Daisuke Furukawa

All Publications

• The mononuclear phagocyte system obscures the accurate diagnosis of infected joint replacements. Journal of translational medicine Manasherob, R., Warren, S. I., Arora, P., Heo, L., Haddock, N. L., Koliesnik, I., Furukawa, D., Otieno-Ayayo, Z. N., Maloney, W. J., Lowenberg, D. W., Goodman, S. B., Amanatullah, D. F. 2024; 22 (1): 1041

  Abstract

  Diagnosing infected joint replacements relies heavily on assessing the neutrophil response to bacteria. Bacteria form biofilms on joint replacements. Biofilms are sessile bacterial communities encased in a protective extracellular matrix, making them notoriously difficult to culture, remarkably tolerant to antibiotics, and able to evade phagocytosis. Phagocytized bacteria dramatically alter cytokine production and compromise macrophage antigen presentation. We hypothesize that a subset of joint replacements have a dormant infection that suppresses the neutrophil response to bacteria but can be distinguished from uninfected joint replacements by the response of the mononuclear phagocyte system (MPS) within periarticular tissue, synovial fluid, and circulating plasma.Single cell RNASeq transcriptomic and OLink proteomic profiling was performed on matched whole blood, synovial fluid, and periarticular tissue samples collected from 4 joint replacements with an active infection and 3 joint replacements without infection as well as 6 joint replacements with a prior infection deemed "infection-free" by the 2018 Musculoskeletal Infection Society criteria (follow-up of 26 ± 3 months).The MPS and neutrophil responses differ by infected state; the cellular distribution of the MPS response in the subset of joints with dormant infections resembled actively infected joints (p = 0.843, Chi-square test) but was significantly different from uninfected joints (p < 0.001, Chi-square test) despite the absence of systemic acute phase reactants and recruitment of neutrophils (p < 0.001, t-test). When compared to no infection, the cellular composition of dormant infection was distinct. There was reduction in classically activated M1 macrophages (p < 0.001, Fischer's test) and alternatively activated M2 macrophages coupled with an increase in classical monocytes (p < 0.001, Fischer's test), myeloid dendritic cells (p < 0.001, Fischer's test), regulatory T-cells (p < 0.001, Fischer's test), natural killer cells (p = 0.009, Fischer's test), and plasmacytoid dendritic cells (p = 0.005, Fischer's test). Hierarchical cluster analysis and single-cell gene expression revealed that classically M1 and alternatively M2 activated macrophages as well as myeloid dendritic cells can independently distinguish the dormant and uninfected patient populations suggesting that a process that modulates neutrophil recruitment (C1QA, C1QB, LY86, SELL, CXCL5, CCL20, CD14, ITGAM), macrophage polarization (FOSB, JUN), immune checkpoint regulation (IFITM2, IFITM3, CST7, THBS1), and T-cell response (VISIG4, CD28, FYN, LAT2, FCGR3A, CD52) was occurring during dormant infection. Gene set variation analysis suggested that activation of the TNF (FDR < 0.01) and IL17 (FDR < 0.01) pathways may distinguish dormant infections from the active and uninfected populations, while an inactivation of neutrophil extracellular traps (NETs) may be involved in the lack of a clinical response to a dormant infection using established diagnostic criteria. Synovial inflammatory proteomics show an increase in synovial CXCL5 associated with dormant infection (p = 0.011, t-test), suggesting the establishment of a chronic inflammatory state by the MPS during a dormant infection involved in neutrophil inhibition. Plasma inflammatory proteomics also support a chronic inflammatory state (EGF, GZMN, FGF2, PTN, MMP12) during dormant infection that involves a reduction in neutrophil recruitment (CXCL5, p = 0.006, t-test), antigen presentation (LAMP3, p = 0.047, t-test), and T-cell function (CD28, p = 0.045, t-test; CD70, p = 0.002, t-test) that are also seen during the development of bacterial tolerance.All current diagnostic criteria assume each patient can mount the same neutrophil response to an implant-associated infection. However, the state of the MPS is of critical importance to accurate diagnosis of an implant-associated infection. A reduction in neutrophil recruitment and function mediated by the MPS may allow joint replacements with a dormant infection to be mischaracterized as uninfected, thus limiting the prognostic capabilities of all current diagnostic tests.

  View details for DOI 10.1186/s12967-024-05866-5

  View details for PubMedID 39563367

  View details for PubMedCentralID 4887354

• No differences in outcomes with stopping or continuing antibiotic suppression in periprosthetic joint infections. Journal of bone and joint infection Furukawa, D., Dunning, M., Shen, S., Chang, A., Aronson, J., Amanatullah, D. F., Suh, G. A., Kappagoda, S. 2024; 9 (3): 143-148

  Abstract

  The data on long-term antibiotic use following debridement, antibiotics, and implant retention (DAIR) for treatment of periprosthetic joint infections are limited. In this single-center retrospective study, we show that patients with eventual cessation of antibiotic suppression after DAIR had similar outcomes to those who remained on chronic antibiotic suppression.

  View details for DOI 10.5194/jbji-9-143-2024

  View details for PubMedID 38899055

  View details for PubMedCentralID PMC11184613

• State-of-the-Art Review: Use of Antimicrobials at the End of Life. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Karlin, D., Pham, C., Furukawa, D., Kaur, I., Martin, E., Kates, O., Vijayan, T. 2024

  Abstract

  Navigating antibiotics at the end of life is a challenge for infectious disease (ID) physicians who remain deeply committed to providing patient-centered care and engaging in shared decision making. ID physicians, who often see patients in both inpatient and outpatient settings and maintain continuity of care for patients with refractory or recurrent infections, are ideally situated to provide guidance that aligns with patients' goals and values. Complex communication skills, including navigating difficult emotions around end-of-life care, can be used to better direct shared decision making and assist with antibiotic stewardship.

  View details for DOI 10.1093/cid/ciad735

  View details for PubMedID 38301076

• Executive Summary: State-of-the-Art Review: Use of Antimicrobials at the End of Life. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Karlin, D., Pham, C., Furukawa, D., Kaur, I., Martin, E., Kates, O., Vijayan, T. 2024

  View details for DOI 10.1093/cid/ciad737

  View details for PubMedID 38301074

• Evaluation of antibiotic escalation in response to nurse-driven inpatient sepsis screen. Antimicrobial stewardship & healthcare epidemiology : ASHE Furukawa, D., Dieringer, T. D., Wong, M. D., Tong, J. T., Cader, I. A., Wisk, L. E., Han, M. A., Gupta, S. M., Kerbel, R. B., Uslan, D. Z., Graber, C. J. 2021; 1 (1): e59

  Abstract

  To determine the frequency and predictors of antibiotic escalation in response to the inpatient sepsis screen at our institution.Retrospective cohort study.Two affiliated academic medical centers in Los Angeles, California.Hospitalized patients aged 18 years and older who had their first positive sepsis screen between January 1, 2019, and December 31, 2019, on acute-care wards.We described the rate and etiology of antibiotic escalation, and we conducted multivariable regression analyses of predictors of antibiotic escalation.Of the 576 cases with a positive sepsis screen, antibiotic escalation occurred in 131 cases (22.7%). New infection was the most documented etiology of escalation, with 76 cases (13.2%), followed by known pre-existing infection, with 26 cases (4.5%). Antibiotics were continued past 3 days in 17 cases (3.0%) in which new or existing infection was not apparent. Abnormal temperature (adjusted odds ratio [aOR], 3.00; 95% confidence interval [CI], 1.91-4.70) and abnormal lactate (aOR, 2.04; 95% CI, 1.28-3.27) were significant predictors of antibiotic escalation. The patient already being on antibiotics (aOR, 0.54; 95% CI, 0.34-0.89) and the positive screen occurred during a nursing shift change (aOR, 0.36; 95% CI, 0.22-0.57) were negative predictors. Pneumonia was the most documented new infection, but only 19 (50%) of 38 pneumonia cases met full clinical diagnostic criteria.Inpatient sepsis screening led to a new infectious diagnosis in 13.2% of all positive sepsis screens, and the risk of prolonged antibiotic exposure without a clear infectious source was low. Pneumonia diagnostics and lactate testing are potential targets for future stewardship efforts.

  View details for DOI 10.1017/ash.2021.232

  View details for PubMedID 36168494

  View details for PubMedCentralID PMC9495422

• Antimicrobial Stewardship in a Pandemic: Picking Up the Pieces. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Furukawa, D., Graber, C. J. 2021; 72 (10): e542-e544

  View details for DOI 10.1093/cid/ciaa1273

  View details for PubMedID 32857832

  View details for PubMedCentralID PMC7665318

• Real-life utilization of BioFire® Filmarray® pneumonia panel as an antibiotic stewardship tool. Infectious diseases (London, England) Furukawa, D., Kim, B., Jeng, A. 2021; 53 (4): 308-313

  View details for DOI 10.1080/23744235.2020.1866774

  View details for PubMedID 33377807

• Antibiotic prophylaxis in beta-lactam allergic patients undergoing cesarean and vaginal delivery: An opportunity for stewardship. Infection control and hospital epidemiology Furukawa, D., Douglas, N., Hsu, J., Davis, M., Pham, C., Kanatani, M., Vijayan, T. 2021: 1-2

  View details for DOI 10.1017/ice.2021.315

  View details for PubMedID 34323207

• Using control charts to understand community variation in COVID-19. PloS one Inkelas, M., Blair, C., Furukawa, D., Manuel, V. G., Malenfant, J. H., Martin, E., Emeruwa, I., Kuo, T., Arangua, L., Robles, B., Provost, L. P. 2021; 16 (4): e0248500

  Abstract

  Decision-makers need signals for action as the coronavirus disease 2019 (COVID-19) pandemic progresses. Our aim was to demonstrate a novel use of statistical process control to provide timely and interpretable displays of COVID-19 data that inform local mitigation and containment strategies. Healthcare and other industries use statistical process control to study variation and disaggregate data for purposes of understanding behavior of processes and systems and intervening on them. We developed control charts at the county and city/neighborhood level within one state (California) to illustrate their potential value for decision-makers. We found that COVID-19 rates vary by region and subregion, with periods of exponential and non-exponential growth and decline. Such disaggregation provides granularity that decision-makers can use to respond to the pandemic. The annotated time series presentation connects events and policies with observed data that may help mobilize and direct the actions of residents and other stakeholders. Policy-makers and communities require access to relevant, accurate data to respond to the evolving COVID-19 pandemic. Control charts could prove valuable given their potential ease of use and interpretability in real-time decision-making and for communication about the pandemic at a meaningful level for communities.

  View details for DOI 10.1371/journal.pone.0248500

  View details for PubMedID 33930013

  View details for PubMedCentralID PMC8087083

• Inpatient antibiotic utilization in the Veterans' Health Administration during the coronavirus disease 2019 (COVID-19) pandemic. Infection control and hospital epidemiology Dieringer, T. D., Furukawa, D., Graber, C. J., Stevens, V. W., Jones, M. M., Rubin, M. A., Goetz, M. B. 2021; 42 (6): 751-753

  Abstract

  Antibiotic prescribing practices across the Veterans' Health Administration (VA) experienced significant shifts during the coronavirus disease 2019 (COVID-19) pandemic. From 2015 to 2019, antibiotic use between January and May decreased from 638 to 602 days of therapy (DOT) per 1,000 days present (DP), while the corresponding months in 2020 saw antibiotic utilization rise to 628 DOT per 1,000 DP.

  View details for DOI 10.1017/ice.2020.1277

  View details for PubMedID 33077000

  View details for PubMedCentralID PMC7653226

• Condyloma latum of the plantar foot: Case report of an unusual manifestation of secondary syphilis. International journal of STD & AIDS Leavens, J., Furukawa, D., Gates, G. 2021: 9564624211032798

  Abstract

  Condyloma lata, a cutaneous manifestation of secondary syphilis, typically presents as verrucous papules or plaques in the anogenital area. Here, we present a case of secondary syphilis presenting in a 38-year-old man as condyloma latum of the plantar foot in the absence of other cutaneous findings of secondary syphilis. The plantar foot is an unusual location for condyloma lata which has not previously been reported in the medical literature. Histopathology was essential to diagnosis in this case and demonstrated verrucous epidermal hyperplasia with a plasma cell-rich infiltrate in the dermis and innumerable spirochetes in the epidermis. The patient was successfully treated with intramuscular penicillin benzathine G. Given the recent rise in the incidence of primary and secondary syphilis, it is essential for clinicians to be aware of atypical presentations of secondary syphilis to avoid delays in treatment and decrease the risk of transmission to sexual partners.

  View details for DOI 10.1177/09564624211032798

  View details for PubMedID 34284668

• A Case of Fever of Unknown Origin Following Cardiac Arrest With Diagnosis Revealed on Autopsy INFECTIOUS DISEASES IN CLINICAL PRACTICE Furukawa, D., McBride, O., Kaneshiro, C., Betancourt, J. 2018; 26 (5): 297-299

  View details for DOI 10.1097/IPC.0000000000000641

  View details for Web of Science ID 000444393100024

• No to Pip-Tazo Identifying Inappropriate Use of Piperacillin-Tazobactam for Treatment of Skin and Soft Tissue Infections INFECTIOUS DISEASES IN CLINICAL PRACTICE Furukawa, D., Graber, C. J. 2017; 25 (4): 209-213

  View details for DOI 10.1097/IPC.0000000000000499

  View details for Web of Science ID 000404127600009