Digital Commons Network^™

Deficiency In Galectin-3, -8, And -9 Impairs Immunity To Chronic Mycobacterium Tuberculosis Infection But Not Acute Infection With Multiple Intracellular Pathogens, Huntly M. Morrison, Wandy L. Beatty, Et Al.

2020-Current year OA Pubs

Macrophages employ an array of pattern recognition receptors to detect and eliminate intracellular pathogens that access the cytosol. The cytosolic carbohydrate sensors Galectin-3, -8, and -9 (Gal-3, Gal-8, and Gal-9) recognize damaged pathogen-containing phagosomes, and Gal-3 and Gal-8 are reported to restrict bacterial growth via autophagy in cultured cells. However, the contribution of these galectins to host resistance during bacterial infection in vivo remains unclear. We found that Gal-9 binds directly to Mycobacterium tuberculosis (Mtb) and Salmonella enterica serovar Typhimurium (Stm) and localizes to Mtb in macrophages. To determine the combined contribution of membrane damage-sensing galectins to immunity, we generated …

Interleukin-18 Signaling Promotes Activation Of Hepatic Stellate Cells In Mouse Liver Fibrosis, Jana Knorr, Joel D. Schilling, Et Al.

2020-Current year OA Pubs

BACKGROUND AND AIMS: Nucleotide-binding oligomerization domain-like receptor-family pyrin domain-containing 3 (NLRP3) inflammasome activation has been shown to result in liver fibrosis. Mechanisms and downstream signaling remain incompletely understood. Here, we studied the role of IL-18 in hepatic stellate cells (HSCs), and its impact on liver fibrosis.

APPROACH AND RESULTS: We observed significantly increased serum levels of IL-18 (128.4 pg/ml vs. 74.9 pg/ml) and IL-18 binding protein (BP; 46.50 ng/ml vs. 15.35 ng/ml) in patients with liver cirrhosis compared with healthy controls. Single cell RNA sequencing data showed that an immunoregulatory subset of murine HSCs highly expresses Il18 and Il18r1 . …

Autophagy Prevents Early Proinflammatory Responses And Neutrophil Recruitment During Mycobacterium Tuberculosis Infection Without Affecting Pathogen Burden In Macrophages, Rachel L. Kinsella, Jacqueline M. Kimmey, Asya Smirnov, Reilly Woodson, Margaret R. Gaggioli, Sthefany M. Chavez, Darren Kreamalmeyer, Christina L. Stallings

2020-Current year OA Pubs

The immune response to Mycobacterium tuberculosis infection determines tuberculosis disease outcomes, yet we have an incomplete understanding of what immune factors contribute to a protective immune response. Neutrophilic inflammation has been associated with poor disease prognosis in humans and in animal models during M. tuberculosis infection and, therefore, must be tightly regulated. ATG5 is an essential autophagy protein that is required in innate immune cells to control neutrophil-dominated inflammation and promote survival during M. tuberculosis infection; however, the mechanistic basis for how ATG5 regulates neutrophil recruitment is unknown. To interrogate what innate immune cells require ATG5 to control neutrophil recruitment …

Participant- And Disease-Related Factors As Independent Predictors Of Treatment Outcomes In The Restore-Imi 2 Clinical Trial: A Multivariable Regression Analysis, Ignacio Martin-Loeches, Andrew F Shorr, Marin H Kollef, Jiejun Du, Maria C Losada, Amanda Paschke, C Andrew Deryke, Michael Wong, Erin H Jensen, Luke F Chen

2020-Current year OA Pubs

BACKGROUND: In the RESTORE-IMI 2 trial, imipenem/cilastatin/relebactam (IMI/REL) was noninferior to piperacillin/tazobactam in treating hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia. This post hoc analysis was conducted to determine independent predictors of efficacy outcomes in the RESTORE-IMI 2 trial, to assist in treatment decision making.

METHODS: A stepwise multivariable regression analysis was conducted to identify variables that were independently associated with day 28 all-cause mortality (ACM), favorable clinical response at early follow-up (EFU), and favorable microbiologic response at end of treatment (EOT). The analysis accounted for the number of baseline infecting pathogens and in vitro susceptibility to randomized treatment.

RESULTS: Vasopressor use, …

Acinetobacter Baumannii Atcc 17978 Encodes A Microcin System With Antimicrobial Properties For Contact-Independent Competition, Fabiana Bisaro, Howard A Shuman, Mario F Feldman, Michael J Gebhardt, Stefan Pukatzki

2020-Current year OA Pubs

No abstract provided.

Healthcare Provider Perspectives On Hiv Cure Research In Ghana, Helena Lamptey, Benjamin Newcomb, Evelyn Y Bonney, James O Aboagye, Peter Puplampu, Vincent J Ganu, Gloria Ansa, Joseph Oliver-Commey, George B Kyei

2020-Current year OA Pubs

INTRODUCTION: Antiretroviral therapy (ART) has reduced mortality and improved life expectancy among HIV patients but does not provide a cure. Patients must remain on lifelong medications and deal with drug resistance and side effects. This underscores the need for HIV cure research. However, participation in HIV cure research has risks without guaranteed benefits. We determined what HIV healthcare providers know about HIV cure research trials, the risks involved, and what kind of cure interventions they are likely to recommend for their patients.

METHODS: We conducted in-depth qualitative interviews with 39 HIV care providers consisting of 12 physicians, 8 counsellors, 14 …

Peptide-Based Nanoparticles For Systemic Extrahepatic Delivery Of Therapeutic Nucleotides, Samuel A Wickline, Kirk K Hou, Hua Pan

2020-Current year OA Pubs

Peptide-based nanoparticles (PBN) for nucleotide complexation and targeting of extrahepatic diseases are gaining recognition as potent pharmaceutical vehicles for fine-tuned control of protein production (up- and/or down-regulation) and for gene delivery. Herein, we review the principles and mechanisms underpinning self-assembled formation of PBN, cellular uptake, endosomal release, and delivery to extrahepatic disease sites after systemic administration. Selected examples of PBN that have demonstrated recent proof of concept in disease models in vivo are summarized to offer the reader a comparative view of the field and the possibilities for clinical application.

A Single-Cell Multiomic Analysis Of Kidney Organoid Differentiation, Yasuhiro Yoshimura, Yoshiharu Muto, Nicolas Ledru, Haojia Wu, Kohei Omachi, Jeffrey H Miner, Benjamin D Humphreys

2020-Current year OA Pubs

Kidney organoids differentiated from pluripotent stem cells are powerful models of kidney development and disease but are characterized by cell immaturity and off-target cell fates. Comparing the cell-specific gene regulatory landscape during organoid differentiation with human adult kidney can serve to benchmark progress in differentiation at the epigenome and transcriptome level for individual organoid cell types. Using single-cell multiome and histone modification analysis, we report more broadly open chromatin in organoid cell types compared to the human adult kidney. We infer enhancer dynamics by cis-coaccessibility analysis and validate an enhancer driving transcription of

Developing Tools For The Implementation And Evaluation Of Participatory Worker Health Promotion Interventions, Ryan J. Walsh

WUSM Theses and Dissertations – All Programs

The chronic disease burden among American workers leads to substantial expenditures on healthcare, lost productivity at work, and reduced quality of life. Workers from communities of lower socioeconomic status (SES) shoulder a disproportionate burden of chronic diseases and costs. A promising strategy for addressing this population health burden is to develop and implement participatory worker health promotion interventions in workplaces. Part of this effort to develop and implement these programs entails improving the quality of evaluation tools and approaches. Thus, we completed a series of secondary analyses of a large participatory worker health promotion program trial called Working For You. …

Diagnosis And Treatment Of Fungal Infections In Lung Transplant Recipients, Jesus E Escamilla, Spenser E January, Rodrigo Vazquez Guillamet

2020-Current year OA Pubs

Fungal infections are a significant source of morbidity in the lung transplant population via direct allograft damage and predisposing patients to the development of chronic lung allograft dysfunction. Prompt diagnosis and treatment are imperative to limit allograft damage. This review article discusses incidence, risk factors, and symptoms with a specific focus on diagnostic and treatment strategies in the lung transplant population for fungal infections caused by

Infection Of Neonatal Mice With The Murine Norovirus Strain Wu23 Is A Robust Model To Study Norovirus Pathogenesis, Amy M Peiper, Emily W Helm, Quyen Nguyen, Matthew Phillips, Caroline G Williams, Dhairya Shah, Sarah Tatum, Neha Iyer, Marco Grodzki, Laura B Eurell, Aqsa Nasir, Megan T Baldridge, Stephanie M Karst

2020-Current year OA Pubs

Noroviruses are the leading cause of severe childhood diarrhea and foodborne disease worldwide. While they are a major cause of disease in all age groups, infections in the very young can be quite severe, with annual estimates of 50,000-200,000 fatalities in children under 5 years old. In spite of the remarkable disease burden associated with norovirus infections, very little is known about the pathogenic mechanisms underlying norovirus diarrhea, principally because of the lack of tractable small animal models. The development of the murine norovirus (MNV) model nearly two decades ago has facilitated progress in understanding host-norovirus interactions and norovirus strain …

Capsular Polysaccharide Inhibits Vaccine-Induced O-Antigen Antibody Binding And Function Across Both Classical And Hypervirulent K2:O1 Strains Of Klebsiella Pneumoniae, Paeton L. Wantuch, Cory J. Knoot, Lloyd S. Robinson, Evgeny Vinogradov, Nichollas E. Scott, Christian M. Harding, David A. Rosen

2020-Current year OA Pubs

Klebsiella pneumoniae presents as two circulating pathotypes: classical K. pneumoniae (cKp) and hypervirulent K. pneumoniae (hvKp). Classical isolates are considered urgent threats due to their antibiotic resistance profiles, while hvKp isolates have historically been antibiotic susceptible. Recently, however, increased rates of antibiotic resistance have been observed in both hvKp and cKp, further underscoring the need for preventive and effective immunotherapies. Two distinct surface polysaccharides have gained traction as vaccine candidates against K. pneumoniae: capsular polysaccharide and the O-antigen of lipopolysaccharide. While both targets have practical advantages and disadvantages, it remains unclear which of these antigens included in a vaccine would …

A Randomized, Open-Label Study Of The Tolerability And Efficacy Of One Or Three Daily Doses Of Ivermectin Plus Diethylcarbamazine And Albendazole (Ida) Versus One Dose Of Ivermectin Plus Albendazole (Ia) For Treatment Of Onchocerciasis, Nicholas O. Opoku, Nicole Fetcho, Kerstin Fischer, Peter U. Fischer, Charles W. Goss, Augustine R. Hong, Daphne Lew, Gary J. Weil, Et Al.

2020-Current year OA Pubs

BACKGROUND: Onchocerciasis ("river blindness") has been targeted for elimination. New treatments that kill or permanently sterilize female worms could accelerate this process. Prior studies have shown that triple drug treatment with ivermectin plus diethylcarbamazine and albendazole (IDA) leads to prolonged clearance of microfilaremia in persons with lymphatic filariasis. We now report results from a randomized clinical trial that compared the tolerability and efficacy of IDA vs. a comparator treatment (ivermectin plus albendazole, IA) in persons with onchocerciasis.

METHODS AND FINDINGS: The study was performed in the Volta region of Ghana. Persons with microfiladermia and palpable subcutaneous nodules were pre-treated with …

Effect Of P2y12 Inhibitors On Organ Support-Free Survival In Critically Ill Patients Hospitalized For Covid-19: A Randomized Clinical Trial, Jeffrey S Berger, Grant V Bochicchio, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Platelet activation is a potential therapeutic target in patients with COVID-19.

OBJECTIVE: To evaluate the effect of P2Y12 inhibition among critically ill patients hospitalized for COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: This international, open-label, adaptive platform, 1:1 randomized clinical trial included critically ill (requiring intensive care-level support) patients hospitalized with COVID-19. Patients were enrolled between February 26, 2021, through June 22, 2022. Enrollment was discontinued on June 22, 2022, by the trial leadership in coordination with the study sponsor given a marked slowing of the enrollment rate of critically ill patients.

INTERVENTION: Participants were randomly assigned to receive a P2Y12 …

Metagenomic Analysis Of Dna Viruses With Targeted Sequence Capture Of Canine Lobular Orbital Adenomas And Normal Conjunctiva, Elizabeth A F Schaefer, Shirley Chu, Kristine M Wylie, Todd N Wylie, Obi L Griffith, Jacqueline W Pearce, Gayle C Johnson, Jeffrey N Bryan, Brian K Flesner

2020-Current year OA Pubs

Our study aims are: (1) to evaluate phenotypically normal canine conjunctival and orbital tissue and tissue from canine lobular orbital adenomas (CLOAs) for the presence of viral genomic material and (2) phylogenetically classify detected DNA viruses to determine if a DNA virus is associated with CLOAs. A total of 31 formalin fixed paraffin embedded CLOA tissue samples, 4 papillomas or sarcoid, and 10 fresh clinically normal conjunctival tissues were included in this study. Genomic DNA was isolated from all samples and sequencing libraries were prepared. The libraries were molecularly indexed and pooled and viral DNA was enriched via targeted sequence …

Activation Of The Plasmodium Egress Effector Subtilisin-Like Protease 1 Is Mediated By Plasmepsin X Destruction Of The Prodomain, Sumit Mukherjee, Armiyaw S. Nasamu, Kelly C. Rubiano, Daniel E. Goldberg

2020-Current year OA Pubs

Following each round of replication, daughter merozoites of the malaria parasite Plasmodium falciparum escape (egress) from the infected host red blood cell (RBC) by rupturing the parasitophorous vacuole membrane (PVM) and the RBC membrane (RBCM). A proteolytic cascade orchestrated by a parasite serine protease, subtilisin-like protease 1 (SUB1), regulates the membrane breakdown. SUB1 activation involves primary autoprocessing of the 82-kDa zymogen to a 54-kDa (p54) intermediate that remains bound to its inhibitory propiece (p31) postcleavage. A second processing step converts p54 to the terminal 47-kDa (p47) form of SUB1. Although the aspartic protease plasmepsin X (PM X) has been implicated …

Are Cross-Sectional Safety Climate Survey Results In Operating Room Staff Associated With The Surgical Site Infection Rates In Swiss Hospitals?, Yvonne Pfeiffer, Andrew Atkinson, Judith Maag, Michael A. Lane, David Schwappach, Jonas Marschall

2020-Current year OA Pubs

OBJECTIVES: The aim of this study was to investigate the association between surgical site infections (SSIs), a major source of patient harm, and safety and teamwork climate. Prior research has been unclear regarding this relationship.

DESIGN: Based on the Swiss national SSI surveillance and a survey study assessing (a) safety climate and (b) teamwork climate, associations were analysed for three kinds of surgical procedures.

SETTING AND PARTICIPANTS: SSI surveillance data from 20 434 surgeries for hip and knee arthroplasty from 41 hospitals, 8321 for colorectal procedures from 28 hospitals and 4346 caesarean sections from 11 hospitals and survey responses from …

Dendritic Cells And Cryptosporidium: From Recognition To Restriction, Iti Saraav, L David Sibley

2020-Current year OA Pubs

Host immune responses are required for the efficient control of cryptosporidiosis. Immunity against

Structure Of Anhydrotetracycline-Bound Tet(X6) Reveals The Mechanism For Inhibition Of Type 1 Tetracycline Destructases, Hirdesh Kumar, Emily E Williford, Kevin S Blake, Brett Virgin-Downey, Gautam Dantas, Timothy A Wencewicz, Niraj H Tolia

2020-Current year OA Pubs

Inactivation of tetracycline antibiotics by tetracycline destructases (TDases) remains a clinical and agricultural threat. TDases can be classified as type 1 Tet(X)-like TDases and type 2 soil-derived TDases. Type 1 TDases are widely identified in clinical pathogens. A combination therapy of tetracycline and a TDase inhibitor is much needed to rescue the clinical efficacy of tetracyclines. Anhydrotetracycline is a pan-TDase inhibitor that inhibits both type 1 and type 2 TDases. Here, we present structural, biochemical, and phenotypic evidence that anhydrotetracycline binds in a substrate-like orientation and competitively inhibits the type 1 TDase Tet(X6) to rescue tetracycline antibiotic activity as a …

Il-15 Enhances Hiv-1 Infection By Promoting Survival And Proliferation Of Ccr5+Cd4+ T Cells, Yuhao Li, Hongbo Gao, Kolin M. Clark, Liang Shan

2020-Current year OA Pubs

HIV-1 usually utilizes CCR5 as its coreceptor and rarely switches to a CXCR4-tropic virus until the late stage of infection. CCR5+CD4+ T cells are the major virus-producing cells in viremic individuals as well as SIV-infected nonhuman primates. The differentiation of CCR5+CD4+ T cells is associated with the availability of IL-15, which increases during acute HIV-1 infection. Here, we report that CCR5 was expressed by CD4+ T cells exhibiting effector or effector memory phenotypes with high expression levels of the IL-2/IL-15 receptor common β and γ chains. IL-15, but not IL-7, improved the survival of CCR5+CD4+ T cells, drove their expansion, …

Factor Xa Cleaves Sars-Cov-2 Spike Protein To Block Viral Entry And Infection, Wenjuan Dong, Sean P J Whelan, Et Al.

2020-Current year OA Pubs

Serine proteases (SP), including furin, trypsin, and TMPRSS2 cleave the SARS-CoV-2 spike (S) protein, enabling the virus to enter cells. Here, we show that factor (F) Xa, an SP involved in blood coagulation, is upregulated in COVID-19 patients. In contrast to other SPs, FXa exerts antiviral activity. Mechanistically, FXa cleaves S protein, preventing its binding to ACE2, and thus blocking viral entry and infection. However, FXa is less effective against variants carrying the D614G mutation common in all pandemic variants. The anticoagulant rivaroxaban, a direct FXa inhibitor, inhibits FXa-mediated S protein cleavage and facilitates viral entry, whereas the indirect FXa …

Cross-Sectional Study To Assess Depression Among Healthcare Workers In Lusaka, Zambia During The Covid-19 Pandemic, Sandra Simbeza, Jacob Mutale, Musunge Mulabe, Lazarus Jere, Chama Bukankala, Kombatende Sikombe, Izukanji Sikazwe, Carolyn Bolton-Moore, Aaloke Mody, Elvin H. Geng, Anjali Sharma, Laura K. Beres, Jake M. Pry

2020-Current year OA Pubs

OBJECTIVES: We sought to assess depression among healthcare workers (HCWs) in the context of COVID-19 in Lusaka Province, Zambia.

DESIGN: This cross-sectional study is nested within a larger study, the Person-Centred Public Health for HIV Treatment in Zambia (PCPH), a cluster-randomised trial to assess HIV care and outcomes.

SETTING: The research was conducted in 24 government-run health facilities from 11 August to 15 October 2020 during the first wave of the COVID-19 pandemic in Lusaka, Zambia.

PARTICIPANTS: We used convenience sampling to recruit HCW participants who were previously enrolled in the PCPH study, had more than 6 months' experience working …

A Dna Damage-Induced Phosphorylation Circuit Enhances Mec1atr Ddc2atrip Recruitment To Replication Protein A, Luke A Yates, Elias A Tannous, R Marc Morgan, Peter M Burgers, Xiaodong Zhang

2020-Current year OA Pubs

The cell cycle checkpoint kinase Mec1

Evaluation Of Birth By Cesarean Delivery And Development Of Early-Onset Colorectal Cancer, Yin Cao, Long H Nguyen, Stefani Tica, Ebunoluwa Otegbeye, Xiaoyu Zong, Bjorn Roelstraete, Andrew T Chan, Barbara B Warner, Olof Stephansson, Jonas F Ludvigsson

2020-Current year OA Pubs

IMPORTANCE: The incidence of early-onset colorectal cancer (CRC), diagnosed younger than 50 years of age, has increased worldwide. Gut dysbiosis throughout the life course is hypothesized as a leading mechanism, yet epidemiologic data are limited.

OBJECTIVE: To prospectively examine the association between birth by cesarean delivery and early-onset CRC among offspring.

DESIGN, SETTING, AND PARTICIPANTS: In this population-based, nationwide case-control study in Sweden, adults diagnosed with CRC between 18 and 49 years of age from 1991 to 2017 were identified through the Epidemiology Strengthened by Histopathology Reports in Sweden (ESPRESSO) cohort. Up to 5 general population control individuals without CRC …

Estimated Clinical Outcomes And Cost-Effectiveness Associated With Provision Of Addiction Treatment In Us Primary Care Clinics, Raagini Jawa, Yjuliana Tin, Samantha Nall, Susan L Calcaterra, Alexandra Savinkina, Laura R Marks, Simeon D Kimmel, Benjamin P Linas, Joshua A Barocas

2020-Current year OA Pubs

IMPORTANCE: US primary care practitioners (PCPs) are the largest clinical workforce, but few provide addiction care. Primary care is a practical place to expand addiction services, including buprenorphine and harm reduction kits, yet the clinical outcomes and health care sector costs are unknown.

OBJECTIVE: To estimate the long-term clinical outcomes, costs, and cost-effectiveness of integrated buprenorphine and harm reduction kits in primary care for people who inject opioids.

DESIGN, SETTING, AND PARTICIPANTS: In this modeling study, the Reducing Infections Related to Drug Use Cost-Effectiveness (REDUCE) microsimulation model, which tracks serious injection-related infections, overdose, hospitalization, and death, was used to examine …

The Value And Impacts Of Academic Public Health Departments, Paul C Erwin, Julie H Grubaugh, Stephanie Mazzucca-Ragan, Ross C Brownson

2020-Current year OA Pubs

The academic health department (AHD) is a partnership between an academic institution and a governmental health agency. These partnerships are meant to provide mutual benefits that include opportunities for student field placements and internships, practice-informed curriculum, and practice-based research. The term academic health department dates back only to 2000, although there are several examples of academic-practice partnerships prior to that date. In addition to AHDs that have been established over the past two decades, other forms of academic-practice engagement provide similar mutual benefits, such as prevention research centers and public health training centers. Current research on AHDs explores how these …

On-The-Go Adaptation Of Implementation Approaches And Strategies In Health: Emerging Perspectives And Research Opportunities, Elvin H Geng, Aaloke Mody, Byron J Powell

2020-Current year OA Pubs

In many cases, implementation approaches (composed of one or more strategies) may need to change over time to work optimally. We use a literature review to inform a mechanistic analysis of such on-the-go adaptations. We suggest that such adaptations of implementation strategies consist of three necessary steps. The first component is the initial effect of the implementation approach on intended implementation, service delivery, or clinical outcomes. Second, these initial effects must in turn be used to modify, alter, intensify, or otherwise change the implementation approach. Third, the modified approach itself has effects. Conceiving of adaptation as all three steps implies …

Strategies To Prevent Clostridioides Difficile Infections In Acute-Care Hospitals: 2022 Update, Larry K Kociolek, Dale N Gerding, Ruth Carrico, Philip Carling, Curtis J Donskey, Ghinwa Dumyati, David T Kuhar, Vivian G Loo, Lisa L Maragakis, Monika Pogorzelska-Maziarz, Thomas J Sandora, David J Weber, Deborah Yokoe, Erik R Dubberke

2020-Current year OA Pubs

No abstract provided.

Corticosteroids Increase The Risk Of Invasive Fungal Infections More Than Tumor Necrosis Factor-Alpha Inhibitors In Patients With Inflammatory Bowel Disease, Martin H Gregory, Andrej Spec, Dustin Stwalley, Anas Gremida, Carlos Mejia-Chew, Katelin B Nickel, Matthew A Ciorba, Richard P Rood, Margaret A Olsen, Parakkal Deepak

2020-Current year OA Pubs

BACKGROUND: Invasive fungal infections are a devastating complication of inflammatory bowel disease (IBD) treatment. We aimed to determine the incidence of fungal infections in IBD patients and examine the risk with tumor necrosis factor-alpha inhibitors (anti-TNF) compared with corticosteroids.

METHODS: In a retrospective cohort study using the IBM MarketScan Commercial Database we identified US patients with IBD and at least 6 months enrollment from 2006 to 2018. The primary outcome was a composite of invasive fungal infections, identified by ICD-9/10-CM codes plus antifungal treatment. Tuberculosis (TB) infections were a secondary outcome, with infections presented as cases/100 000 person-years (PY). A …

Failure Of Early Mycological Clearance In Hiv-Negative Cryptococcal Meningitis, Zhihui Su, Chongliang Luo, Kai Dai, Dasen Yuan, Bang-E Qin, Meifeng Gu, Junyu Liu, Yong Chen, Fuhua Peng, Ying Jiang

2020-Current year OA Pubs

BACKGROUND: Negative cerebrospinal fluid (CSF) cultures at 2 weeks after antifungal treatment (early mycological clearance [EMC]) should be a treatment goal of cryptococcal meningitis (CM). However, EMC in human immunodeficiency virus (HIV)-negative patients with CM is poorly understood.

METHODS: We conducted a retrospective review of medical records and 1-year follow-up of 141 HIV-negative patients with CM with an initial positive CSF culture for

RESULTS: Of 141 patients, 28 (19.9%) had EMC failure. The 1-year mortality rate was 5.7% (8/141). Multivariate analysis showed that non-amphotericin B (AmB)-based regimens, baseline log

CONCLUSIONS: EMC failure in HIV-negative CM is attributed to non-AmB-based therapy …