Several demographic and clinical characteristics, including age, sex, medication use and presence... more Several demographic and clinical characteristics, including age, sex, medication use and presence of comorbid conditions are considered risk factors for recurrent CDI (rCDI). We examined the efficacy of an investigational purified oral microbiome therapeutic, SER-109, versus placebo in an exploratory analysis of subgroups of patients with risk factors for recurrence who enrolled in ECOSPOR III, a double-blind, placebo controlled trial. Forest Plot of Relative Risks for Recurrence at Week 8 for Selected Baseline Characteristics in the ITT population Patients with ≥ 3 CDI episodes were treated with SER-109 or placebo (four capsules daily for three days) following standard treatment of CDI. The primary efficacy objective was to demonstrate superiority of SER-109 versus placebo in reducing rCDI up to 8 weeks after treatment. In this exploratory analysis, we analyzed the rate of CDI recurrence among SER-109 treated subjects compared to placebo in subgroups defined by rCDI baseline risk f...
Vestibular neuritis is a disorder selectively affecting the vestibular portion of the eighth cran... more Vestibular neuritis is a disorder selectively affecting the vestibular portion of the eighth cranial nerve generally considered to be inflammatory in nature. There have been no reports of severe acute respiratory syndrome coronavirus 2 causing vestibular neuritis. We present the case of a 42-year-old Caucasian male physician, providing care to COVID-19 patients, with no significant past medical history, who developed acute vestibular neuritis, 2 weeks following a mild respiratory illness, later diagnosed as COVID-19. Physicians should keep severe acute respiratory syndrome coronavirus 2 high on the list as a possible etiology when suspecting vestibular neuritis, given the extent and implications of the current pandemic and the high contagiousness potential.
The gastrointestinal microbiota is the first line of defense against colonization with antimicrob... more The gastrointestinal microbiota is the first line of defense against colonization with antimicrobial resistant (AR) bacteria, particularly in vulnerable hosts with frequent antibiotic exposure. In a double-blind Phase 3 trial of rCDI patients, SER-109, an orally formulated consortia of purified Firmicutes spores, was superior to placebo in reducing CDI recurrence at week 8 post clinical resolution on standard-of-care (SoC) antibiotics. Overall recurrence rates were lower in SER-109 vs placebo (12.4% vs 39.8%, respectively) relative risk, 0.32 [95% CI, 0.18–0.58; p< 0.001 for RR< 1.0; p< 0.001 for RR< 0.833]. This is a post-hoc analysis examining the impact of SER-109 on antimicrobial resistance genes (ARGs) abundance in the intestinal microbiota compared to placebo. Subjects with rCDI received SoC antibiotics, then were randomized 1:1 to SER-109 or placebo at baseline. Of 182 subjects, 140 who had paired stool samples at baseline and 1-week post-treatment were included i...
Background Although the risk of exposure to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS... more Background Although the risk of exposure to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is higher for frontline healthcare workers, not all personnel have similar risks. Determining infection rate is difficult due to the limits on testing and the high rate of asymptomatic individuals. Detection of antibodies against SARS-CoV-2 may be useful for determining prior exposure to the virus and assessing mitigation strategies, such as isolation, masks, and other protective equipment. Methods An online assessment that included demographic, clinical, and exposure information and a blood sample was collected from 20 614 participants out of ~43 000 total employees at Beaumont Health, which includes 8 hospitals distributed across the Detroit metropolitan area in southeast Michigan. The presence of anti-SARS-CoV-2 IgG was determined using the EUROIMMUN assay. Results A total of 1818 (8.8%) participants were seropositive between April 13 and May 28, 2020. Among the seropositive i...
Background Prospectively identifying patients at highest risk for hospital-acquired and ventilato... more Background Prospectively identifying patients at highest risk for hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) by implementing a risk assessment scoring tool may help focus prevention efforts, optimize the screening process to improve clinical trial feasibility, and enhance development of new antibacterial agents. Methods Within the intensive care units (ICU) of 28 US hospitals, between February 6, 2016 and October 7, 2016, patients hospitalized >48 hours and receiving high levels of respiratory support were prospectively followed for meeting the definition of HABP/VABP recommended in US FDA draft guidance. Patient demographics, medical comorbidities, and treatment exposures were recorded. The association between candidate risk factors and odds of developing HABP/VABP was evaluated with a multivariable logistic regression model. Risk factors were selected using backward selection with α = 0.1 for model inclusion. A web-based scoring system was devel...
We describe an outbreak of Pseudomonas aeruginosa respiratory tract infections related to intrins... more We describe an outbreak of Pseudomonas aeruginosa respiratory tract infections related to intrinsically contaminated ultrasound gel used for intraoperative transesophageal echocardiograms in cardiovascular surgery patients. This investigation led to a product safety alert by the Food and Drug Administration and the development of guidelines for appropriate use of ultrasound gel.
... de Sanctis, Jorgelina T. MD*; Oostendorp, Sarah Beth MD; Boyanton, Bobby L. Jr MD; Robinson... more ... de Sanctis, Jorgelina T. MD*; Oostendorp, Sarah Beth MD; Boyanton, Bobby L. Jr MD; Robinson-Dunn, Barbara PhD, DABMM; Hughes, Mark PhD§; Olson, Ken E. PhD∥; Sims, Matthew D ... She had urinary retention; a Foley catheter yielded copious amounts of clear urine. ...
Background Accurate diagnosis of rCDI is challenging because of limitations in test performance a... more Background Accurate diagnosis of rCDI is challenging because of limitations in test performance and alternative causes of recurrent diarrhea, such as post-infectious irritable bowel syndrome (IBS). Stool enzyme immunoassay (EIA) toxin testing (TOX) is the best predictor of active disease, but may miss cases of CDI when toxins are below the limit of detection. In contrast, glutamate dehydrogenase (GDH) or PCR have high sensitivity but cannot differentiate colonization from infection, leading to possible overdiagnosis due to low specificity. In ECOSPOR III, SER-109, an investigational purified microbiome therapeutic, was superior to placebo in reducing rCDI (12.4% vs 39.8%, respectively; p-value < 0.001). We examined diagnostic testing patterns among screened subjects. Methods Patients with ≥2 prior episodes and ≥3 unformed bowel movements over 48 hours were screened. To ensure enrollment of patients with active CDI, toxin testing was required at entry via a local certified or cent...
Background The natural history of CDI recurrence after antibiotics may be helpful to understand t... more Background The natural history of CDI recurrence after antibiotics may be helpful to understand the window of opportunity for microbiome repair. ECOSPOR III evaluated the efficacy of SER-109, an investigational microbiome therapeutic, compared to placebo with rates of rCDI as the primary endpoint. SER-109 was superior to placebo in reducing the rate of rCDI following standard-of-care antibiotics at 8 weeks (12.4% vs 39.8%, respectively; P < 0.001). Herein, we describe results from the secondary endpoint, time to recurrence, in this well-characterized study population. Methods A total of 182 C. difficile toxin+ adults with ≥ 3 CDI episodes and symptom resolution on CDI antibiotics were randomly assigned to SER-109 (4 capsules orally x 3 days) or placebo. Recurrence for this analysis was defined as ≥ 3 unformed stools/day for ≥ 48 hours, ± C. difficile stool toxin test, and an investigator decision to treat. Time to CDI recurrence was analyzed using observed data and Kaplan-Meier m...
The use of nasopharyngeal (NP) swab sampling for the detection of various respiratory pathogens h... more The use of nasopharyngeal (NP) swab sampling for the detection of various respiratory pathogens has been a standard procedure in medicine for many years. While this is a fairly common procedure, there has been a significant increase in utilization recently due to the SARS-CoV-2 pandemic. We describe a case of a 40-year-old SARS-CoV-2 positive patient with no prior cardiac history who developed asystole while an NP swab was being used to obtain a sample for a SARS-CoV-2 assay. Return of normal sinus rhythm was achieved with chest compressions alone. The incident was deemed to have been an exaggerated vagal response to intranasal stimulation; better known as the trigeminocardiac reflex. This is the first reported case describing asystole during use of an NP swab. This case occurred in a patient with no known cardiac disease and highlights the potential importance of the arrhythmogenic nature of COVID-19 that could potentiate the vagal response in susceptible individuals undergoing NP ...
Several demographic and clinical characteristics, including age, sex, medication use and presence... more Several demographic and clinical characteristics, including age, sex, medication use and presence of comorbid conditions are considered risk factors for recurrent CDI (rCDI). We examined the efficacy of an investigational purified oral microbiome therapeutic, SER-109, versus placebo in an exploratory analysis of subgroups of patients with risk factors for recurrence who enrolled in ECOSPOR III, a double-blind, placebo controlled trial. Forest Plot of Relative Risks for Recurrence at Week 8 for Selected Baseline Characteristics in the ITT population Patients with ≥ 3 CDI episodes were treated with SER-109 or placebo (four capsules daily for three days) following standard treatment of CDI. The primary efficacy objective was to demonstrate superiority of SER-109 versus placebo in reducing rCDI up to 8 weeks after treatment. In this exploratory analysis, we analyzed the rate of CDI recurrence among SER-109 treated subjects compared to placebo in subgroups defined by rCDI baseline risk f...
Vestibular neuritis is a disorder selectively affecting the vestibular portion of the eighth cran... more Vestibular neuritis is a disorder selectively affecting the vestibular portion of the eighth cranial nerve generally considered to be inflammatory in nature. There have been no reports of severe acute respiratory syndrome coronavirus 2 causing vestibular neuritis. We present the case of a 42-year-old Caucasian male physician, providing care to COVID-19 patients, with no significant past medical history, who developed acute vestibular neuritis, 2 weeks following a mild respiratory illness, later diagnosed as COVID-19. Physicians should keep severe acute respiratory syndrome coronavirus 2 high on the list as a possible etiology when suspecting vestibular neuritis, given the extent and implications of the current pandemic and the high contagiousness potential.
The gastrointestinal microbiota is the first line of defense against colonization with antimicrob... more The gastrointestinal microbiota is the first line of defense against colonization with antimicrobial resistant (AR) bacteria, particularly in vulnerable hosts with frequent antibiotic exposure. In a double-blind Phase 3 trial of rCDI patients, SER-109, an orally formulated consortia of purified Firmicutes spores, was superior to placebo in reducing CDI recurrence at week 8 post clinical resolution on standard-of-care (SoC) antibiotics. Overall recurrence rates were lower in SER-109 vs placebo (12.4% vs 39.8%, respectively) relative risk, 0.32 [95% CI, 0.18–0.58; p< 0.001 for RR< 1.0; p< 0.001 for RR< 0.833]. This is a post-hoc analysis examining the impact of SER-109 on antimicrobial resistance genes (ARGs) abundance in the intestinal microbiota compared to placebo. Subjects with rCDI received SoC antibiotics, then were randomized 1:1 to SER-109 or placebo at baseline. Of 182 subjects, 140 who had paired stool samples at baseline and 1-week post-treatment were included i...
Background Although the risk of exposure to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS... more Background Although the risk of exposure to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is higher for frontline healthcare workers, not all personnel have similar risks. Determining infection rate is difficult due to the limits on testing and the high rate of asymptomatic individuals. Detection of antibodies against SARS-CoV-2 may be useful for determining prior exposure to the virus and assessing mitigation strategies, such as isolation, masks, and other protective equipment. Methods An online assessment that included demographic, clinical, and exposure information and a blood sample was collected from 20 614 participants out of ~43 000 total employees at Beaumont Health, which includes 8 hospitals distributed across the Detroit metropolitan area in southeast Michigan. The presence of anti-SARS-CoV-2 IgG was determined using the EUROIMMUN assay. Results A total of 1818 (8.8%) participants were seropositive between April 13 and May 28, 2020. Among the seropositive i...
Background Prospectively identifying patients at highest risk for hospital-acquired and ventilato... more Background Prospectively identifying patients at highest risk for hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) by implementing a risk assessment scoring tool may help focus prevention efforts, optimize the screening process to improve clinical trial feasibility, and enhance development of new antibacterial agents. Methods Within the intensive care units (ICU) of 28 US hospitals, between February 6, 2016 and October 7, 2016, patients hospitalized >48 hours and receiving high levels of respiratory support were prospectively followed for meeting the definition of HABP/VABP recommended in US FDA draft guidance. Patient demographics, medical comorbidities, and treatment exposures were recorded. The association between candidate risk factors and odds of developing HABP/VABP was evaluated with a multivariable logistic regression model. Risk factors were selected using backward selection with α = 0.1 for model inclusion. A web-based scoring system was devel...
We describe an outbreak of Pseudomonas aeruginosa respiratory tract infections related to intrins... more We describe an outbreak of Pseudomonas aeruginosa respiratory tract infections related to intrinsically contaminated ultrasound gel used for intraoperative transesophageal echocardiograms in cardiovascular surgery patients. This investigation led to a product safety alert by the Food and Drug Administration and the development of guidelines for appropriate use of ultrasound gel.
... de Sanctis, Jorgelina T. MD*; Oostendorp, Sarah Beth MD; Boyanton, Bobby L. Jr MD; Robinson... more ... de Sanctis, Jorgelina T. MD*; Oostendorp, Sarah Beth MD; Boyanton, Bobby L. Jr MD; Robinson-Dunn, Barbara PhD, DABMM; Hughes, Mark PhD§; Olson, Ken E. PhD∥; Sims, Matthew D ... She had urinary retention; a Foley catheter yielded copious amounts of clear urine. ...
Background Accurate diagnosis of rCDI is challenging because of limitations in test performance a... more Background Accurate diagnosis of rCDI is challenging because of limitations in test performance and alternative causes of recurrent diarrhea, such as post-infectious irritable bowel syndrome (IBS). Stool enzyme immunoassay (EIA) toxin testing (TOX) is the best predictor of active disease, but may miss cases of CDI when toxins are below the limit of detection. In contrast, glutamate dehydrogenase (GDH) or PCR have high sensitivity but cannot differentiate colonization from infection, leading to possible overdiagnosis due to low specificity. In ECOSPOR III, SER-109, an investigational purified microbiome therapeutic, was superior to placebo in reducing rCDI (12.4% vs 39.8%, respectively; p-value < 0.001). We examined diagnostic testing patterns among screened subjects. Methods Patients with ≥2 prior episodes and ≥3 unformed bowel movements over 48 hours were screened. To ensure enrollment of patients with active CDI, toxin testing was required at entry via a local certified or cent...
Background The natural history of CDI recurrence after antibiotics may be helpful to understand t... more Background The natural history of CDI recurrence after antibiotics may be helpful to understand the window of opportunity for microbiome repair. ECOSPOR III evaluated the efficacy of SER-109, an investigational microbiome therapeutic, compared to placebo with rates of rCDI as the primary endpoint. SER-109 was superior to placebo in reducing the rate of rCDI following standard-of-care antibiotics at 8 weeks (12.4% vs 39.8%, respectively; P < 0.001). Herein, we describe results from the secondary endpoint, time to recurrence, in this well-characterized study population. Methods A total of 182 C. difficile toxin+ adults with ≥ 3 CDI episodes and symptom resolution on CDI antibiotics were randomly assigned to SER-109 (4 capsules orally x 3 days) or placebo. Recurrence for this analysis was defined as ≥ 3 unformed stools/day for ≥ 48 hours, ± C. difficile stool toxin test, and an investigator decision to treat. Time to CDI recurrence was analyzed using observed data and Kaplan-Meier m...
The use of nasopharyngeal (NP) swab sampling for the detection of various respiratory pathogens h... more The use of nasopharyngeal (NP) swab sampling for the detection of various respiratory pathogens has been a standard procedure in medicine for many years. While this is a fairly common procedure, there has been a significant increase in utilization recently due to the SARS-CoV-2 pandemic. We describe a case of a 40-year-old SARS-CoV-2 positive patient with no prior cardiac history who developed asystole while an NP swab was being used to obtain a sample for a SARS-CoV-2 assay. Return of normal sinus rhythm was achieved with chest compressions alone. The incident was deemed to have been an exaggerated vagal response to intranasal stimulation; better known as the trigeminocardiac reflex. This is the first reported case describing asystole during use of an NP swab. This case occurred in a patient with no known cardiac disease and highlights the potential importance of the arrhythmogenic nature of COVID-19 that could potentiate the vagal response in susceptible individuals undergoing NP ...
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