About

Kyle G. Rodino, Ph.D., is an Assistant Professor of Clinical Pathology and Laboratory Medicine at the Perelman School of Medicine at the University of Pennsylvania. He serves as the Assistant Director of the Clinical Microbiology Laboratory at the Hospital of the University of Pennsylvania and is the Director of the PSOM Clinical Microbiology Pathology Resident Rotation at the same hospital. Additionally, he co-directs the CPEP Clinical Microbiology Fellowship at Penn/CHOP and directs the Rittenhouse Molecular Laboratory at the Hospital of the University of Pennsylvania. Dr. Rodino's research and professional focus are centered on clinical microbiology, molecular diagnostics, and infectious diseases. His work involves laboratory leadership, microbiology diagnostics, and education within the Department of Pathology and Laboratory Medicine.

Research topics

• Biology
• Zoology
• Virology
• Medicine
• Evolutionary biology

Selected publications

• Delayed diagnosis of disseminated <i>Mycobacterium intracellulare</i> subsp. <i>chimaera</i> infective endocarditis via cell-free metagenomic next-generation sequencing: a case report

  ASM Case Reports · 2025-05-30 · 1 citations

  articleOpen access

  ABSTRACT Background Mycobacterium intracellulare subsp. chimaera infective endocarditis associated with contaminated heater-cooler units has been well documented, leading to the discontinuation of these devices in most hospitals by 2018. The rarity of this infection and its nonspecific symptoms often result in delayed diagnosis. Case Summary We describe a 56-year-old female diagnosed with M. intracellulare subsp. chimaera infective endocarditis with disseminated intracranial abscess 7 years after aortic and mitral valve replacement. Diagnosis was achieved using cell-free microbial DNA next-generation sequencing (cfmNGS). She underwent left temporal craniotomy for abscess drainage and aortic and mitral valve replacement. Diagnosis was confirmed via mycobacterial culture from blood, brain tissue, and explanted valve tissue. Treatment included rifabutin, ethambutol, azithromycin, and amikacin, alongside a prednisone taper prescribed for a previously diagnosed undifferentiated inflammatory process. Amikacin was discontinued 6 weeks after valve surgery because of unilateral hearing loss. She remained clinically stable 5 months after valve surgery. Conclusion This case highlights that M. intracellulare subsp. chimaera infections may continue to emerge years after heater-cool unit discontinuation, suggesting that the time window for case incidence may still be active. cfmNGS may serve as a valuable diagnostic tool for disseminated M. intracellulare subsp. chimaera . Finally, we discuss pharmacotherapeutic factors, including the need for multiple agents over long durations, in this case with specific considerations given to the dissemination of infection into the central nervous system and potential drug-drug interactions, including steroids.

  PublisherDOI

• HIV Testing and Counseling

  2025-07-01

  book-chapterSenior author

  Abstract This chapter provides an overview of key principles in HIV screening and counseling. Readers are introduced to universal HIV screening recommendations, as well as HIV testing recommendations among special populations and environments, including blood-supply screening, perinatal and newborn screening, and indications for repeat testing. Pre-test counseling and strategies to improve uptake of HIV testing are discussed. HIV testing terminology, laboratory markers, and testing algorithms are presented to the reader, along with descriptive figures. The various laboratory and home-testing methods used for screening and diagnosis of HIV infections are discussed. An overview of post-test counseling for both positive and negative test results is provided, including disclosure, partner notification, and confidentiality.

  PublisherDOI

• Single-Set Blood Culture Restriction During the 2024 National Blood Culture Bottle Shortage: An Interrupted Time Series Analysis of Patient Outcomes

  medRxiv · 2025-09-25

  preprintOpen access

  Abstract Importance The 2024 national blood culture bottle shortage led some hospitals to adopt single-set blood culture restrictions, conflicting with professional society guidance for 2–3 sets and risking underdiagnosis. Patient outcomes are not well studied. Objective To evaluate the impact of single-set blood culture restriction on patient outcomes, culture use, and antimicrobial therapy. Design, Setting, and Participants Interrupted time series analysis of 147,214 hospitalizations (36,909 with ≥1 blood culture) across 3 tertiary hospitals in an urban academic center, June 26, 2023–June 25, 2025. Periods were categorized as pre-restriction, restriction, and post-restriction. Analyses were conducted overall, among hospitalizations with ≥1 blood culture set (≥1-BC hospitalizations), and by hospital. Exposure Strict electronic health record order restriction limiting to 1 blood culture set per patient every 24 hours (June 26–December 23, 2024). Main Outcomes and Measures Primary outcomes included in-hospital mortality or hospice discharge, 30-day revisits, and length of stay (LOS). Secondary outcomes included blood culture metrics (positivity, number, timing, proportion with ≥1 culture) and receipt and days of antimicrobials. Odds or incidence rate ratios were reported. Results Among all hospitalizations, in-hospital mortality/hospice discharge declined pre-restriction (–1.3%/week, P&lt;.001), plateaued during restriction (+0.6%/week, P=.33), and resumed decline post-restriction (–2.8%/week, P&lt;.001). Among ≥1-BC hospitalizations, trends were similar, with additional 37.6% increase upon restriction onset (P=.005); LOS increased 14.9% upon restriction onset (P&lt;.001) then decreased post-restriction (–0.9%/week, P&lt;.001). 30-day revisits were unchanged. Overall culture positivity increased 37.8% upon restriction onset (P&lt;.001) and decreased 27.1% upon restriction withdrawal (P&lt;.001). The proportion of hospitalizations with ≥1 culture decreased 37.7% among all hospitalizations (P&lt;.001) and mean number of cultures per hospitalization decreased 49.2% among ≥1-BC hospitalizations (P&lt;.001) upon restriction onset, both partially rebounding afterward. Among ≥1-BC hospitalizations, time from admission to first culture collection and antimicrobial administration increased 72.2% (P&lt;.001) and 21.5% (P=.001), respectively, upon restriction onset; antimicrobial use increased 24.9% upon restriction onset (P=.02) and decreased 14.7% upon post-restriction onset (P=.19). Conclusions and Relevance Single-set blood culture restriction was associated with decreased and delayed testing, delayed antimicrobial start, and increased in-hospital mortality/hospice discharge. Findings underscore the need for optimal diagnostic stewardship practices and supply-chain resiliency for critical diagnostic supplies. Key Points Question What was the impact of restricting hospitals to 1 blood culture set per patient every 24 hours during the 2024 national shortage of blood culture bottles? Findings In this interrupted time series analysis of 147,214 hospitalizations (36,909 with ≥1 blood culture), single-set restriction was associated with decreased culture utilization, delays in time to obtaining cultures and antimicrobial administration, and increased in-hospital mortality/hospice discharge which interrupted otherwise declining trends. Meaning Single-set blood culture restrictions may impede detection of true bloodstream infections, delay antimicrobial prescribing, and worsen patient outcomes, underscoring the need for diagnostic stewardship and resilient supply chains for critical testing supplies.

  PublisherOA PDFDOI

• Update on North American tick-borne diseases and how to diagnose them

  Journal of Clinical Microbiology · 2025-07-11 · 1 citations

  reviewOpen access1st authorCorresponding

  Recent decades have seen a rise in the incidence of tick-borne diseases in the US, along with an increased number of pathogens transmitted by ticks, and geographic expansion of tick populations. A variety of laboratory testing methodologies are available for the diagnosis of tick-borne diseases, including serology, microscopy, and molecular-based methods. The preferred approach varies by the specific disease, locally available test options, and the stage of illness at patient presentation. This mini-review focuses on updates in our understanding of the epidemiology of tick-borne diseases in the US and advances in the field of laboratory diagnostics.

  PublisherDOI

• Selection of Nucleic Acid Amplification Systems

  2025-05-19

  otherSenior author
  PublisherDOI

• 263 An institutional review of Karius utilization: Medical setting, indication, and derived changes in clinical management

  American Journal of Clinical Pathology · 2025-11-01

  articleOpen access

  Abstract Introduction/Objective Karius Spectrum (Karius, Inc., Redwood City, CA, USA) is a metagenomic cell-free DNA assay performed on patient plasma to identify microbial pathogens, often when traditional diagnostic methods are unrevealing. However, the use of plasma metagenomics necessitates careful clinical interpretation towards determining disease relevance and treatment modification. Methods/Case Report An institutional review of Karius testing was conducted at the Hospital of the University of Pennsylvania between 10/6/2022 and 3/20/2025 to evaluate test result-mediated influence on patient management. Patients were stratified according to test results and clinical management. Results Out of 61 patients who underwent Karius testing, 29 (48%) were negative, 25(40%) were positive, and 7(12%) were alert positive. A meaningful change in management occurred in 12 patients (19.7%). Change in management was further stratified as the following: 4(33%) used result to rule out infection when biopsy was not feasible, 3(25%) narrowed antibiotics, 2(17%) withdrew antibiotics, 2(17%) initiated targeted therapy, and 1(8%) were switched from antibiotics to antifungals. Conclusion Our review suggests that while Karius has the capability to reveal previously undetected causative infectious organisms, a minority of patients underwent actionable management changes. Given this, it is imperative to practice proper stewardship of this test through clinician education to maximize Karius testing clinical utility.

  PublisherOA PDFDOI

• Help Us to Help You: Recommendations for Continued Enforcement Discretion for Common Infectious Disease Test Modifications under the FDA Final Rule

  Clinical Chemistry · 2025-04-09 · 1 citations

  article1st authorCorresponding
  PublisherDOI

• Orientia tsutsugamushi Ank5 promotes NLRC5 cytoplasmic retention and degradation to inhibit MHC class I expression

  Nature Communications · 2024-09-14 · 10 citations

  articleOpen access

  How intracellular bacteria subvert the major histocompatibility complex (MHC) class I pathway is poorly understood. Here, we show that the obligate intracellular bacterium Orientia tsutsugamushi uses its effector protein, Ank5, to inhibit nuclear translocation of the MHC class I gene transactivator, NLRC5, and orchestrate its proteasomal degradation. Ank5 uses a tyrosine in its fourth ankyrin repeat to bind the NLRC5 N-terminus while its F-box directs host SCF complex ubiquitination of NLRC5 in the leucine-rich repeat region that dictates susceptibility to Orientia- and Ank5-mediated degradation. The ability of O. tsutsugamushi strains to degrade NLRC5 correlates with ank5 genomic carriage. Ectopically expressed Ank5 that can bind but not degrade NLRC5 protects the transactivator during Orientia infection. Thus, Ank5 is an immunoevasin that uses its bipartite architecture to rid host cells of NLRC5 and reduce surface MHC class I molecules. This study offers insight into how intracellular pathogens can impair MHC class I expression. Viruses and bacteria are known to subvert the immune system using mimic or inhibitory proteins. Here the authors show that the protein Ank5 from the bacterium Orientia tsutsugamushi inhibits nuclear translocation and promotes proteasomal degradation of the MHC class I gene transactivator NLRC5.

  PublisherOA PDFDOI

• Comparison of SARS-CoV-2 variants of concern in primary human nasal cultures demonstrates Delta as most cytopathic and Omicron as fastest replicating

  mBio · 2024-03-13 · 42 citations

  articleOpen access

  The SARS-CoV-2 pandemic was marked with emerging viral variants, some of which were designated as variants of concern (VOCs) due to selection and rapid circulation in the human population. Here, we elucidate functional features of each VOC linked to variations in replication rate. Patient-derived primary nasal cultures grown at air-liquid interface were used to model upper respiratory infection and compared to cell lines derived from human lung epithelia. All VOCs replicated to higher titers than the ancestral virus, suggesting a selection for replication efficiency. In primary nasal cultures, Omicron replicated to the highest titers at early time points, followed by Delta, paralleling comparative studies of population sampling. All SARS-CoV-2 viruses entered the cell primarily via a transmembrane serine protease 2 (TMPRSS2)-dependent pathway, and Omicron was more likely to use an endosomal route of entry. All VOCs activated and overcame dsRNA-induced cellular responses, including interferon (IFN) signaling, oligoadenylate ribonuclease L degradation, and protein kinase R activation. Among the VOCs, Omicron infection induced expression of the most IFN and IFN-stimulated genes. Infections in nasal cultures resulted in cellular damage, including a compromise of cell barrier integrity and loss of nasal cilia and ciliary beating function, especially during Delta infection. Overall, Omicron was optimized for replication in the upper respiratory tract and least favorable in the lower respiratory cell line, and Delta was the most cytopathic for both upper and lower respiratory cells. Our findings highlight the functional differences among VOCs at the cellular level and imply distinct mechanisms of pathogenesis in infected individuals. IMPORTANCE: Comparative analysis of infections by SARS-CoV-2 ancestral virus and variants of concern, including Alpha, Beta, Delta, and Omicron, indicated that variants were selected for efficiency in replication. In infections of patient-derived primary nasal cultures grown at air-liquid interface to model upper respiratory infection, Omicron reached the highest titers at early time points, a finding that was confirmed by parallel population sampling studies. While all infections overcame dsRNA-mediated host responses, infections with Omicron induced the strongest interferon and interferon-stimulated gene response. In both primary nasal cultures and lower respiratory cell line, infections by Delta were most damaging to the cells as indicated by syncytia formation, loss of cell barrier integrity, and nasal ciliary function.

  PublisherDOI

• SARS-CoV-2 evolution during prolonged infection in immunocompromised patients

  mBio · 2024-02-16 · 33 citations

  articleOpen access

  ABSTRACT Prolonged infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in immunocompromised patients provides an opportunity for viral evolution, potentially leading to the generation of new pathogenic variants. To investigate the pathways of viral evolution, we carried out a study on five patients experiencing prolonged SARS-CoV-2 infection (quantitative polymerase chain reaction-positive for 79–203 days) who were immunocompromised due to treatment for lymphoma or solid organ transplantation. For each timepoint analyzed, we generated at least two independent viral genome sequences to assess the heterogeneity and control for sequencing error. Four of the five patients likely had prolonged infection; the fifth apparently experienced a reinfection. The rates of accumulation of substitutions in the viral genome per day were higher in hospitalized patients with prolonged infection than those estimated for the community background. The spike coding region accumulated a significantly greater number of unique mutations than other viral coding regions, and the mutation density was higher. Two patients were treated with monoclonal antibodies (bebtelovimab and sotrovimab); by the next sampled timepoint, each virus population showed substitutions associated with monoclonal antibody resistance as the dominant forms ( spike K444N and spike E340D). All patients received remdesivir, but remdesivir-resistant substitutions were not detected. These data thus help elucidate the trends of emergence, evolution, and selection of mutational variants within long-term infected immunocompromised individuals. IMPORTANCE SARS-CoV-2 is responsible for a global pandemic, driven in part by the emergence of new viral variants. Where do these new variants come from? One model is that long-term viral persistence in infected individuals allows for viral evolution in response to host pressures, resulting in viruses more likely to replicate efficiently in humans. In this study, we characterize replication in several hospitalized and long-term infected individuals, documenting efficient pathways of viral evolution.

  PublisherDOI

Frequent coauthors

• Brendan J. Kelly

  22 shared

• Frederic D. Bushman

  18 shared

• Ronald G. Collman

  Pulmonary and Allergy Associates

  16 shared

• Melissa Richard-Greenblatt

  University of Toronto

  14 shared

• Laurel Glaser

  13 shared

• Jason A. Carlyon

  Virginia Commonwealth University Medical Center

  12 shared

• Paul J. Planet

  Children's Hospital of Philadelphia

  12 shared

• Andrew D. Marques

  University of Pennsylvania

  11 shared

Labs

• Pathology and Laboratory MedicinePI

Education

• PhD, Microbiology and Immunology

  Virginia Commonwealth University