Pathogen genomics in healthcare: overcoming barriers to proactive surveillance.

Pathogen genomic surveillance in healthcare has the potential to enhance patient safety by detecting outbreaks earlier, thereby reducing morbidity and mortality. Despite benefits, there are barriers to adoption, including cost, expertise, and lack of standardized methodologies and incentives. This commentary advocates for 1) investment from healthcare payors, public health, and regulatory bodies and 2) additional research on genomic surveillance for improving patient outcomes and reducing infections.

Amoxicillin-Clavulanate Breakpoints Against Enterobacterales: Rationale for Revision by the Clinical and Laboratory Standards Institute.

Amoxicillin-clavulanate (AMC) is among the most frequently prescribed antibiotics globally. It has broad antibacterial activity against gram-positive, gram-negative, and anaerobic bacteria and has been used to treat infections caused by a broad range of pathogens. AMC breakpoints against Enterobacterales were initially set in the 1980s.

Comparison of Daily Versus Admission and Discharge Surveillance Cultures for Multidrug-Resistant Organism Detection in an Intensive Care Unit.

Background: Admission and discharge screening of patients for asymptomatic gut colonization with multidrug-resistant organisms (MDROs) is a common approach to active surveillance, but its sensitivity for detecting colonization is uncertain.

Methods: Daily rectal or fecal swab samples and associated clinical data were collected over 12 months from patients in one 25-bed medical intensive care unit (ICU) in Chicago, IL and tested for the following MDROs: vancomycin-resistant enterococci; third-generation cephalosporin-resistant Enterobacterales, including extended-spectrum β-lactamase-producing Enterobacterales; and carbapenem-resistant Enterobacterales. MDRO detection by (1) admission and discharge surveillance cultures or (2) clinical cultures were compared to daily surveillance cultures.

Development and Validation of Three Automated High-Throughput Molecular Tests to Detect Monkeypox Virus Infections.

Background: The 2022 outbreak of the clade IIb monkeypox virus and subsequent global spread lead to an urgent need for the development of high-throughput, sensitive, and reproducible diagnostic tests.

Methods: We developed 3 assays to detect monkeypox virus, 2 (MPXV+ and MPXV) for m2000 RealTime and 1 (MPXV) for Alinity m platforms. Dual targets in E9L and B6R (MPXV+) and J2L and B7R (MPXV) increased mutation resistance.

Utilization of an immunochromatographic lateral flow assay for rapid detection of carbapenemase production in gram negative bacilli.

Background: Rapid detection of carbapenemase production in gram negative bacilli has important treatment considerations.

Objective: We evaluated a lateral flow assay (LFA) for carbapenemase production compared with molecular detection of 5 (blaKPC, blaNDM, blaVIM, blaIMP, and blaOXA-48) carbapenemase genes.

Methods: A total of 218 carbapenem nonsusceptible strains, including species of Enterobacterales, Pseudomonas aeruginosa isolated from clinical cultures were tested using the Cepheid Xpert Carba-R assay and the NG Biotech Carba-5 lateral flow immunoassay.

Change of Plans: Overview of Bacterial Taxonomy, Recent Changes of Medical Importance, and Potential Areas of Impact.

The process of bacterial nomenclature change has evolved in complexity over time and continues to be an iterative process that is not without challenges. The importance and feasibility of such changes vary among basic researchers, clinical microbiologists, and clinicians. In recent years, clinically relevant changes have been made across Gram-positive and Gram-negative organism groups, as well as the mycobacteria.

Genomic Investigation to Identify Sources of Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Healthcare Personnel in an Acute Care Hospital.

Background: Identifying the source of healthcare personnel (HCP) coronavirus disease 2019 (COVID-19) is important to guide occupational safety efforts. We used a combined whole genome sequencing (WGS) and epidemiologic approach to investigate the source of HCP COVID-19 at a tertiary-care center early in the COVID-19 pandemic.

Methods: Remnant nasopharyngeal swab samples from HCP and patients with polymerase chain reaction-proven COVID-19 from a period with complete sample retention (14 March 2020 to 10 April 2020) at Rush University Medical Center in Chicago, Illinois, underwent viral RNA extraction and WGS.

Utility of the Signal-to-Cutoff Ratio and Antigen Index from Fourth- and Fifth-Generation HIV-1/HIV-2 Antigen/Antibody Assays for the Diagnosis of Acute HIV Infection: Applicability for Real-Time Use for Immediate Initiation of Antiretroviral Therapy.

Identification of individuals with acute HIV infection (AHI) and rapid initiation of antiretroviral therapy (ART) are priorities for HIV elimination efforts. Fourth- and fifth-generation HIV-1/HIV-2 antigen (Ag)/antibody (Ab) combination assays can quickly identify patients with AHI, but false-positive results can occur. Confirmatory nucleic acid amplification testing (NAAT) may not be rapidly available.

Duration of Replication-Competent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Shedding Among Patients With Severe or Critical Coronavirus Disease 2019 (COVID-19).

Background: Patterns of shedding replication-competent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in severe or critical COVID-19 are not well characterized. We investigated the duration of replication-competent SARS-CoV-2 shedding in upper and lower airway specimens from patients with severe or critical coronavirus disease 2019 (COVID-19).

Methods: We enrolled patients with active or recent severe or critical COVID-19 who were admitted to a tertiary care hospital intensive care unit (ICU) or long-term acute care hospital (LTACH) because of COVID-19.

Whole-genome sequencing for neonatal intensive care unit outbreak investigations: Insights and lessons learned.

Infectious diseases outbreaks are a cause of significant morbidity and mortality among hospitalized patients. Infants admitted to the neonatal intensive care unit (NICU) are particularly vulnerable to infectious complications during hospitalization. Thus, rapid recognition of and response to outbreaks in the NICU is essential.

Comparison of Two Commercial Molecular Tests and a Laboratory-Developed Modification of the CDC 2019-nCoV Reverse Transcriptase PCR Assay for the Detection of SARS-CoV-2.

We compared the ability of 2 commercial molecular amplification assays (RealTime SARS-CoV-2 on the 2000 [abbreviated ACOV; Abbott] and ID Now COVID-19 [abbreviated IDNOW; Abbott]) and a laboratory-developed test (modified CDC 2019-nCoV reverse transcriptase PCR [RT-PCR] assay with RNA extraction by eMag [bioMérieux] and amplification on QuantStudio 6 or ABI 7500 real-time PCR system [abbreviated CDC COV]) to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in upper respiratory tract specimens. Discrepant results were adjudicated by medical record review. A total of 200 nasopharyngeal swab specimens in viral transport medium (VTM) were collected from symptomatic patients between 27 March and 9 April 2020.

Increased Relative Abundance of Klebsiella pneumoniae Carbapenemase-producing Klebsiella pneumoniae Within the Gut Microbiota Is Associated With Risk of Bloodstream Infection in Long-term Acute Care Hospital Patients.

Background: An association between increased relative abundance of specific bacterial taxa in the intestinal microbiota and bacteremia has been reported in some high-risk patient populations.

Methods: We collected weekly rectal swab samples from patients at 1 long-term acute care hospital (LTACH) in Chicago from May 2015 to May 2016. Samples positive for Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) by polymerase chain reaction and culture underwent 16S rRNA gene sequence analysis; relative abundance of the operational taxonomic unit containing KPC-Kp was determined.

Gut Microbiota and Clinical Features Distinguish Colonization With Carbapenemase-Producing at the Time of Admission to a Long-term Acute Care Hospital.

Background: Identification of gut microbiota features associated with antibiotic-resistant bacterial colonization may reveal new infection prevention targets.

Methods: We conducted a matched, case-control study of long-term acute care hospital (LTACH) patients to identify gut microbiota and clinical features associated with colonization by carbapenemase-producing (KPC-Kp), an urgent antibiotic resistance threat. Fecal or rectal swab specimens were collected and tested for KPC-Kp; 16S rRNA gene-based sequencing was performed.

Severe acute respiratory distress syndrome in a liver transplant patient.

This case report presents a 46-year old man with a failed liver transplant who presented with malaise and dyspnea. Imaging studies revealed diffuse reticulonodular infiltrates and innumerable miliary nodules and a left upper lobe consolidative mass. Examination of bronchoalveolar lavage fluid demonstrated yeast cells with broad-based budding.

Multicenter Evaluation of the Xpert Carba-R Assay for Detection of Carbapenemase Genes in Gram-Negative Isolates.

This multicenter study evaluated the performance of the Cepheid Xpert Carba-R assay, a qualitative PCR test designed for the rapid detection of , , , , and carbapenem resistance genes from bacterial isolates grown on blood agar or MacConkey agar. The results were compared to those obtained from bidirectional DNA sequence analysis of nucleic acid extracted from pure colonies. Isolates of , , and that tested as either intermediate or resistant to a carbapenem antibiotic were analyzed.

Rapid Identification of Five Classes of Carbapenem Resistance Genes Directly from Rectal Swabs by Use of the Xpert Carba-R Assay.

Carbapenemase-producing organisms (CPO) have been identified by global health leaders as an urgent threat. Detection of patients with gastrointestinal carriage of CPO is necessary to interrupt their spread within health care facilities. In this multisite study, we assessed the performance of the Xpert Carba-R test, a rapid real-time quantitative PCR (qPCR) assay that detects five families of carbapenemase genes (, , , , and ) directly from rectal swab specimens.

Modifiable Risk Factors for the Spread of Klebsiella pneumoniae Carbapenemase-Producing Enterobacteriaceae Among Long-Term Acute-Care Hospital Patients.

OBJECTIVE To identify modifiable risk factors for acquisition of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae (KPC) colonization among long-term acute-care hospital (LTACH) patients. DESIGN Multicenter, matched case-control study. SETTING Four LTACHs in Chicago, Illinois.

Comparison of stool versus rectal swab samples and storage conditions on bacterial community profiles.

Background: Sample collection for gut microbiota analysis from in-patients can be challenging. Collection method and storage conditions are potential sources of variability. In this study, we compared the bacterial microbiota from stool stored under different conditions, as well as stool and swab samples, to assess differences due to sample storage conditions and collection method.

Duration of Colonization With Carbapenemase-Producing Bacteria at Long-Term Acute Care Hospitals in Chicago, Illinois.

 High prevalence of carbapenemase (KPC)-producing has been reported in long-term acute care hospitals (LTACHs), in part because of frequent readmissions of colonized patients. Knowledge of the duration of colonization with KPC is essential to identify patients at risk of KPC colonization upon readmission and to make predictions on the effects of transmission control measures.  We analyzed data on surveillance isolates that were collected at 4 LTACHs in the Chicago region during a period of bundled interventions, to simultaneously estimate the duration of colonization during an LTACH admission and between LTACH (re)admissions.

Modeling spread of KPC-producing bacteria in long-term acute care hospitals in the Chicago region, USA.

Objective: Prevalence of bla KPC-encoding Enterobacteriaceae (KPC) in Chicago long-term acute care hospitals (LTACHs) rose rapidly after the first recognition in 2007. We studied the epidemiology and transmission capacity of KPC in LTACHs and the effect of patient cohorting.

Methods: Data were available from 4 Chicago LTACHs from June 2012 to June 2013 during a period of bundled interventions.

Prevention of colonization and infection by Klebsiella pneumoniae carbapenemase-producing enterobacteriaceae in long-term acute-care hospitals.

Background: Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae (hereafter "KPC") are an increasing threat to healthcare institutions. Long-term acute-care hospitals (LTACHs) have especially high prevalence of KPC.

Methods: Using a stepped-wedge design, we tested whether a bundled intervention (screening patients for KPC rectal colonization upon admission and every other week; contact isolation and geographic separation of KPC-positive patients in ward cohorts or single rooms; bathing all patients daily with chlorhexidine gluconate; and healthcare-worker education and adherence monitoring) would reduce colonization and infection due to KPC in 4 LTACHs with high endemic KPC prevalence.

Understanding staff perceptions about Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae control efforts in Chicago long-term acute care hospitals.

Objective: To identify differences in organizational culture and better understand motivators to implementation of a bundle intervention to control Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae (KPC).

Design: Mixed-methods study.

Setting: Four long-term acute care hospitals (LTACHs) in Chicago.