in Haiti: A nationwide cross-sectional survey.

OBJECTIVE: Critical illness affects health systems globally, but low- and middle-income countries (LMICs) bear a disproportionate burden. Due to a paucity of data, the capacity to care for critically ill patients in LMICs is largely unknown. Haiti has the lowest health indices in the Western Hemisphere. In this study, we report results of the first known nationwide survey of critical care capacity in Haiti. DESIGN: Nationwide, cross-sectional survey of Haitian hospitals in 2017-2018. SETTING: Haiti. SUBJECTS: All Haitian health facilities with at least six hospital beds. INTERVENTIONS: Electronic- and paper-based survey. RESULTS: Of 51 health facilities identified, 39 (76.5%) from all ten Haitian administrative departments completed the survey, reporting 124 reported ICU beds nationally. Of facilities without an ICU, 20 (83.3%) care for critically ill patients in the emergency department. There is capacity to ventilate 62 patients nationally within ICUs and six patients outside of the ICU. One-third of facilities with ICUs report formal critical care training for their physicians. Only five facilities met criteria for a Level 1 ICU as defined by the World Federation of Societies of Intensive and Critical Care Medicine. Self-identified barriers to providing more effective critical care services include lack of physical space for critically ill patients, lack of equipment, and few formally trained physicians and nurses. CONCLUSIONS: Despite a high demand for critical care services in Haiti, current capacity remains insufficient to meet need. A significant amount of critical care in Haiti is provided outside of the ICU, highlighting the important overlap between emergency and critical care medicine in LMICs. Many ICUs in Haiti lack basic components for critical care delivery. Streamlining critical care services through protocol development, education, and training may improve important clinical outcomes.

The Impact of Reducing Antibiotics on the Transmission of Multidrug-Resistant Organisms.

OBJECTIVE Antibiotic resistance is a major threat to public health. Resistance is largely driven by antibiotic usage, which in many cases is unnecessary and can be improved. The impact of decreasing overall antibiotic usage on resistance is unknown and difficult to assess using standard study designs. The objective of this study was to explore the potential impact of reducing antibiotic usage on the transmission of multidrug-resistant organisms (MDROs). DESIGN We used agent-based modeling to simulate interactions between patients and healthcare workers (HCWs) using model inputs informed by the literature. We modeled the effect of antibiotic usage as (1) a microbiome effect, for which antibiotic usage decreases competing bacteria and increases the MDRO transmission probability between patients and HCWs and (2) a mutation effect that designates a proportion of patients who receive antibiotics to subsequently develop a MDRO via genetic mutation. SETTING Intensive care unit INTERVENTIONS Absolute reduction in overall antibiotic usage by experimental values of 10% and 25% RESULTS Reducing antibiotic usage absolutely by 10% (from 75% to 65%) and 25% (from 75% to 50%) reduced acquisition rates of high-prevalence MDROs by 11.2% (P<.001) and 28.3% (P<.001), respectively. We observed similar effect sizes for low-prevalence MDROs. CONCLUSIONS In a critical care setting, where up to 50% of antibiotic courses may be inappropriate, even a moderate reduction in antibiotic usage can reduce MDRO transmission. Infect Control Hosp Epidemiol 2017;38:663-669.

Research Methods in Healthcare Epidemiology and Antimicrobial Stewardship-Mathematical Modeling.

Mathematical modeling is a valuable methodology used to study healthcare epidemiology and antimicrobial stewardship, particularly when more traditional study approaches are infeasible, unethical, costly, or time consuming. We focus on 2 of the most common types of mathematical modeling, namely compartmental modeling and agent-based modeling, which provide important advantages-such as shorter developmental timelines and opportunities for extensive experimentation-over observational and experimental approaches. We summarize these advantages and disadvantages via specific examples and highlight recent advances in the methodology. A checklist is provided to serve as a guideline in the development of mathematical models in healthcare epidemiology and antimicrobial stewardship. Infect Control Hosp Epidemiol 2016;1-7.

Preventing the transmission of multidrug-resistant organisms: modeling the relative importance of hand hygiene and environmental cleaning interventions.

OBJECTIVE: Hand hygiene and environmental cleaning are essential infection prevention strategies, but the relative impact of each is unknown. This information is important in assessing resource allocation. METHODS: We developed an agent-based model of patient-to-patient transmission-via the hands of transiently colonized healthcare workers and incompletely terminally cleaned rooms-in a 20-patient intensive care unit. Nurses and physicians were modeled and had distinct hand hygiene compliance levels on entry and exit to patient rooms. We simulated the transmission of Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant enterococci for 1 year using data from the literature and observed data to inform model input parameters. RESULTS: We simulated 175 parameter-based scenarios and compared the effects of hand hygiene and environmental cleaning on rates of multidrug-resistant organism acquisition. For all organisms, increases in hand hygiene compliance outperformed equal increases in thoroughness of terminal cleaning. From baseline, a 2∶1 improvement in terminal cleaning compared with hand hygiene was required to match an equal reduction in acquisition rates (eg, a 20% improvement in terminal cleaning was required to match the reduction in acquisition due to a 10% improvement in hand hygiene compliance). CONCLUSIONS: Hand hygiene should remain a priority for infection control programs, but environmental cleaning can have significant benefit for hospitals or individual hospital units that have either high hand hygiene compliance levels or low terminal cleaning thoroughness.

Contribution of interfacility patient movement to overall methicillin-resistant Staphylococcus aureus prevalence levels.

OBJECTIVES: The effect of patient movement between hospitals and long-term care facilities (LTCFs) on methicillin-resistant Staphylococcus aureus (MRSA) prevalence levels is unknown. We investigated these effects to identify scenarios that may lead to increased prevalence in either facility type. METHODS: We used a hybrid simulation model to simulate MRSA transmission among hospitals and LTCFs. Transmission within each facility was determined by mathematical model equations. The model predicted the long-term prevalence of each facility and was used to assess the effects of facility size, patient turnover, and decolonization. RESULTS: Analyses of various healthcare networks suggest that the effect of patients moving from a LTCF to a hospital is negligible unless the patients are consistently admitted to the same unit. In such cases, MRSA prevalence can increase significantly regardless of the endemic level. Hospitals can cause sustained increases in prevalence when transferring patients to LTCFs, where the population size is smaller and patient turnover is less frequent. For 1 particular scenario, the steady-state prevalence of a LTCF increased from 6.9% to 9.4% to 13.8% when the transmission rate of the hospital increased from a low to a high transmission rate. CONCLUSIONS: These results suggest that the relative facility size and the patient discharge rate are 2 key factors that can lead to sustained increases in MRSA prevalence. Consequently, small facilities or those with low turnover rates are especially susceptible to sustaining increased prevalence levels, and they become more so when receiving patients from larger, high-prevalence facilities. Decolonization is an infection-control strategy that can mitigate these effects.

Resistin-like molecule beta (RELMbeta/FIZZ2) is highly expressed in the ileum of SAMP1/YitFc mice and is associated with initiation of ileitis.

SAMP1/Fc mice develop spontaneous ileitis that shares many features with human Crohn's disease. One of the earliest features of ileitis in SAMP1/Fc mice is an increase in the number of ileal goblet and intermediate cells. Resistin-like molecule beta (RELMbeta) is a goblet cell-specific, cysteine-rich peptide previously shown to function as part of the innate immune response. In this study, we examined the role of expression of RELMbeta in the initiation of ileal inflammation in SAMP1/Fc mice. RELMbeta was highly induced in the ilea of SAMP1/Fc mice beginning at age 5 wk, coincident with the histological appearance of inflammation. RELMbeta was found in ileal goblet cells and some intermediate and Paneth cells. Surprisingly, RELMbeta mRNA levels were significantly increased in the ilea of 80% of germ-free SAMP1/Fc mice examined compared with specific pathogen-free AKR control mice of similar age. Ileitis was observed in germfree SAMP1/Fc mice, although it was attenuated relative to specific pathogen-free SAMP1/Fc mice. These data suggest that neither the early induction of RELMbeta expression nor ileal inflammation requires the presence of viable intestinal flora. Neither was the induction of RELMbeta dependent on the major Th1 or Th2 cytokines. However, RELMbeta stimulated naive bone marrow-derived macrophages to secrete significant amounts of TNF-alpha, IL-6, and RANTES. Our data suggest that RELMbeta is involved in the initiation of ileitis in SAMP1/Fc mice and may act through the induction of proinflammatory cytokines from resident immune cells within the mucosa.

Absence of bacterially induced RELMbeta reduces injury in the dextran sodium sulfate model of colitis.

Although inflammatory bowel disease (IBD) is the result of a dysregulated immune response to commensal gut bacteria in genetically predisposed individuals, the mechanism(s) by which bacteria lead to the development of IBD are unknown. Interestingly, deletion of intestinal goblet cells protects against intestinal injury, suggesting that this epithelial cell lineage may produce molecules that exacerbate IBD. We previously reported that resistin-like molecule beta (RELMbeta; also known as FIZZ2) is an intestinal goblet cell-specific protein that is induced upon bacterial colonization whereupon it is expressed in the ileum and colon, regions of the gut most often involved in IBD. Herein, we show that disruption of this gene reduces the severity of colitis in the dextran sodium sulfate (DSS) model of murine colonic injury. Although RELMbeta does not alter colonic epithelial proliferation or barrier function, we show that recombinant protein activates macrophages to produce TNF-alpha both in vitro and in vivo. RELMbeta expression is also strongly induced in the terminal ileum of the SAMP1/Fc model of IBD. These results suggest a model whereby the loss of epithelial barrier function by DSS results in the activation of the innate mucosal response by RELMbeta located in the lumen, supporting the hypothesis that this protein is a link among goblet cells, commensal bacteria, and the pathogenesis of IBD.

Ethanol inhibits benzo[a]pyrene-DNA adduct removal and increases 8-oxo-deoxyguanosine formation in human mammary epithelial cells.

The effect of ethanol and acetaldehyde treatment on the removal of benzo[a]pyrene diol-epoxide (BPDE)-DNA adducts in the immortalized, human mammary epithelial cell line MCF-10F was examined. Treatment of cells with 15 mM and 25 mM ethanol resulted in significantly more BPDE-DNA adducts/unit DNA remaining at multiple time points, compared to controls. The half-life of BPDE-DNA adducts in cells exposed to both 15 and 25 mM ethanol were 11.9 and 12.3 h, respectively, compared to a half-life of 9.8 h for the control cells. In contrast, for cells exposed to acetaldehyde at doses of 2.5 and 5.0 microM no significant trend in BPDE-DNA adduct persistence occurred, compared to controls. The inhibition of adduct removal for cells treated with ethanol was not associated with any changes in cell viability due to ethanol exposure. However, BP-treated cells exposed to 25 mM ethanol exhibited a significant 2-fold increase in 8-oxo-deoxyguanosine (8-oxo-deG) adducts compared to BP-treated cells alone. No significant increase in 8-oxo-deG was observed for cells treated with BP and exposed to 5.0 microM acetaldehyde. Thus, ethanol exposure of human mammary epithelial cells is associated with a decreased capacity to remove BPDE-DNA adducts. This inhibitory effect of ethanol on adduct removal in part may be related to ethanol-associated oxidative stress.