Mycobacterium immunogenum acquisition from hospital tap water: a genomic and epidemiologic analysis.

We identified 23 cases of Mycobacterium immunogenum respiratory acquisition linked to a colonized plumbing system at a new hospital addition. We conducted a genomic and epidemiologic investigation to assess for clonal acquisition of M. immunogenum from hospital water sources and improve understanding of genetic distances between M. immunogenum isolates. We performed whole-genome sequencing on 28 M. immunogenum isolates obtained from August 2013 to July 2021 from patients and water sources on four intensive care and intermediate units at an academic hospital. Study hospital isolates were recovered from 23 patients who experienced de novo respiratory isolation of M. immunogenum and from biofilms obtained from five tap water outlets. We also analyzed 10 M. immunogenum genomes from previously sequenced clinical (n = 7) and environmental (n = 3) external control isolates. The 38-isolate cohort clustered into three clades with pairwise single-nucleotide polymorphism (SNP) distances ranging from 0 to 106,697 SNPs. We identified two clusters of study hospital isolates in Clade 1 and one cluster in Clade 2 for which clinical and environmental isolates differed by fewer than 10 SNPs and had less than 0.5% accessory genome variation. A less restrictive combined threshold of 40 SNPs and 5% accessory genes reliably captured additional isolates that met clinical criteria for hospital acquisition, but 12 (4%) of 310 epidemiologically unrelated isolate pairs also met this threshold. Core and accessory genome analyses confirmed respiratory acquisition of multiple clones of M. immunogenum from hospital water sources to patients. When combined with epidemiologic investigation, genomic thresholds accurately distinguished hospital acquisition.

Risk Factors for and Outcomes Following Early Acquisition of Mycobacterium abscessus Complex After Lung Transplantation.

Background: Lung transplant recipients are at increased risk of Mycobacterium abscessus complex (MABC) acquisition and invasive infection. We analyzed risk factors and outcomes of early post-lung transplant MABC acquisition. Methods: We conducted a retrospective matched case-control study of patients who underwent lung transplant from 1/1/2012 to 12/31/2021 at a single large tertiary care facility. Cases had de novo MABC isolation within 90 days post-transplant. Controls had no positive MABC cultures and were matched 3:1 with cases based on age and transplant date. Recipient demographics and pre-/peri-operative characteristics were analyzed, and a regression model was used to determine independent risk factors for MABC acquisition. We also assessed 1-year post-transplant outcomes, including mortality. Results: Among 1145 lung transplants, we identified 79 cases and 237 matched controls. Post-transplant mechanical ventilation for >48 hours was independently associated with MABC acquisition (adjusted odds ratio, 2.46; 95% CI, 1.29-4.72; P = .007). Compared with controls, cases required more days of hospitalization after the MABC index date (28 vs 12 days; P = .01) and had decreased 1-year post-transplant survival (78% vs 89%; log-rank P = .02). One-year mortality appeared highest for cases who acquired M. abscessus subsp. abscessus (31% mortality) or had extrapulmonary infections (43% mortality). Conclusions: In this large case-control study, prolonged post-transplant ventilator duration was associated with early post-lung transplant MABC acquisition, which in turn was associated with increased hospital-days and mortality. Further studies are needed to determine the best strategies for MABC prevention, surveillance, and management.

Risk factors, management, and clinical outcomes of invasive Mycoplasma and Ureaplasma infections after lung transplantation.

Mollicute infections, caused by Mycoplasma and Ureaplasma species, are serious complications after lung transplantation; however, understanding of the epidemiology and outcomes of these infections remains limited. We conducted a single-center retrospective study of 1156 consecutive lung transplants performed from 2010-2019. We used log-binomial regression to identify risk factors for infection and analyzed clinical management and outcomes. In total, 27 (2.3%) recipients developed mollicute infection. Donor characteristics independently associated with recipient infection were age ≤40 years (prevalence rate ratio [PRR] 2.6, 95% CI 1.0-6.9), White race (PRR 3.1, 95% CI 1.1-8.8), and purulent secretions on donor bronchoscopy (PRR 2.3, 95% CI 1.1-5.0). Median time to diagnosis was 16 days posttransplant (IQR: 11-26 days). Mollicute-infected recipients were significantly more likely to require prolonged ventilatory support (66.7% vs 21.4%), undergo dialysis (44.4% vs 6.3%), and remain hospitalized ≥30 days (70.4% vs 27.4%) after transplant. One-year posttransplant mortality in mollicute-infected recipients was 12/27 (44%), compared to 148/1129 (13%) in those without infection (P <.0001). Hyperammonemia syndrome occurred in 5/27 (19%) mollicute-infected recipients, of whom 3 (60%) died within 10 weeks posttransplant. This study highlights the morbidity and mortality associated with mollicute infection after lung transplantation and the need for better screening and management protocols.

A cluster of three extrapulmonary Mycobacterium abscessus infections linked to well-maintained water-based heater-cooler devices.

BACKGROUND: Various water-based heater-cooler devices (HCDs) have been implicated in nontuberculous mycobacteria outbreaks. Ongoing rigorous surveillance for healthcare-associated M. abscessus (HA-Mab) put in place following a prior institutional outbreak of M. abscessus alerted investigators to a cluster of 3 extrapulmonary M. abscessus infections among patients who had undergone cardiothoracic surgery. METHODS: Investigators convened a multidisciplinary team and launched a comprehensive investigation to identify potential sources of M. abscessus in the healthcare setting. Adherence to tap water avoidance protocols during patient care and HCD cleaning, disinfection, and maintenance practices were reviewed. Relevant environmental samples were obtained. Patient and environmental M. abscessus isolates were compared using multilocus-sequence typing and pulsed-field gel electrophoresis. Smoke testing was performed to evaluate the potential for aerosol generation and dispersion during HCD use. The entire HCD fleet was replaced to mitigate continued transmission. RESULTS: Clinical presentations of case patients and epidemiologic data supported intraoperative acquisition. M. abscessus was isolated from HCDs used on patients and molecular comparison with patient isolates demonstrated clonality. Smoke testing simulated aerosolization of M. abscessus from HCDs during device operation. Because the HCD fleet was replaced, no additional extrapulmonary HA-Mab infections due to the unique clone identified in this cluster have been detected. CONCLUSIONS: Despite adhering to HCD cleaning and disinfection strategies beyond manufacturer instructions for use, HCDs became colonized with and ultimately transmitted M. abscessus to 3 patients. Design modifications to better contain aerosols or filter exhaust during device operation are needed to prevent NTM transmission events from water-based HCDs.

Complete genome sequence of Mycobacterium immunogenum strain C14-1.MIM isolated from a hospitalized lung transplant recipient.

Mycobacterium immunogenum is a rapidly growing nontuberculous mycobacteria species that can cause healthcare-associated infections. We report the complete genome of C14-1.MIM, isolated via culture of a respiratory specimen obtained from a hospitalized lung transplant recipient. The circular chromosome contains 5,407,919 bp with a G + C content of 64.24% and 5,217 coding sequences.

Impact of measurement and feedback on chlorhexidine gluconate bathing among intensive care unit patients: A multicenter study.

OBJECTIVE: To assess whether measurement and feedback of chlorhexidine gluconate (CHG) skin concentrations can improve CHG bathing practice across multiple intensive care units (ICUs). DESIGN: A before-and-after quality improvement study measuring patient CHG skin concentrations during 6 point-prevalence surveys (3 surveys each during baseline and intervention periods). SETTING: The study was conducted across 7 geographically diverse ICUs with routine CHG bathing. PARTICIPANTS: Adult patients in the medical ICU. METHODS: CHG skin concentrations were measured at the neck, axilla, and inguinal region using a semiquantitative colorimetric assay. Aggregate unit-level CHG skin concentration measurements from the baseline period and each intervention period survey were reported back to ICU leadership, which then used routine education and quality improvement activities to improve CHG bathing practice. We used multilevel linear models to assess the impact of intervention on CHG skin concentrations. RESULTS: We enrolled 681 (93%) of 736 eligible patients; 92% received a CHG bath prior to survey. At baseline, CHG skin concentrations were lowest on the neck, compared to axillary or inguinal regions (P < .001). CHG was not detected on 33% of necks, 19% of axillae, and 18% of inguinal regions (P < .001 for differences in body sites). During the intervention period, ICUs that used CHG-impregnated cloths had a 3-fold increase in patient CHG skin concentrations as compared to baseline (P < .001). CONCLUSIONS: Routine CHG bathing performance in the ICU varied across multiple hospitals. Measurement and feedback of CHG skin concentrations can be an important tool to improve CHG bathing practice.

Living kidney donors with HIV: experience and outcomes from a case series by the HOPE in Action Consortium.

Background: Living kidney donation is possible for people living with HIV (PLWH) in the United States within research studies under the HIV Organ Policy Equity (HOPE) Act. There are concerns that donor nephrectomy may have an increased risk of end-stage renal disease (ESRD) in PLWH due to HIV-associated kidney disease and antiretroviral therapy (ART) nephrotoxicity. Here we report the first 3 cases of living kidney donors with HIV under the HOPE Act in the United States. Methods: Within the HOPE in Action Multicenter Consortium, we conducted a prospective study of living kidney donors with HIV. Pre-donation, we estimated the 9-year cumulative incidence of ESRD, performed genetic testing of apolipoprotein L1 (APOL1), excluding individuals with high-risk variants, and performed pre-donation kidney biopsies (HOPE Act requirement). The primary endpoint was ≥grade 3 nephrectomy-related adverse events (AEs) in year one. Post-donation, we monitored glomerular filtration rate (measured by iohexol/Tc-99m DTPA [mGFR] or estimated with serum creatinine [eGFR]), HIV RNA, CD4 count, and ART. Findings: There were three donors with two-four years of follow-up: a 35 year-old female, a 52 year-old male, and a 47 year-old male. Pre-donation 9-year estimated cumulative incidence of ESRD was 3.01, 8.01, and 7.76 per 10,000 persons, respectively. In two donors with APOL1 testing, no high-risk variants were detected. Biopsies from all three donors showed no kidney disease. Post-donation, two donors developed nephrectomy-related ≥grade 3 AEs: a medically-managed ileus and a laparoscopically-repaired incisional hernia. GFR declined from 103 to 84 mL/min/1.73 m2 at four years (mGFR) in donor 1, from 77 to 52 mL/min/1.73 m2 at three years (eGFR) in donor 2, and from 65 to 39 mL/min/1.73 m2 at two years (eGFR) in donor 3. HIV RNA remained <20 copies/mL and CD4 count remained stable in all donors. Interpretation: The first three living kidney donors with HIV under the HOPE Act in the United States have had promising outcomes at two-four years, providing proof-of-concept to support living donation from PLWH to recipients with HIV. Funding: National Institute of Allergy and Infectious Diseases, National Institutes of Health.

Management of nontuberculous mycobacteria in lung transplant cases: an international Delphi study.

Rationale: Nontuberculous mycobacterial (NTM) diseases are difficult-to-treat infections, especially in lung transplant (LTx) candidates. Currently, there is a paucity of recommendations on the management of NTM infections in LTx, focusing on Mycobacterium avium complex (MAC), M. abscessus and M. kansasii. Methods: Pulmonologists, infectious disease specialists, LTx surgeons and Delphi experts with expertise in NTM were recruited. A patient representative was also invited. Three questionnaires comprising questions with multiple response statements were distributed to panellists. Delphi methodology with a Likert scale of 11 points (5 to -5) was applied to define the agreement between experts. Responses from the first two questionnaires were collated to develop a final questionnaire. The consensus was described as a median rating >4 or <-4 indicating for or against the given statement. After the last round of questionnaires, a cumulative report was generated. Results: Panellists recommend performing sputum cultures and a chest computed tomography scan for NTM screening in LTx candidates. Panellists recommend against absolute contraindication to LTx even with multiple positive sputum cultures for MAC, M. abscessus or M. kansasii. Panellists recommend MAC patients on antimicrobial treatment and culture negative can be listed for LTx without further delay. Panellists recommend 6 months of culture-negative for M. kansasii, but 12 months of further treatment from the time of culture-negative for M. abscessus before listing for LTx. Conclusion: This NTM LTx study consensus statement provides essential recommendations for NTM management in LTx and can be utilised as an expert opinion while awaiting evidence-based contributions.

Epidemiology, management, and clinical outcomes of extrapulmonary Mycobacterium abscessus complex infections in heart transplant and ventricular assist device recipients.

Nontuberculous mycobacteria are emerging pathogens, yet data on the epidemiology and management of extrapulmonary nontuberculous mycobacteria infections in orthotopic heart transplantation (OHT) and ventricular assist device (VAD) recipients are scarce. We retrospectively reviewed records of OHT and VAD recipients who underwent cardiac surgery at our hospital and developed Mycobacterium abscessus complex (MABC) infection from 2013 to 2016 during a hospital outbreak of MABC linked to heater-cooler units. We analyzed patient characteristics, medical and surgical management, and long-term outcomes. Ten OHT patients and 7 patients with VAD developed extrapulmonary M. abscessus subspecies abscessus infection. The median time from presumed inoculation during cardiac surgery to the first positive culture was 106 days in OHT and 29 days in VAD recipients. The most common sites of positive cultures were blood (n = 12), sternum/mediastinum (n = 8), and the VAD driveline exit site (n = 7). The 14 patients diagnosed when alive received combination antimicrobial therapy for a median of 21 weeks, developed 28 antibiotic-related adverse events, and underwent 27 surgeries. Only 8 (47%) patients survived longer than 12 weeks after diagnosis, including 2 patients with VAD who experienced long-term survival after an explantation of infected VADs and OHT. Despite aggressive medical and surgical management, OHT and VAD patients with MABC infection experienced substantial morbidity and mortality.

Impact of Adherence to a Standardized Oxytocin Induction Protocol on Obstetric and Neonatal Outcomes.

BACKGROUND: Oxytocin protocols are employed to induce uterine contractions and progressive cervical changes, but they are associated with adverse maternal and neonatal outcomes. The aim of this study was to determine whether compliance with a checklist-based protocol for oxytocin administration was associated with changes in neonatal and maternal outcomes. METHODS: A retrospective cohort study of 86,786 pregnant women undergoing term (> 37 weeks) induction of labor between January 2015 and December 2017 was performed. Systemwide training in the use of an oxytocin administration protocol was provided to obstetricians and nurses. Pre-use and in-use oxytocin checklists were incorporated into each unit's policies and procedures. Subsequently, charts were reviewed and individually audited by an obstetric nurse who scored each record based on the documentation of variables in an oxytocin administration protocol and ranked adherence as complete or absent. Primary outcomes were postpartum hemorrhage, neonatal ICU (NICU) admission, and delivery by cesarean section. Bivariate analyses (t-tests) were performed on adherent and nonadherent groups for comparison of selected demographic variables and the primary outcome variables. Logistic regression was completed on the primary outcome variable with eight covariates. RESULTS: Among patients with complete adherence to the oxytocin administration protocol, the rate of cesarean section in the unadjusted analysis was 16.20%, compared to 18.54% for those with incomplete adherence; the rates of postpartum hemorrhage were 2.64% vs. 3.14%, respectively, and the rates of NICU admission were 3.03% vs. 3.86%, respectively. In the multivariable logistic regression, complete protocol adherence was associated with significantly lower odds of postpartum hemorrhage (adjusted odds ratio [OR] 0.85, 95% confidence interval [CI] 0.76-0.94) but higher odds of Cesarean section (adjusted OR 1.07, 95% CI 1.01-1.13); the adjusted OR for NICU admission was 0.90, which did not reach statistical significance (95% CI 0.81-1.00). Among the covariates, nulliparity and elective induction were the strongest predictors of the primary outcomes of cesarean section, postpartum hemorrhage, and NICU admission. CONCLUSION: Adherence to the oxytocin administration protocol was associated with a decrease in postpartum hemorrhage but an increased risk of delivery by cesarean section.

Use of Statistical Process Control Methods for Early Detection of Healthcare Facility-Associated Nontuberculous Mycobacteria Outbreaks: A Single-Center Pilot Study.

BACKGROUND: Nontuberculous mycobacteria (NTM) are emerging pathogens increasingly implicated in healthcare facility-associated (HCFA) infections and outbreaks. We analyzed the performance of statistical process control (SPC) methods in detecting HCFA NTM outbreaks. METHODS: We retrospectively analyzed 3 NTM outbreaks that occurred from 2013 to 2016 at a tertiary care hospital. The outbreaks consisted of pulmonary Mycobacterium abscessus complex (MABC) acquisition, cardiac surgery-associated extrapulmonary MABC infection, and a bronchoscopy-associated pseudo-outbreak of Mycobacterium avium complex (MAC). We analyzed monthly case rates of unique patients who had positive respiratory cultures for MABC, non-respiratory cultures for MABC, and bronchoalveolar lavage cultures for MAC, respectively. For each outbreak, we used these rates to construct a pilot moving average (MA) SPC chart with a rolling baseline window. We also explored the performance of numerous alternative control charts, including exponentially weighted MA, Shewhart, and cumulative sum charts. RESULTS: The pilot MA chart detected each outbreak within 2 months of outbreak onset, preceding actual outbreak detection by an average of 6 months. Over a combined 117 months of pre-outbreak and post-outbreak surveillance, no false-positive SPC signals occurred (specificity, 100%). Prospective use of this chart for NTM surveillance could have prevented an estimated 108 cases of NTM. Six high-performing alternative charts detected all outbreaks during the month of onset, with specificities ranging from 85.7% to 94.9%. CONCLUSIONS: SPC methods have potential to substantially improve HCFA NTM surveillance, promoting early outbreak detection and prevention of NTM infections. Additional study is needed to determine the best application of SPC for prospective HCFA NTM surveillance in other settings.

Surgical site infection trends in community hospitals from 2013 to 2018.

OBJECTIVE: Sparse recent data are available on the epidemiology of surgical site infections (SSIs) in community hospitals. Our objective was to provide updated epidemiology data on complex SSIs in community hospitals and to characterize trends of SSI prevalence rates over time. DESIGN: Retrospective cohort study. METHODS: SSI data were collected from patients undergoing 26 commonly performed surgical procedures at 32 community hospitals in the southeastern United States from 2013 to 2018. SSI prevalence rates were calculated for each year and were stratified by procedure and causative pathogen. RESULTS: Over the 6-year study period, 3,561 complex (deep incisional or organ-space) SSIs occurred following 669,467 total surgeries (prevalence rate, 0.53 infections per 100 procedures). The overall complex SSI prevalence rate did not change significantly during the study period: 0.58 of 100 procedures in 2013 versus 0.53 of 100 procedures in 2018 (prevalence rate ratio [PRR], 0.84; 95% CI, 0.66-1.08; P = .16). Methicillin-sensitive Staphylococcus aureus (MSSA) complex SSIs (n = 480, 13.5%) were more common than complex SSIs caused by methicillin-resistant S. aureus (MRSA; n = 363, 10.2%). CONCLUSIONS: The complex SSI rate did not decrease in our cohort of community hospitals from 2013 to 2018, which is a change from prior comparisons. The reason for this stagnation is unclear. Additional research is needed to determine the proportion of or remaining SSIs that are preventable and what measures would be effective to further reduce SSI rates.

SEIR Model to address the impact of face masks amid COVID-19 pandemic.

Early in the pandemic of coronavirus disease 2019 (COVID-19), face masks were used extensively by the general public in several Asian countries. The lower transmission rate of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Asian countries compared with Western countries suggested that the wider community use of face masks has the potential to decrease transmission of SARS-CoV-2. A risk assessment model named Susceptible, Exposed, Infectious, Recovered (SEIR) model is used to quantitatively evaluate the potential impact of community face masks on SARS-CoV-2 reproduction number (R0 ) and peak number of infectious persons. For a simulated population of one million, the model showed a reduction in R0 of 49% and 50% when 60% and 80% of the population wore masks, respectively. Moreover, we present a modified model that considers the effect of mask-wearing after community vaccination. Interestingly mask-wearing still provided a considerable benefit in lowering the number of infectious individuals. The results of this research are expected to help public health officials in making prompt decisions involving resource allocation and crafting legislation.

Colon surgical-site infections and the impact of "present at the time of surgery (PATOS)" in a large network of community hospitals.

OBJECTIVES: To describe the epidemiology of complex colon surgical procedures (COLO), stratified by present at time of surgery (PATOS) surgical-site infections (SSIs) and non-PATOS SSIs and their impact on the epidemiology of colon-surgery SSIs. DESIGN: Retrospective cohort study. METHODS: SSI data were prospectively collected from patients undergoing colon surgical procedures (COLOs) as defined by the National Healthcare Safety Network (NHSN) at 34 community hospitals in the southeastern United States from January 2015 to June 2019. Logistic regression models identified specific characteristics of complex COLO SSIs, complex non-PATOS COLO SSIs, and complex PATOS COLO SSIs. RESULTS: Over the 4.5-year study period, we identified 720 complex COLO SSIs following 28,188 COLO surgeries (prevalence rate, 2.55 per 100 procedures). Overall, 544 complex COLO SSIs (76%) were complex non-PATOS COLO SSIs (prevalence rate [PR], 1.93 per 100 procedures) and 176 (24%) complex PATOS COLO SSIs (PR, 0.62 per 100 procedures). Age >75 years and operation duration in the >75th percentile were independently associated with non-PATOS SSIs but not PATOS SSIs. Conversely, emergency surgery and hospital volume for COLO procedures were independently associated with PATOS SSIs but not non-PATOS SSIs. The proportion of polymicrobial SSIs was significantly higher for non-PATOS SSIs compared with PATOS SSIs. CONCLUSIONS: Complex PATOS COLO SSIs have distinct features from complex non-PATOS COLO SSIs. Removal of PATOS COLO SSIs from public reporting allows more accurate comparisons among hospitals that perform different case mixes of colon surgeries.

Early recognition and response to increases in surgical site infections using optimised statistical process control charts-The early 2RIS trial: A multicentre stepped wedge cluster randomised controlled trial.

Background: Traditional approaches for surgical site infection (SSI) surveillance have deficiencies that delay detection of SSI outbreaks and other clinically important increases in SSI rates. We investigated whether use of optimised statistical process control (SPC) methods and feedback for SSI surveillance would decrease rates of SSI in a network of US community hospitals. Methods: We conducted a stepped wedge cluster randomised trial of patients who underwent any of 13 types of common surgical procedures across 29 community hospitals in the Southeastern United States. We divided the 13 procedures into six clusters; a cluster of procedures at a single hospital was the unit of randomisation and analysis. In total, 105 clusters were randomised to 12 groups of 8-10 clusters. All participating clusters began the trial in a 12-month baseline period of control or "traditional" SSI surveillance, including prospective analysis of SSI rates and consultative support for SSI outbreaks and investigations. Thereafter, a group of clusters transitioned from control to intervention surveillance every three months until all clusters received the intervention. Electronic randomisation by the study statistician determined the sequence by which clusters crossed over from control to intervention surveillance. The intervention was the addition of weekly application of optimised SPC methods and feedback to existing traditional SSI surveillance methods. Epidemiologists were blinded to hospital identity and randomisation status while adjudicating SPC signals of increased SSI rates, but blinding was not possible during SSI investigations. The primary outcome was the overall SSI prevalence rate (PR=SSIs/100 procedures), evaluated via generalised estimating equations with a Poisson regression model. Secondary outcomes compared traditional and optimised SPC signals that identified SSI rate increases, including the number of formal SSI investigations generated and deficiencies identified in best practices for SSI prevention. This trial was registered at ClinicalTrials.gov, NCT03075813. Findings: Between Mar 1, 2016, and Feb 29, 2020, 204,233 unique patients underwent 237,704 surgical procedures. 148,365 procedures received traditional SSI surveillance and feedback alone, and 89,339 procedures additionally received the intervention of optimised SPC surveillance. The primary outcome of SSI was assessed for all procedures performed within participating clusters. SSIs occurred after 1171 procedures assigned control surveillance (prevalence rate [PR] 0.79 per 100 procedures), compared to 781 procedures that received the intervention (PR 0·87 per 100 procedures; model-based PR ratio 1.10, 95% CI 0.94-1.30, p=0.25). Traditional surveillance generated 24 formal SSI investigations that identified 120 SSIs with deficiencies in two or more perioperative best practices for SSI prevention. In comparison, optimised SPC surveillance generated 74 formal investigations that identified 458 SSIs with multiple best practice deficiencies. Interpretation: The addition of optimised SPC methods and feedback to traditional methods for SSI surveillance led to greater detection of important SSI rate increases and best practice deficiencies but did not decrease SSI rates. Additional research is needed to determine how to best utilise SPC methods and feedback to improve adherence to SSI quality measures and prevent SSIs. Funding: Agency for Healthcare Research and Quality.

Clinical Features and Treatment Outcomes of Pulmonary Mycobacterium avium-intracellulare Complex With and Without Coinfections.

Coinfections are more common in patients with cystic fibrosis and bronchiectasis. Infiltrates on imaging studies are seen more commonly in patients with coinfections, but coinfections did not affect treatment outcomes of pulmonary Mycobacterium avium complex.

Persisting uropathogenic Escherichia coli lineages show signatures of niche-specific within-host adaptation mediated by mobile genetic elements.

Large-scale genomic studies have identified within-host adaptation as a hallmark of bacterial infections. However, the impact of physiological, metabolic, and immunological differences between distinct niches on the pathoadaptation of opportunistic pathogens remains elusive. Here, we profile the within-host adaptation and evolutionary trajectories of 976 isolates representing 119 lineages of uropathogenic Escherichia coli (UPEC) sampled longitudinally from both the gastrointestinal and urinary tracts of 123 patients with urinary tract infections. We show that lineages persisting in both niches within a patient exhibit increased allelic diversity. Habitat-specific selection results in niche-specific adaptive mutations and genes, putatively mediating fitness in either environment. Within-lineage inter-habitat genomic plasticity mediated by mobile genetic elements (MGEs) provides the opportunistic pathogen with a mechanism to adapt to the physiological conditions of either habitat, and reduced MGE richness is associated with recurrence in gut-adapted UPEC lineages. Collectively, our results establish niche-specific adaptation as a driver of UPEC within-host evolution.

COVID-19 Trials: Who Participates and Who Benefits?

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has disproportionately afflicted vulnerable populations. Older adults, particularly residents of nursing facilities, represent a small percentage of the population but account for 40% of mortality from COVID-19 in the United States. Racial and ethnic minority individuals, particularly Black, Hispanic, and Indigenous Americans have experienced higher rates of infection and death than the White population. Although there has been an unprecedented explosion of clinical trials to examine potential therapies, participation by members of these vulnerable communities is crucial to obtaining data generalizable to those communities. METHODS: We undertook an open-label, factorial randomized clinical trial examining hydroxychloroquine and/or azithromycin for hospitalized patients. RESULTS: Of 53 screened patients, 11 (21%) were enrolled. Ten percent (3/31) of Black patients were enrolled, 33% (7/21) of White patients, and 50% (6/12) of Hispanic patients. Forty-seven percent (25/53) of patients declined participation despite eligibility; 58%(18/31) of Black patients declined participation. Forty percent (21/53) of screened patients were from a nursing facility and 10% (2/21) were enrolled. Enrolled patients had fewer comorbidities than nonenrolled patients: median modified Charlson comorbidity score 2.0 (interquartile range 0-2.5), versus 4.0 (interquartile range 2-6) for nonenrolled patients (P = 0.006). The limitations of the study were the low participation rate and the multiple treatment trials concurrently recruiting at our institution. CONCLUSIONS: The high rate of nonparticipation in our trial of nursing facility residents and Black people emphasizes the concern that clinical trials for therapeutics may not target key populations with high mortality rates.

Cytomegalovirus prevention in thoracic organ transplantation: A single-center evaluation of letermovir prophylaxis.

BACKGROUND: Cytomegalovirus (CMV) infection is common following thoracic organ transplantation and causes substantial morbidity and mortality. Letermovir is a novel antiviral agent used off-label in this population for CMV prevention. Our goal was to understand patterns of letermovir use and effectiveness when applied for CMV prophylaxis after thoracic transplantation. METHODS: We retrospectively evaluated letermovir use among thoracic transplant recipients at an academic transplant center who initiated letermovir from January 2018 to October2019 for CMV prophylaxis. We analyzed indication, timing, and duration of prophylaxis; tolerability; and occurrence of breakthrough CMV DNAemia and disease. RESULTS: Forty-two episodes of letermovir prophylaxis occurred in 41 patients, including 37 lung and 4 heart transplant recipients. Primary prophylaxis (26/42, 61.9%) was utilized mainly due to myelosuppression (25/26, 96.2%) and was initiated a median of 315 days post-transplant (interquartile range [IQR] 125-1139 days). Sixteen episodes of secondary prophylaxis (16/42, 38.1%) were initiated a median of 695 days post-transplant (IQR 537-1156 days) due to myelosuppression (10/16, 62.5%) or prior CMV resistance (6/16, 37.5%). Median duration of letermovir prophylaxis was 282 days (IQR 131-433 days). Adverse effects required letermovir cessation in 5/42 (11.9%) episodes. Only one episode (2.4%) was complicated by clinically significant breakthrough CMV infection. Transient low-level CMV DNAemia (<450 IU/ml) occurred in 15 episodes (35.7%) but did not require letermovir cessation. CONCLUSIONS: Letermovir was well tolerated and effective during extended prophylactic courses with only one case of breakthrough CMV infection in this cohort of thoracic transplant recipients. Further prospective trials of letermovir prophylaxis in this population are warranted.