Reduced vancomycin susceptibility among clinical Staphylococcus aureus isolates (‘the MIC Creep’): implications for therapy

Methicillin-resistant S. aureus (MRSA) has emerged as the most common hospital-acquired pathogen and is associated with increased morbidity and mortality compared with other strains. Vancomycin has been the cornerstone of treatment of patients with serious MRSA infections for some decades and while more than 99% of clinical S. aureus isolates remain susceptible to vancomycin, we are beginning to see strains of MRSA with reduced susceptibility. This review discusses this phenomenon, the predictors of infection with such forms of MRSA, and current and future management options

Evolution and Mutations Predisposing to Daptomycin Resistance in Vancomycin-Resistant Enterococcus faecium ST736 Strains

We recently identified a novel vancomycin-resistant Enterococcus faecium (VREfm) clone ST736 with reduced daptomycin susceptibility. The objectives of this study were to assess the population dynamics of local VREfm strains and genetic alterations predisposing to daptomycin resistance in VREfm ST736 strains. Multilocus sequence typing and single nucleotide variant data were derived from whole-genome sequencing of 250 E. faecium isolates from 1994-1995 (n = 43), 2009-2012 (n = 115) and 2013 (n = 92). A remarkable change was noticed in the clonality and antimicrobial resistance profiles of E. faecium strains between 1994-1995 and 2013. VREfm sequence type 17 (ST17), the prototype strain of clade A1, was the dominant clone (76.7%) recognized in 1994-1995. By contrast, clone ST736 accounted for 46.7% of VREfm isolates, followed by ST18 (26.1%) and ST412 (20.7%) in 2013. Bayesian evolutionary analysis suggested that clone ST736 emerged between 1996 and 2009. Co-mutations (liaR.W73C and liaS.T120A) of the liaFSR system were identified in all ST736 isolates (n = 111, 100%) examined. Thirty-eight (34.2%) ST736 isolates exhibited daptomycin-resistant phenotype, of which 13 isolates had mutations in both the liaFSR and cardiolipin synthase (cls) genes and showed high level of resistance with a daptomycin MIC50 of 32 mug/mL. The emergence of ST736 strains with mutations predisposing to daptomycin resistance and subsequent clonal spread among inpatients contributed to the observed high occurrence of daptomycin resistance in VREfm at our institution. The expanding geographic distribution of ST736 strains in other states and countries raises concerns about its global dissemination

COVID-19 and Solid Organ Transplantation: Role of Anti-SARS-Cov-2 Monoclonal Antibodies

PURPOSE OF REVIEW: Solid organ transplant recipients (SOTRs) are ideal candidates for early treatment or prevention of coronavirus disease 2019 (COVID-19) using anti-SARS-CoV-2 monoclonal antibodies because of multiple underlying medical conditions, chronic immune-suppression, sub-optimal immunogenic response to vaccination, and evolving epidemiological risks. In this article, we review pertinent challenges regarding the management of COVID-19 in SOTRs, describe the role of active and passive immunity in the treatment and prevention of COVID-19, and review real-world data regarding the use of anti-SARS-CoV-2 monoclonal antibodies in SOTRs. RECENT FINDINGS: The use of an anti-SARS-CoV-2 monoclonal antibody in high-risk solid organ transplant recipients is associated with a reduction in the risk of hospitalization, need for intensive care, and death related to COVID-19. Overall, the early experiences from a diverse population of solid organ transplant recipients who were treated with anti-spike monoclonal antibodies are encouraging with no reported acute graft injury, severe adverse events, or deaths related to COVID-19. SUMMARY: Anti-SARS-CoV-2 antibodies are currently authorized for treatment of mild-moderate COVID-19 and post-exposure prophylaxis, including in SOTRs. Potential future uses include pre-exposure prophylaxis in certain high-risk persons and synergistic use along with emerging oral treatment options. Successful timely administration of anti-SARS-CoV-2 monoclonal antibodies requires a multidisciplinary team approach, effective communication between patients and providers, awareness of circulating viral variants, acknowledgement of various biases affecting treatment, and close monitoring for efficacy and tolerability

1-Year Outcomes of Lung Transplantation for Coronavirus Disease 2019-Associated End-Stage Lung Disease in the United States

BACKGROUND: Lung transplantation can provide quality of life and survival benefits for patients with coronavirus disease 2019 (COVID-19)-associated end-stage lung disease. Characteristics and outcomes of these lung transplant recipients are limited to mostly single-center experiences or provide a short-term follow-up. METHODS: Characteristics of deceased donors and adult lung transplant recipients for COVID-19-associated end-stage lung disease between August-2020 and June-2022 were analyzed using deidentified United Network for Organ Sharing database. Post-transplant patient survival of COVID-19 recipients was analyzed and compared with non-COVID-19 recipients. Secondary outcomes were length of hospitalization, post-transplant complications, and rates of organ rejection. RESULTS: During the study period, 400 lung transplants for COVID-associated end-stage lung disease comprised 8.7% of all lung transplants performed in United States. In the COVID-19 group, Hispanic males received lung transplants at significantly higher rates. The COVID-19 group was younger and had greater need for intensive care unit stay, mechanical ventilation, hemodialysis, extracorporeal membrane oxygenation support, and receipt of antibiotics pre-lung transplant. They had higher lung allocation score, with a shorter wait-list time and received more double lung transplants compared with non-COVID-19 recipients. Post-transplant, the COVID-19 cohort had longer hospital stays, with similar 1-year patient survival (COVID, 86.6% vs non-COVID, 86.3%). Post-transplant, COVID-19-associated deaths were 9.2% of all deaths among lung transplant recipients. CONCLUSIONS: Lung transplantation offers a effective option for carefully selected patients with end-stage lung disease from prior COVID-19, with short-term and long-term outcomes similar to those for lung transplant recipients of non-COVID-19 etiology