Tigecycline Opposes Bortezomib Effect on Myeloma Cells Decreasing Mitochondrial Reactive Oxygen Species Production.

Multiple myeloma is an incurable plasma cell malignancy. Most patients end up relapsing and developing resistance to antineoplastic drugs, like bortezomib. Antibiotic tigecycline has activity against myeloma. This study analyzed tigecycline and bortezomib combination on cell lines and plasma cells from myeloma patients. Apoptosis, autophagic vesicles, mitochondrial mass, mitochondrial superoxide, cell cycle, and hydrogen peroxide were studied by flow cytometry. In addition, mitochondrial antioxidants and electron transport chain complexes were quantified by reverse transcription real-time PCR (RT-qPCR) or western blot. Cell metabolism and mitochondrial activity were characterized by Seahorse and RT-qPCR. We found that the addition of tigecycline to bortezomib reduces apoptosis in proportion to tigecycline concentration. Supporting this, the combination of both drugs counteracts bortezomib in vitro individual effects on the cell cycle, reduces autophagy and mitophagy markers, and reverts bortezomib-induced increase in mitochondrial superoxide. Changes in mitochondrial homeostasis and MYC upregulation may account for some of these findings. These data not only advise to avoid considering tigecycline and bortezomib combination for treating myeloma, but caution on the potential adverse impact of treating infections with this antibiotic in myeloma patients under bortezomib treatment.

Efficacy and safety of oral fosfomycin for asymptomatic bacteriuria in kidney transplant recipients: Results from a Spanish multicenter cohort.

Current guidelines recommend against systematic screening or treating asymptomatic bacteriuria (AB) among kidney transplant (KT) recipients, although the evidence regarding episodes occurring early after transplantation or in the presence of anatomical abnormalities is inconclusive. Oral fosfomycin may constitute a good option for the treatment of post-transplant AB, particularly due to the emergence of multidrug-resistant (MDR) uropathogens. Available clinical evidence supporting its use in this specific setting, however, remains scarce. We performed a retrospective study in 14 Spanish institutions from January 2005 to December 2017. Overall, 137 episodes of AB diagnosed in 133 KT recipients treated with oral fosfomycin (calcium and trometamol salts) with a test-of-cure urine culture within the first 30 days were included. Median time from transplantation to diagnosis was 3.1 months (interquartile range [IQR]: 1.1 - 10.5). Most episodes (96.4% [132/137]) were caused by gram-negative bacteria (GNB), and 56.9% (78/137) were categorized as MDR (extended-spectrum ß-lactamase-producing Enterobacterales [20.4%] and carbapenem-resistant GNB [2.9%]). Rate of microbiological failure at month 1 was 40.1% (95% confidence interval [95%CI]: 31.9 - 48.9) for the whole cohort and 42.3% (95%CI: 31.2 - 54.0) for episodes due to MDR pathogens. Previous urinary tract infection (odds ratio [OR]: 2.42; 95%CI: 1.11 - 5.29; P-value = 0.027) and use of fosfomycin as salvage therapy (OR: 8.31; 95%CI: 1.67 - 41.35; P-value = 0.010) were predictors of microbiological failure. No severe treatment-related adverse event were detected. Oral fosfomycin appears to be a suitable and safe alternative for the treatment (if indicated) of AB after KT, including those episodes due to MDR uropathogens.

A Pilot Study for the Evaluation of an Interferon Gamma Release Assay (IGRA) To Measure T-Cell Immune Responses after SARS-CoV-2 Infection or Vaccination in a Unique Cloistered Cohort.

Assessment of T-cell responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens may be of value to determine long-lasting protection to breakthrough infections or reinfections. Interferon gamma release assay is a validated method to test cellular immunity in mycobacterial infections and has been proposed for patients with SARS-CoV-2 infection or vaccination. Quantitative IgG to spike and qualitative IgG to nucleocapsid antigens were determined by chemiluminescence microparticle immunoassay using the Architect platform (Abbott), and interferon gamma release assays against two Qiagen proprietary mixes of SARS-CoV-2 spike protein (antigen 1 and antigen 2) were performed for a selected group of subjects. A total of 121 subjects in a cloistered institution after a COVID-19 outbreak was studied. IgG spike levels and interferon gamma concentrations were highest among subjects after two doses of vaccine, followed by patients with a longer history of past COVID-19 and no vaccination. The best cutoff for the interferon gamma assay was 25 IU/L for all subgroups of individuals and the two sets of SARS-CoV-2 antigens studied. Testing T-cell response may be of clinical utility to determine immunity after exposure to SARS-CoV-2 antigens, with the interferon gamma concentration of 25 IU/L as the best cutoff either after infection or vaccination.

SARS-CoV-2 detection in wastewater as an early warning indicator for COVID-19 pandemic. Madrid region case study.

COVID-19 pandemic is ongoing for more than a year and has changed priorities and boosted some WBE studies. The aim of this work is to contributed to our knowledge sharing the methodology developed for SARS-CoV-2 detection in wastewater of Madrid region of over six million and a half inhabitants, where the sewer system is a combined system. At first, a pilot test in a small metropolitan area was carried out in order to define the criteria for the selection of the sampling points to be applied to the entire region. Methodologys for laboratory analysis and statistical analysis and interpretation of data are also presented. This work relies highly on fieldwork, so sewer network safe accessibility is paramount. A total of 289 sampling points were weekly characterised. Each sampling point represents a sewershed, some of them in a cascade distribution. Samples are tested for SARS-CoV-2 concentration (gc/L, genome copies per litre) and physicochemical parameters are also analysed to validate or discard what at first could be an unusual virus presence. Field results are correlated with health indicators such as incidence rates and hospitalisation data. This information is daily shared with regional health authorities, disaggregated by municipalities, or aggregated for the entire Madrid region. Results have proved to anticipate health indicators. The tool is used as an early warning indicator for COVID-19 pandemic. Further work is planned to apply the current scheme for a permanent epidemiological surveillance system of 87 sampling points to pinpoint infection hotspots and activate the linked sewersheds in the event of an outbreak.

Hemophagocytic syndrome triggered by donor-transmitted toxoplasmosis as a complication in same-donor recipients of renal transplantation: Case report and review of the literature.

BACKGROUND: Hemophagocytic syndrome (HPS) is an infrequent complication of transplantation caused by an inflammatory response with a benign proliferation of macrophages and defective lytic capability of T lymphocytes and NK cells that can lead to multiorgan failure. Transplant patients are particularly exposed as a result of the increased risk of both infections and malignancies derived from immunosuppressive drugs. There is no consensus for therapy or immunosuppression; mortality is high. We report a case and present a review of all cases of HPS occurring in solid organ transplant recipients.  CASE REPORT: We report two cases of infection by Toxoplasma gondii transmitted by the kidney allograft. One of the recipients was seronegative before transplantation and developed disseminated primary toxoplasmosis. An immune reaction compatible with an HPS ensued. Both were treated with Trimethoprim/sulfamethoxazole, immunosuppression was tapered, and after a 2-week period a complete response was obtained. CONCLUSION: HPS presents therapeutic challenges in the context of transplantation. If HPS is suspected, the search of a very likely underlying infection should be central to the management.

The demography and characteristics of SARS-CoV-2 seropositive residents and staff of nursing homes for older adults in the Community of Madrid: the SeroSOS study.

BACKGROUND: Nursing homes for older adults have concentrated large numbers of severe cases and deaths for coronavirus disease 2019 (COVID-19). METHODS: Point seroprevalence study of nursing homes to describe the demography and characteristic of severe acute respiratory syndrome by coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG)-positive residents and staff. RESULTS: Clinical information and blood samples were available for 9,332 residents (mean age 86.7 ± 8.1 years, 76.4% women) and 10,614 staff (mean age 45.6 ± 11.5, 86.2% women). Up to 84.4% of residents had frailty, 84.9% co-morbidity and 69.3% cognitive impairment; 65.2% of workers were health-aides.COVID-19 seroprevalence was 55.4% (95% confidence interval (CI), 54.4-56.4) for older adults and 31.5% (30.6-32.4) for staff. In multivariable analysis, frailty of residents was related with seropositivity (odds ratio (OR): 1.19, P = 0.02). In the case of staff, age > 50 years (2.10, P < 0.001), obesity (1.19, P = 0.01), being a health-aide (1.94, P < 0.001), working in a center with high seroprevalence in residents (3.49, P < 0.001) and contact with external cases of COVID-19 (1.52, P < 0.001) were factors associated with seropositivity. Past symptoms of COVID-19 were good predictors of seropositivity for residents (5.41, P < 0.001) and staff (2.52, P < 0.001). CONCLUSIONS: Level of dependency influences risk of COVID-19 among residents. Individual and work factors, contacts outside the nursing home are associated with COVID-19 exposure in staff members. It is key to strengthen control measures to prevent the introduction of COVID-19 into care facilities from the community.

Oral fosfomycin for the treatment of lower urinary tract infections among kidney transplant recipients-Results of a Spanish multicenter cohort.

Oral fosfomycin may constitute an alternative for the treatment of lower urinary tract infections (UTIs) in kidney transplant recipients (KTRs), particularly in view of recent safety concerns with fluroquinolones. Specific data on the efficacy and safety of fosfomycin in KTR are scarce. We performed a retrospective study in 14 Spanish hospitals including KTRs treated with oral fosfomycin (calcium and trometamol salts) for posttransplant cystitis between January 2005 and December 2017. A total of 133 KTRs developed 143 episodes of cystitis. Most episodes (131 [91.6%]) were produced by gram-negative bacilli (GNB), and 78 (54.5%) were categorized as multidrug resistant (including extended-spectrum ß-lactamase-producing Enterobacteriaceae [14%] or carbapenem-resistant GNB [3.5%]). A median daily dose of 1.5 g of fosfomycin (interquartile range [IQR]: 1.5-2) was administered for a median of 7 days (IQR: 3-10). Clinical cure (remission of UTI-attributable symptoms at the end of therapy) was achieved in 83.9% (120/143) episodes. Among those episodes with follow-up urine culture, microbiological cure at month 1 was achieved in 70.2% (59/84) episodes. Percutaneous nephrostomy was associated with a lower probability of clinical cure (adjusted odds ratio: 10.50; 95% confidence interval: 0.98-112.29; P = 0.052). In conclusion, fosfomycin is an effective orally available alternative for treating cystitis among KTRs.

Human T-Cell Lymphotropic Virus Type 1 and associated diseases in Latin America.

This narrative review, which is based on a systematic literature search following the PRISMA guidelines, provides a general overview of Human T-cell Lymphotropic Virus type 1 (HTLV-1) and associated diseases: Adult T-cell Leukaemia-Lymphoma (ATLL) and HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) in Latin America, focusing on epidemiology and prevention. Using the published information on HTLV-1, ATLL and HAM/TSP prevalence, we present comprehensive and accurate maps and tables, and developed an algorithm to assist in the prevention of HTLV-1 transmission through breastfeeding while considering socio-economic status. Latin America is an interesting scenario to study HTLV-1 because of the diverse origin of its population. Apart from the expected high prevalence in inhabitants of African ancestry, the presence of endemic foci affecting indigenous populations is particularly striking. ATLL prevention is the biggest challenge in this field. Most ATLL cases are transmitted through breastfeeding; thus, prevention methods to avoid ATLL in endemic countries have to be focused on this. In view of the high inequality in most Latin American countries, reduction in breastfeeding duration, freezing/thawing and pasteurisation of breastmilk can be suitable interventions in poor settings, considering that avoiding the risk of malnutrition and infant mortality must be the priority.

Cette revue narrative, qui repose sur une recherche bibliographique systématique conforme aux recommandations de PRISMA, fournit un aperçu général sur le virus lymphotropique des lymphocytes T humaines de type 1 (HTLV-1) et les maladies associées: Le lymphome leucémique des cellules T d'adulte (ATLL)) et la myélopathie/paraparésie spastique tropicale (HAM/TSP) associée à HTLV-1 en Amérique latine, en se focalisant sur l'épidémiologie et la prévention. En utilisant les informations publiées sur la prévalence de HTLV-1, ATLL et HAM/TSP, nous présentons des cartes et des tableaux complets et précis et avons développé un algorithme pour aider à la prévention de la transmission du HTLV-1 par l'allaitement tout en tenant compte du statut socioéconomique. L'Amérique latine est un scénario intéressant pour l'étude de HTLV-1 en raison de la diversité des origines de sa population. Outre la forte prévalence escomptée chez les habitants de descendance africaine, la présence de foyers endémiques affectant les populations autochtones est particulièrement frappante. La prévention de l'ATLL est le plus gros défi dans ce domaine. La plupart des cas d'ATLL sont transmis par l'allaitement. Ainsi, les méthodes de prévention pour éviter l'ATLL dans les pays d'endémie doivent être concentrées sur cela. Compte tenu de la forte inégalité qui règne dans la plupart des pays d'Amérique latine, la réduction de la durée de l'allaitement, la congélation/décongélation et la pasteurisation du lait maternel peuvent constituer des interventions appropriées dans les milieux pauvres, tout en considérant que la priorité est d'éviter les risques de malnutrition et de mortalité infantile.

Effect of the inadequacy of antibiotic therapy in the Emergency Department on hospital stays. / Efecto de la inadecuación de la antibioterapia en Urgencias sobre la eficiencia en la hospitalización.

INTRODUCTION: The main objective of the study was to determine the frequency of patients receiving inappropriate empiric antibiotic therapy and to assess the impact in terms of increase length of hospital stay, 30-day re-admissions, and 30-day mortality. METHODS: An observational retrospective cohort study was conducted over a one-month period that included all patients hospitalised from an Emergency Department (ED) due to infection. Demographic variables, comorbidity, multi-resistance risk factors, site of infection, microbiological findings, and antibiotic prescribed in ED were collected. Outcomes were length of hospital stay, 30-day re-admissions, and 30-day mortality. RESULTS: A total of 376 patients were included, with a mean age of 71.1 (SD 21) years. The most frequent causes were respiratory (45.7%) and urine (23.9%) infections. The number of patients with length of stay over the median (≥9 days) was 165 (46.1%), with re-admissions 74 (19.7%), and mortality at 30 days 44 (11.7%). There was inappropriate antibiotic treatment in 42 (11.2%) cases. After adjusting for demographic data, comorbidity, risk factors for multidrug resistant organism, presence of sepsis criteria in ED, and site of infection, inappropriate treatment was associated with an extended length of hospital stay (OR 2.22; 95% CI; 1.07-4.60; P=.032), but did not to an increase in mortality (P=.271) or re-admission (P=.784) at 30 days. CONCLUSION: The inappropriate empirical antibiotic therapy in patients admitted from the ED leads to an extended hospital stay, but did not increase mortality or readmission.

Strategies for prevention and treatment of SARS-COV-2 infection in patients with chronic kidney disease: Literature review.

COVID-19 has proven to be particularly aggressive in patients with chronic kidney disease (CKD). The lower immune response rate and the greater susceptibility to progress to severe forms of the disease have contributed to this phenomenon, which has persisted in the post-vaccination era of the pandemic. Paradoxically, CKD has been excluded from most clinical trials of the main therapeutic tools developed against SARS-CoV-2. However, experience in the use of these drugs has been accumulating in different stages of CKD, supporting their use with guarantees of efficacy and safety. The objective of this review is to gather all treatment indications for COVID-19 in the different phases of the disease, tailored to CKD in its various stages, including renal replacement therapy.

Design of a panel of indicators for antibiotic stewardship programs in the Emergency Department. / Diseño de un panel de indicadores para programas de optimización del uso de antimicrobianos en los Servicios de Urgencias.

OBJECTIVE: To develop a panel of indicators to monitor antimicrobial stewardship programs activity in the emergency department. METHODS: A multidisciplinary group consisting of experts in the management of infection in emergency departments and the implementation of antimicrobial stewardship programs (ASP) evaluated a proposal of indicators using a modified Delphi methodology. In the first round, each expert classified the relevance of each proposed indicators in two dimensions (healthcare impact and ease of implementation) and two attributes (prioritization level and frequency). The second round was conducted based on the modified questionnaire according to the suggestions raised and new indicators suggested. Experts modified the prioritization order and rated the new indicators in the same manner as in the first round. RESULTS: 61 potential indicators divided into four groups were proposed: consumption indicators, microbiological indicators, process indicators, and outcome indicators. After analyzing the scores and comments from the first round, 31 indicators were classified as high priority, 25 as intermediate priority, and 5 as low priority. Moreover, 18 new indicators were generated. Following the second round, all 61 initially proposed indicators were retained, and 18 new indicators were incorporated: 11 classified as high priority, 3 as intermediate priority, and 4 as low priority. CONCLUSIONS: The experts agreed on a panel of ASP indicators adapted to the emergency services prioritized by level of relevance. This is as a helpful tool for the development of these programs and will contribute to monitoring the appropriateness of the use of antimicrobials in these units.

A Real-World Data Observational Analysis of the Impact of Liposomal Amphotericin B on Renal Function Using Machine Learning in Critically Ill Patients.

BACKGROUND: Liposomal amphotericin B (L-AmB) has become the mainstay of treatment for severe invasive fungal infections. However, the potential for renal toxicity must be considered. AIMS: To evaluate the incidence of acute kidney injury (AKI) in critically ill patients receiving L-AmB for more than 48 h. METHODS: Retrospective, observational, single-center study. Clinical, demographic and laboratory variables were obtained automatically from the electronic medical record. AKI incidence was analyzed in the entire population and in patients with a "low" or "high" risk of AKI based on their creatinine levels at the outset of the study. Factors associated with the development of AKI were studied using random forest models. RESULTS: Finally, 67 patients with a median age of 61 (53-71) years, 67% male, a median SOFA of 4 (3-6.5) and a crude mortality of 34.3% were included. No variations in serum creatinine were observed during the observation period, except for a decrease in the high-risk subgroup. A total of 26.8% (total population), 25% (low risk) and 13% (high risk) of patients developed AKI. Norepinephrine, the SOFA score, furosemide (general model), potassium, C-reactive protein and procalcitonin (low-risk subgroup) were the variables identified by the random forest models as important contributing factors to the development of AKI other than L-AmB administration. CONCLUSIONS: The development of AKI is multifactorial and the administration of L-AmB appears to be safe in this group of patients.

[Translated article] Design of a panel of indicators for antibiotic stewardship programs in the Emergency Department.

OBJECTIVE: To develop a panel of indicators to monitor antimicrobial stewardship programs activity in the emergency department. METHODS: A multidisciplinary group consisting of experts in the management of infection in emergency departments and the implementation of antimicrobial stewardship programs (ASP) evaluated a proposal of indicators using a modified Delphi methodology. In the first round, each expert classified the relevance of each proposed indicators in two dimensions (healthcare impact and ease of implementation) and two attributes (prioritisation level and frequency). The second round was conducted based on the modified questionnaire according to the suggestions raised and new indicators suggested. Experts modified the prioritisation order and rated the new indicators in the same manner as in the first round. RESULTS: 61 potential indicators divided into four groups were proposed: consumption indicators, microbiological indicators, process indicators, and outcome indicators. After analysing the scores and comments from the first round, 31 indicators were classified as high priority, 25 as intermediate priority, and 5 as low priority. Moreover, 18 new indicators were generated. Following the second round, all 61 initially proposed indicators were retained, and 18 new indicators were incorporated: 11 classified as high priority, 3 as intermediate priority, and 4 as low priority. CONCLUSIONS: The experts agreed on a panel of ASP Indicators adapted to the emergency services prioritised by level of relevance. This is as a helpful tool for the development of these programs and will contribute to monitoring the appropriateness of the use of antimicrobials in these units.

Factors Associated with SARS-CoV-2 Infection in Fully Vaccinated Nursing Home Residents and Workers.

Persons living or working in nursing homes faced a higher risk of SARS-CoV-2 infections during the pandemic, resulting in heightened morbidity and mortality among older adults despite robust vaccination efforts. This prospective study evaluated the humoral and cellular immunity in fully vaccinated residents and workers from two nursing homes in Madrid, Spain, from 2020 to 2021. Measurements of IgG levels were conducted in August 2020 (pre-vaccination) and June and September 2021 (post-vaccination), alongside assessments of neutralizing antibodies and cellular responses in September 2021 among the most vulnerable individuals. Follow-up extended until February 2022 to identify risk factors for SARS-CoV-2 infection or mortality, involving 267 residents (mean age 87.6 years, 81.3% women) and 302 workers (mean age 50.7 years, 82.1% women). Residents exhibited a significantly higher likelihood of experiencing COVID-19 before June 2021 compared with nursing staff (OR [95% CI], 7.2 [3.0 to 17.2], p < 0.01). Participants with a history of previous COVID-19 infection showed more significant increases in IgG levels in August 2020, June 2021 and September 2021, alongside an increased proportion of neutralizing antibodies in the most vulnerable individuals. However, IgG decay remained the same between June and September 2021 based on the previous COVID-19 status. During the Omicron variant wave, residents and staff showed a similar rate of SARS-CoV-2 infection. Notably, preceding clinical or immunological factors before receiving three vaccination doses did not demonstrate associations with COVID-19 infection or overall mortality in our participant cohort.

[Antibiotics and timing in infectious disease in the emergency department]. / Antibióticos y el factor tiempo en la infección en urgencias.

Infectious diseases, besides being a major cause of mortality in developing countries, are one of the main reasons for consultation in emergency medicine. In the last few years, there have been numerous published studies on the importance of starting antibiotic treatment at an early stage in the Emergency Department. However, this issue is of great controversy, owing to some contradictory studies as well as the implications this may have on the pressure of the patient care. This review is presents a summary of the scientific evidence published in this regard, and makes some recommendations based on this published evidence to improve the initial management of patients with an infection; a question of great importance as it can reduce mortality in some specific situations.

Temporal Series Analysis of Population Cycle Threshold Counts as a Predictor of Surge in Cases and Hospitalizations during the SARS-CoV-2 Pandemic.

Tools to predict surges in cases and hospitalizations during the COVID-19 pandemic may help guide public health decisions. Low cycle threshold (CT) counts may indicate greater SARS-CoV-2 concentrations in the respiratory tract, and thereby may be used as a surrogate marker of enhanced viral transmission. Several population studies have found an association between the oscillations in the mean CT over time and the evolution of the pandemic. For the first time, we applied temporal series analysis (Granger-type causality) to validate the CT counts as an epidemiological marker of forthcoming pandemic waves using samples and analyzing cases and hospital admissions during the third pandemic wave (October 2020 to May 2021) in Madrid. A total of 22,906 SARS-CoV-2 RT-PCR-positive nasopharyngeal swabs were evaluated; the mean CT value was 27.4 (SD: 2.1) (22.2% below 20 cycles). During this period, 422,110 cases and 36,727 hospital admissions were also recorded. A temporal association was found between the CT counts and the cases of COVID-19 with a lag of 9-10 days (p ≤ 0.01) and hospital admissions by COVID-19 (p < 0.04) with a lag of 2-6 days. According to a validated method to prove associations between variables that change over time, the short-term evolution of average CT counts in the population may forecast the evolution of the COVID-19 pandemic.

Ten Issues to Update in Nosocomial or Hospital-Acquired Pneumonia: An Expert Review.

Nosocomial pneumonia, or hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP) are important health problems worldwide, with both being associated with substantial morbidity and mortality. HAP is currently the main cause of death from nosocomial infection in critically ill patients. Although guidelines for the approach to this infection model are widely implemented in international health systems and clinical teams, information continually emerges that generates debate or requires updating in its management. This scientific manuscript, written by a multidisciplinary team of specialists, reviews the most important issues in the approach to this important infectious respiratory syndrome, and it updates various topics, such as a renewed etiological perspective for updating the use of new molecular platforms or imaging techniques, including the microbiological diagnostic stewardship in different clinical settings and using appropriate rapid techniques on invasive respiratory specimens. It also reviews both Intensive Care Unit admission criteria and those of clinical stability to discharge, as well as those of therapeutic failure and rescue treatment options. An update on antibiotic therapy in the context of bacterial multiresistance, in aerosol inhaled treatment options, oxygen therapy, or ventilatory support, is presented. It also analyzes the out-of-hospital management of nosocomial pneumonia requiring complete antibiotic therapy externally on an outpatient basis, as well as the main factors for readmission and an approach to management in the emergency department. Finally, the main strategies for prevention and prophylactic measures, many of them still controversial, on fragile and vulnerable hosts are reviewed.

Expert Consensus: Main Risk Factors for Poor Prognosis in COVID-19 and the Implications for Targeted Measures against SARS-CoV-2.

The clinical evolution of patients infected with the Severe Acute Respiratory Coronavirus type 2 (SARS-CoV-2) depends on the complex interplay between viral and host factors. The evolution to less aggressive but better-transmitted viral variants, and the presence of immune memory responses in a growing number of vaccinated and/or virus-exposed individuals, has caused the pandemic to slowly wane in virulence. However, there are still patients with risk factors or comorbidities that put them at risk of poor outcomes in the event of having the coronavirus infectious disease 2019 (COVID-19). Among the different treatment options for patients with COVID-19, virus-targeted measures include antiviral drugs or monoclonal antibodies that may be provided in the early days of infection. The present expert consensus is based on a review of all the literature published between 1 July 2021 and 15 February 2022 that was carried out to establish the characteristics of patients, in terms of presence of risk factors or comorbidities, that may make them candidates for receiving any of the virus-targeted measures available in order to prevent a fatal outcome, such as severe disease or death. A total of 119 studies were included from the review of the literature and 159 were from the additional independent review carried out by the panelists a posteriori. Conditions found related to strong recommendation of the use of virus-targeted measures in the first days of COVID-19 were age above 80 years, or above 65 years with another risk factor; antineoplastic chemotherapy or active malignancy; HIV infection with CD4+ cell counts < 200/mm3; and treatment with anti-CD20 immunosuppressive drugs. There is also a strong recommendation against using the studied interventions in HIV-infected patients with a CD4+ nadir <200/mm3 or treatment with other immunosuppressants. Indications of therapies against SARS-CoV-2, regardless of vaccination status or history of infection, may still exist for some populations, even after COVID-19 has been declared to no longer be a global health emergency by the WHO.

Ten Issues for Updating in Community-Acquired Pneumonia: An Expert Review.

Community-acquired pneumonia represents the third-highest cause of mortality in industrialized countries and the first due to infection. Although guidelines for the approach to this infection model are widely implemented in international health schemes, information continually emerges that generates controversy or requires updating its management. This paper reviews the most important issues in the approach to this process, such as an aetiologic update using new molecular platforms or imaging techniques, including the diagnostic stewardship in different clinical settings. It also reviews both the Intensive Care Unit admission criteria and those of clinical stability to discharge. An update in antibiotic, in oxygen, or steroidal therapy is presented. It also analyzes the management out-of-hospital in CAP requiring hospitalization, the main factors for readmission, and an approach to therapeutic failure or rescue. Finally, the main strategies for prevention and vaccination in both immunocompetent and immunocompromised hosts are reviewed.