A Complete Genome Screening Program of Clinical Methicillin-Resistant Staphylococcus aureus Isolates Identifies the Origin and Progression of a Neonatal Intensive Care Unit Outbreak.

Whole-genome sequencing (WGS) of Staphylococcus aureus is increasingly used as part of infection prevention practices. In this study, we established a long-read technology-based WGS screening program of all first-episode methicillin-resistant Staphylococcus aureus (MRSA) blood infections at a major urban hospital. A survey of 132 MRSA genomes assembled from long reads enabled detailed characterization of an outbreak lasting several months of a CC5/ST105/USA100 clone among 18 infants in a neonatal intensive care unit (NICU). Available hospital-wide genome surveillance data traced the origins of the outbreak to three patients admitted to adult wards during a 4-month period preceding the NICU outbreak. The pattern of changes among complete outbreak genomes provided full spatiotemporal resolution of its progression, which was characterized by multiple subtransmissions and likely precipitated by equipment sharing between adults and infants. Compared to other hospital strains, the outbreak strain carried distinct mutations and accessory genetic elements that impacted genes with roles in metabolism, resistance, and persistence. This included a DNA recognition domain recombination in the hsdS gene of a type I restriction modification system that altered DNA methylation. Transcriptome sequencing (RNA-Seq) profiling showed that the (epi)genetic changes in the outbreak clone attenuated agr gene expression and upregulated genes involved in stress response and biofilm formation. Overall, our findings demonstrate the utility of long-read sequencing for hospital surveillance and for characterizing accessory genomic elements that may impact MRSA virulence and persistence.

"We are Getting Those Old People Things." Polypharmacy Management and Medication Adherence Among Adult HIV Patients with Multiple Comorbidities: A Qualitative Study.

Introduction: Improvements in treatment have led to a growing population of older adults living with HIV. As this population ages, polypharmacy, or the use of more than five medications, may become more common among people living with HIV (PLWH). Methods: Two qualitative focus groups (N=7, N=8) were conducted among a sample of patients who participated in a larger study regarding differential medication adherence. Open-ended questions and probes focused on barriers and facilitators to multiple medication management as well as differential adherence. Results: Overall, patients were able to manage their polypharmacy. Social support facilitated adherence while long-term antiretroviral (ARV) use, medication-specific requirements and emotional fatigue were barriers to management. A small number of participants reported differential adherence that prioritized non-HIV medications over ARVs due to more immediate effects of non-adherence. Discussion: Findings suggest that PLWH have learned to manage their polypharmacy, but still face significant challenges adhering to multiple medications in the long-term. Future research may focus on the emotional toll of long-term ARV use and how patients' own management strategies may be leveraged to promote adherence.

Coronavirus disease 2019 and extra-pulmonary tuberculosis co-infection - A case report and review of literature.

The Coronavirus disease 2019 (COVID-19) pandemic continues to cause significant global morbidity and mortality, leading to the need to study the course of the disease in different clinical circumstances and patient populations. While co-infection between COVID-19 and many pathogens has been reported, there has been limited published research regarding co-infection with Mycobacterium tuberculosis. We describe a case of co-infection involving COVID-19 and extra-pulmonary tuberculosis in a patient with cirrhosis, and review the current literature regarding COVID-19 and tuberculosis co-infection. In spite of several co-morbidities that have been shown to portend a poor prognosis in patients with COVID-19 infection, our patient fully recovered.

Mucormycosis after Coronavirus disease 2019 infection in a heart transplant recipient - Case report and review of literature.

Mucormycosis is an invasive fungal infection (IFI) due to several species of saprophytic fungi, occurring in patients with underlying co-morbidities (including organ transplantation). During the ongoing Coronavirus disease 2019 (COVID-19) pandemic, there have been increasing reports of bacterial and fungal co-infections occurring in COVID-19 patients, including COVID-19 associated pulmonary aspergillosis (CAPA). We describe a case of mucormycosis occurring after COVID-19, in an individual who received a recent heart transplant for severe heart failure. Two months after heart transplant, our patient developed upper respiratory and systemic symptoms and was diagnosed with COVID-19. He was managed with convalescent plasma therapy and supportive care. Approximately three months after COVID-19 diagnosis, he developed cutaneous mucormycosis at an old intravascular device site. He underwent extensive surgical interventions, combined with broad-spectrum antifungal therapy. Despite the aggressive therapeutic measures, he died after a prolonged hospital stay. In this case report, we also review the prior well-reported cases of mucormycosis occurring in COVID-19 patients and discuss potential mechanisms by which COVID-19 may predispose to IFIs. Similar to CAPA, mucormycosis with COVID-19 may need to be evaluated as an emerging disease association. Clinicians should be vigilant to evaluate for invasive fungal infections such as mucormycosis in patients with COVID-19 infection.

A comparison of COVID-19 inpatients by HIV status.

COVID-19 in-hospital morbidity and mortality in people living with HIV (PLWH) were compared to HIV-negative COVID-19 patients within a New York City metropolitan health system, the hardest hit region in the United States early in the pandemic. A total of 10,202 inpatients were diagnosed with COVID-19, of which 99 were PLWH. PLWH were younger (58.3 years (SD = 12.42) versus 64.32 years (SD = 16.77), p < 0.001) and had a higher prevalence of men (73.7% versus 57.9%, p = 0.002) and Blacks (43.4% versus 21.7%, p < 0.001) than the HIV-negative population. PLWH had a higher prevalence of malignancies (18% versus 7%, p = < 0.001), chronic liver disease (12% versus 3%, p < 0.001), and end-stage renal disease (11% versus 4%, p = 0.007). Use of a ventilator, admission to the ICU, and in-hospital mortality were not different. Of the 99 PLWH, 12 were virally unsuppressed and 9 had CD4% < 14. Two of the 12 virally unsuppressed patients and 4/9 patients with CD4% < 14 died. Ninety-one of the 99 PLWH were on treatment for HIV, and 5 of the 8 not on treatment died. Among PLWH with prior values, absolute CD4 count decreased an average of 192 cells/mm3 at the time of COVID-19 diagnosis (p < 0.001). Hospitalized patients with HIV and COVID-19 coinfection did not have worse outcomes than the general population. Among PLWH, those with CD4%<14 or not on treatment for HIV had higher mortality rates. Those PLWH who received IL-6 inhibitors had lower mortality rates. PLWH given antifungal medications, hydroxychloroquine, antibiotics (including azithromycin), steroids, and vasopressors had higher mortality rates.

Toward a Test Protocol for Surface Decontamination Using a Mobile Whole-room UVGI Device†.

Mobile whole-room UVGI devices are used in healthcare settings to control surface-borne pathogens. Unfortunately, no standard method comparing the efficacy of these devices is available. We accessed the effect of shadows on UVC 254 nm inactivation. The evaluation of a mobile whole-room UVGI device used spores of Bacillus atrophaeus as a surrogate for Clostridium difficile and Staphylococcus aureus as a surrogate for MSRA. Inactivation after 10 min of exposure varied significantly depending on whether the spores received direct UV exposure (4.3 log reduction), both direct and reflected UV exposure (3.0-4.0 log reduction) or reflected UV exposure alone (<1.0 log reduction). The susceptibility (z-value) for inactivation of B. atrophaeus spores on a glass surface was estimated to be 0.00312 m2  J-1 . Staphylococcus aureus microbial log reductions were approximately 5.5 for direct UV exposure, 3.6-5.2 for both direct and reflected UV exposure and approximately 2.75 for only reflected UV exposure. Our measurement of reflected dose ranged from 0.46% to 1.47%. Based on our findings, B. atrophaeus spores should be considered as a model organism for testing the impact of shadows on mobile whole-room UVGI device inactivation. Optimizing the reflected component of whole-room UVGI is important, especially for UVC-resistant organisms.

Coronavirus disease 2019 (Covid-19) presenting as purulent fulminant myopericarditis and cardiac tamponade: A case report and literature review.

The vast majority of patients in the ongoing coronavirus Disease 2019 (Covid-19) pandemic primarily present with severe respiratory illness. We report a Covid-19 patient who presented with findings of acute coronary syndrome and was found to have purulent fulminant myopericarditis and cardiac tamponade. We compare our case to the previously reported instances of Covid-19-associated myocarditis. Through review of the available literature, we also highlight the potential mechanisms of cardiac injury in Covid-19. We hope to increase awareness amongst clinicians about this unusual presentation of Covid-19.

Epigenomic characterization of Clostridioides difficile finds a conserved DNA methyltransferase that mediates sporulation and pathogenesis.

Clostridioides (formerly Clostridium) difficile is a leading cause of healthcare-associated infections. Although considerable progress has been made in the understanding of its genome, the epigenome of C. difficile and its functional impact has not been systematically explored. Here, we perform a comprehensive DNA methylome analysis of C. difficile using 36 human isolates and observe a high level of epigenomic diversity. We discovered an orphan DNA methyltransferase with a well-defined specificity, the corresponding gene of which is highly conserved across our dataset and in all of the approximately 300 global C. difficile genomes examined. Inactivation of the methyltransferase gene negatively impacts sporulation, a key step in C. difficile disease transmission, and these results are consistently supported by multiomics data, genetic experiments and a mouse colonization model. Further experimental and transcriptomic analyses suggest that epigenetic regulation is associated with cell length, biofilm formation and host colonization. These findings provide a unique epigenetic dimension to characterize medically relevant biological processes in this important pathogen. This study also provides a set of methods for comparative epigenomics and integrative analysis, which we expect to be broadly applicable to bacterial epigenomic studies.

Antibiotic prophylaxis and risk of Clostridium difficile infection after coronary artery bypass graft surgery.

OBJECTIVE: Antibiotic use, particularly type and duration, is a crucial modifiable risk factor for Clostridium difficile. Cardiac surgery is of particular interest because prophylactic antibiotics are recommended for 48 hours or less (vs ≤24 hours for noncardiac surgery), with increasing vancomycin use. We aimed to study associations between antibiotic prophylaxis (duration/vancomycin use) and C difficile among patients undergoing coronary artery bypass grafting. METHODS: We extracted data on coronary artery bypass grafting procedures from the national Premier Perspective claims database (2006-2013, n = 154,200, 233 hospitals). Multilevel multivariable logistic regressions measured associations between (1) duration (<2 days, "standard" vs ≥2 days, "extended") and (2) type of antibiotic used ("cephalosporin," "cephalosporin + vancomycin," "vancomycin") and C difficile as outcome. RESULTS: Overall C difficile prevalence was 0.21% (n = 329). Most patients (59.7%) received a cephalosporin only; in 33.1% vancomycin was added, whereas 7.2% received vancomycin only. Extended prophylaxis was used in 20.9%. In adjusted analyses, extended prophylaxis (vs standard) was associated with significantly increased C difficile risk (odds ratio, 1.43; confidence interval, 1.07-1.92), whereas no significant associations existed for vancomycin use as adjuvant or primary prophylactic compared with the use of cephalosporins (odds ratio, 1.21; confidence interval, 0.92-1.60, and odds ratio, 1.39; confidence interval, 0.94-2.05, respectively). Substantial inter-hospital variation exists in the percentage of extended antibiotic prophylaxis (interquartile range, 2.5-35.7), use of adjuvant vancomycin (interquartile range, 4.2-61.1), and vancomycin alone (interquartile range, 2.3-10.4). CONCLUSIONS: Although extended use of antibiotic prophylaxis was associated with increased C difficile risk after coronary artery bypass grafting, vancomycin use was not. The observed hospital variation in antibiotic prophylaxis practices suggests great potential for efforts aimed at standardizing practices that subsequently could reduce C difficile risk.

Healthcare-associated Infections: epidemiology, prevention, and therapy.

Reducing nosocomial infection rates is a major component of healthcare improvement. This article reviews the epidemiology, prevention, and therapy for some of the most common healthcare-associated infections, including central line-associated bloodstream infections and catheter-associated urinary tract infections, and 3 common organisms: methicillin-resistant Staphylococcus aureus, multidrug- resistant gram-negative bacteria, and Clostridium difficile.