Dr. Marisa Holubar specializes in the treatment of infectious diseases and works primarily in the inpatient setting. She is particularly interested in antimicrobial stewardship and hospital epidemiology.

Clinical Focus

  • Infectious Disease

Academic Appointments

Administrative Appointments

  • Associate Medical Director, Stanford Antimicrobial Safety and Sustainability Program (2015 - Present)
  • Associate Medical Director, Infection Prevention, Stanford Hospital and Clinics (2015 - Present)

Boards, Advisory Committees, Professional Organizations

  • Physician, California Department of Public Health Healthcare Associated Infections Advisory Committee (2016 - Present)

Professional Education

  • Fellowship:Stanford University School of Medicine Registrar (2013) CA
  • Board Certification: Infectious Disease, American Board of Internal Medicine (2012)
  • Board Certification: Internal Medicine, American Board of Internal Medicine (2009)
  • Residency:Brown University (2009) RI
  • Medical Education:University of Wisconsin School of Medicine (2005) WI
  • Masters, Stanford University, Epidemiology and Clinical Research (2014)


All Publications

  • Feasibility and applicability of antimicrobial stewardship in immunocompromised patients. Current opinion in infectious diseases Robilotti, E., Holubar, M., Seo, S. K., Deresinski, S. 2017


    Antimicrobial stewardship is the primary intervention in the battle against antimicrobial resistance, but clinicians do not always apply many key antimicrobial stewardship principles to patients with significant immune defects due to lack of data and fear of bad outcomes. We review evidence regarding the application of stewardship principles to immunocompromised patients, with a focus on solid organ and hematopoietic stem cell transplant recipients.Antimicrobial stewardship programs (ASPs), targeting immunocompromised patient populations such as oncology and transplant, are gaining traction. Emerging literature suggests that several stewardship interventions can be adapted to immunocompromised hosts and improve antimicrobial utilization, but data supporting improved outcomes is very limited.The application of antimicrobial stewardship principles to immunocompromised patients is feasible, necessary, and urgent. As antimicrobial stewardship programs gain momentum across a diverse range of healthcare settings more immunocompromised patients will fall under their purview. It is imperative that centers applying antimicrobial stewardship principles share their experience and establish collaborative research efforts to advance our knowledge base in applying antimicrobial stewardship initiatives to immunocompromised host populations, both in terms of programmatic success and patient outcomes.

    View details for DOI 10.1097/QCO.0000000000000380

    View details for PubMedID 28542093

  • Detection of Emerging Vaccine-Related Polioviruses by Deep Sequencing. Journal of clinical microbiology Sahoo, M. K., Holubar, M., Huang, C., Mohamed-Hadley, A., Liu, Y., Waggoner, J. J., Troy, S. B., Garcia-Garcia, L., Ferreyra-Reyes, L., Maldonado, Y., Pinsky, B. A. 2017


    Oral poliovirus vaccine can mutate to regain neurovirulence. To date, evaluation of these mutations has been performed primarily on culture-enriched isolates by using conventional Sanger sequencing. We therefore developed a culture-independent, deep-sequencing method targeting the 5' untranslated region (UTR) and P1 genomic region to characterize vaccine-related poliovirus variants. Error analysis of the deep-sequencing method demonstrated reliable detection of poliovirus mutations at levels of <1%, depending on read depth. Sequencing of viral nucleic acids from the stool of vaccinated, asymptomatic children and their close contacts collected during a prospective cohort study in Veracruz, Mexico, revealed no vaccine-derived polioviruses. This was expected given that the longest duration between sequenced sample collection and the end of the most recent national immunization week was 66 days. However, we identified many low-level variants (<5%) distributed across the 5' UTR and P1 genomic region in all three Sabin serotypes, as well as vaccine-related viruses with multiple canonical mutations associated with phenotypic reversion present at high levels (>90%). These results suggest that monitoring emerging vaccine-related poliovirus variants by deep sequencing may aid in the poliovirus endgame and efforts to ensure global polio eradication.

    View details for DOI 10.1128/JCM.00144-17

    View details for PubMedID 28468861

  • Impact of vaccine herd-protection effects in cost-effectiveness analyses of childhood vaccinations. A quantitative comparative analysis. PloS one Holubar, M., Stavroulakis, M. C., Maldonado, Y., Ioannidis, J. P., Contopoulos-Ioannidis, D. 2017; 12 (3)


    Inclusion of vaccine herd-protection effects in cost-effectiveness analyses (CEAs) can impact the CEAs-conclusions. However, empirical epidemiologic data on the size of herd-protection effects from original studies are limited.We performed a quantitative comparative analysis of the impact of herd-protection effects in CEAs for four childhood vaccinations (pneumococcal, meningococcal, rotavirus and influenza). We considered CEAs reporting incremental-cost-effectiveness-ratios (ICERs) (per quality-adjusted-life-years [QALY] gained; per life-years [LY] gained or per disability-adjusted-life-years [DALY] avoided), both with and without herd protection, while keeping all other model parameters stable. We calculated the size of the ICER-differences without vs with-herd-protection and estimated how often inclusion of herd-protection led to crossing of the cost-effectiveness threshold (of an assumed societal-willingness-to-pay) of $50,000 for more-developed countries or X3GDP/capita (WHO-threshold) for less-developed countries.We identified 35 CEA studies (20 pneumococcal, 4 meningococcal, 8 rotavirus and 3 influenza vaccines) with 99 ICER-analyses (55 per-QALY, 27 per-LY and 17 per-DALY). The median ICER-absolute differences per QALY, LY and DALY (without minus with herd-protection) were $15,620 (IQR: $877 to $48,376); $54,871 (IQR: $787 to $115,026) and $49 (IQR: $15 to $1,636) respectively. When the target-vaccination strategy was not cost-saving without herd-protection, inclusion of herd-protection always resulted in more favorable results. In CEAs that had ICERs above the cost-effectiveness threshold without herd-protection, inclusion of herd-protection led to crossing of that threshold in 45% of the cases. This impacted only CEAs for more developed countries, as all but one CEAs for less developed countries had ICERs below the WHO-cost-effectiveness threshold even without herd-protection. In several analyses, recommendation for the adoption of the target vaccination strategy depended on the inclusion of the herd protection effect.Inclusion of herd-protection effects in CEAs had a substantial impact in the estimated ICERs and made target-vaccination strategies more attractive options in almost half of the cases where ICERs were above the societal-willingness to pay threshold without herd-protection. More empirical epidemiologic data are needed to determine the size of herd-protection effects across diverse settings and also the size of negative vaccine effects, e.g. from serotype substitution.

    View details for DOI 10.1371/journal.pone.0172414

    View details for PubMedID 28249046

    View details for PubMedCentralID PMC5332092

  • Bacteremia due to Methicillin-Resistant Staphylococcus aureus New Therapeutic Approaches INFECTIOUS DISEASE CLINICS OF NORTH AMERICA Holubar, M., Meng, L., Deresinski, S. 2016; 30 (2): 491-?


    This article reviews recent clinical evidence for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Vancomycin remains the initial antibiotic of choice for the treatment of patients with MRSA bacteremia and endocarditis due to isolates with vancomycin minimum inhibitory concentration ≤2 μg/mL, whereas daptomycin is an effective alternative, and ceftaroline seems promising. Treatment options for persistent MRSA bacteremia or bacteremia due to vancomycin-intermediate or vancomycin-resistant strains include daptomycin, ceftaroline, and combination therapies. There is a critical need for high-level evidence from clinical trials to allow optimally informed decisions in the treatment of MRSA bacteremia and endocarditis.

    View details for DOI 10.1016/j.idc.2016.02.009

    View details for Web of Science ID 000378466900010

    View details for PubMedID 27208769

  • Shedding of Oral Poliovirus Vaccine (OPV) by HIV-Infected and -Uninfected Mothers of OPV-Vaccinated Zimbabwean Infants. Journal of the Pediatric Infectious Diseases Society Holubar, M., Troy, S. B., Nathoo, K., Stranix-Chibanda, L., Musingwini, G., Srinivas, N., Huang, C., Junn, A., Halpern, M. S., Maldonado, Y. A. 2016


    Community circulation of oral poliovirus vaccine (OPV) likely begins with household transmission. We analyzed stool collected from Zimbabwean mothers who were infected with human immunodeficiency virus (HIV) and those who were uninfected with HIV 1 to 24 weeks after infant oral poliovirus vaccination. Overall, only 5% of the mothers had detectable OPV (16 of 304) despite high infant shedding rates. OPV shedding was similar between HIV-infected mothers and those who were uninfected (11 [6.4%] of 171 vs 5 [3.8%] of 133, respectively) and between mothers of HIV-infected infants and those of uninfected infants (2 [3.5%] of 57 vs 9 [6.3%] of 144, respectively). Mothers of vaccinated infants are unlikely to shed OPV, even when they are infected with HIV.

    View details for PubMedID 26759497

  • Immunodeficiency-related vaccine-derived poliovirus (iVDPV) cases: A systematic review and implications for polio eradication VACCINE Guo, J., Bolivar-Wagers, S., Srinivas, N., Holubar, M., Maldonado, Y. 2015; 33 (10): 1235-1242


    Vaccine-derived polioviruses (VDPVs), strains of poliovirus mutated from the oral polio vaccine, pose a challenge to global polio eradication. Immunodeficiency-related vaccine-derived polioviruses (iVDPVs) are a type of VDPV which may serve as sources of poliovirus reintroduction after the eradication of wild-type poliovirus. This review is a comprehensive update of confirmed iVDPV cases published in the scientific literature from 1962 to 2012, and describes clinically relevant trends in reported iVDPV cases worldwide.We conducted a systematic review of published iVDPV case reports from January 1960 to November 2012 from four databases. We included cases in which the patient had a primary immunodeficiency, and the vaccine virus isolated from the patient either met the sequencing definition of VDPV (>1% divergence for serotypes 1 and 3 and >0.6% for serotype 2) and/or was previously reported as an iVDPV by the World Health Organization.We identified 68 iVDPV cases in 49 manuscripts reported from 25 countries and the Palestinian territories. 62% of case patients were male, 78% presented clinically with acute flaccid paralysis, and 65% were iVDPV2. 57% of cases occurred in patients with predominantly antibody immunodeficiencies, and the overall all-cause mortality rate was greater than 60%. The median age at case detection was 1.4 years [IQR: 0.8, 4.5] and the median duration of shedding was 1.3 years [IQR: 0.7, 2.2]. We identified a poliovirus genome VP1 region mutation rate of 0.72% per year and a higher median percent divergence for iVDPV1 cases. More cases were reported from high income countries, which also had a larger age variation and different distribution of immunodeficiencies compared to upper and lower middle-income countries.Our study describes the incidence and characteristics of global iVDPV cases reported in the literature in the past five decades. It also highlights the regional and economic disparities of reported iVDPV cases.

    View details for DOI 10.1016/j.vaccine.2015.01.018

    View details for Web of Science ID 000350083600004

    View details for PubMedID 25600519

  • Community circulation patterns of oral polio vaccine serotypes 1, 2, and 3 after mexican national immunization weeks. journal of infectious diseases Troy, S. B., Ferreyra-Reyes, L., Huang, C., Sarnquist, C., Canizales-Quintero, S., Nelson, C., Báez-Saldaña, R., Holubar, M., Ferreira-Guerrero, E., García-García, L., Maldonado, Y. A. 2014; 209 (11): 1693-1699


    Background. With wild poliovirus nearing eradication, preventing circulating vaccine-derived poliovirus (cVDPV) by understanding oral polio vaccine (OPV) community circulation is increasingly important. Mexico, where OPV is given only during biannual national immunization weeks (NIWs) but where children receive inactivated polio vaccine (IPV) as part of their primary regimen, provides a natural setting to study OPV community circulation. Methods. In total, 216 children and household contacts in Veracruz, Mexico, were enrolled, and monthly stool samples and questionnaires collected for 1 year; 2501 stool samples underwent RNA extraction, reverse transcription, and real-time polymerase chain reaction (PCR) to detect OPV serotypes 1, 2, and 3. Results. OPV was detected up to 7 months after an NIW, but not at 8 months. In total, 35% of samples collected from children vaccinated the prior month, but only 4% of other samples, contained OPV. Although each serotype was detected in similar proportions among OPV strains shed as a result of direct vaccination, 87% of OPV acquired through community spread was serotype 2 (P < .0001). Conclusions. Serotype 2 circulates longer and is transmitted more readily than serotypes 1 or 3 after NIWs in a Mexican community primarily vaccinated with IPV. This may be part of the reason why most isolated cVDPV has been serotype 2.

    View details for DOI 10.1093/infdis/jit831

    View details for PubMedID 24367038

  • Incident Hepatitis C Virus Infection among US HIV-Infected Men Enrolled in Clinical Trials CLINICAL INFECTIOUS DISEASES Taylor, L. E., Holubar, M., Wu, K., Bosch, R. J., Wyles, D. L., Davis, J. A., Mayer, K. H., Sherman, K. E., Tashima, K. T. 2011; 52 (6): 812-818


    Outbreaks of sexually transmitted hepatitis C virus (HCV) infection have been reported among human immunodeficiency virus (HIV)-infected men who have sex with men in Europe, Australia, and New York. Whether this is occurring across the United States is unknown.We determined incidence of HCV infection during 1996-2008 among male participants of the AIDS Clinical Trial Group Longitudinal Linked Randomized Trials cohort, a long-term study of HIV-infected persons randomized into selected US-based clinical trials. We evaluated associations with self-reported injection drug use (IDU), time-varying CD4(+) cell count, and HIV RNA level with use of multivariate Poisson regression. No sexual or non-IDU risk factor data was available.A total of 1830 men had an initial negative HCV antibody test result and at least 1 subsequent HCV antibody test result, contributing >7000 person-years. At the time of the initial negative HCV antibody test result, 94% of men were receiving highly active antiretroviral therapy (HAART) and 6% reported current or prior IDU. Thirty-six seroconverted, with overall incidence of .51 cases per 100 person-years (95% confidence interval, .36-.70). Mean age at seroconversion was 46 years. Seroconversion was associated with IDU (25% of seroconverters reported IDU history vs 5% of nonseroconverters; P < .001), whereas 75% (n = 27) of seroconverters reported no IDU (incidence, 2.67 cases per 100 person-years among IDUs, .40 cases per 100 person-years among non-IDUs). Seroconversion was associated with HIV RNA level >400 copies/mL (44% at time of antibody positivity vs 21% at time of last negative antibody test result; P = .02) but not with CD4(+) cell count.Incident HCV infection occurs in HIV-infected men involved in US HIV therapeutic trials, primarily through nonparenteral means, despite engagement in care and HAART. HCV antibody development was not related to immune status but was associated with inadequate HIV suppression. At-risk HIV-infected persons should have access to HCV surveillance.

    View details for DOI 10.1093/cid/ciq201

    View details for Web of Science ID 000288020300018

    View details for PubMedID 21282184