Matthew Oughton | McGill University (original) (raw)

Papers by Matthew Oughton

Research paper thumbnail of Comparison of Pulsed-Field Gel Electrophoresis and Whole Genome Sequencing in Clostridium difficile Typing

Open Forum Infectious Diseases, 2016

Research paper thumbnail of <i>Clostridium difficile</i>: Investigating Transmission Patterns Between Infected and Colonized Patients Using Whole Genome Sequencing

Clinical Infectious Diseases, May 28, 2018

See the Editorial Commentary by O'Hagan and McDonald on pages 210-2.) Background. Whole genome se... more See the Editorial Commentary by O'Hagan and McDonald on pages 210-2.) Background. Whole genome sequencing (WGS) studies can enhance our understanding of the role of patients with asymptomatic Clostridium difficile colonization in transmission. Methods. Isolates obtained from patients with Clostridium difficile infection (CDI) and colonization identified in a study conducted during 2006-2007 at 6 Canadian hospitals underwent typing by pulsed-field gel electrophoresis, multilocus sequence typing, and WGS. Isolates from incident CDI cases not in the initial study were also sequenced where possible. Ward movement and typing data were combined to identify plausible donors for each CDI case, as defined by shared time and space within predefined limits. Proportions of plausible donors for CDI cases that were colonized, infected, or both were examined. Results. Five hundred fifty-four isolates were sequenced successfully, 353 from colonized patients and 201 from CDI cases. The NAP1/027/ST1 strain was the most common strain, found in 124 (62%) of infected and 92 (26%) of colonized patients. A donor with a plausible ward link was found for 81 CDI cases (40%) using WGS with a threshold of ≤2 single nucleotide polymorphisms to determine relatedness. Sixty-five (32%) CDI cases could be linked to both infected and colonized donors. Exclusive linkages to infected and colonized donors were found for 28 (14%) and 12 (6%) CDI cases, respectively. Conclusions. Colonized patients contribute to transmission, but CDI cases are more likely linked to other infected patients than colonized patients in this cohort with high rates of the NAP1/027/ST1 strain, highlighting the importance of local prevalence of virulent strains in determining transmission dynamics.

Research paper thumbnail of Medical Management for the Treatment of Nontuberculous Mycobacteria Infection of the Parotid Gland: Avoiding Surgery May Be Possible

Case Reports in Medicine, 2016

Infection with nontuberculous mycobacteria (NTM) is uncommon in the head and neck; therefore ther... more Infection with nontuberculous mycobacteria (NTM) is uncommon in the head and neck; therefore there is no clear consensus on treating these infections. Our objective was to report our experience with a unique case of NTM infection of the parotid in an immunocompetent patient, in order to determine appropriate management through our experience with this pathology. A 57year-old man, known for numerous comorbid diseases, presented to our institution complaining of right parotid swelling and pain. A computed tomography (CT) of the neck showed a multiloculated collection in the inferior portion of the right parotid gland, compatible with abscess formation. This abscess was drained by interventional radiology (IR) but required repeat drainage twice due to lack of initial improvement. He was treated with several antibiotics as culture results initially indicated Gram-positive bacilli and then Mycobacterium species, with final identification by a reference laboratory as Mycobacterium abscessus. Imipenem was initiated with amikacin and clarithromycin. His infection clinically and radiologically resolved after 5 months of antibiotherapy. In our case, the patient improved following intravenous antibiotic therapy. Our experience demonstrates that appropriate antibiotherapy can lead to resolution of Mycobacterium abscessus infection in the parotid without the risks associated with surgical intervention.

Research paper thumbnail of Clinical and Epidemiological Aspects of Clostridium difficile

Clinical Microbiology Newsletter, Jun 1, 2008

Clostridium difficile-associated disease (CDAD) has increased in frequency and severity throughou... more Clostridium difficile-associated disease (CDAD) has increased in frequency and severity throughout North America and Europe over the last 5 years, largely due to the emergence of the NAP1 epidemic strain. This transformation of a formerly mild disease into one that can cause severe morbidity and mortality within a few days has challenged our entire approach to this serious infection. Institutions require accurate and rapid diagnostics for early detection of cases and possible outbreaks in order to initiate specific therapy and implement effective infection control. The optimal hand hygiene techniques, barrier methods and environmental cleaning practices that would diminish transmission remain uncertain. Clinicians need reliable research that can pinpoint the most important factors determining severity of disease and relapse. Epidemiologic and molecular analyses are vital in order to understand the local and international transmission of this disease, as well as its recent change in pathogenicity. As well, further examination of this infection is crucial in order to find effective prophylactic maneuvers and optimal therapies. This review discusses the changing epidemiology of CDAD across North America and internationally, as well as the common diagnostic methods and molecular typing tools for this pathogen. Finally, the current evidence supporting conventional, novel, and non-antimicrobial preventative and therapeutic options is examined.

Research paper thumbnail of Evaluation and Management of Seasonal Influenza in the Emergency Department

Emergency Medicine Clinics of North America, May 1, 2012

Influenza is an acute infectious respiratory disease of viral cause that occurs annually in outbr... more Influenza is an acute infectious respiratory disease of viral cause that occurs annually in outbreaks, epidemics, and occasionally pandemics of varying severity and attack rates depending on the influenza virus subtype involved. Although most seasonal flu cases do not produce long-term sequelae, influenza continues to cause substantial morbidity and mortality despite multiple landmark discoveries in infectious diseases during the previous century. 1,2 In the past 2 decades, influenza mortality has even risen, in large part because of an aging population. 3 Worldwide, flu epidemics account for an estimated 3 to 5 million cases leading to approximately 245,000 to 500,000 deaths annually. 4 The Centers for Disease Control and Prevention (CDC) estimates there are about 36,000 influenza-related deaths each year in the United States, and between 1972 and 1992, influenza accounted for an estimated 426,000 deaths. 1,5 In Canada, the Laboratory Center for Disease Control estimates that 70,000 to 75,000 influenza-associated hospitalizations and 6000 to 7000 deaths occur from influenza each year. 6 In Europe, between 40,000 and 220,000 deaths are estimated to be caused by influenza in a moderate flu season and during a severe epidemic respectively. 7 Influenza also imposes a huge financial burden on health care systems and society overall. Data from the United States reveal that influenza accounts for more than The authors have nothing to disclose.

Research paper thumbnail of Monkeypox in Montréal: Epidemiology, Phylogenomics, and Public Health Response to a Large North American Outbreak

Annals of Internal Medicine

Research paper thumbnail of Host and Pathogen Factors forClostridium difficileInfection and Colonization

New England Journal of Medicine, 2011

Background Clostridium difficile infection is the leading cause of health care-associated diarrhe... more Background Clostridium difficile infection is the leading cause of health care-associated diarrhea, and the bacterium can also be carried asymptomatically. The objective of this study was to identify host and bacterial factors associated with health care-associated acquisition of C. difficile infection and colonization. Methods We conducted a 15-month prospective study in six Canadian hospitals in Quebec and Ontario. Demographic information, known risk factors, potential confounding factors, and weekly stool samples or rectal swabs were collected. Pulsed-field gel electrophoresis (PFGE) was performed on C. difficile isolates to determine the genotype. Levels of serum antibodies against C. difficile toxins A and B were measured. Results A total of 4143 patients were included in the study; 117 (2.8%) and 123 (3.0%) had health care-associated C. difficile infection and colonization, respectively. Older age and use of antibiotics and proton-pump inhibitors were significantly associated with health care-associated C. difficile infection. Hospitalization in the previous 2 months; use of chemotherapy, proton-pump inhibitors, and H 2 blockers; and antibodies against toxin B were associated with health care-associated C. difficile colonization. Among patients with health care-associated C. difficile infection and those with colonization, 62.7% and 36.1%, respectively, had the North American PFGE type 1 (NAP1) strain. Conclusions In this study, health care-associated C. difficile infection and colonization were differentially associated with defined host and pathogen variables. The NAP1 strain was predominant among patients with C. difficile infection, whereas asymptomatic patients were more likely to be colonized with other strains. (Funded by the Consortium de Recherche sur le Clostridium difficile.

Research paper thumbnail of Importance of Adequate qPCR Controls in Infection Control

Diagnostics

Respiratory screening assays lacking Sample Adequacy Controls (SAC) may result in inadequate samp... more Respiratory screening assays lacking Sample Adequacy Controls (SAC) may result in inadequate sample quality and thus false negative results. The non-adequate samples might represent a significant proportion of the total performed tests, thus resulting in sub-optimal infection control measures with implications that may be critical during pandemic times. The quantitative sample adequacy threshold can be established empirically, measuring the change in the frequency of positive results, as a function of the numerical value of “sample adequacy”. Establishing a quantitative threshold for SAC requires a big number/volume of tests to be analyzed in order to have a statistically valid result. Herein, we are offering for the first time clear clinical evidence that a subset of results, which did not pass minimal sample adequacy criteria, have a significantly lower frequency of positivity compared with the “adequate” samples. Flagging these results and/or re-sampling them is a mitigation stra...

Research paper thumbnail of Sample Adequacy Control (SAC) Lowers False Negatives and Increases the Quality of Screening: Introduction of “Non-Competitive” SAC for qPCR Assays

Diagnostics, 2021

Sample Adequacy Control (SAC) has critical analytical, clinical and epidemiological value that in... more Sample Adequacy Control (SAC) has critical analytical, clinical and epidemiological value that increases confidence in a negative test result. The SAC is an integral qPCR assay control, which ensures that all pre-analytical and analytical steps are adequate for accurate testing and reporting. As such, a negative SAC with a negative result on pathogen screen specifies that the result should be reported as inconclusive instead of negative. Despite this, many regulatory approved tests do not incorporate SAC into their assay design. Herein, we emphasize the universal value of SAC and offer for the first time, a simple technical strategy to introduce non-competitive SAC which does not interfere with the limit of detection for the screened pathogen. Integration of SAC can provide key benefits towards identifying, isolating, quarantining and contact tracing infected individuals and in turn can improve worldwide efforts in infection control.

Research paper thumbnail of Unreliable Detection of Methicillin-Resistant Staphylococcus aureus (MRSA) with Chromogenic Agar Due to Poor Inter-Observer Variability

Research paper thumbnail of A Fundamental Change in Antibiotic Susceptibility Testing Would Better Prevent Therapeutic Failure: From Individual to Population-Based Analysis

Frontiers in Microbiology

Research paper thumbnail of Maximizing confidence in a negative result: Quantitative sample adequacy control

Journal of Infection and Public Health

Research paper thumbnail of Detection and Isolation of Clostridium difficile Asymptomatic Carriers During Clostridium difficile Infection Outbreaks: An Exploratory Study

Clinical Infectious Diseases

During 4 Clostridium difficile infection outbreaks, unit-wide screening of 114 patients led to de... more During 4 Clostridium difficile infection outbreaks, unit-wide screening of 114 patients led to detection and isolation of 15 (13%) C. difficile asymptomatic carriers. Carriage prevalence varied between outbreaks, from 0% to 29% (P = .004). Isolating carriers was not associated with significantly shorter outbreak durations, compared with historical controls.

Research paper thumbnail of Absolute versus relative presentation of tcdB Clostridium difficile biomarker

Integrative Molecular Medicine

Clostridium difficile infection is the major etiologic agent of antibiotic-associated pseudomembr... more Clostridium difficile infection is the major etiologic agent of antibiotic-associated pseudomembranous colitis, a disease that can be fatal if unrecognized, or untreated. On average, there are 15000 deaths and 500000 new cases per year, in the USA. Diagnostic biomarkers currently used are the tcdB gene, or its gene product (toxin B). Clinical interpretation of the assay is particularly challenging: (1) biomarker detection is possible without manifestation of symptoms and (2) missing biomarker due to assay sensitivity limitations can be fatal. To resolve clinical uncertainty, quantitative analysis has been considered. Despite multiple efforts, a quantitative tcdB/toxB threshold with a meaningful clinical impact has yet to be established. Herein we shed light as to why mass/volume-based normalisations were fruitless in the past. Specifically, measuring total bacterial flora (using "universal bacterial" 16S qPCR rDNA assay) to calculate relative abundance of C difficile, we demonstrate a strong and significant negative correlation between tcdB biomarker of C difficile (R 2 =0.73, N=227, P=10-39) and the rest of gut microorganisms. The new parameter (Cq (toxB)-Cq (16SrDNA)) is calculated from two biomarkers, is independent of sampling variability and inherently incorporates the destructive character of C difficile on the rest of micro-flora. By incorporating relative abundance of tcdB (in context of the total bacterial flora), and correcting for "biomass wash-out/dilution effects of acute diarrhea , these biomarkers could collectively enhance the predictive value of CDI testing.

Research paper thumbnail of Laboratory-developed test for detection of acute Clostridium difficile infections (CDI) with the capacity for quantitative sample normalization

Diagnostic Microbiology and Infectious Disease

Research paper thumbnail of Clostridium difficile: Investigating Transmission Patterns Between Infected and Colonized Patients Using Whole Genome Sequencing

Clinical Infectious Diseases

Research paper thumbnail of Rectal swab screening assays of public health importance in molecular diagnostics: Sample adequacy control

Journal of Infection and Public Health

Research paper thumbnail of Comparison of Pulsed-Field Gel Electrophoresis and Whole Genome Sequencing in Clostridium difficile Typing

Open Forum Infectious Diseases, 2016

Research paper thumbnail of Medical Management for the Treatment of Nontuberculous Mycobacteria Infection of the Parotid Gland: Avoiding Surgery May Be Possible

Case Reports in Medicine, 2016

Infection with nontuberculous mycobacteria (NTM) is uncommon in the head and neck; therefore ther... more Infection with nontuberculous mycobacteria (NTM) is uncommon in the head and neck; therefore there is no clear consensus on treating these infections. Our objective was to report our experience with a unique case of NTM infection of the parotid in an immunocompetent patient, in order to determine appropriate management through our experience with this pathology. A 57-year-old man, known for numerous comorbid diseases, presented to our institution complaining of right parotid swelling and pain. A computed tomography (CT) of the neck showed a multiloculated collection in the inferior portion of the right parotid gland, compatible with abscess formation. This abscess was drained by interventional radiology (IR) but required repeat drainage twice due to lack of initial improvement. He was treated with several antibiotics as culture results initially indicated Gram-positive bacilli and thenMycobacteriumspecies, with final identification by a reference laboratory asMycobacterium abscessus...

Research paper thumbnail of Hand hygiene with soap and water is superior to alcohol rub and antiseptic wipes for removal of Clostridium difficile

Infection Control and Hospital Epidemiology, Oct 1, 2009

objective. To evaluate common hand hygiene methods for efficacy in removing Clostridium difficile... more objective. To evaluate common hand hygiene methods for efficacy in removing Clostridium difficile. design. Randomized crossover comparison among 10 volunteers with hands experimentally contaminated by nontoxigenic C. difficile. methods. Interventions included warm water with plain soap, cold water with plain soap, warm water with antibacterial soap, antiseptic hand wipes, alcohol-based handrub, and a control involving no intervention. All interventions were evaluated for mean reduction in colonyforming units (CFUs) under 2 contamination protocols: "whole hand" and "palmar surface." Results were analyzed according to a Bayesian approach, by using hierarchical models adjusted for multiple observations. results. Under the whole-hand protocol, the greatest adjusted mean reductions were achieved by warm water with plain soap (2.14 log 10 CFU/mL [95% credible interval (CrI), 1.74-2.54 log 10 CFU/mL]), cold water with plain soap (1.88 log 10 CFU/mL [95% CrI, 1.48-2.28 log 10 CFU/mL), and warm water with antibacterial soap (1.51 log 10 CFU/mL [95% CrI, 1.12-1.91 log 10 CFU/mL]), followed by antiseptic hand wipes (0.57 log 10 CFU/mL [95% CrI, 0.17-0.96 log 10 CFU/mL]). Alcohol-based handrub (0.06 log 10 CFU/mL [95% CrI, Ϫ0.34 to 0.45 log 10 CFU/mL]) was equivalent to no intervention. Under the palmar surface protocol, warm water with plain soap, cold water with plain soap, and warm water with antibacterial soap again yielded the greatest mean reductions, followed by antiseptic hand wipes (26.6, 26.6, 26.6, and 21.9 CFUs per plate, respectively), when compared with alcohol-based handrub. Hypothenar (odds ratio, 10.98 [95% CrI, 1.96-37.65]) and thenar (odds ratio, 6.99 [95% CrI, 1.25-23.41]) surfaces were more likely than fingertips to remain heavily contaminated after handwashing. conclusions. Handwashing with soap and water showed the greatest efficacy in removing C. difficile and should be performed preferentially over the use of alcohol-based handrubs when contact with C. difficile is suspected or likely.

Research paper thumbnail of Comparison of Pulsed-Field Gel Electrophoresis and Whole Genome Sequencing in Clostridium difficile Typing

Open Forum Infectious Diseases, 2016

Research paper thumbnail of <i>Clostridium difficile</i>: Investigating Transmission Patterns Between Infected and Colonized Patients Using Whole Genome Sequencing

Clinical Infectious Diseases, May 28, 2018

See the Editorial Commentary by O'Hagan and McDonald on pages 210-2.) Background. Whole genome se... more See the Editorial Commentary by O'Hagan and McDonald on pages 210-2.) Background. Whole genome sequencing (WGS) studies can enhance our understanding of the role of patients with asymptomatic Clostridium difficile colonization in transmission. Methods. Isolates obtained from patients with Clostridium difficile infection (CDI) and colonization identified in a study conducted during 2006-2007 at 6 Canadian hospitals underwent typing by pulsed-field gel electrophoresis, multilocus sequence typing, and WGS. Isolates from incident CDI cases not in the initial study were also sequenced where possible. Ward movement and typing data were combined to identify plausible donors for each CDI case, as defined by shared time and space within predefined limits. Proportions of plausible donors for CDI cases that were colonized, infected, or both were examined. Results. Five hundred fifty-four isolates were sequenced successfully, 353 from colonized patients and 201 from CDI cases. The NAP1/027/ST1 strain was the most common strain, found in 124 (62%) of infected and 92 (26%) of colonized patients. A donor with a plausible ward link was found for 81 CDI cases (40%) using WGS with a threshold of ≤2 single nucleotide polymorphisms to determine relatedness. Sixty-five (32%) CDI cases could be linked to both infected and colonized donors. Exclusive linkages to infected and colonized donors were found for 28 (14%) and 12 (6%) CDI cases, respectively. Conclusions. Colonized patients contribute to transmission, but CDI cases are more likely linked to other infected patients than colonized patients in this cohort with high rates of the NAP1/027/ST1 strain, highlighting the importance of local prevalence of virulent strains in determining transmission dynamics.

Research paper thumbnail of Medical Management for the Treatment of Nontuberculous Mycobacteria Infection of the Parotid Gland: Avoiding Surgery May Be Possible

Case Reports in Medicine, 2016

Infection with nontuberculous mycobacteria (NTM) is uncommon in the head and neck; therefore ther... more Infection with nontuberculous mycobacteria (NTM) is uncommon in the head and neck; therefore there is no clear consensus on treating these infections. Our objective was to report our experience with a unique case of NTM infection of the parotid in an immunocompetent patient, in order to determine appropriate management through our experience with this pathology. A 57year-old man, known for numerous comorbid diseases, presented to our institution complaining of right parotid swelling and pain. A computed tomography (CT) of the neck showed a multiloculated collection in the inferior portion of the right parotid gland, compatible with abscess formation. This abscess was drained by interventional radiology (IR) but required repeat drainage twice due to lack of initial improvement. He was treated with several antibiotics as culture results initially indicated Gram-positive bacilli and then Mycobacterium species, with final identification by a reference laboratory as Mycobacterium abscessus. Imipenem was initiated with amikacin and clarithromycin. His infection clinically and radiologically resolved after 5 months of antibiotherapy. In our case, the patient improved following intravenous antibiotic therapy. Our experience demonstrates that appropriate antibiotherapy can lead to resolution of Mycobacterium abscessus infection in the parotid without the risks associated with surgical intervention.

Research paper thumbnail of Clinical and Epidemiological Aspects of Clostridium difficile

Clinical Microbiology Newsletter, Jun 1, 2008

Clostridium difficile-associated disease (CDAD) has increased in frequency and severity throughou... more Clostridium difficile-associated disease (CDAD) has increased in frequency and severity throughout North America and Europe over the last 5 years, largely due to the emergence of the NAP1 epidemic strain. This transformation of a formerly mild disease into one that can cause severe morbidity and mortality within a few days has challenged our entire approach to this serious infection. Institutions require accurate and rapid diagnostics for early detection of cases and possible outbreaks in order to initiate specific therapy and implement effective infection control. The optimal hand hygiene techniques, barrier methods and environmental cleaning practices that would diminish transmission remain uncertain. Clinicians need reliable research that can pinpoint the most important factors determining severity of disease and relapse. Epidemiologic and molecular analyses are vital in order to understand the local and international transmission of this disease, as well as its recent change in pathogenicity. As well, further examination of this infection is crucial in order to find effective prophylactic maneuvers and optimal therapies. This review discusses the changing epidemiology of CDAD across North America and internationally, as well as the common diagnostic methods and molecular typing tools for this pathogen. Finally, the current evidence supporting conventional, novel, and non-antimicrobial preventative and therapeutic options is examined.

Research paper thumbnail of Evaluation and Management of Seasonal Influenza in the Emergency Department

Emergency Medicine Clinics of North America, May 1, 2012

Influenza is an acute infectious respiratory disease of viral cause that occurs annually in outbr... more Influenza is an acute infectious respiratory disease of viral cause that occurs annually in outbreaks, epidemics, and occasionally pandemics of varying severity and attack rates depending on the influenza virus subtype involved. Although most seasonal flu cases do not produce long-term sequelae, influenza continues to cause substantial morbidity and mortality despite multiple landmark discoveries in infectious diseases during the previous century. 1,2 In the past 2 decades, influenza mortality has even risen, in large part because of an aging population. 3 Worldwide, flu epidemics account for an estimated 3 to 5 million cases leading to approximately 245,000 to 500,000 deaths annually. 4 The Centers for Disease Control and Prevention (CDC) estimates there are about 36,000 influenza-related deaths each year in the United States, and between 1972 and 1992, influenza accounted for an estimated 426,000 deaths. 1,5 In Canada, the Laboratory Center for Disease Control estimates that 70,000 to 75,000 influenza-associated hospitalizations and 6000 to 7000 deaths occur from influenza each year. 6 In Europe, between 40,000 and 220,000 deaths are estimated to be caused by influenza in a moderate flu season and during a severe epidemic respectively. 7 Influenza also imposes a huge financial burden on health care systems and society overall. Data from the United States reveal that influenza accounts for more than The authors have nothing to disclose.

Research paper thumbnail of Monkeypox in Montréal: Epidemiology, Phylogenomics, and Public Health Response to a Large North American Outbreak

Annals of Internal Medicine

Research paper thumbnail of Host and Pathogen Factors forClostridium difficileInfection and Colonization

New England Journal of Medicine, 2011

Background Clostridium difficile infection is the leading cause of health care-associated diarrhe... more Background Clostridium difficile infection is the leading cause of health care-associated diarrhea, and the bacterium can also be carried asymptomatically. The objective of this study was to identify host and bacterial factors associated with health care-associated acquisition of C. difficile infection and colonization. Methods We conducted a 15-month prospective study in six Canadian hospitals in Quebec and Ontario. Demographic information, known risk factors, potential confounding factors, and weekly stool samples or rectal swabs were collected. Pulsed-field gel electrophoresis (PFGE) was performed on C. difficile isolates to determine the genotype. Levels of serum antibodies against C. difficile toxins A and B were measured. Results A total of 4143 patients were included in the study; 117 (2.8%) and 123 (3.0%) had health care-associated C. difficile infection and colonization, respectively. Older age and use of antibiotics and proton-pump inhibitors were significantly associated with health care-associated C. difficile infection. Hospitalization in the previous 2 months; use of chemotherapy, proton-pump inhibitors, and H 2 blockers; and antibodies against toxin B were associated with health care-associated C. difficile colonization. Among patients with health care-associated C. difficile infection and those with colonization, 62.7% and 36.1%, respectively, had the North American PFGE type 1 (NAP1) strain. Conclusions In this study, health care-associated C. difficile infection and colonization were differentially associated with defined host and pathogen variables. The NAP1 strain was predominant among patients with C. difficile infection, whereas asymptomatic patients were more likely to be colonized with other strains. (Funded by the Consortium de Recherche sur le Clostridium difficile.

Research paper thumbnail of Importance of Adequate qPCR Controls in Infection Control

Diagnostics

Respiratory screening assays lacking Sample Adequacy Controls (SAC) may result in inadequate samp... more Respiratory screening assays lacking Sample Adequacy Controls (SAC) may result in inadequate sample quality and thus false negative results. The non-adequate samples might represent a significant proportion of the total performed tests, thus resulting in sub-optimal infection control measures with implications that may be critical during pandemic times. The quantitative sample adequacy threshold can be established empirically, measuring the change in the frequency of positive results, as a function of the numerical value of “sample adequacy”. Establishing a quantitative threshold for SAC requires a big number/volume of tests to be analyzed in order to have a statistically valid result. Herein, we are offering for the first time clear clinical evidence that a subset of results, which did not pass minimal sample adequacy criteria, have a significantly lower frequency of positivity compared with the “adequate” samples. Flagging these results and/or re-sampling them is a mitigation stra...

Research paper thumbnail of Sample Adequacy Control (SAC) Lowers False Negatives and Increases the Quality of Screening: Introduction of “Non-Competitive” SAC for qPCR Assays

Diagnostics, 2021

Sample Adequacy Control (SAC) has critical analytical, clinical and epidemiological value that in... more Sample Adequacy Control (SAC) has critical analytical, clinical and epidemiological value that increases confidence in a negative test result. The SAC is an integral qPCR assay control, which ensures that all pre-analytical and analytical steps are adequate for accurate testing and reporting. As such, a negative SAC with a negative result on pathogen screen specifies that the result should be reported as inconclusive instead of negative. Despite this, many regulatory approved tests do not incorporate SAC into their assay design. Herein, we emphasize the universal value of SAC and offer for the first time, a simple technical strategy to introduce non-competitive SAC which does not interfere with the limit of detection for the screened pathogen. Integration of SAC can provide key benefits towards identifying, isolating, quarantining and contact tracing infected individuals and in turn can improve worldwide efforts in infection control.

Research paper thumbnail of Unreliable Detection of Methicillin-Resistant Staphylococcus aureus (MRSA) with Chromogenic Agar Due to Poor Inter-Observer Variability

Research paper thumbnail of A Fundamental Change in Antibiotic Susceptibility Testing Would Better Prevent Therapeutic Failure: From Individual to Population-Based Analysis

Frontiers in Microbiology

Research paper thumbnail of Maximizing confidence in a negative result: Quantitative sample adequacy control

Journal of Infection and Public Health

Research paper thumbnail of Detection and Isolation of Clostridium difficile Asymptomatic Carriers During Clostridium difficile Infection Outbreaks: An Exploratory Study

Clinical Infectious Diseases

During 4 Clostridium difficile infection outbreaks, unit-wide screening of 114 patients led to de... more During 4 Clostridium difficile infection outbreaks, unit-wide screening of 114 patients led to detection and isolation of 15 (13%) C. difficile asymptomatic carriers. Carriage prevalence varied between outbreaks, from 0% to 29% (P = .004). Isolating carriers was not associated with significantly shorter outbreak durations, compared with historical controls.

Research paper thumbnail of Absolute versus relative presentation of tcdB Clostridium difficile biomarker

Integrative Molecular Medicine

Clostridium difficile infection is the major etiologic agent of antibiotic-associated pseudomembr... more Clostridium difficile infection is the major etiologic agent of antibiotic-associated pseudomembranous colitis, a disease that can be fatal if unrecognized, or untreated. On average, there are 15000 deaths and 500000 new cases per year, in the USA. Diagnostic biomarkers currently used are the tcdB gene, or its gene product (toxin B). Clinical interpretation of the assay is particularly challenging: (1) biomarker detection is possible without manifestation of symptoms and (2) missing biomarker due to assay sensitivity limitations can be fatal. To resolve clinical uncertainty, quantitative analysis has been considered. Despite multiple efforts, a quantitative tcdB/toxB threshold with a meaningful clinical impact has yet to be established. Herein we shed light as to why mass/volume-based normalisations were fruitless in the past. Specifically, measuring total bacterial flora (using "universal bacterial" 16S qPCR rDNA assay) to calculate relative abundance of C difficile, we demonstrate a strong and significant negative correlation between tcdB biomarker of C difficile (R 2 =0.73, N=227, P=10-39) and the rest of gut microorganisms. The new parameter (Cq (toxB)-Cq (16SrDNA)) is calculated from two biomarkers, is independent of sampling variability and inherently incorporates the destructive character of C difficile on the rest of micro-flora. By incorporating relative abundance of tcdB (in context of the total bacterial flora), and correcting for "biomass wash-out/dilution effects of acute diarrhea , these biomarkers could collectively enhance the predictive value of CDI testing.

Research paper thumbnail of Laboratory-developed test for detection of acute Clostridium difficile infections (CDI) with the capacity for quantitative sample normalization

Diagnostic Microbiology and Infectious Disease

Research paper thumbnail of Clostridium difficile: Investigating Transmission Patterns Between Infected and Colonized Patients Using Whole Genome Sequencing

Clinical Infectious Diseases

Research paper thumbnail of Rectal swab screening assays of public health importance in molecular diagnostics: Sample adequacy control

Journal of Infection and Public Health

Research paper thumbnail of Comparison of Pulsed-Field Gel Electrophoresis and Whole Genome Sequencing in Clostridium difficile Typing

Open Forum Infectious Diseases, 2016

Research paper thumbnail of Medical Management for the Treatment of Nontuberculous Mycobacteria Infection of the Parotid Gland: Avoiding Surgery May Be Possible

Case Reports in Medicine, 2016

Infection with nontuberculous mycobacteria (NTM) is uncommon in the head and neck; therefore ther... more Infection with nontuberculous mycobacteria (NTM) is uncommon in the head and neck; therefore there is no clear consensus on treating these infections. Our objective was to report our experience with a unique case of NTM infection of the parotid in an immunocompetent patient, in order to determine appropriate management through our experience with this pathology. A 57-year-old man, known for numerous comorbid diseases, presented to our institution complaining of right parotid swelling and pain. A computed tomography (CT) of the neck showed a multiloculated collection in the inferior portion of the right parotid gland, compatible with abscess formation. This abscess was drained by interventional radiology (IR) but required repeat drainage twice due to lack of initial improvement. He was treated with several antibiotics as culture results initially indicated Gram-positive bacilli and thenMycobacteriumspecies, with final identification by a reference laboratory asMycobacterium abscessus...

Research paper thumbnail of Hand hygiene with soap and water is superior to alcohol rub and antiseptic wipes for removal of Clostridium difficile

Infection Control and Hospital Epidemiology, Oct 1, 2009

objective. To evaluate common hand hygiene methods for efficacy in removing Clostridium difficile... more objective. To evaluate common hand hygiene methods for efficacy in removing Clostridium difficile. design. Randomized crossover comparison among 10 volunteers with hands experimentally contaminated by nontoxigenic C. difficile. methods. Interventions included warm water with plain soap, cold water with plain soap, warm water with antibacterial soap, antiseptic hand wipes, alcohol-based handrub, and a control involving no intervention. All interventions were evaluated for mean reduction in colonyforming units (CFUs) under 2 contamination protocols: "whole hand" and "palmar surface." Results were analyzed according to a Bayesian approach, by using hierarchical models adjusted for multiple observations. results. Under the whole-hand protocol, the greatest adjusted mean reductions were achieved by warm water with plain soap (2.14 log 10 CFU/mL [95% credible interval (CrI), 1.74-2.54 log 10 CFU/mL]), cold water with plain soap (1.88 log 10 CFU/mL [95% CrI, 1.48-2.28 log 10 CFU/mL), and warm water with antibacterial soap (1.51 log 10 CFU/mL [95% CrI, 1.12-1.91 log 10 CFU/mL]), followed by antiseptic hand wipes (0.57 log 10 CFU/mL [95% CrI, 0.17-0.96 log 10 CFU/mL]). Alcohol-based handrub (0.06 log 10 CFU/mL [95% CrI, Ϫ0.34 to 0.45 log 10 CFU/mL]) was equivalent to no intervention. Under the palmar surface protocol, warm water with plain soap, cold water with plain soap, and warm water with antibacterial soap again yielded the greatest mean reductions, followed by antiseptic hand wipes (26.6, 26.6, 26.6, and 21.9 CFUs per plate, respectively), when compared with alcohol-based handrub. Hypothenar (odds ratio, 10.98 [95% CrI, 1.96-37.65]) and thenar (odds ratio, 6.99 [95% CrI, 1.25-23.41]) surfaces were more likely than fingertips to remain heavily contaminated after handwashing. conclusions. Handwashing with soap and water showed the greatest efficacy in removing C. difficile and should be performed preferentially over the use of alcohol-based handrubs when contact with C. difficile is suspected or likely.