Characterizing Patients Presenting on Hospital Admission with Central Line-Associated Bloodstream Infections: A Multicenter Study.

BACKGROUND: There are no systematic measures of central line-associated bloodstream infections (CLABSIs) in patients maintaining central venous catheters (CVCs) outside acute care hospitals. To improve understanding of the burden of CLABSIs outside acute care hospitals, we characterized patients with CLABSI present on hospital admission (POA). METHODS: Retrospective cross-sectional analysis of patients with CLABSI-POA in three health systems covering eleven hospitals across Maryland, Washington DC, and Missouri from November 2020 to October 2021. CLABSI-POA was defined using an adaptation of the acute care CLABSI definition. Patient demographics, clinical characteristics, and outcomes were collected via chart review. Cox proportional hazard analysis was used to assess factors associated with all-cause mortality within 30 days. RESULTS: 461 patients were identified as having CLABSI-POA. CVCs were most commonly maintained in home infusion therapy (32.8%) or oncology clinics (31.2%). Enterobacterales were the most common etiologic agent (29.2%). Recurrent CLABSIs occurred in a quarter of patients (25%). Eleven percent of patients died during the hospital admission. Among CLABSI-POA patients, mortality risk increased with age (versus ages <20: ages 20-44 years: HR: 11.21, 95% CI: 1.46-86.22; ages 45-64: HR: 20.88, 95% CI: 2.84-153.58; at least 65 years of age: HR: 22.50, 95% CI: 2.98-169.93), and lack of insurance (HR: 2.46; 95% CI: 1.08-5.59), and decreased with CVC removal (HR: 0.57, 95% CI: 0.39-0.84). CONCLUSION: CLABSI-POA is associated with significant in-hospital mortality. Surveillance is required to understand the burden of CLABSI in the community to identify targets for CLABSI prevention initiatives outside acute care settings.

Long-term evaluation of clinical success and safety of omadacycline in nontuberculous mycobacteria infections: a retrospective, multicenter cohort of real-world health outcomes.

Infections due to nontuberculous mycobacteria (NTM) continue to increase in prevalence, leading to problematic clinical outcomes. Omadacycline (OMC) is an aminomethylcycline antibiotic with FDA orphan drug and fast-track designations for pulmonary NTM infections, including Mycobacteroides abscessus (MAB). This multicenter retrospective study across 16 U.S. medical institutions from January 2020 to March 2023 examined the long-term clinical success, safety, and tolerability of OMC for NTM infections. The cohort included patients aged ≥18 yr, who were clinically evaluable, and` had been treated with OMC for ≥3 mo without a previous diagnosis of cystic fibrosis. The primary outcome was 3 mo clinical success, with secondary outcomes including clinical improvement and mortality at 6- and 12 mo, persistence or reemergence of infection, adverse effects, and reasons for OMC utilization. Seventy-five patients were included in this analysis. Most patients were female (48/75, 64.0%) or Caucasian (58/75, 77.3%), with a median (IQR) age of 59 yr (49-67). Most had NTM pulmonary disease (33/75, 44.0%), skin and soft tissue disease (19/75, 25.3%), or osteomyelitis (10/75, 13.3%), and Mycobacterium abscessus (60/75, 80%) was the most commonly isolated NTM pathogen. The median (IQR) treatment duration was 6 mo (4 - 14), and the most commonly co-administered antibiotic was azithromycin (33/70, 47.1%). Three-month clinical success was observed in 80.0% (60/75) of patients, and AEs attributable to OMC occurred in 32.0% (24/75) of patients, leading to drug discontinuation in 9.3% (7/75).

Spatial Epidemiologic Analysis and Risk Factors for Nontuberculous Mycobacteria Infections, Missouri, USA, 2008-2019.

Nontuberculous mycobacteria (NTM) infections are caused by environmental exposure. We describe spatial distribution of NTM infections and associations with sociodemographic factors and flooding in Missouri, USA. Our retrospective analysis of mycobacterial cultures reported to the Missouri Department of Health and Social Services surveillance system during January 1, 2008-December 31, 2019, detected geographic clusters of infection. Multilevel Poisson regression quantified small-area geographic variations and identified characteristics associated with risk for infection. Median county-level NTM infection rate was 66.33 (interquartile range 51-91)/100,000 persons. Risk of clustering was significantly higher in rural areas (rate ratio 2.82, 95% CI 1.90-4.19) and in counties with >5 floodings per year versus no flooding (rate ratio 1.38, 95% CI 1.26-1.52). Higher risk for NTM infection was associated with older age, rurality, and more flooding. Clinicians and public health professionals should be aware of increased risk for NTM infections, especially in similar environments.

Genomic Analyses of Longitudinal Mycobacterium abscessus Isolates in a Multicenter Cohort Reveal Parallel Signatures of In-Host Adaptation.

BACKGROUND: Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and an increasingly frequent cause of opportunistic infections. Mycobacterium abscessus complex (MABC) is one of the major NTM lung pathogens that disproportionately colonize and infect the lungs of individuals with cystic fibrosis (CF). MABC infection can persist for years, and antimicrobial treatment is frequently ineffective. METHODS: We sequenced the genomes of 175 isolates longitudinally collected from 30 patients with MABC lung infection. We contextualized our cohort amidst the broader MABC phylogeny and investigated genes undergoing parallel adaptation across patients. Finally, we tested the phenotypic consequences of parallel mutations by conducting antimicrobial resistance and mercury-resistance assays. RESULTS: We identified highly related isolate pairs across hospital centers with low likelihood of transmission. We further annotated nonrandom parallel mutations in 22 genes and demonstrated altered macrolide susceptibility co-occurring with a nonsynonymous whiB1 mutation. Finally, we highlighted a 23-kb mercury-resistance plasmid whose loss during chronic infection conferred phenotypic susceptibility to organic and nonorganic mercury compounds. CONCLUSIONS: We characterized parallel genomic processes through which MABC is adapting to promote survival within the host. The within-lineage polymorphisms we observed have phenotypic effects, potentially benefiting fitness in the host at the putative detriment of environmental survival.

Corticosteroids Increase the Risk of Invasive Fungal Infections More Than Tumor Necrosis Factor-Alpha Inhibitors in Patients With Inflammatory Bowel Disease.

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 proportional hazards model was used to determine the association of IBD medications (as time-dependent variables) and invasive fungal infections, controlling for comorbidities and IBD severity. Results: Among 652 920 patients with IBD, the rate of invasive fungal infections was 47.9 cases per 100 000 PY (95% CI 44.7-51.4), which was more than double the TB rate (22 cases [CI 20-24], per 100 000 PY). Histoplasmosis was the most common invasive fungal infection (12.0 cases [CI 10.4-13.8] per 100 000 PY). After controlling for comorbidities and IBD severity, corticosteroids (hazard ratio [HR] 5.4; CI 4.6-6.2) and anti-TNFs (HR 1.6; CI 1.3-2.1) were associated with invasive fungal infections. Conclusions: Invasive fungal infections are more common than TB in patients with IBD. The risk of invasive fungal infections with corticosteroids is more than double that of anti-TNFs. Minimizing corticosteroid use in IBD patients may decrease the risk of fungal infections.

Missed Opportunities in the Diagnosis of Tuberculosis Meningitis.

Background: Tuberculosis meningitis (TBM) has high mortality and morbidity. Diagnostic delays can impact TBM outcomes. We aimed to estimate the number of potentially missed opportunities (MOs) to diagnose TBM and determine its impact on 90-day mortality. Methods: This is a retrospective cohort of adult patients with a central nervous system (CNS) TB International Classification of Diseases, Ninth/Tenth Revision (ICD-9/10) diagnosis code (013*, A17*) identified in the Healthcare Cost and Utilization Project, State Inpatient and State Emergency Department (ED) Databases from 8 states. Missed opportunity was defined as composite of ICD-9/10 diagnosis/procedure codes that included CNS signs/symptoms, systemic illness, or non-CNS TB diagnosis during a hospital/ED visit 180 days before the index TBM admission. Demographics, comorbidities, admission characteristics, mortality, and admission costs were compared between those with and without a MO, and 90-day in-hospital mortality, using univariate and multivariable analyses. Results: Of 893 patients with TBM, median age at diagnosis was 50 years (interquartile range, 37-64), 61.3% were male, and 35.2% had Medicaid as primary payer. Overall, 407 (45.6%) had a prior hospital or ED visit with an MO code. In-hospital 90-day mortality was not different between those with and without an MO, regardless of the MO coded during an ED visit (13.7% vs 15.2%, P = .73) or a hospitalization (28.2% vs 30.9%, P = .74). Independent risk of 90-day in-hospital mortality was associated with older age, hyponatremia (relative risk [RR], 1.62; 95% confidence interval [CI], 1.1-2.4; P = .01), septicemia (RR, 1.6; 95% CI, 1.03-2.45; P = .03), and mechanical ventilation (RR, 3.4; 95% CI, 2.25-5.3; P < .001) during the index admission. Conclusions: Approximately half the patients coded for TBM had a hospital or ED visit in the previous 6 months meeting the MO definition. We found no association between having an MO for TBM and 90-day in-hospital mortality.

Risk Factors for Nontuberculous Mycobacteria Infections in Solid Organ Transplant Recipients: A Multinational Case-Control Study.

BACKGROUND: Risk factors for nontuberculous mycobacteria (NTM) infections after solid organ transplant (SOT) are not well characterized. Here we aimed to describe these factors. METHODS: Retrospective, multinational, 1:2 matched case-control study that included SOT recipients ≥12 years old diagnosed with NTM infection from 1 January 2008 to 31 December 2018. Controls were matched on transplanted organ, NTM treatment center, and post-transplant survival greater than or equal to the time to NTM diagnosis. Logistic regression on matched pairs was used to assess associations between risk factors and NTM infections. RESULTS: Analyses included 85 cases and 169 controls (59% male, 88% White, median age at time of SOT of 54 years [interquartile range {IQR} 40-62]). NTM infection occurred in kidney (42%), lung (35%), heart and liver (11% each), and pancreas transplant recipients (1%). Median time from transplant to infection was 21.6 months (IQR 5.3-55.2). Most underlying comorbidities were evenly distributed between groups; however, cases were older at the time of NTM diagnosis, more frequently on systemic corticosteroids and had a lower lymphocyte count (all P < .05). In the multivariable model, older age at transplant (adjusted odds ratio [aOR] 1.04; 95 confidence interval [CI], 1.01-1.07), hospital admission within 90 days (aOR, 3.14; 95% CI, 1.41-6.98), receipt of antifungals (aOR, 5.35; 95% CI, 1.7-16.91), and lymphocyte-specific antibodies (aOR, 7.73; 95% CI, 1.07-56.14), were associated with NTM infection. CONCLUSIONS: Risk of NTM infection in SOT recipients was associated with older age at SOT, prior hospital admission, receipt of antifungals or lymphocyte-specific antibodies. NTM infection should be considered in SOT patients with these risk factors.

Metabolic syndrome in people with HIV from Guatemala: analysis of components and risk factors.

BACKGROUND: People with HIV (PWH) in Latin America are at a greater risk of developing comorbidities due to the increasing burden of obesity and metabolic syndrome in the region. We explored the associations between social, cardiovascular and HIV-related risk factors with metabolic syndrome in PWH from Guatemala. METHODS: Cross-sectional study analyzing demographic, clinical and laboratory data from PWH. Metabolic syndrome diagnosis and components are defined by the harmonized Joint Scientific Statement criteria. Data were collected from July 2019 to March 2020 and analyzed using correlations and logistic regression. RESULTS: Median age was 39 years [IQR 31-48], 56.8% of participants were male and 31.5% (n = 266, 95% CI 0.28-0.34) had metabolic syndrome. Age (adjusted odds ratio (aOR): 1.03, 95% CI 1.02-1.05, p <0.001), urban dweller (aOR: 1.48, 95% CI 1.00-2.18, p = 0.049), low physical activity (aOR: 1.45, 95% CI 1.01-2.08, p = 0.046), hyperuricemia (aOR: 3.31, 95% CI 1.93-5.67, p <0.001), current CD4+ T cell count < 200 cells/mm3 (aOR: 1.96, 95% CI 1.19-3.23, p = 0.009), 6 months of efavirenz (aOR: 1.89, 95% CI 1.29-2.77, p = 0.001), and obesity (aOR: 37.0, 95% CI 7.70-178.2, p < 0.001) were independently associated with metabolic syndrome. CONCLUSIONS: Prevalence of metabolic syndrome in this study was high and driven mainly by social and cardiovascular risk factors such as age, urban dwelling, obesity, hyperuricemia and low physical activity. Efavirenz use and CD4 count were the only HIV-related factors associated with metabolic syndrome.

Risk factors for mortality and multidrug resistance in pulmonary tuberculosis in Guatemala: A retrospective analysis of mandatory reporting.

BACKGROUND: Risk factors for mortality and MDR-TB in Guatemala are poorly understood. We aimed to identify risk factors to assist in targeting public health interventions. METHODS: We performed a retrospective study of adults with pulmonary TB reported to the Guatemalan TB Program between January 1, 2016 and December 31, 2017. The primary objective was to determine risk factors for mortality in pulmonary TB. The secondary objective was to determine risk factors associated with MDR-TB. RESULTS: Among 3,945 patients with pulmonary TB, median age was 39 years (IQR 25-54), 59% were male, 25% of indigenous ethnicity, 1.1% had MDR-TB and 3.9% died. On multivariable analysis, previous TB treatment (odds ratio [OR] 3.57, CI 2.24-5.68 [p < 0.001]), living with HIV (OR 3.98, CI 2.4-6.17 [p < 0.001]), unknown HIV diagnosis (OR 2.65, CI 1.68-4.18 [p < 0.001]), indigenous ethnicity (OR 1.79, CI 1.18-2.7 [p = 0.005]), malnutrition (OR 7.33, CI 3.24-16.59 [p < 0.001]), and lower educational attainment (OR 2.86, CI 1.43-5.88 [p = 0.003]) were associated with mortality. Prior treatment (OR 53.76, CI 25.04-115.43 [p < 0.001]), diabetes (OR 4.13, CI 2.04-8.35 [p < 0.001]), and indigenous ethnicity (OR 11.83, CI 1.46-95.73 [p = 0.02]) were associated with MDR-TB. CONCLUSIONS: In Guatemala, both previous TB treatment and indigenous ethnicity were associated with higher TB mortality and MDR-TB risk among patients with pulmonary TB.

Factors associated with viremia in people living with HIV on antiretroviral therapy in Guatemala.

INTRODUCTION: Viral suppression prevents HIV transmission and disease progression, but socio-economic and clinical factors can hinder the goal of suppression. We evaluated factors associated with viral non suppression (VNS) and persistent viremia (PV) in people living with HIV (PLHIV) receiving antiretroviral therapy (ART) in Guatemala. METHODS: We conducted a cross sectional analysis using data from an ongoing cohort of PLHIV attending the largest HIV clinic in Guatemala. Univariable and multivariable analyses were conducted between PLHIV with viral suppression and detectable viremia. VNS was defined as most recent HIV RNA ≥ 200 copies/ml and PV as two consecutive HIV RNA ≥ 200 copies/ml. RESULTS: Of 664 participants, 13.3% had VNS and 7.1% had PV. In univariable analysis disaggregated by gender, low income, poor education, perceived difficulty attending healthcare, and alcohol use were associated with VNS in men while low CD4 at diagnosis, multiple prior ART regimens and treatment interruptions were significant in both genders. Multiple prior ART regimens (adjusted Odds Ratio (aOR) 2.82, [95% confidence interval (CI) 1.59, 4.99], p < 0.01), treatment interruptions (aOR 4.51, [95% CI 2.13, 9.58], p < 0.01), excessive alcohol consumption (aOR 2.56, [95% CI 1.18, 5.54], p < 0.05) perceived difficulty attending healthcare (aOR 2.07, [ 95% CI 1.25, 3.42], p < 0.01) and low CD4 at diagnosis (aOR 2.34, 95% [CI 1.30, 4.20], p < 0.01) were independently associated with VNS on multivariable regression. CONCLUSIONS: We conclude that socio-economic and clinical factors influence viral suppression in our cohort and vary between men and women. Gender specific approaches are necessary to achieve the 90% suppression goal.

Comparative Genomics of Mycobacterium avium Complex Reveals Signatures of Environment-Specific Adaptation and Community Acquisition.

Nontuberculous mycobacteria, including those in the Mycobacterium avium complex (MAC), constitute an increasingly urgent threat to global public health. Ubiquitous in soil and water worldwide, MAC members cause a diverse array of infections in humans and animals that are often multidrug resistant, intractable, and deadly. MAC lung disease is of particular concern and is now more prevalent than tuberculosis in many countries, including the United States. Although the clinical importance of these microorganisms continues to expand, our understanding of their genomic diversity is limited, hampering basic and translational studies alike. Here, we leveraged a unique collection of genomes to characterize MAC population structure, gene content, and within-host strain dynamics in unprecedented detail. We found that different MAC species encode distinct suites of biomedically relevant genes, including antibiotic resistance genes and virulence factors, which may influence their distinct clinical manifestations. We observed that M. avium isolates from different sources-human pulmonary infections, human disseminated infections, animals, and natural environments-are readily distinguished by their core and accessory genomes, by their patterns of horizontal gene transfer, and by numerous specific genes, including virulence factors. We identified highly similar MAC strains from distinct patients within and across two geographically distinct clinical cohorts, providing important insights into the reservoirs which seed community acquisition. We also discovered a novel MAC genomospecies in one of these cohorts. Collectively, our results provide key genomic context for these emerging pathogens and will facilitate future exploration of MAC ecology, evolution, and pathogenesis. IMPORTANCE Members of the Mycobacterium avium complex (MAC), a group of mycobacteria encompassing M. avium and its closest relatives, are omnipresent in natural environments and emerging pathogens of humans and animals. MAC infections are difficult to treat, sometimes fatal, and increasingly common. Here, we used comparative genomics to illuminate key aspects of MAC biology. We found that different MAC species and M. avium isolates from different sources encode distinct suites of clinically relevant genes, including those for virulence and antibiotic resistance. We identified highly similar MAC strains in patients from different states and decades, suggesting community acquisition from dispersed and stable reservoirs, and we discovered a novel MAC species. Our work provides valuable insight into the genomic features underlying these versatile pathogens.

A Canker Barking at the Wrong Knee: Thyronectria austroamericana Septic Arthritis.

The mold Thyronectria austroamericana is a plant pathogen that causes canker in honey locust trees. We describe the first case of this mold causing septic arthritis in humans.

IL-7 Immunotherapy in a Nonimmunocompromised Patient With Intractable Fungal Wound Sepsis.

A nonimmunocompromised patient developed life-threatening soft tissue infection with Trichosporon asahii, Fusarium, and Saksenaea that progressed despite maximum antifungal therapies and aggressive debridement. Interleukin-7 immunotherapy resulted in clinical improvement, fungal clearance, reversal of lymphopenia, and improved T-cell function. Immunoadjuvant therapies to boost host immunity may be efficacious in life-threatening fungal infections.

Diagnostic Accuracy of Health Care Administrative Diagnosis Codes to Identify Nontuberculous Mycobacteria Disease: A Systematic Review.

BACKGROUND: Health care administrative database research frequently uses standard medical codes to identify diagnoses or procedures. The aim of this review was to establish the diagnostic accuracy of codes used in administrative data research to identify nontuberculous mycobacterial (NTM) disease, including lung disease (NTMLD). METHODS: We searched Ovid Medline, Embase, Scopus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to April 2019. We included studies assessing the diagnostic accuracy of International Classification of Diseases, 9th edition, Clinical Modification (ICD-9-CM) diagnosis codes to identify NTM disease and NTMLD. Studies were independently assessed by 2 researchers, and the Quality Assessment of Diagnostic Accuracy Studies 2 tool was used to assess bias and quality. RESULTS: We identified 5549 unique citations. Of the 96 full-text articles reviewed, 7 eligible studies of moderate quality (3730 participants) were included in our review. The diagnostic accuracy of ICD-9-CM diagnosis codes to identify NTM disease varied widely across studies, with positive predictive values ranging from 38.2% to 100% and sensitivity ranging from 21% to 93%. For NTMLD, 4 studies reported diagnostic accuracy, with positive predictive values ranging from 57% to 64.6% and sensitivity ranging from 21% to 26.9%. CONCLUSIONS: Diagnostic accuracy measures of codes used in health care administrative data to identify patients with NTM varied across studies. Overall the positive predictive value of ICD-9-CM diagnosis codes alone is good, but the sensitivity is low; this method is likely to underestimate case numbers, reflecting the current limitations of coding systems to capture NTM diagnoses.

Preliminary, Real-world, Multicenter Experience With Omadacycline for Mycobacterium abscessus Infections.

Twelve patients were treated with omadacycline (OMC) as part of a multidrug regimen for Mycobacterium abscessus. The majority of infections were of pulmonary origin (7/12; 58.3%). The median (interquartile range) duration of OMC was 6.2 (4.2-11.0) months. Clinical success occurred in 9/12 (75.0%) patients. Three patients experienced a possible adverse effect while on therapy.

Treatment and mortality outcomes in patients with other extrapulmonary cryptococcal disease compared with central nervous system disease.

BACKGROUND: Determining the extent of cryptococcal disease (CD) is key to therapeutic management. Treatment with fluconazole is only recommended for localised pulmonary disease. Induction therapy with amphotericin B (AmB) and flucytosine is recommended for disease at other sites, irrespective of central nervous system (CNS) involvement, but this is not often followed in patients without meningitis. In this study, we compared treatment and mortality between patients with CD of the CNS and other extrapulmonary (OE) sites. METHODS: This is a retrospective, single-centre study of all hospitalised patients with nonpulmonary cryptococcal infection from 2002 to 2015 who underwent lumbar puncture. Demographics, predisposing factors, comorbidities, clinical presentation, laboratory values, antifungal treatment and mortality data were collected to evaluate 90-day mortality and treatment differences between patients with OE and CNS CD. Survival analysis was performed using multivariable Cox regression analysis. RESULTS: Of 193 patients analysed, 143 (74%) had CNS CD and 50 (26%) had OE CD. Ninety-day mortality was 23% and similar between the OE and CNS CD groups (22% vs 23%, p = .9). In the comorbidity-adjusted multivariable Cox regression model, mortality risk was similar in the OE and CNS groups. Fewer patients with OE CD received induction therapy with AmB and flucytosine compared to those with CNS disease (28% vs 71.3%, p < .001). CONCLUSION: Patients with OE CD had similar 90-day mortality compared to those with CNS disease. Despite current guideline recommendations, patients with OE disease were less likely to receive appropriate induction therapy with AmB and flucytosine compared to patients with CNS disease.

Accuracy of the tuberculosis point-of-care Alere determine lipoarabinomannan antigen diagnostic test using α-mannosidase treated and untreated urine in a cohort of people living with HIV in Guatemala.

BACKGROUND: Improved point-of-care diagnostic tests for tuberculosis (TB) in severe immune suppressed people living with HIV (PLWH) are needed to decrease morbidity and mortality outcomes. The aim of the study is to evaluate the performance of the lipoarabinomannan antigen test (LAM-test) with and without α-mannosidase pre-treated urine in a cohort of PLWH in primary care clinics in Guatemala. We further determined TB incidence, and mortality rates and its risk factors in PLWH with TB symptoms. METHODS: Prospective longitudinal study of PLWH with TB symptoms. Urine samples were collected at 2 HIV sites to test the sensitivity of the LAM-test in urine with and without α-mannosidase pre-treatment. A composite reference standard of either a positive Mycobacterium tuberculosis complex culture and/or GeneXpert® MTB/RIF (Xpert, Cepheid, Sunnyvale, CA, USA) results was used in the LAM-test diagnostic accuracy studies. Cox proportional hazards regression was used to study mortality predictors. RESULTS: The overall sensitivity of the LAM-test was of 56.1% with 95% CI of (43.3-68.3). There were no differences in the LAM-test sensitivity neither by hospital nor by CD4 T cell values. LAM-test sensitivity in PLWH with < 200 CD4 T cells/µl was of 62.2% (95% CI 46.5-76.2). There were no significant differences in sensitivity when comparing LAM-test results obtained from untreated vs. α-mannosidase treated urine [55.2% (95% CI 42.6-67.4) vs. 56.9% (95% CI 44-69.2), respectively]. TB incidence in our cohort was of 21.4/100 person years (PYs) (95% CI 16.6-27.6), and mortality rate was of 11.1/100 PYs (95% CI 8.2-15.0). Importantly, PLWH with a positive LAM-test result had an adjusted hazard ratio (aHR) of death of 1.98 (1.0-3.8) with a significant p value of 0.044 when compared to PLWH with a negative LAM-test result. CONCLUSIONS: In this study, α-mannosidase treatment of urine did not significantly increase the LAM-test performance, however; this needs to be further evaluated in a large-scale study due to our study limitations. Importantly, high rates of TB incidence and mortality were found, and a positive LAM-test result predicted mortality in PLWH with TB clinical symptoms.

And then there were none / Remedando a Agatha Christie: ¿qué microorganismo es el culpable?

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