Thomas J Walsh

Weill Cornell Medicine of Cornell University and New York Presbyterian Hospital

Broad-spectrum antiviral agents that are effective against many viruses are difficult to develop, as the key molecules, as well as the biochemical pathways by which they cause infection, differ largely from one virus to another. This was more strongly highlighted by the COVID-19 pandemic, which found health systems all over the world largely unprep...

Monolayers of bacterial cells of Staphylococcus aureus and Pseudomonas aeruginosa were inoculated on glass slide carriers using an automated inoculum spray deposition system. The use of bacterial monolayers allows for control of critical variables for testing and verification of light-based disinfection technologies. This approach avoids the variab...

Background Echinocandins are commonly used in treatment and prophylaxis of invasive fungal diseases. Intravenous daily dosing for prophylaxis in the outpatient setting can however become a hurdle for adequate compliance in the paediatric population. Objectives Simulations were performed to assess extended twice-weekly dosing for antifungal prophyl...

Stool specimens are frequently used to detect gastrointestinal tract colonization with antimicrobial-resistant enteric bacteria, but they cannot be rapidly collected. Perianal swab specimens can be collected more quickly and efficiently, but data evaluating their suitability as a specimen type for this purpose are sparse. We performed selective cul...

Background Rising antimicrobial resistance rates may impact the efficacy of empirical antibiotic treatment for febrile neutropenia in high-risk cancer patients. Lacking contemporary data about the epidemiology, antibiotic resistance patterns, and clinical outcomes from bloodstream infections (BSI) in U.S. cancer patients, it is unclear if current g...

Background: Patients with bacteremia due to carbapenem-resistant Enterobacterales (CRE) experience delays until appropriate therapy and high mortality rates. Rapid molecular diagnostics for carbapenemases and new β-lactam/β-lactamase inhibitors may improve outcomes. Methods: We conducted an observational study of patients with CRE bacteremia fro...

Since the time of its appearance until present, COVID-19 has spread worldwide, with over 71 million confirmed cases and over 1.6 million deaths reported by the World Health Organization (WHO). In addition to the fact that cases of COVID-19 are increasing worldwide, the Delta and Omicron variants have also made the situation more challenging. Herein...

Focused Multivector Ultraviolet (FMUV) technology rapidly killed the SARS-CoV-2 coronavirus in-vitro. Plates were inoculated with a mean of greater than 10⁶ plaque forming units (PFUs) of USA-WA1 Washington index patient strain of SARS-CoV-2 and exposed to ultraviolet, resulting in mean reductions of 99.99% within 30 seconds, 99.999% within 60 seco...

Invasive fungal diseases due to resistant yeasts and molds are an important and increasing public health threat, likely due to a growing population of immunosuppressed hosts, increases in antifungal resistance, and improvements in laboratory diagnostics. The significant morbidity and mortality associated with these pathogens bespeaks the urgent nee...

Background Candida species are a major cause of invasive and mucocutaneouls infections. There are limited oral treatment options available for patients with Candida infections who are unresponsive to or who are intolerant of currently available antifungals. Oral ibrexafungerp is an investigational broad-spectrum glucan synthase inhibitor antifungal...

Background Stenotrophomonas maltophilia causes lethal pneumonia, bacteremia, and sepsis in immunocompromised patients. As a standard of care, trimethoprim-sulfamethoxazole (T/S) is considered to be the first-line therapy for Stenotrophomonas pneumonia. Cefiderocol (CFDC) is a new parenteral siderophore cephalosporin that is transported through the...

Background Candida albicans is the predominant organism causing esophageal candidiasis (EC) and oropharyngel candidiasis (OPC). These infections may arise from subjects colonized with Candida who are predisposed due to illness, debility or a local reduction in host resistance to an overgrowth of their own indigenous flora. Patients with mucocutaneo...

The incidence of adenovirus viremia and the role of screening in preventing adenovirus disease in adult transplant recipients are not well defined. Between January 2017 and May 2020, 262 allogeneic transplants were performed using in vivo T-cell depletion. Adenovirus viremia was found in 59 patients for a cumulative incidence of 10% by one hundred...

MRSA infections of surgically implanted subcutaneous vascular catheters (SISVCs) cause serious morbidity in patients with chronic illnesses. Previous in vitro and murine models demonstrated synergistic interaction of equimolar concentrations of meropenem/piperacillin/tazobactam (M/P/T; VIO-001) against MRSA infection. We investigated the pharmacoki...

Background: Acute pyelonephritis is a common and potentially life-threatening form of urinary tract infection. There is lack in comprehensive pyelonephritis study models in vitro. Here, we have introduced a novel translational ex vivo porcine renal tissue explant model, which recapitulates the complexity of host interface and thereby permits invest...

Invasive fungal diseases due to resistant yeasts and molds are an important and increasing public health threat, likely due to a growing population of immunosuppressed hosts, increases in antifungal resistance, and improvements in laboratory diagnostics. The significant morbidity and mortality associated with these pathogens bespeaks the urgent nee...

Isavuconazole, administered as the water-soluble prodrug isavuconazonium sulfate, is a new triazole agent used to treat invasive fungal infections. This phase 1 study evaluated the pharmacokinetics (PK), safety, and tolerability of isavuconazole in 46 immunocompromised pediatric patients, stratified by age (1 to <6 [intravenous (IV) only], 6 to <12...

Background: Levofloxacin prophylaxis is recommended to prevent Gram-negative bloodstream infections (BSIs) in patients with prolonged chemotherapy-induced neutropenia. However, increasing fluoroquinolone resistance may decrease the effectiveness of this approach. Methods: We assessed the prevalence of colonization with fluoroquinolone-resistant...

Stenotrophomonas maltophilia is an emerging multidrug-resistant pathogen responsible for high morbidity and mortality among immunocompromised patients. Therefore, novel decolonization and treatment strategies are needed for better management the infections caused by multidrug-resistant S. maltophilia (MDRSA). Herein, a novel lytic bacteriophage vB_...

Invasive pulmonary aspergillosis (IPA) is increasingly recognized as a life-threatening superinfection of severe respiratory viral infections, such as influenza. The pandemic of Coronavirus Disease 2019 (COVID-19) due to emerging SARS-CoV-2 rose concern about the eventuality of IPA complicating COVID-19 in intensive care unit mechanically-ventilate...

Ustekinumab, an IL-12/23 inhibitor, is an important agent in treatment of inflammatory bowel disease and psoriasis. Clinical trials have not demonstrated significantly increased infection risk with ustekinumab. We report a case of disseminated histoplasmosis in the setting of ustekinumab and methotrexate following a hike in the Catskill Mountains,...

With increasing numbers of patients needing intensive care or who are immunosuppressed, infections caused by moulds other than Aspergillus spp or Mucorales are increasing. Although antifungal prophylaxis has shown effectiveness in preventing many invasive fungal infections, selective pressure has caused an increase of breakthrough infections caused...

Fungal infections are a rising threat to our immunocompromised patient population as well as other non-immunocompromised patients with various medical conditions. However, little progress has been made in the past decade to improve fungal diagnostics. To jointly address this diagnostic challenge, the Fungal Diagnostics Laboratory Consortium (FDLC)...

Background Trichosporon species are uncommon but emerging pathogens that cause life-threatening infections that are resistant to amphotericin B and echinocandins. Diagnosis of deeply invasive trichosporonosis is often elusive to conventional culture methods until locally advanced or disseminated disease has advanced. CT scans Pulmonary Trichosporon...

Background Limited data are available for risk assessment and outcome of COVID-19 in patients with hematologic malignancies (HM). We present a single center study of COVID-19 pneumonia in a cohort of 31 patients with HM. Methods Data were abstracted from electronic medical records for patients admitted to NYPH between 3/5/20 and 4/17/20 and entere...

Candida endophthalmitis is a serious sight-threatening complication of candidemia that may occur before or during antifungal therapy. Hematogenous Candida meningoencephalitis (HCME) is also a serious manifestation of disseminated candidiasis in premature infants, immunosuppressed children, and immunocompromised adults. We evaluated the antifungal e...

Treatment options for Exserohilum rostratum meningoencephalitis and other causes of phaeohyphomycosis of the central nervous system (CNS) are limited, while mortality and morbidity remain high. We therefore evaluated isavuconazole, a new antifungal triazole in comparison to liposomal amphotericin B (LAMB), in vitro and in the rabbit model of Exsero...

Background. Aspergillus galactomannan antigenemia is an accepted tool for the diagnosis of invasive pulmonary aspergillosis (IPA) in neutropenic patients. Little is known, however, about the utility of this biomarker to assess the efficacy of antifungal therapies. Methods . The pharmacokinetics and pharmacodynamics (PK/PD) of posaconazole in treatm...

The U.S. Food and Drug Administration (FDA) hosted a public workshop entitled “Advancing Animal Models for Antibacterial Drug Development” on March 5, 2020. The workshop mainly focused on models of pneumonia caused by Pseudomonas aeruginosa and Acinetobacter baumannii . The program included discussions from academic investigators, industry, and U.S...

Animal model systems are a critical component of the process of discovery and development of new antifungal agents for treatment and prevention of invasive aspergillosis. The persistently neutropenic rabbit model of invasive pulmonary aspergillosis (IPA) has been a highly predictive system in identifying new antifungal agents for treatment and prev...

Patients with cancer may be at increased risk of severe coronavirus disease 2019 (COVID-19), but the role of viral load on this risk is unknown. We measured SARS-CoV-2 viral load using cycle threshold (CT) values from reverse-transcription polymerase chain reaction assays applied to nasopharyngeal swab specimens in 100 patients with cancer and 2,91...

Candida auris is an emerging multidrug-resistant fungal pathogen reported worldwide. Infections due to C. auris are usually nosocomial and associated with high rates of fluconazole resistance and mortality. Echinocandins are utilized as the first-line treatment. However, echinocandins are only available intravenously and are associated with increas...

In recent years, the global public health community has increasingly recognized the importance of antimicrobial stewardship (AMS) in the fight to improve outcomes, decrease costs, and curb increases in antimicrobial resistance around the world. However, the subject of antifungal stewardship (AFS) has received less attention. While the principles of...

The GPI-anchor biosynthesis inhibitor gepinacin demonstrates broad-spectrum antifungal activity and negligible mammalian toxicity in culture but is metabolically labile. The stability and bioactivity of 39 analogs were tested in vitro, to identify LCUT-08, a stabilized lead with increased potency and promising single-dose pharmacokinetics. Unfortun...

Purpose: To investigate the antimycotic activity of amphotericin B deoxycholate that has been previously frozen for 28 days before supplementation of Optisol-GS. Methods: Triplicate Optisol-GS samples were inoculated with 10 colony-forming units (CFU) of Candida albicans. Each set of triplicate cultures was supplemented with 2.5 μg/mL of amphote...

Solid organ transplant recipients may be at a high risk for SARS‐CoV2 infection and poor associated outcomes. We herein report our initial experience with solid organ transplant recipients with SARS‐CoV2 infection at two centers during the first 3 weeks of the outbreak in New York City. Baseline characteristics, clinical presentation, antiviral and...

Introduction: Osteoarticular fungal infections (OAFIs) complicate the clinical course of high-risk patients, including immunosuppressed individuals. Their management, however, despite being intricate, is governed by evidence arising from sub-optimal quality research, such as case series. Guidelines are scarce and when present result in recommendati...

Ibrexafungerp (formerly SCY-078) is a semisynthetic triterpenoid and potent (1→3)-β-D-glucan synthase inhibitor. We investigated the in vitro activity, pharmacokinetics, and in vivo efficacy of ibrexafungerp (SCY) alone and in combination with anti-mould triazole isavuconazole (ISA) against invasive pulmonary aspergillosis (IPA). The combination of...

This report addresses a topic of high current interest - the ultraviolet susceptibility of SARS-CoV-2, the virus that causes COVID-19 disease. The results of a literature review are presented and summarized to provide a basis for estimating the ultraviolet susceptibility of SARS-CoV-2, and relevant supplemental information is provided on COVID-19 b...

Phaeohyphomycosis of the central nervous system (CNS) is a life-threatening infection associated with severe morbidity. New approaches to treatment of CNS phaeohyphomycosis are critically needed. We therefore studied posaconazole with or without caspofungin for treatment of experimental CNS phaeohyphomycosis caused by Exserohilum rostratum. Each cl...

Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC- Kp ) is an emerging global public health threat that causes life-threatening pneumonia and bacteremia. Ceftazidime-avibactam represents a promising advance for the treatment of serious infections caused by KPC- Kp . We investigated the pharmacokinetics and efficacy of ceftazi...

Hyaline molds, widely distributed in nature, are an important and increasing cause of invasive fungal infections in humans, likely due to an expanding population of immunosuppressed hosts, increases in antifungal resistance, and improvements in laboratory diagnostics. Sinopulmonary disease and disseminated infection are common manifestations in neu...

Histoplasmosis is a common endemic mycosis due to the dimorphic fungus Histoplasma capsulatum. It is most common in the Ohio and Mississippi River valleys of the United States but has been found throughout the world. Infection is typically asymptomatic. Clinical syndromes include acute pulmonary infection after heavy fungal exposure, chronic cavita...

Background. Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnost...

Background: Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnos...

Introduction Admissions for acute bacterial skin and skin structure infections (ABSSSI) are often prolonged because of intravenous (IV) antibiotics. Use of a long-acting IV antibiotic may reduce length of stay (LOS) on a hospitalist service. The ENHANCE ABSSSI trial sought to determine the impact on LOS and work productivity in patients treated wit...

Background and Objectives: Uropathogenic Escherichia coli (UPEC) are common pathogens causing urinary tract infections (UTIs). We aimed to investigate the relationship among clinical manifestation, serogroups, phylogenetic groups, and antimicrobial resistance among UPEC. Materials and Methods: One-hundred Escherichia coli isolates recovered from ur...

Background: Diarrhea is common and associated with substantial morbidity among hematopoietic cell transplant (HCT) recipients, but the etiology is often not identified. Multiplexed PCR assays increase the detection of diarrheal pathogens, but the impact of this technology in this population has not been evaluated. Methods: Our center replaced st...

Candida osteomyelitis is a debilitating disease that is difficult to diagnose and treat. As there are no animal models or prospective studies for this uncommon infection, little is known about the pathogenesis, diagnosis, or treatment. We therefore sought to establish an animal model for the study of the pathophysiology, diagnostic modalities, and...

Mucormycosis is a difficult to diagnose rare disease with high morbidity and mortality. Diagnosis is often delayed, and disease tends to progress rapidly. Urgent surgical and medical intervention is lifesaving. Guidance on the complex multidisciplinary management has potential to improve prognosis, but approaches differ between health-care settings...

Background: This non-randomized comparative observational study evaluated the performance of a standard manual-chemical disinfection process with an automated process employing focused multivector ultraviolet (FMUV) light technology during operating room (OR) terminal cleaning. Methods: An Association of periOperative Registered Nurses terminal...

Background In this prospective nation-wide survey of bloodstream isolates associated with first episode of FN in high-risk cancer patients from 14 US cancer centers (December 2016 and June 2018), viridans group Streptococci (VGS) were the most common Gram-positive isolate. We sought to clinically and microbiologically characterize VGS bloodstream i...

Background Patients with bloodstream infections (BSIs) due to carbapenem-resistant Enterobacteriaceae (CRE) have long delays until receipt of appropriate antimicrobial therapy and high mortality rates. Rapid molecular diagnostics and novel therapies, such as ceftazidime–avibactam (CAZ-AVI), offer promise to improve outcomes, but their clinical impa...

Background Community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP) are the leading causes of death from infection in developed countries. Mannose-binding lectin (MBL) is a C-type serum lectin that plays a central role in the innate pulmonary host defenses against respiratory pathogens. We hypothesized that MBL polymorphisms may inc...

Background Pneumocystis jirovecii pneumonia is an uncommon and life-threatening disease that can occur following hematopoietic stem cell transplantation (HSCT). Trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis greatly reduces the incidence of PJP. We aim to determine what factors contribute to the development of PJP following HSCT where TMP-SMX...

Background Prolonged admissions for acute bacterial skin and skin structure infections (ABSSSI) present an opportunity to improve efficiency and quality of care. A primary reason for admission for ABSSSI is to receive intravenous (IV) antibiotics, where multiple guidelines support shifting care to outpatient settings for appropriate patients. A hos...

Background Disseminated fusariosis in patients with hematological malignancies is a frequently fatal and emerging invasive mycosis. Fusarium spp. are often resistant to safely achievable concentrations of mould active triazoles and amphotericin B. We aimed to determine the efficacy of isavuconazonium sulfate (ISA) alone or in combination with micaf...

Hematogenous Candida meningoencephalitis (HCME) is a life-threatening complication of neonates and immunocompromised children. Amphotericin B (AmB) shows poor permeability and low cerebrospinal fluid (CSF) concentrations, but is effective in treatment of HCME. In order to better understand the mechanism of CNS penetration of AmB, we hypothesized th...

Introduction: Therapeutic drug monitoring (TDM) has been shown to optimize the management of invasive fungal infections (IFIs), particularly for select antifungal agents with a well-defined exposure-response relationship and an unpredictable pharmacokinetic profile or a narrow therapeutic index. Select triazoles (itraconazole, voriconazole, and pos...

Background Uropathogenic Escherichia coli (UPEC) are common pathogens causing urinary tract infections (UTIs). We aimed to investigate the relationship among clinical manifestation, serogroups, phylogenetic groups, and antimicrobial resistance among UPEC. Methods One-hundred Escherichia coli isolates recovered from urine and ureteral scrapings were...

Necrotizing mucormycosis is a devastating complication of wounds incurred in the setting of military (combat) injuries, natural disasters, burns, or other civilian trauma. Apophysomyces species, Saksenaea species and Lichtheimia (formerly Absidia) species, although uncommon as causes of sinopulmonary mucormycosis, are relatively frequent agents of...