Young doctors' perspectives on antibiotic use and resistance: a multinational and inter-specialty cross-sectional European Society of Clinical Microbiology and Infectious Diseases (ESCMID) survey.

BACKGROUND: Postgraduate training has the potential to shape the prescribing practices of young doctors. OBJECTIVES: To investigate the practices, attitudes and beliefs on antibiotic use and resistance in young doctors of different specialties. METHODS: We performed an international web-based exploratory survey. Principal component analysis (PCA) and bivariate and multivariate [analysis of variance (ANOVA)] analyses were used to investigate differences between young doctors according to their country of specialization, specialty, year of training and gender. RESULTS: Of the 2366 participants from France, Greece, Italy, Portugal, Slovenia and Spain, 54.2% of young doctors prescribed antibiotics predominantly as instructed by a mentor. Associations between the variability of answers and the country of training were observed across most questions, followed by variability according to the specialty. Very few differences were associated with the year of training and gender. PCA revealed five dimensions of antibiotic prescribing culture: self-assessment of knowledge, consideration of side effects, perception of prescription patterns, consideration of patient sickness and perception of antibiotic resistance. Only the country of specialization (partial η2 0.010-0.111) and the type of specialization (0.013-0.032) had a significant effect on all five identified dimensions (P < 0.01). The strongest effects were observed on self-assessed knowledge and in the perception of antibiotic resistance. CONCLUSIONS: The country of specialization followed by the type of specialization are the most important determinants of young doctors' perspectives on antibiotic use and resistance. The inclusion of competencies in antibiotic use in all specialty curricula and international harmonization of training should be considered.

Empiric Therapy With Carbapenem-Sparing Regimens for Bloodstream Infections due to Extended-Spectrum ß-Lactamase-Producing Enterobacteriaceae: Results From the INCREMENT Cohort.

BACKGROUND: There is little information about the efficacy of active alternative drugs to carbapenems except ß-lactam/ß-lactamase inhibitors for the treatment of bloodstream infections (BSIs) due to extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E). The objective of this study was to assess the outcomes of patients with BSI due to ESBL-E who received empiric therapy with such drugs (other active drugs [OADs]) or carbapenems. METHODS: A multinational retrospective cohort study of patients with BSI due to ESBL-E who received empiric treatment with OADs or carbapenems was performed. Cox regression including a propensity score for receiving OADs was performed to analyze 30-day all-cause mortality as main outcome. Clinical failure and length of stay were also analyzed. RESULTS: Overall, 335 patients were included; 249 received empiric carbapenems and 86 OADs. The most frequent OADs were aminoglycosides (43 patients) and fluoroquinolones (20 patients). Empiric therapy with OADs was not associated with mortality (hazard ratio [HR], 0.75; 95% confidence interval [CI], .38-1.48) in the Cox regression analysis. Propensity score-matched pairs, subgroups, and sensitivity analyses did not show different trends; specifically, the adjusted HR for aminoglycosides was 1.05 (95% CI, .51-2.16). OADs were neither associated with 14-day clinical failure (adjusted odds ratio, 0.62; 95% CI, .29-1.36) nor length of hospital stay. CONCLUSIONS: We were unable to show that empiric treatment with OAD was associated with a worse outcome compared with carbapenems. This information allows more options to be considered for empiric therapy, at least for some patients, depending on local susceptibility patterns of ESBL-E.

Identifying priorities to improve paediatric in-hospital antimicrobial use by cross-sectional evaluation of prevalence and appropriateness of prescription.

INTRODUCTION: Information about paediatric in-hospital antimicrobial usage and prescribing patterns to guide improvement strategies is scant. We aim to use an evaluation of the prevalence and appropriateness of antimicrobial prescription to identify antimicrobial stewardship priorities in children. METHODS: A cross-sectional point study was performed on hospitalised paediatric patients in a Spanish tertiary hospital, assessing the prevalence of antimicrobial prescription (PAP) and appropriateness of antimicrobial prescription (AAP). AAP was defined as a correct indication plus an appropriate prescribing pattern (dose, spectrum and interval). Evaluation was performed using established antimicrobial guidelines. Other factors that may have a bearing on antimicrobial prescription were also analysed. RESULTS: A total of 171 patients were included. PAP was 49.7% (85/171) and AAP was 60.9% (91/161). The most common indications for antimicrobial use were antimicrobial prophylaxis (28.3%, 32/113) and pneumonia (8.2%, 8/113). Overall, 161 antimicrobials were prescribed (1.9 antimicrobials per patient): 55.3% (89/161) were empiric, 16.1% (26/161) were targeted and 28.6% (46/161) were prophylactic. Amoxicillin/clavulanate (8.2%, 14/171) and sulfamethoxazole/trimethoprim (8.2%, 14/171) were the most prescribed antimicrobials. The prescription of antifungals (11.7%, 20/171) and antivirals (1.8%, 3/171) was analysed. Major causes of inappropriate antibiotic use were prolonged prescriptions (21.7%, 35/161) and use of agents with an excessively broad coverage spectrum (21.1%, 34/161). PAP and AAP varied between wards and antimicrobials. CONCLUSIONS: Measurement of PAP and AAP offers valuable information for detecting priorities in hospital settings and monitoring antimicrobial usage prior to the development of antimicrobial stewardship programmes. In our setting, the main areas for improvement are duration of therapy and proper use of broad-spectrum antimicrobials.

Infections caused by carbapenemase-producing Enterobacteriaceae: risk factors, clinical features and prognosis.

Infections caused by carbapenem-producing Enterobacteriaceae (CPE) can present as several infectious syndromes, but they primarily present as respiratory, urinary and blood stream infections (primary or catheter-related) that are usually found as nosocomial or healthcare-associated infections. The risk of CPE infection is influenced by individual factors, such as the length of the hospital stay and their exposure to invasive procedures and/or to antimicrobials. Of note, exposure to several antimicrobials, not only carbapenems, has been linked to CPE colonization; the duration of antibiotic exposure is one of the primary drivers of CPE acquisition. Individual risk factors must be considered jointly with the local epidemiology of these microorganisms in healthcare institutions. Overall, these infections have a high associated mortality. Mortality is influenced by host factors (e.g., age, comorbidity and immune deficiency), infection-related variables (e.g., type and severity of the infection) and treatment-related factors such as the delay in the initiation of appropriate antimicrobial therapy and the use or monotherapy or combined antimicrobial therapy. Gaining knowledge concerning the epidemiology, clinical features and prognostic features of CPE infection could be useful for improving infection prevention and for the management of patients with infections caused by these microorganisms.

Selective Detection of Active Extracellular Granzyme A by Using a Novel Fluorescent Immunoprobe with Application to Inflammatory Diseases.

Granzymes (Gzms), a family of serine proteases, expressed by immune and nonimmune cells, present perforin-dependent and independent intracellular and extracellular functions. When released in the extracellular space, GzmA, with trypsin-like activity, is involved in the pathophysiology of different inflammatory diseases. However, there are no validated specific systems to detect active forms of extracellular GzmA, making it difficult to assess its biological relevance and potential use as a biomarker. Here, we have developed fluorescence-energy resonance-transfer (FRET)-based peptide probes (FAM-peptide-DABCYL) to specifically detect GzmA activity in tissue samples and biological fluids in both mouse and human samples during inflammatory diseases. An initial probe was developed and incubated with GzmA and different proteases like GzmB and others with similar cleavage specificity as GzmA like GzmK, thrombin, trypsin, kallikrein, or plasmin. After measuring fluorescence, the probe showed very good specificity and sensitivity for human and mouse GzmA when compared to GzmB, its closest homologue GzmK, and with thrombin. The specificity of this probe was further refined by incubating the samples in a coated plate with a GzmA-specific antibody before adding the probe. The results show a high specific detection of soluble GzmA even when compared with other soluble proteases with very similar cleavage specificity like thrombin, GzmK, trypsin, kallikrein, or plasmin, which shows nearly no fluorescence signal. The high specific detection of GzmA was validated, showing that using pure proteins and serum and tissue samples from GzmA-deficient mice presented a significant reduction in the signal compared with WT mice. The utility of this system in humans was confirmed, showing that GzmA activity was significantly higher in serum samples from septic patients in comparison with healthy donors. Our results present a new immunoprobe with utility to detect extracellular GzmA activity in different biological fluids, confirming the presence of active forms of the soluble protease in vivo during inflammatory and infectious diseases.

CAR Immunotherapy for the treatment of infectious diseases: a systematic review.

Immunotherapy treatments aim to modulate the host's immune response to either mitigate it in inflammatory/autoimmune disease or enhance it against infection or cancer. Among different immunotherapies reaching clinical application during the last years, chimeric antigen receptor (CAR) immunotherapy has emerged as an effective treatment for cancer where different CAR T cells have already been approved. Yet their use against infectious diseases is an area still relatively poorly explored, albeit with tremendous potential for research and clinical application. Infectious diseases represent a global health challenge, with the escalating threat of antimicrobial resistance underscoring the need for alternative therapeutic approaches. This review aims to systematically evaluate the current applications of CAR immunotherapy in infectious diseases and discuss its potential for future applications. Notably, CAR cell therapies, initially developed for cancer treatment, are gaining recognition as potential remedies for infectious diseases. The review sheds light on significant progress in CAR T cell therapy directed at viral and opportunistic fungal infections.

Antimicrobial stewardship programs in acute-care hospitals: A multicenter assessment of structure, process, and outcome indicators in Italy and Spain.

BACKGROUND: Antimicrobial stewardship (AMS) programs have been differently implemented across Europe. This study primarily aimed to compare AMS in two European regions. Secondarily, the study explored the COVID-19 pandemic impact on surrogate outcome indicators of AMS. METHODS: A retrospective observational study was conducted in Piedmont (Italy) and Catalonia (Spain). AMS programs were compared through structure and process indicators in 2021. Changes in surrogate outcome indicators (antimicrobial usage; alcohol-based sanitizer consumption; antimicrobial resistance, AMR) from 2017 to 2021 described the pandemic impact. RESULTS: Seventy-eight facilities provided structure and process indicators. Catalonia showed better structure scores (p < 0.001) and less dispersion in both indicators. The greatest areas to improve were accountability (Piedmont) and diversification of strategies (Catalonia). Overall, the regions reported consistent changes in outcome indicators. Antimicrobial usage decreased in 2020, returning to near-pre-pandemic levels in 2021. Alcohol-based sanitizer consumption surged in 2020, then dipped remaining above pre-pandemic levels. AMR trends were minimally affected. CONCLUSIONS: The centralized approach of Catalonia ensured consistent attainment of quality objectives across all facilities, but it may limit facility-specific strategies. In Piedmont, accountability remain one of the most critical factors as in previous years. The pandemic did not substantially disrupt surrogate outcome measures of AMS. However, the data on AMR suggest that maintaining vigilance against this issue remains paramount.

Infections caused by OXA-48-producing Klebsiella pneumoniae in a tertiary hospital in Spain in the setting of a prolonged, hospital-wide outbreak.

OBJECTIVES: We describe clinical and microbiological features of infections caused by OXA-48-producing Klebsiella pneumoniae (O48KP) in the setting of a prolonged, hospital-wide outbreak detected in January 2011. METHODS: Clinical, demographic and microbiological data of patients with growth of O48KP in clinical specimens were collected until December 2011. PCR was used to detect carbapenemase and ß-lactamase genes. The genetic relationships were determined by automated repetitive-sequence-based PCR. RESULTS: Seventy-one patients with clinically guided cultures showing growth of O48KP were identified. Nine were considered to be colonizing rather than causing infection. The most frequent source of infection was the urinary tract (22/62), followed by surgical site infections (17/62). Blood cultures were positive in 23/62 patients. Many patients had significant comorbidity and prolonged hospital stays. In-hospital mortality among patients with O48KP infections was 43.5%. The MIC(90)s of ertapenem, imipenem and meropenem were >32, 16 and 16 mg/L, respectively. No single antimicrobial was active against all the isolates. The antibiotics most active against O48KP were amikacin (97.2% susceptible), colistin (90.1%), tigecycline (73%) and fosfomycin (66.2%). Although eight clones were identified, a predominant clone caused 73.2% of the infections. Multilocus sequence typing (MLST) of the predominant clone gave sequence type (ST) 405 and bla(TEM-1), bla(SHV-76), bla(CTX-M-15) and bla(OXA-1) genes and the insertion sequence IS1999 of the Tn1999 transposon were associated with bla(OXA-48) in this clone. CONCLUSIONS: To our knowledge, this is the largest reported series of infections caused by O48KP in the setting of a single-centre outbreak and provides further input on the clinical relevance of infections caused by O48KP and the difficulties associated with its detection and control.

Initiatives and resources to promote antimicrobial stewardship.

The development of an antimicrobial stewardship program (ASP) requires institutional support. However, obtaining sufficient institutional support is often a complex task that requires convincing the hospital's managers of the benefits of these programs. Additionally, in the design and implementation of an ASP, antimicrobial stewardship (AS) leaders need tools for diverse purposes, such as measuring antimicrobial consumption, education and training and designing protocols. In this review we provide useful information for AS promoters to facilitate the task of designing and implementing an ASP. First, we summarize information about various institutions that promote AS and include evidence that supports the need for and benefits of these programs. Then, several campaigns promoting AS are described. Finally, online resources for professionals dealing with AS are briefly summarized.

Knowledge and perceptions of junior and senior Spanish resident doctors about antibiotic use and resistance: results of a multicenter survey.

BACKGROUND: Antibiotic resistance has been recognized as a worldwide problem. Our aim was to assess the perceptions of Spanish residents about antibiotic use and resistance. METHODS: An online cross-sectional survey was conducted on all resident doctors in five teaching hospitals (September to November 2010). A link to the questionnaire was e-mailed to 844 doctors. The questionnaire collected demographical characteristics, residents' knowledge about microorganisms of known clinical relevance, their habits in the antibiotic prescription process, and their perceptions on the activities aimed to improve antibiotic use. RESULTS: We received 279 responses corresponding to 33.05% of all targeted residents. The response rate was higher among junior than among senior residents (39.95% vs. 26.12%; p<0.05). Residents of all hospitals, specialties and seniority mostly considered that antimicrobial resistance was a significant problem at national level (94.3%), at their institution (91.3%), and for their daily practice (83.8%). Residents considered their training regarding antibiotics insufficient, although up to 86.5% had prescribed antibiotics in the last month. They preferred the availability of local antibiotic guidelines (65%), specific teaching sessions, specific antimicrobial management teams or readily accessible advice from a group or an infectious diseases specialist, to improve antibiotic prescribing, rather than other restrictive interventions. CONCLUSIONS: Most residents at the hospitals surveyed believed that antibiotic resistance was a serious problem. The results of this survey provided very important information to optimize adherence to Antimicrobial Stewardship Programs (ASPs). Educational strategies and non-restrictive aids are the most valuable interventions, which ASPs should capitalize on to improve antimicrobial prescription.

Management of patients with suspected or confirmed antibiotic allergy. Executive summary of guidance from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Allergy and Clinical Immunology (SEAIC), the Spanish Society of Hospital Pharmacy (SEFH) and the Spanish Society of Intensive Medicine and Coronary Care Units (SEMICYUC).

Suspected or confirmed antibiotic allergy is a frequently encountered clinical circumstance that influences antimicrobial prescribing and often leads to the avoidable use of less efficacious and/or more toxic or costly drugs than first-line antimicrobials. Optimizing antimicrobial therapy in patients with antibiotic allergy labels has become one of the priorities of antimicrobial stewardship programs (ASP) in several countries. This guidance document aims to make recommendations for the systematic approach to patients with suspected or confirmed antibiotic allergy based on current evidence. A panel of eleven members of involved Scientific Societies with expertise in the management of patients with suspected or confirmed antibiotic allergy formulated questions about the management of patients with suspected or confirmed antibiotic allergy. A systematic literature review was performed by a medical librarian. The questions were distributed among panel members who selected the most relevant references, summarized the evidence and formulated graded recommendations when possible. The answers to all questions were finally reviewed by all panel members. A systematic approach to patients with suspected or confirmed antibiotic allergy is recommended to improve antibiotic selection and, consequently clinical outcomes. A clinically oriented, 3-category risk-stratification strategy was recommended for patients with suspected antibiotic allergy. Complementary assessments should consider both clinical risk category and preferred antibiotic agent. Empirical therapy recommendations for the most relevant clinical syndromes in patients with suspected or confirmed ß-lactam allergy were formulated. Recommendations on the implementation and monitoring of the impact of the guidelines were formulated. ASP and allergists should design and implement activities that facilitate the most adequate antibiotic use in these patients.

Executive summary of the consensus document of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) on the diagnosis and antimicrobial treatment of infections due to carbapenem-resistant Gram-negative bacteria.

Infections caused by multidrug resistant Gram-negative bacteria are becoming a worldwide problem due to their increasing incidence and associated high mortality. Carbapenem-resistant bacteria such as Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii are the most important in clinical practice. The objective of these guidelines is to update the recommendations for the diagnosis and treatment of infections caused by these multidrug resistant bacteria. Although 'old' antibiotics such as aminoglycosides, colistin, or tigecycline are frequently used for therapy of these bacteria, the 'new' beta-lactams such as ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam or cefiderocol are progressively becoming the first-line therapy for most of these microorganisms. The Spanish Society of Infectious Diseases and Clinical Microbiology (Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica) designated a panel of experts in the field to provide evidence-based recommendations in response to common clinical questions. This document is primarily focused on microbiological diagnosis, clinical management, and targeted antimicrobial therapy of these infections, with special attention to defining the role of the new antimicrobials in the treatment of these bacteria.

Antimicrobial stewardship in hospitals: Expert recommendation guidance document for activities in specific populations, syndromes and other aspects (PROA-2) from SEIMC, SEFH, SEMPSPGS, SEMICYUC and SEIP.

In 2012, The Spanish Societies of Infectious Diseases and Clinical Microbiology (SEIMC), Hospital Pharmacy (SEFH), and Preventive Medicine, Public Health and Healthcare Management (SEMPSGS) lead a consensus document including recommendations for the implementation of antimicrobial stewardship (AMS) programs (AMSP; PROA in Spanish) in acute care hospitals in Spain. While these recommendations were critical for the development of these programs in many centres, there is a need for guidance in the development of AMS activities for specific patient populations, syndromes or other specific aspects which were not included in the previous document or have developed significantly since then. The objective of this expert recommendation guidance document is to review the available information about these activities in these patient populations or circumstances, and to provide guidance recommendations about them. With this objective the SEIMC, SEFH, SEMPSPGS, the Spanish Society of Intensive Care Medicine (SEMICYUC) and the Spanish Pediatric Infectious Disease Society (SEIP) selected a panel of experts who chose the different aspects to include in the document. Because of the lack of high-level evidence in the implementation of the activities, the panel opted to perform a narrative review of the literature for the different topics for which recommendations were agreed by consensus. The document was open to public consultation for the members of these societies for their comments and suggestions, which were reviewed and considered by the panel.

Pregnancy, obesity and other risk factors for complications in influenza A(H1N1) pdm09 infection.

Although influenza is usually a self-limited disease, patients who develop complications are at increased risk of hospitalization, intensive care unit admission and death. Since preventive and early therapeutic measures should be prioritized in higher risk patients, identification of the risk factors for severe infection is important from a public health perspective. Risk factors for complications in pandemics may show some differences with regard to seasonal influenza. During the influenza A(H1N1)pmd09 pandemic, although many cases occurred in younger adults, the risk factors identified for severe infections and complications were similar to those for seasonal influenza, including chronic respiratory, renal, liver, and heart diseases. Aged patients, although less frequently affected, were also at higher risk. Obesity, and particularly morbid obesity (>40 body mass index) has been noted as a significant risk factor for severe disease in the 2009 influenza pandemic. Some interesting recent studies provide insights into the biological reasons behind the poor outcomes in morbidly obese patients. In terms of pregnancy, the studies have shown contradictory results due to variations in methodology and medical care. However, it seems that pregnancy, particularly during the third trimester, increases the risk of complications, and that early antiviral treatment is associated with improved outcomes.

[Community-acquired methicillin resistant Staphylococcus aureus skin and soft tissue infections in Madrid: prevalence study]. / Prevalencia de infecciones de piel y tejidos blandos producidas por Staphylococcus aureus resistente a Meticilina Comunitario en Madrid.

INTRODUCTION: Since it was first described in the 1990s, Methicillin-Resistant Staphylococcus aureus infection among people with no contact with a hospital setting or with no traditional risk factors, has spread worldwide and is now an important epidemiological and public health problem. METHODS: The present prospective and observational study was carried out from April to November 2010. All adult patients with community-acquired suppurative skin and soft tissue infection (SSTI) attending the Emergency Department were enrolled. Clinical, microbiological and epidemiological features of the infection were assessed. RESULTS: A total of 59 samples were collected from 59 patients and CA-MRSA was isolated in 13 of them. Prevalence of CA-MRSA in patients with suppurative SSTI seen in the emergency department was 22.03%, and was 33.3% in patients with staphylococcal infection. Is worth noting the greater presence of necrosis detected in CA-MRSA lesions. Only 3 patients required hospital admission. Eleven of the 13 strains were Panton-Valentine leucocidin producers, and 5 were resistant to non-betalactam antibiotics. CA MRSA infection is still more frequent in the immigrant population. CONCLUSION: Data on CA-MRSA prevalence in Spain are sparse. This study aims to emphasise the current importance of this emergent pathogen in our area. About one third of suppurative staphylococcal SSTI presenting in our emergency department are caused by this agent, confirming a rapid spread in our country. Some clinical features, such as the high presence of necrosis, are closely related to CA-MRSA.

[Programs for optimizing the use of antibiotics (PROA) in Spanish hospitals: GEIH-SEIMC, SEFH and SEMPSPH consensus document]. / Programas de optimización de uso de antimicrobianos (PROA) en hospitales españoles: documento de consenso GEIH-SEIMC, SEFH y SEMPSPH.

The antimicrobial agents are unique drugs for several reasons. First, their efficacy is higher than other drugs in terms of reduction of morbidity and mortality. Also, antibiotics are the only group of drugs associated with ecological effects, because their administration may contribute to the emergence and spread of microbial resistance. Finally, they are used by almost all medical specialties. Appropriate use of antimicrobials is very complex because of the important advances in the management of infectious diseases and the spread of antibiotic resistance. Thus, the implementation of programs for optimizing the use of antibiotics in hospitals (called PROA in this document) is necessary. This consensus document defines the objectives of the PROA (namely, to improve the clinical results of patients with infections, to minimise the adverse events associated to the use of antimicrobials including the emergence and spread of antibiotic resistance, and to ensure the use of the most cost-efficacious treatments), and provides recommendations for the implementation of these programs in Spanish hospitals. The key aspects of the recommendations are as follows. Multidisciplinary antibiotic teams should be formed, under the auspices of the Infection Committees. The PROA need to be considered as part of institutional programs and the strategic objectives of the hospital. The PROA should include specific objectives based on measurable indicators, and activities aimed at improving the use of antimicrobials, mainly through educational activities and interventions based more on training activities directed to prescribers than just on restrictive measures.

European society of clinical microbiology and infectious diseases guidelines for coronavirus disease 2019: an update on treatment of patients with mild/moderate disease.

SCOPE: Despite the large availability of vaccines, coronavirus disease 2019 (COVID-19), induced by severe acute respiratory syndrome coronavirus 2, continues to be a major threat for health-care providers and fragile people. A number of options are now available for outpatients with mild-to-moderate COVID-19 at the risk of disease progression for the prevention of deaths or hospitalization. METHODS: A European Society of Clinical Microbiology and Infectious Diseases COVID-19 guidelines task force was established by the European Society of Clinical Microbiology and Infectious Diseases Executive Committee. A small group was established, half appointed by the chair and the remaining selected based on an open call. Each panel met virtually once a week. For all decisions, a simple majority vote was used. A long list of clinical questions using the population, intervention, comparison, outcome format was developed at the beginning of the process. For each population, intervention, comparison, outcome, two panel members performed a literature search, with a third panelist involved in case of inconsistent results. Voting was based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RECOMMENDATIONS: In this update, we focus on anti-viral agents, monoclonal antibodies (mAbs) and other treatment options proposed for patients with mild or moderate COVID-19 who are at the risk of hospitalization or death. Although the use of anti-virals is recommended, especially nirmatrelvir/ritonavir and remdesivir or, alternatively, molnupirarvir, the administration of mAbs against the spike protein strictly depends on circulating variants or the ability to test timely for variants and sub-variants. At the time of writing (April-June 2022), the only active mAb was tixagevimab/cilgavimab given the predominance of the Omicron BA.2, BA.3, BA.4 and BA.5 sub-lineages in Europe. However, considering that the epidemiological scenario is extremely dynamic, constant monitoring of variants of concern is mandatory.

ESCMID COVID-19 living guidelines: drug treatment and clinical management.

SCOPE: In January 2021, the ESCMID Executive Committee decided to launch a new initiative to develop ESCMID guidelines on several COVID-19-related issues, including treatment of COVID-19. METHODS: An ESCMID COVID-19 guidelines task force was established by the ESCMID Executive Committee. A small group was established, half appointed by the chair, and the remaining selected with an open call. Each panel met virtually once a week. For all decisions, a simple majority vote was used. A long list of clinical questions using the PICO (population, intervention, comparison, outcome) format was developed at the beginning of the process. For each PICO, two panel members performed a literature search with a third panellist involved in case of inconsistent results. Voting was based on the GRADE approach. QUESTIONS ADDRESSED BY THE GUIDELINE AND RECOMMENDATIONS: A synthesis of the available evidence and recommendations is provided for each of the 15 PICOs, which cover use of hydroxychloroquine, bamlanivimab alone or in combination with etesevimab, casirivimab combined with imdevimab, ivermectin, azithromycin and empirical antibiotics, colchicine, corticosteroids, convalescent plasma, favipiravir, remdesivir, tocilizumab and interferon ß-1a, as well as the utility of antifungal prophylaxis and enoxaparin. In general, the panel recommended against the use of hydroxychloroquine, ivermectin, azithromycin, colchicine and interferon ß-1a. Conditional recommendations were given for the use of monoclonal antibodies in high-risk outpatients with mild-moderate COVID-19, and remdesivir. There was insufficient evidence to make a recommendation for use of favipiravir and antifungal prophylaxis, and it was recommended that antibiotics should not be routinely prescribed in patients with COVID-19 unless bacterial coinfection or secondary infection is suspected or confirmed. Tocilizumab and corticosteroids were recommended for treatment of severe COVID-19 but not in outpatients with non-severe COVID-19. SCOPE: The aim of the present guidance is to provide evidence-based recommendations for management of adults with coronavirus disease 2019 (COVID-19). More specifically, the goal is to aid clinicians managing patients with COVID-19 at various levels of severity including outpatients, hospitalized patients, and those admitted to intensive care unit. Considering the composition of the panel, mostly clinical microbiologists or infectious disease specialists with no pulmonology or intensive care background, we focus only on pharmacological treatment and do not give recommendations on oxygen supplement/support. Similarly, as no paediatricians were included in the panel; the recommendations are only for adult patients with COVID-19. Considering the current literature, no guidance was given for special populations such as the immunocompromised.