Browsing by Author "Mehta, Sanjay R"
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Item Open Access Broad spectrum triazoles for invasive mould infections in adults: Which drug and when?(Medical mycology, 2019-04) Jenks, Jeffrey D; Mehta, Sanjay R; Hoenigl, MartinInvasive mould infections are an increasing cause of morbidity and mortality globally, mainly due to increasing numbers of immunocompromised individuals at risk for fungal infections. The introduction of broad spectrum triazoles, which are much better tolerated compared to conventional amphotericin B formulations, has increased survival, particularly in invasive mould infection. However, early initiation of appropriate antifungal treatment remains a major predictor of outcome in invasive mould infection, but despite significant advances in diagnosis of these diseases, early diagnosis remains a challenge. As a result, prophylaxis with mould-active triazoles is widely used for those patients at highest risk for invasive mould infection, including patients with prolonged neutropenia after induction chemotherapy for acute myeloid leukemia and patients with graft-versus-host-disease. Posaconazole is the recommended drug of choice for antimould prophylaxis in these high-risk patients. Voriconazole has its primary role in treatment of invasive aspergillosis but not in prophylaxis. Recently, isavuconazole has been introduced as an excellent alternative to voriconazole for primary treatment of invasive aspergillosis in patients with hematological malignancies. Compared to voriconazole, isavuconazole and posaconazole have broader activity against moulds and are therefore also an option for treatment of mucormycosis in the presence of intolerance or contraindications against liposomal amphotericin B.Item Open Access Bronchoalveolar lavage Aspergillus Galactomannan lateral flow assay versus Aspergillus-specific lateral flow device test for diagnosis of invasive pulmonary Aspergillosis in patients with hematological malignancies.(The Journal of infection, 2019-03) Jenks, Jeffrey D; Mehta, Sanjay R; Taplitz, Randy; Law, Nancy; Reed, Sharon L; Hoenigl, MartinItem Open Access Development and validation of the San Diego Early Test Score to predict acute and early HIV infection risk in men who have sex with men.(Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2015-08) Hoenigl, Martin; Weibel, Nadir; Mehta, Sanjay R; Anderson, Christy M; Jenks, Jeffrey; Green, Nella; Gianella, Sara; Smith, Davey M; Little, Susan JBackground
Although men who have sex with men (MSM) represent a dominant risk group for human immunodeficiency virus (HIV), the risk of HIV infection within this population is not uniform. The objective of this study was to develop and validate a score to estimate incident HIV infection risk.Methods
Adult MSM who were tested for acute and early HIV (AEH) between 2008 and 2014 were retrospectively randomized 2:1 to a derivation and validation dataset, respectively. Using the derivation dataset, each predictor associated with an AEH outcome in the multivariate prediction model was assigned a point value that corresponded to its odds ratio. The score was validated on the validation dataset using C-statistics.Results
Data collected at a single HIV testing encounter from 8326 unique MSM were analyzed, including 200 with AEH (2.4%). Four risk behavior variables were significantly associated with an AEH diagnosis (ie, incident infection) in multivariable analysis and were used to derive the San Diego Early Test (SDET) score: condomless receptive anal intercourse (CRAI) with an HIV-positive MSM (3 points), the combination of CRAI plus ≥5 male partners (3 points), ≥10 male partners (2 points), and diagnosis of bacterial sexually transmitted infection (2 points)-all as reported for the prior 12 months. The C-statistic for this risk score was >0.7 in both data sets.Conclusions
The SDET risk score may help to prioritize resources and target interventions, such as preexposure prophylaxis, to MSM at greatest risk of acquiring HIV infection. The SDET risk score is deployed as a freely available tool at http://sdet.ucsd.edu.Item Open Access Performance of the Bronchoalveolar Lavage Fluid Aspergillus Galactomannan Lateral Flow Assay With Cube Reader for Diagnosis of Invasive Pulmonary Aspergillosis: A Multicenter Cohort Study.(Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2021-10) Jenks, Jeffrey D; Prattes, Juergen; Frank, Johanna; Spiess, Birgit; Mehta, Sanjay R; Boch, Tobias; Buchheidt, Dieter; Hoenigl, MartinBackground
The Aspergillus Galactomannan Lateral Flow Assay (LFA) is a rapid test for the diagnosis of invasive aspergillosis (IA) that has been almost exclusively evaluated in patients with hematologic malignancies. An automated digital cube reader that allows for quantification of results has recently been added to the test kits.Methods
We performed a retrospective multicenter study on bronchoalveolar lavage fluid (BALF) samples obtained from 296 patients with various underlying diseases (65% without underlying hematological malignancy) who had BALF galactomannan (GM) ordered between 2013 and 2019 at the University of California, San Diego, the Medical University of Graz, Austria, and the Mannheim University Hospital, Germany.Results
Cases were classified as proven (n = 2), probable (n = 56), putative (n = 30), possible (n = 45), and no IA (n = 162). The LFA showed an area under the curve (AUC) of 0.865 (95% confidence interval [CI] .815-.916) for differentiating proven/probable or putative IA versus no IA, with a sensitivity of 74% and a specificity of 83% at an optical density index cutoff of 1.5. After exclusion of GM as mycological criterion for case classification, diagnostic performance of the LFA was highly similar to GM testing (AUC 0.892 vs 0.893, respectively). LFA performance was consistent across different patient cohorts and centers.Conclusions
In this multicenter study the LFA assay from BALF demonstrated good diagnostic performance for IA that was consistent across patient cohorts and locations. The LFA may serve a role as a rapid test that may replace conventional GM testing in settings where GM results are not rapidly available.Item Open Access Persistent Bacillus cereus Bacteremia in 3 Persons Who Inject Drugs, San Diego, California, USA.(Emerging infectious diseases, 2016-09) Schaefer, Gabrielle; Campbell, Wesley; Jenks, Jeffrey; Beesley, Cari; Katsivas, Theodoros; Hoffmaster, Alex; Mehta, Sanjay R; Reed, SharonBacillus cereus is typically considered a blood culture contaminant; however, its presence in blood cultures can indicate true bacteremia. We report 4 episodes of B. cereus bacteremia in 3 persons who inject drugs. Multilocus sequence typing showed that the temporally associated infections were caused by unrelated clones.Item Open Access Point-of-care diagnosis of invasive aspergillosis in non-neutropenic patients: Aspergillus Galactomannan Lateral Flow Assay versus Aspergillus-specific Lateral Flow Device test in bronchoalveolar lavage.(Mycoses, 2019-03) Jenks, Jeffrey D; Mehta, Sanjay R; Taplitz, Randy; Aslam, Saima; Reed, Sharon L; Hoenigl, MartinBackground
We compared new Aspergillus Galactomannan Lateral Flow Assay with the newly formatted Aspergillus-specific Lateral Flow device tests for the diagnosis of invasive pulmonary aspergillosis (IPA) in non-neutropenic patients.Methods
We performed both tests in 82 bronchoalveolar lavage fluid samples from 82 patients at risk for IPA but without underlying haematologic malignancy. Samples were collected between September 2016 and September 2018 at the University of California San Diego, United States. IPA was classified following two published consensus criteria.Results
Classification of cases varied widely between the two consensus criteria. When using criteria established for the intensive care unit, 26/82 patients (32%) met criteria for proven or putative IPA. Both point-of-care assays showed sensitivities ranging between 58% and 69%, with specificities between 68% and 75%. Sensitivity increased up to 81% when both tests were combined.Conclusion
The study outlines the need for updated, unified and more broadly applicable consensus definitions for classifying IPA in non-neutropenic patients, a work that is currently in progress. Both point-of-care tests showed comparable performance, with sensitivities and specificities in the 60%-70% range when used alone and increasing to 80% when used in combination. The new point-of-care tests may serve a role at the bedside in those with clinical suspicion of IPA.Item Open Access Rare mould infections caused by Mucorales, Lomentospora prolificans and Fusarium, in San Diego, CA: the role of antifungal combination therapy.(International journal of antimicrobial agents, 2018-11) Jenks, Jeffrey D; Reed, Sharon L; Seidel, Danila; Koehler, Philipp; Cornely, Oliver A; Mehta, Sanjay R; Hoenigl, MartinNon-Aspergillus invasive mould infections (IMIs) are associated with devastating morbidity and mortality rates and are increasingly diagnosed in immunocompromised hosts. The aim of this study was to describe the epidemiology and outcomes of non-Aspergillus IMIs at a university hospital in San Diego, California, USA. A retrospective chart review of the medical records of all patients with cultures growing non-Aspergillus moulds at the microbiology laboratory in the Center for Academic Laboratory Medicine, Department of Pathology, University of California, San Diego (UCSD) Health between mid-2014 and mid-2017 (3-year period) was performed. A total of 23 cases of non-Aspergillus IMI were identified, including 10 cases of mucormycosis, 8 cases of lomentosporiosis and 5 cases of fusariosis. Antifungal susceptibility testing was performed for 14 isolates, and 10/11 Fusarium and Lomentospora isolates had minimum inhibitory concentrations (MICs) of >16 µg/mL for voriconazole and/or posaconazole. Overall 180-day mortality was significantly lower among those who received combination antifungal therapy than among those who received single-agent therapy [3/13 (23%) vs. 9/10 (90%); P = 0.003]. In conclusion, Lomentospora prolificans (35% of non-Aspergillus IMIs) and Fusarium spp. (22%) accounted for high proportions of non-Aspergillus IMIs during the study period. Non-Aspergillus IMIs were detected in patients with various underlying diseases and were associated with high mortality rates, which was significantly lower in those who received antifungal combination therapy.Item Open Access Universal Digital High Resolution Melt for the detection of pulmonary mold infections.(bioRxiv, 2023-11-09) Goshia, Tyler; Aralar, April; Wiederhold, Nathan; Jenks, Jeffrey D; Mehta, Sanjay R; Sinha, Mridu; Karmakar, Aprajita; Sharma, Ankit; Shrivastava, Rachit; Sun, Haoxiang; White, P Lewis; Hoenigl, Martin; Fraley, Stephanie IBACKGROUND: Invasive mold infections (IMIs) such as aspergillosis, mucormycosis, fusariosis, and lomentosporiosis are associated with high morbidity and mortality, particularly in immunocompromised patients, with mortality rates as high as 40% to 80%. Outcomes could be substantially improved with early initiation of appropriate antifungal therapy, yet early diagnosis remains difficult to establish and often requires multidisciplinary teams evaluating clinical and radiological findings plus supportive mycological findings. Universal digital high resolution melting analysis (U-dHRM) may enable rapid and robust diagnosis of IMI. This technology aims to accomplish timely pathogen detection at the single genome level by conducting broad-based amplification of microbial barcoding genes in a digital polymerase chain reaction (dPCR) format, followed by high-resolution melting of the DNA amplicons in each digital reaction to generate organism-specific melt curve signatures that are identified by machine learning. METHODS: A universal fungal assay was developed for U-dHRM and used to generate a database of melt curve signatures for 19 clinically relevant fungal pathogens. A machine learning algorithm (ML) was trained to automatically classify these 19 fungal melt curves and detect novel melt curves. Performance was assessed on 73 clinical bronchoalveolar lavage (BAL) samples from patients suspected of IMI. Novel curves were identified by micropipetting U-dHRM reactions and Sanger sequencing amplicons. RESULTS: U-dHRM achieved an average of 97% fungal organism identification accuracy and a turn-around-time of 4hrs. Pathogenic molds (Aspergillus, Mucorales, Lomentospora and Fusarium) were detected by U-dHRM in 73% of BALF samples suspected of IMI. Mixtures of pathogenic molds were detected in 19%. U-dHRM demonstrated good sensitivity for IMI, as defined by current diagnostic criteria, when clinical findings were also considered. CONCLUSIONS: U-dHRM showed promising performance as a separate or combination diagnostic approach to standard mycological tests. The speed of U-dHRM and its ability to simultaneously identify and quantify clinically relevant mold pathogens in polymicrobial samples as well as detect emerging opportunistic pathogens may provide information that could aid in treatment decisions and improve patient outcomes.Item Open Access Universal digital high-resolution melting for the detection of pulmonary mold infections(Journal of Clinical Microbiology) Goshia, Tyler; Aralar, April; Wiederhold, Nathan; Jenks, Jeffrey D; Mehta, Sanjay R; Karmakar, Aprajita; E S, Monish; Sharma, Ankit; Sun, Haoxiang; Kebadireng, Refilwe; White, P Lewis; Sinha, Mridu; Hoenigl, Martin; Fraley, Stephanie IABSTRACT Invasive mold infections (IMIs) are associated with high morbidity, particularly in immunocompromised patients, with mortality rates between 40% and 80%. Early initiation of appropriate antifungal therapy can substantially improve outcomes, yet early diagnosis remains difficult to establish and often requires multidisciplinary teams evaluating clinical and radiological findings plus supportive mycological findings. Universal digital high-resolution melting (U-dHRM) analysis may enable rapid and robust diagnoses of IMI. A universal fungal assay was developed for U-dHRM and used to generate a database of melt curve signatures for 19 clinically relevant fungal pathogens. A machine learning algorithm (ML) was trained to automatically classify these pathogen curves and detect novel melt curves. Performance was assessed on 73 clinical bronchoalveolar lavage samples from patients suspected of IMI. Novel curves were identified by micropipetting U-dHRM reactions and Sanger sequencing amplicons. U-dHRM achieved 97% overall fungal organism identification accuracy and a turnaround time of ~4 hrs. U-dHRM detected pathogenic molds ( Aspergillus , Mucorales , Lomentospora , and Fusarium ) in 73% of 30 samples classified as IMI, including mixed infections. Specificity was optimized by requiring the number of pathogenic mold curves detected in a sample to be > 8 and a sample volume to be 1 mL, which resulted in 100% specificity in 21 at-risk patients without IMI. U-dHRM showed promise as a separate or combination diagnostic approach to standard mycological tests. U-dHRM’s speed, ability to simultaneously identify and quantify clinically relevant mold pathogens in polymicrobial samples, and detect emerging opportunistic pathogens may aid treatment decisions, improving patient outcomes. IMPORTANCE Improvements in diagnostics for invasive mold infections are urgently needed. This work presents a new molecular detection approach that addresses technical and workflow challenges to provide fast pathogen detection, identification, and quantification that could inform treatment to improve patient outcomes.