Alex Nathaniel Zimmet

All Publications

• Concordance of non-invasive plasma cell-free DNA with invasive diagnostics for diagnosis of invasive fungal disease. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Lieu, A., Zimmet, A. N., Pozdol, J., Kushner, L. E., Ho, D., Banaei, N. 2025

  Abstract

  Mold plasma cell-free DNA (cfDNA) PCR is a promising non-invasive diagnostic modality for early diagnosis of invasive mold disease (IMD) in immunocompromised patients. Although mold cfDNA PCR has been shown to be highly accurate, the value of invasive procedures to collect specimens for conventional fungal diagnostics following plasma cfDNA testing remains unclear.This retrospective single-center cohort study included patients with mold plasma cfDNA PCR performed 7 days before or 2 days after invasive specimen collection. Mold PCR detected Aspergillus species, Mucorales agents, Fusarium species, and Scedosporium species. Invasive procedures included tissue biopsy and bronchoscopy. The primary endpoint was the concordance of mold plasma cfDNA PCR results with results of conventional fungal tests performed on tissue and bronchoalveolar lavage fluid (BAL).Five hundred and six patients with mold plasma cfDNA PCR resulting ahead of invasive specimen (123 tissue and 426 BAL) results were included, and 437 (86.4%) were immunocompromised. After adjudicating discordant results based on the EORTC/MSGERC definitions for IMD, mold plasma cfDNA PCR and invasive test results were 88.5% (448/506) concordant. In proven cases, 64.7% (11/17) of negative mold plasma cfDNA PCR results occurred in patients with fungal sinusitis (8) and limb infection (3). Non-hematologic malignancy and non-neutropenic states were statistically associated with negative mold plasma cfDNA PCR in patients with proven or probable IMD.Non-invasive mold plasma cfDNA PCR results were highly concordant with invasive specimen fungal test results, thus indicating risk-prone invasive specimen collection can be safely curtailed in immunocompromised patients with suspected IMD.

  View details for DOI 10.1093/cid/ciaf021

  View details for PubMedID 39823293

• No "One-Size-Fits All": chronic "Carryover" diagnoses dilute antibiotic prescribing rates for sinusitis among adults in primary and urgent care settings. Infection control and hospital epidemiology Smith, M., Hawkins, M., Laikijrung, C., Mui, E., Alegria, W., Leung, T., Zimmet, A., Ha, D., Holubar, M. 2024: 1-3

  Abstract

  International Classification of Diseases, Tenth Revision (ICD-10) billing data used in outpatient stewardship metrics is under-described for acute and chronic sinusitis. We found that different sinusitis ICD-10 definitions impacted antibiotic prescribing rates (APRs). Chronic sinusitis ICD-10s dilute overall sinusitis APR, particularly in primary care settings and should be examined separately.

  View details for DOI 10.1017/ice.2024.200

  View details for PubMedID 39725661

• A Novel Intersection: Cytomegalovirus Gastritis Following Cemiplimab and Talimogene Laherparepvec in a Patient With Advanced Cutaneous Squamous Cell Carcinoma. Clinical case reports Egoryan, G., Zimmet, A., Yu, M., Pozdol, J., Subramanian, A., Reddy, S., Nelson, J. 2024; 12 (12): e9632

  Abstract

  Cytomegalovirus (CMV) reactivation is a rare complication in patients treated with immune checkpoint inhibitors (ICIs), typically occurring after immunosuppressive therapy for immune-related adverse events (irAEs). Here, we report a unique case of severe CMV gastritis in a patient receiving cemiplimab, an anti-PD-1 antibody, and talimogene laherparepvec (T-VEC), an oncolytic virus, without prior irAEs or immunosuppressive treatment. A 63-year-old man with advanced cutaneous squamous cell carcinoma received cemiplimab for one year and a single T-VEC injection for recurrent disease. He presented with progressive dyspepsia, significant weight loss, and malnutrition requiring total parenteral nutrition. Endoscopy revealed extensive gastric ulceration, and biopsies confirmed CMV gastritis. Initial treatment with intravenous ganciclovir improved his viral load but provided minimal symptomatic relief. After six weeks of therapy, biopsies showed resolution of CMV infection, and the patient transitioned to oral valganciclovir for prophylaxis while resuming cancer treatment. This case highlights the potential for CMV reactivation in patients undergoing ICI therapy, even without prior immunosuppression or irAEs. Notably, the concurrent use of T-VEC raises questions about the interplay between oncolytic viruses, ICIs, and immune modulation. Although T-VEC is not known to directly cause CMV reactivation, its role in amplifying immune responses warrants further investigation. As ICIs and oncolytic viruses become increasingly integral in oncology, clinicians must remain vigilant for rare infectious complications like CMV reactivation. Further research is needed to elucidate mechanisms, identify risk factors, and optimize management strategies for these events.

  View details for DOI 10.1002/ccr3.9632

  View details for PubMedID 39687659

  View details for PubMedCentralID PMC11646813

• "Electronic Phenotyping" Antimicrobials to Facilitate Outpatient Stewardship for Asymptomatic Bacteriuria and Urinary Tract Infection in Renal Transplant. Open forum infectious diseases Zimmet, A. N., Ha, D., Mui, E., Smith, M., Hawkins, M., Alegria, W., Holubar, M. 2024; 11 (3): ofae119

  Abstract

  Asymptomatic bacteriuria and urinary tract infection in renal transplant are important antimicrobial stewardship targets but are difficult to identify within electronic medical records. We validated an "electronic phenotype" of antibacterials prescribed for these indications. This may be more useful than billing data in assessing antibiotic indication in this outpatient setting.

  View details for DOI 10.1093/ofid/ofae119

  View details for PubMedID 38533270

  View details for PubMedCentralID PMC10964979

• Pathophysiological responses to bloodstream infection in critically ill transplant recipients compared to non-transplant recipients. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Qiu, J., Zimmet, A. N., Bell, T. D., Gadrey, S., Brandberg, J., Maldonado, S., Zimmet, A. M., Ratcliffe, S., Chernyavskiy, P., Moorman, J. R., Clermont, G., Henry, T. R., Nguyen, N. R., Moore, C. C. 2023

  Abstract

  BACKGROUND: Identification of bloodstream infection (BSI) in transplant recipients may be difficult due to immunosuppression. Accordingly, we aimed to compare responses to BSI in critically ill transplant and non-transplant recipients and to modify systemic inflammatory response syndrome (SIRS) criteria for transplant recipients.METHODS: We analyzed univariate risks and developed multivariable models of BSI with 27 clinical variables from adult intensive care unit (ICU) patients at the University of Virginia (UVA) and at the University of Pittsburgh (Pitt). We used Bayesian inference to adjust SIRS criteria for transplant recipients.RESULTS: We analyzed 38.7 million hourly measurements from 41,725 patients at UVA, including 1,897 transplant recipients with 193 episodes of BSI, and 53,608 patients at Pitt, including 1,614 transplant recipients with 768 episodes of BSI. The univariate responses to BSI were comparable in transplant and non-transplant recipients. The area under the receiver operating characteristic curve (AUC) was 0.82 (95% confidence interval [CI], 0.80-0.83) for the model using all UVA patient data and 0.80 (95% CI, 0.76-0.83) when using only transplant recipient data. The UVA all-patient model had an AUC of 0.77 (95%CI, 0.76-0.79) in non-transplant recipients and 0.75 (95% CI, 0.71-0.79) in transplant recipients at Pitt. The relative importance of the 27 predictors was similar in transplant and non-transplant models. An upper temperature of 37.5°C in SIRS criteria improved reclassification performance in transplant recipients.CONCLUSION: Critically ill transplant and non-transplant recipients had similar responses to BSI. An upper temperature of 37.5°C in SIRS criteria improved BSI screening in transplant recipients.

  View details for DOI 10.1093/cid/ciad662

  View details for PubMedID 37889515

• Low infectivity among asymptomatic patients with a positive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) admission test at a tertiary care center, 2020-2022. Infection control and hospital epidemiology Tayyar, R., Kiener, M. A., Liang, J. W., Contreras, G., Rodriguez-Nava, G., Zimmet, A. N., Contag, C. A., Srinivasan, K., McIntyre, K., Subramanian, A., Shepard, J., Tompkins, L. S., Pinsky, B. A., Salinas, J. L. 2023: 1-3

  Abstract

  We used a strand-specific RT-qPCR to evaluate viral replication as a surrogate for infectiousness among 242 asymptomatic inpatients with a positive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) admission test. Only 21 patients (9%) had detectable SARS-CoV-2 minus-strand RNA. Because most patients were found to be noninfectious, our findings support the suspension of asymptomatic admission testing.

  View details for DOI 10.1017/ice.2023.210

  View details for PubMedID 37746805

• Use of a severe acute respiratory coronavirus virus 2 (SARS-CoV-2) strand-specific assay to evaluate for prolonged viral replication >20 days from illness onset. Infection control and hospital epidemiology Ferguson, J. D., Tayyar, R., Contreras, G., Kiener, M., Zimmet, A. N., Contag, C. A., Rodriguez Nava, G., Tompkins, L. S., Shepard, J., Rosenthal, A., Subramanian, A. K., Pinsky, B. A., Salinas, J. L. 2023: 1-3

  Abstract

  Severe acute respiratory coronavirus virus 2 (SARS-CoV-2) real-time reverse-transcription polymerase chain reaction (rRT-PCR) strand-specific assay can be used to identify active SARS-CoV-2 viral replication. We describe the characteristics of 337 hospitalized patients with at least 1 minus-strand SARS-CoV-2 assay performed >20 days after illness onset. This test is a novel tool to identify high-risk hospitalized patients with prolonged SARS-CoV-2 replication.

  View details for DOI 10.1017/ice.2023.105

  View details for PubMedID 37381726

• Answer to June 2023 Photo Quiz. Journal of clinical microbiology Zimmet, A. N., Mah, J. K., Budvytiene, I., Banaei, N., Salinas, J. 2023; 61 (6): e0175422

  View details for DOI 10.1128/jcm.01754-22

  View details for PubMedID 37338230

• Photo Quiz: A 50-Year Old Man with Fever and Headache. Journal of clinical microbiology Zimmet, A. N., Mah, J. K., Budvytiene, I., Banaei, N., Salinas, J. L. 2023; 61 (6): e0172522

  View details for DOI 10.1128/jcm.01725-22

  View details for PubMedID 37338227

• Disseminated cryptococcosis with gastrointestinal involvement and false-negative cryptococcal antigen testing due to postzone phenomenon: a case report and review of the literature. BMC infectious diseases Zimmet, A. N., Cullen, G. D., Mische, L., Deftos, M., Bogler, Y., Nguyen, N. L., Ray, M. 2023; 23 (1): 217

  Abstract

  BACKGROUND: Cryptococcosis is an increasingly common infection given the growing immunocompromised population worldwide. Cryptococcal antigen (CrAg) testing demonstrates excellent sensitivity and specificity and is the mainstay of diagnosis. However, there may be rare instances in which false-negative CrAg results can delay diagnosis and early treatment, which are critical to ensure positive outcomes.CASE PRESENTATION: A 31-year-old man living with HIV/AIDS who was not taking antiretroviral therapy was hospitalized with fever, diarrhea, and headaches. CD4 count on presentation was 71 cells/uL, and HIV viral load was 3,194,949 copies/mL. Serum CrAg testing was initially negative, however CSF CrAg performed several days later was positive at 1:40 and blood and CSF cultures grew Cryptococcus neoformans. Colonoscopy revealed mucosal papules throughout the sigmoid colon, and tissue biopsy showed yeast within the lamina propria consistent with GI cryptococcosis. Given the high burden of disease, the original serum CrAg specimen was serially diluted and subsequently found to be positive at 1:2,560, confirming the postzone phenomenon.CONCLUSION: Cryptococcosis has a wide array of presentations including intraluminal GI disease, as seen in this patient. While serum CrAg testing displays excellent test characteristics, it is important for clinicians to be aware of the rare instances in which false-negative results may occur in the presence of excess antigen, as in this case.

  View details for DOI 10.1186/s12879-023-08141-y

  View details for PubMedID 37024821