European Society Of Clinical Microbiology And Infectious Diseases Research Articles

Comparison of international guidelines for CT prior to lumbar puncture in patients with suspected meningitis.

To compare the performance of multiple international guidelines in selecting patients for head CT prior to lumbar puncture (LP) in suspected meningitis, focusing on identification of potential contraindications to immediate LP. Retrospective study of 196 patients with suspected meningitis presenting to an emergency department between March 2013 and March 2023 and undergoing head CT prior to LP. UK Joint Specialist Society Guidelines (UK), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Infectious Diseases Society of America (IDSA) guidelines were evaluated by cross-referencing imaging criteria with clinical characteristics present at time of presentation. Sensitivity of each guideline for recommending neuroimaging in cases with brain shift on CT was evaluated, along with the number of normal studies and incidental or spurious findings. 2/196 (1%) patients had abnormal CTs with evidence of brain shift, while 14/196 (7%) had other abnormalities on CT without brain shift. UK, ESCMID and IDSA guidelines recommended imaging in 10%, 14% and 33% of cases respectively. All three guidelines recommended imaging pre-LP in 2/2 (100%) cases with brain shift. IDSA guidelines recommended more CT studies with normal findings (59 vs 16 and 24 for UK and ESCMID guidelines respectively) and CT abnormalities without brain shift (4 vs 1 and 2 respectively) than the other guidelines. UK, ESCMID and IDSA guidelines are all effective at identifying the small cohort of patients who benefit from a head CT prior to LP. Following the more selective UK/ESCMID guidelines limits the number of normal studies and incidental or spurious CT findings.

Evaluation of the in vitro susceptibility of clinical isolates of NDM-producing Klebsiella pneumoniae to new antibiotics included in a treatment regimen for infections.

Due to the growing resistance to routinely used antibiotics, the search for new antibiotics or their combinations with effective inhibitors against multidrug-resistant microorganisms is ongoing. In our study, we assessed the in vitro drug susceptibility of Klebsiella pneumoniae strains producing New Delhi metallo-β-lactamases (NDM) to antibiotics included in the Infectious Diseases Society of America (IDSA) and European Society of Clinical Microbiology and Infectious Diseases (ESCMID) recommendations. A total of 60 strains of NDM-producing K. pneumoniae were obtained from different patients hospitalized at the 4th Military Hospital in Wroclaw between 2019 and 2022 and subjected to drug susceptibility to selected antibiotics, including the effects of drug combinations. Among the tested antibiotics, the highest sensitivity (100%) was observed for cefiderocol, eravacycline (interpreted according to the European Committee on Antimicrobial Susceptibility Testing [EUCAST]), and tigecycline. Sensitivity to intravenous fosfomycin varied depending on the method used. Using the "strip stacking" method, determining cumulative sensitivity to ceftazidime/avibactam and aztreonam demonstrated 100% in vitro sensitivity to this combination among the tested strains. The in vitro susceptibility assessment demonstrated that, the best therapeutic option for treating infections caused by carbapenemase-producing strains seems to be a combination of ceftazidime/avibactam with aztreonam. Due to the safety of using both drugs, cost effectiveness, and the broadest indications for use among the tested antibiotics, this therapy should be the first-line treatment for carbapenemase-producing Enterobacterales infections. Nevertheless, a comprehensive evaluation of the efficacy of treating infections caused by NDM-producing K. pneumoniae strains should include not only in vitro susceptibility assessment but also an analysis of clinical cases.

Current management of SARS-CoV-2 infection in solid organ transplant recipients: Experience derived from an ESGICH-ESOT survey.

Solid organ transplant (SOT) recipients have a poorer SARS-CoV-2 vaccine response and higher risk for COVID-19-associated complications. However, there is no consensus on the current management of COVID-19 and data on persistent COVID-19 rates in SOT recipients are lacking. An electronic survey concerning the management of COVID-19 in SOT recipients was distributed among all members of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) and of the European Society for Organ Transplantation (ESOT). Four major sections were covered: prevention, early COVID-19, late COVID-19, and persistent COVID-19. We developed a structured questionnaire including eight multiple-choice questions with branching logic in case of positive answers and three open-ended questions related to clinical practice. Questions were asked separately for lung and non-lung transplantation. Thirty-two physicians from 24 different centers participated. Most answers (n = 30) were provided by European physicians. Thirty of 32 (93.75%) physicians managed non-lung transplant recipients and 12 of 32 (33.3%) lung transplant recipients. There was a huge variability in practice regarding the treatment of COVID-19, and particularly noticeable when considering lung and non-lung transplant recipients. Main discordances included the use of nirmatrelvir alone or in combination therapy for early COVID-19, the use of immunomodulatory drugs other than steroids for late COVID-19, and the need for treating asymptomatic viral shedding in persistent COVID-19. There was more similarity in terms of prophylaxis recommendations. Despite a low number of respondents, this survey shows that there are many differences on how experts manage SARS-CoV-2 infections in SOT recipients.

European Practice for CDI Treatment.

Clostridioides difficile infection (CDI) remains a significant cause of morbidity and mortality worldwide. Historically, two antibiotics (metronidazole and vancomycin) and a recent third (fidaxomicin) have been used for CDI treatment; convincing data are now available showing that metronidazole is the least efficacious agent. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) management guidance for CDI were updated in 2021. This guidance document outlines the treatment options for a variety of CDI clinical scenarios and for non-antimicrobial management (e.g., faecal microbiota transplantation, FMT). One of the main changes is that metronidazole is no longer recommended as first-line CDI treatment. Rather, fidaxomicin is preferred on the basis of reduced recurrence rates with vancomycin as an acceptable alternative. Recommended options for recurrent CDI now include bezlotoxumab as well as FMT.A 2017 survey of 20 European countries highlighted variation internationally in CDI management strategies. A variety of restrictions were in place in 65% countries prior to use of new anti-CDI treatments, including committee/infection specialist approval or economic review/restrictions. This survey was repeated in November 2022 to assess the current landscape of CDI management practices in Europe. Of 64 respondents from 17 countries, national CDI guidelines existed in 14 countries, and 11 have already/plan to incorporate the ESCMID 2021 CDI guidance, though implementation has not been surveyed in 6. Vancomycin is the most commonly used first-line agent for the treatment of CDI (n=42, 66%), followed by fidaxomicin (n=30, 47%). Six (9%) respondents use metronidazole as first-line agent for CDI treatment, whereas 22 (34%) only in selected low-risk patient groups. Fidaxomicin is more likely to be used in high-risk patient groups. Availability of anti-CDI therapy influenced prescribing in six respondents (9%). Approval pre-prescription was required before vancomycin (n=3, 5%), fidaxomicin (n=10, 6%), bezlotoxumab (n=11, 17%) and FMT (n=10, 6%). Implementation of CDI guidelines is rarely audited.Novel anti-CDI agents are being evaluated; it is not yet clear what will be the roles of these agents. The treatment of recurrent CDI is particularly troublesome, and several different live biotherapeutics are being developed, in addition to FMT.

The ESCMID Study Group for Clostridioides difficile: History, Role, and Perspectives.

Clostridioides difficile (C. difficile) is a major nosocomial pathogen but is also increasingly recognised as an important diarrhoeal pathogen in the community, not always associated with antibiotics. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for C. difficile (ESGCD) is a group of clinicians, scientists, and others from many European countries and further afield, who share a common interest in C. difficile. The aims of the Study Group are centred around raising the profile of C. difficile infection (CDI) in humans and animals, fostering collaboration amongst centres in different European countries and providing a forum for discussing and disseminating information. One of the principal aims of the Study Group is to raise awareness of C. difficile infections in Europe. ESGCD has a particular interest in the development and dissemination of European guidance on prevention, diagnosis, and treatment of CDI. This chapter will discuss the organisation of ESGCD within the ESCMID Study Group structure, the origins of the Study Group, the aims, and objectives of the group, and will highlight some of the past and present activities of ESGCD in relation to these.

Management of nonfermenting gram-negative infections: a critique of the guidelines.

In the present narrative review, we discuss the characteristics and differences between the Infectious Diseases Society of America (IDSA) and European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines in terms on their recommendations/suggestions for the treatment of Pseudomonas aeruginosa and Acinetobacter baumannii infections. Treatment of severe infections caused by nonfermenting gram-negative bacteria (NF-GNB) is posing both novel hopes and novel challenges to physicians worldwide, and both the IDSA and the ESCMID have recently updated/released their guidelines or guidance documents, based on different philosophies and providing recommendations for the treatment of NF-GNB infections. In order to correctly exploit recent advances in the treatment of such infections, IDSA and ESCMID approaches should be viewed as complementary and evolving, and should not preclude further revision based on accumulating evidence on the use of novel β-lactams and β-lactam/β-lactamase inhibitor combinations. A joint consideration of both philosophies should leave the door opened for the wise use of novel agents, ultimately building precious experience on their use that could favorably influence future guidelines revisions.

International consensus recommendations for the use of prolonged-infusion beta-lactam antibiotics: Endorsed by the American College of Clinical Pharmacy, British Society for Antimicrobial Chemotherapy, Cystic Fibrosis Foundation, European Society of Clinical Microbiology and Infectious Diseases, Infectious Diseases Society of America, Society of Critical Care Medicine, and Society of Infectious Diseases Pharmacists.

Intravenous β-lactam antibiotics remain a cornerstone in the management of bacterial infections due to their broad spectrum of activity and excellent tolerability. β-lactams are well established to display time-dependent bactericidal activity, where reductions in bacterial burden are directly associated with the time that free drug concentrations remain above the minimum inhibitory concentration (MIC) of the pathogen during the dosing interval. In an effort to take advantage of these bactericidal characteristics, prolonged (extended and continuous) infusions (PIs) can be applied during the administration of intravenous β-lactams to increase time above the MIC. PI dosing regimens have been implemented worldwide, but implementation is inconsistent. We report consensus therapeutic recommendations for the use of PI β-lactams developed by an expert international panel with representation from clinical pharmacy and medicine. This consensus guideline provides recommendations regarding pharmacokinetic and pharmacodynamic targets, therapeutic drug-monitoring considerations, and the use of PI β-lactam therapy in the following patient populations: severely ill and nonseverely ill adult patients, pediatric patients, and obese patients. These recommendations provide the first consensus guidance for the use of β-lactam therapy administered as PIs and have been reviewed and endorsed by the American College of Clinical Pharmacy (ACCP), the British Society for Antimicrobial Chemotherapy (BSAC), the Cystic Fibrosis Foundation (CFF), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the Infectious Diseases Society of America (IDSA), the Society of Critical Care Medicine (SCCM), and the Society of Infectious Diseases Pharmacists (SIDP).

International consensus recommendations for the use of prolonged-infusion beta-lactam antibiotics: Endorsed by the American College of Clinical Pharmacy, British Society for Antimicrobial Chemotherapy, Cystic Fibrosis Foundation, European Society of Clinical Microbiology and Infectious Diseases, Infectious Diseases Society of America, Society of Critical Care Medicine, and Society of Infectious Diseases Pharmacists: An executive summary.

Intravenous β-lactam antibiotics remain a cornerstone in the management of bacterial infections due to their broad spectrum of activity and excellent tolerability. β-lactams are well established to display time-dependent bactericidal activity, where reductions in bacterial burden are directly associated with the time that free drug concentrations remain above the minimum inhibitory concentration (MIC) of the pathogen during the dosing interval. In an effort to take advantage of these bactericidal characteristics, prolonged (extended and continuous) infusions (PI) can be applied during the administration of intravenous β-lactams to increase time above the MIC. PI dosing regimens have been implemented worldwide, but implementation is inconsistent. We report consensus therapeutic recommendations for the use of β-lactam PI developed by an expert international panel with representation from clinical pharmacy and medicine. This consensus guideline provides recommendations regarding pharmacokinetic and pharmacodynamic targets, therapeutic drug monitoring considerations, and the use of PI β-lactam therapy in the following patient populations: severely ill and nonseverely ill adult patients, pediatric patients, and obese patients. These recommendations provide the first consensus guidance for the use of β-lactam therapy administered as PIs and have been reviewed and endorsed by the American College of Clinical Pharmacy (ACCP), the British Society for Antimicrobial Chemotherapy (BSAC), the Cystic Fibrosis Foundation (CFF), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the Infectious Diseases Society of America (IDSA), the Society of Critical Care Medicine (SCCM), and the Society of Infectious Diseases Pharmacists (SIDP).

The management of Clostridioides difficile infection: from empirism to evidence.

Clostridioides difficile infection (CDI) in clinical practice represents a challenge for its management and also prevention of recurrence. Even though there are updated guidelines for infection prevention, control and treatment, CDI remains a leading cause of healthcare acquired diarrhea with increasing incidence in the community. We present here a synthesis of the most recent international guidelines on the management of CDI. In 2021 updated guidelines on the treatment of CDI in adults were published by the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA), American College of Gastroenterology (ACG) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). These guidelines focused on CDI management in adults, including new data on the clinical efficacy of Fidaxomicin (FDX) and Bezlotoxumab. The 2017 publication of IDSA and SHEA - Clinical Practice Guidelines for Clostridium difficile infection also included pediatric treatment recommendations that are not a part of the 2021 update. Vancomycin (VAN) treatment for an initial CDI episode remains an acceptable alternative to FDX, considering the monetary and logistical challenge of acquiring FDX. There is growing literature on fecal microbiota transplantation (FMT) and the 2021 guidelines describe its role in severe complicated refractory CDI cases and for which surgical management is not feasible. Moreover, there are new data on the secondary prophylaxis with VAN in refractory CDI in patients with risk factors who receive broad spectrum antibiotics.

A cost-utility analysis of two Clostridioides difficile infection guideline treatment pathways

ObjectivesTreatment guidelines are key drivers of prescribing practice in the management of Clostridioides difficile infection (CDI), but recommendations on best practice can vary. We conducted a cost-utility analysis to compare the treatment pathway recommended by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guideline with the pathway proposed by the National Institute for Health and Care Excellence (NICE) guideline, from the perspective of the UK National Health Service. MethodsA decision tree modelling approach was adopted to reflect the treatment pathway for CDI as outlined in ESCMID and NICE guidelines. Patients experiencing a CDI infection received up to three treatments per infection to achieve a response and could subsequently experience up to two recurrences. Data on patient demographics, treatment response, recurrence, utilities, CDI-related mortality, and costs were taken from published literature. ResultsThe ESCMID treatment pathway was cost-effective versus the NICE treatment pathway at a threshold of £20 000 per quality-adjusted life year gained, with an incremental cost-effectiveness ratio of £4931. Cost-effectiveness was driven by differences in index infection recommendations (ESCMID recommends fidaxomicin as first-line treatment whereas NICE recommends vancomycin). The model results were robust to variations in inputs investigated in scenarios and sensitivity analyses, and probabilistic sensitivity analysis demonstrated that the ESCMID guideline treatment strategy had a 100% likelihood of being cost-effective versus the NICE treatment strategy. DiscussionCompared with the NICE guideline, the ESCMID guideline recommendations for treating an index CDI represent the most cost-effective use of healthcare resources from the perspective of the UK National Health Service.

Providing Expert Consultation in a World Living with COVID-19

After a welcome by Paolo Antonio Grossi, the appointed chair by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Department of Medicine & Surgery, University of Insubria, Varese, Italy; Ann-Brit Eg Hansen, Department of Infectious Diseases, Copenhagen University Hospital – Amager and Hvidovre, Denmark and Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark, summarised the objectives of the meeting and introduced the speakers. In their opening presentation, Tobias Welte, Department of Pulmonary and Infectious Diseases, Hannover University School of Medicine, Germany, described how the COVID-19 pandemic has evolved, in terms of variants, mortality rates, vaccinations, immunity, and antivirals. Welte then presented a hypothetical case study to illustrate how older patients with comorbidities can initially have mild symptoms, but may then deteriorate and require hospitalisation. Stephen Thomas, State University of New York Upstate Medical University, Syracuse, USA, then described the efficacy and potential side effects of the BNT162b2 (Pfizer–BioNTech, New York City, USA, and Mainz, Germany, respectively) vaccine, and the need for, and benefits of, booster doses. Thomas also described the added benefits of the newer bivalent vaccines in a world where COVID-19 is constantly mutating. Marta Boffito, HIV, Sexual and Gender Health, Dermatology, Chelsea and Westminster Hospital NHS Foundation Trust, Imperial College London, UK, then outlined various factors that increase the risk of progression to severe COVID-19 disease, including older age, immunocompromised status, and underlying health conditions (e.g., obesity, hypertension, heart disease, and chronic kidney disease [CKD]). Such patients can benefit from antiviral medications such as nirmatrelvir/ritonavir, although potential drug–drug interactions must be considered. Roger Paredes, Department of Infectious Diseases and IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain, and Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA, revisited the case study to highlight the importance of early COVID-19 diagnosis among high-risk patients to enable the use of nirmatrelvir/ritonavir, which is only approved within 5 days of symptom onset for non-hospitalised adults at increased risk of progression to severe COVID-19. Paredes went on to discuss antiviral treatments in more detail, describing a randomised controlled trial (EPIC-HR) and two large real-world studies that showed that nirmatrelvir/ritonavir could significantly reduce the risk of hospitalisation and death due to COVID-19 among high-risk patients. To conclude, Hansen highlighted the importance of regular updates to COVID-19 management guidelines, given the ongoing and evolving nature of COVID-19, as well as the importance of identifying high-risk patients early in their disease course to enable the use of nirmatrelvir/ritonavir.

Prosthetic Joint Infections due to Candida spp: a multicenter international observational study

Prosthetic joint infection (PJI) due to Candida spp. is a severe complication of arthroplasty but is little reported. This study describes Candida PJI epidemiology, management and outcome. We performed a retrospective, observational multinational study with support of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). Patients diagnosed with PJI due to Candida between 1990-2021 were included. Demographic, clinical, laboratory, imaging, medical/surgical treatment, and outcome data were collected within a standardized database. Treatment failure was defined either as a Candida infection recurrence, superinfection, or death due to infection. Data from 151 patients, across 18 centers were analyzed. Mean age was 69.5±13.1yo, 78 (51.7%) patients were male, and 21 (13.9%) were immunosuppressed. Site of infection included hip (55.0%), knee (41.7%), shoulder (2.6%), and femur (0.7%). Twenty-five (16.6%) patients were febrile, and 58 (38.4%) had fistula. Mean number of previous surgeries on the same anatomical site was 3.3±2.3. Surgeries were DAIR (33.8%), one-stage exchange (19.9%), two-stage exchange (39.1%), implant removal (6.0%). Candida species identified were C. albicans (60.3%), C. parapsilosis (26.5%), C. glabrata (7.3%), and C. tropicalis (5.3%). Co-infection with bacteria was found in 69 (45.7%) cases. Fluconazole (62.9%) and caspofungin (14.6%) were the main antifungal agents prescribed for 148.6±167.5 days. Favorable outcome was found in 54/144 (37.5%) cases. Failure was associated with the number of previous surgeries (OR 1.249, 95%CI 1.061-1.469; p-value=0.007), while treatment by fluconazole was associated with cure (OR 0.336, 95%CI 0.160-0.707; p-value=0.004). This study provides epidemiologic and outcome data on Candida PJIs. Although poor overall, the prognosis didn't seem associated with immunosuppression, type of surgery, fungal species or treatment duration. Aucun lien d'intérêt

Update of European Society of Clinical Microbiology and Infectious Diseases coronavirus disease 2019 guidelines: diagnostic testing for severe acute respiratory syndrome coronavirus 2

ScopeSince the onset of COVID-19, several assays have been deployed for the diagnosis of SARS-CoV-2. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) published the first set of guidelines on SARS-CoV-2 in vitro diagnosis in February 2022. Because the COVID-19 landscape is rapidly evolving, the relevant ESCMID guidelines panel releases an update of the previously published recommendations on diagnostic testing for SARS-CoV-2. This update aims to delineate the best diagnostic approach for SARS-CoV-2 in different populations based on current evidence. MethodsAn 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. The panel met virtually once a week. For all decisions, a simple majority vote was used. A list of clinical questions using the population, intervention, comparison, and outcome (PICO) format was developed at the beginning of the process. For each PICO, 2 panel members performed a literature search focusing on systematic reviews with a third panellist involved in case of inconsistent results. The panel reassessed the PICOs previously defined as priority in the first set of guidelines and decided to address 49 PICO questions, because 6 of them were discarded as outdated/non-clinically relevant. The ‘Grading of Recommendations Assessment, Development and Evaluation (GRADE)-adoption, adaptation, and de novo development of recommendations (ADOLOPMENT)’ evidence-to-decision framework was used to produce the guidelines. Questions addressed by the guidelines and recommendationsAfter literature search, we updated 16 PICO questions; these PICOs address the use of antigen-based assays among symptomatic and asymptomatic patients with different ages, COVID-19 severity status or risk for severe COVID-19, time since the onset of symptoms/contact with an infectious case, and finally, types of biomaterials used.

ERS/ESICM/ESCMID/ALAT guidelines for the management of severe community-acquired pneumonia.

Severe community-acquired pneumonia (sCAP) is associated with high morbidity and mortality, and whilst European and non-European guidelines are available for community-acquired pneumonia, there are no specific guidelines for sCAP. The European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), and Latin American Thoracic Association (ALAT) launched a task force to develop the first international guidelines for sCAP. The panel comprised a total of 18 European and four non-European experts, as well as two methodologists. Eight clinical questions for sCAP diagnosis and treatment were chosen to be addressed. Systematic literature searches were performed in several databases. Meta-analyses were performed for evidence synthesis, whenever possible. The quality of evidence was assessed with GRADE (Grading of Recommendations, Assessment, Development and Evaluation). Evidence to Decision frameworks were used to decide on the direction and strength of recommendations. Recommendations issued were related to diagnosis, antibiotics, organ support, biomarkers and co-adjuvant therapy. After considering the confidence in effect estimates, the importance of outcomes studied, desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention and implications to health equity, recommendations were made for or against specific treatment interventions. In these international guidelines, ERS, ESICM, ESCMID, and ALAT provide evidence-based clinical practice recommendations for diagnosis, empirical treatment, and antibiotic therapy for sCAP, following the GRADE approach. Furthermore, current knowledge gaps have been highlighted and recommendations for future research have been made.

ERS/ESICM/ESCMID/ALAT guidelines for the management of severe community-acquired pneumonia

Severe community-acquired pneumonia (sCAP) is associated with high morbidity and mortality, and while European and non-European guidelines are available for community-acquired pneumonia, there are no specific guidelines for sCAP. The European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Latin American Thoracic Association (ALAT) launched a task force to develop the first international guidelines for sCAP. The panel comprised a total of 18 European and four non-European experts, as well as two methodologists. Eight clinical questions for sCAP diagnosis and treatment were chosen to be addressed. Systematic literature searches were performed in several databases. Meta-analyses were performed for evidence synthesis, whenever possible. The quality of evidence was assessed with GRADE (Grading of Recommendations, Assessment, Development and Evaluation). Evidence to Decision frameworks were used to decide on the direction and strength of recommendations. Recommendations issued were related to diagnosis, antibiotics, organ support, biomarkers and co-adjuvant therapy. After considering the confidence in effect estimates, the importance of outcomes studied, desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention and implications to health equity, recommendations were made for or against specific treatment interventions. In these international guidelines, ERS, ESICM, ESCMID and ALAT provide evidence-based clinical practice recommendations for diagnosis, empirical treatment and antibiotic therapy for sCAP, following the GRADE approach. Furthermore, current knowledge gaps have been highlighted and recommendations for future research have been made.

Editorial introductions.

Current Opinion in Infectious Diseases was launched in 1988. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of infectious diseases is divided into 11 sections that are reviewed once a year. Each section is assigned to a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Section Editors for this issue. SECTION EDITORS Matteo BassettiMatteo BassettiMatteo Bassetti is Head of the Infectious Diseases Clinic of the Policlinico San Martino University Hospital in Genoa and Full Professor of Infectious Diseases of the University of Genoa, Italy. Dr Bassetti studied at the University of Genoa School of Medicine and continued his medical education at the Yale University School of Medicine, New Haven, USA with an Infectious Diseases fellowship. Dr Bassetti is Chair of the Critically Ill Study Group of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), president of the Italian Society of Anti-infective Therapy (SITA) and member of executive committee for the battle against antimicrobial resistance of the Italian Minister of Health (PNCAR). He is member-elected (2018-2022) of International Council of the Immunocompromised Host Society (ICHS). From 2019, he is member of the council of International Sepsis Forum (ISF). He serves on the editorial board of several prestigious international journals. He is author or co-author of 750 papers (H index 85; 30000 citations) published in International peer-review journals and several chapter's book on antibiotic therapy, fungal infections, antimicrobial resistances, infections in immunocompromised patients and critically ill patients. Wei Shen LimWei Shen LimProfessor Wei Shen Lim is consultant respiratory physician at Nottingham University Hospitals NHS Trust and Honorary Professor of Respiratory Medicine, University of Nottingham, UK. He is Chair of COVID-19 Immunisation on the Joint Committee of Vaccination and Immunisation (JCVI), UK and a member of various national advisory groups including the New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG) to the Chief Medical Officer for England. He was Chief Investigator of the hibernated ASAP Trial of Dexamethasone in Pandemic Influenza (2012-2022), and co-led the evaluation of Dexamethasone for COVID-19 in the RECOVERY TRIAL He has been involved with the British Thoracic Society (BTS) and the National Institute for Health and Care Excellence (NICE) in the development of various national clinical management guidelines for acute respiratory infections including community acquired pneumonia, pandemic influenza and COVID-19. He developed the CURB-65 severity assessment score for community acquired pneumonia and the BTS community acquired pneumonia care bundle. He was awarded the British Thoracic Society Meritorious Award in 2016 for contributions towards respiratory infections, and in 2021 the Moxon Medal by the Royal College of Physicians (London).

Controversies in the Prevention and Treatment of Clostridioides difficile Infection in Adults: A Narrative Review.

Clostridioides difficile remains a problematic pathogen resulting in significant morbidity and mortality, especially for high-risk groups that include immunocompromised patients. Both the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America (IDSA/SHEA), as well as the American College of Gastroenterology (ACG) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) recently provided guideline updates for C. difficile infection (CDI). In this narrative review, the authors reviewed available literature regarding the prevention or treatment of CDI in adults and focused on disagreements between the IDSA/SHEA and ACG guidelines, as well as articles that have been published since the updates. Several options for primary prophylaxis are available, including probiotics and antibiotics (vancomycin, fidaxomicin). The literature supporting fidaxomicin is currently quite limited. While there are more studies evaluating probiotics and vancomycin, the optimal patient populations and regimens for their use have yet to be defined. While the IDSA/SHEA guidelines discourage metronidazole use for mild CDI episodes, evidence exists that it may remain a reasonable option for these patients. Fidaxomicin has an advantage over vancomycin in reducing recurrences, but its use is limited by cost. Despite this, recent studies suggest fidaxomicin's cost-effectiveness as a first-line therapy, though this is highly dependent on institutional contracts and payment structures. Secondary prophylaxis should focus on non-antimicrobial options to lessen the impact on the microbiome. The oral option of fecal microbiota transplantation (FMT), SER109, and the now FDA-approved RBX2660 represent exciting new options to correct dysbiosis. Bezlotoxumab is another attractive option to prevent recurrences. Further head-to-head studies of newer agents will be needed to guide selection of the optimal therapies for CDI primary and secondary prophylaxis.

Diagnosis and Management of Pulmonary NTM with a Focus on Mycobacterium avium Complex and Mycobacterium abscessus: Challenges and Prospects.

Nontuberculous mycobacteria (NTM) are ubiquitous. NTM can affect different organs and may cause disseminated diseases, but the pulmonary form is the most common form. Pulmonary NTM is commonly seen in patients with underlying diseases. Pulmonary Mycobacterium avium complex (MAC) is the most common NTM disease and M. abscessus (MAB) is the most challenging to treat. This review is prepared with the following objectives: (a) to evaluate new methods available for the diagnosis of pulmonary MAC or MAB, (b) to assess advances in developing new therapeutics and their impact on treatment of pulmonary MAC or MAB, and (c) to evaluate the prospects of preventive strategies including vaccines against pulmonary MAC or MAB. A literature search was conducted using PubMed/MEDLINE and multiple search terms. The search was restricted to the English language and human studies. The database query resulted in a total of 197 publications. After the title and abstract review, 64 articles were included in this analysis. The guidelines by the American Thoracic Society (ATS), European Respiratory Society (ERS), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), and Infectious Diseases Society of America (IDSA) are widely applicable. The guidelines are based on expert opinion and there may be a need to broaden criteria to include those with underlying lung diseases who may not fulfill some of the criteria as 'probable cases' for better follow up and management. Some cases with only one culture-positive sputum sample or suggestive histology without a positive culture may benefit from new methods of confirming NTM infection. Amikacin liposomal inhalation suspension (ALIS), gallium containing compounds and immunotherapies will have potential in the management of pulmonary MAC and MAB. the prevalence of pulmonary NTM is increasing. The efforts to optimize diagnosis and treatment of pulmonary NTM are encouraging. There is still a need to develop new diagnostics and therapeutics.

Osteosynthesis-associated infection of the lower limbs by multidrug-resistant and extensively drug-resistant Gram-negative bacteria: a multicentre cohort study.

Purpose: The purpose of this study was the clinical and therapeutic assessment of lower-limb osteosynthesis-associated infection (OAI) by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria (GNB), which have been poorly studied to date. Methods: A prospective multicentre observational study was conducted on behalf of ESGIAI (the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group on Implant-Associated Infections). Factors associated with remission of the infection were evaluated by multivariate and Cox regression analysis for a 24-month follow-up period. Results: Patients ( ) had a history of trauma (87.7 %), tumour resection (7 %) and other bone lesions (5.3 %). Pathogens included Escherichia coli ( ), Pseudomonas aeruginosa ( ; XDR 50 %), Klebsiella spp.( ), Enterobacter spp. ( ), Acinetobacter spp.( ), Proteus mirabilis ( ), Serratia marcescens ( ) and Stenotrophomonas maltophilia ( ). The prevalence of ESBL (extended-spectrum -lactamase), fluoroquinolone and carbapenem resistance were 71.9 %, 59.6 % and 17.5 % respectively. Most patients ( ; 64.9 %) were treated with a combination including carbapenems ( ) and colistin ( ) for a mean of 63.3 d. Implant retention with debridement occurred in early OAI (66.7 %), whereas the infected device was removed in late OAI (70.4 %) ( ). OAI remission was achieved in 29 cases (50.9 %). The type of surgery, antimicrobial resistance and duration of treatment did not significantly influence the outcome. Independent predictors of the failure to eradicate OAI were age years (hazard ratio, HR, of 3.875; 95 % confidence interval, CI95 %, of 1.540-9.752; ) and multiple surgeries for OAI (HR of 2.822; CI95 % of 1.144-6.963; ). Conclusions: Only half of the MDR/XDR GNB OAI cases treated by antimicrobials and surgery had a successful outcome. Advanced age and multiple surgeries hampered the eradication of OAI. Optimal therapeutic options remain a challenge.

1802. Off-label Use of Antimicrobial Agents at the University Hospital for Infectious Diseases, Zagreb, Croatia

Abstract Background Antimicrobial agents' (AMAs) off-label use can be associated with the prescriber's education. Little is known about the AMAs' off-label use by infectious disease (ID) specialists. We have conducted research at the University Hospital for Infectious Diseases (UHID), Zagreb, Croatia, a 230-bed tertiary center where ID specialists primarily prescribe AMAs. Methods A retrospective cross-sectional analysis was conducted on the day with the highest hospitalization number, January 17, 2019. Any use of AMA not complying with the SmPC was considered off-label and evaluated regarding modality (indication, dose, regimen, route of administration, and age) and justification by institutional or/and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines. Results The study included 155 patients, 63 (40.6%) adults and 92 (59.4%) children. 61 (96.8%) adult patients had at least one AMA. There were 134 AMA prescriptions in adults, 42 (31.3%) off-label. AMAs were most frequently prescribed off-label regarding regimen (21), dose (17), and indication (14). Institutional guidelines justified off-label in 5 cases regarding dose, 4 regarding indication, and 2 regarding regimen. ESCMID guidelines justified off-label prescriptions in 5 cases regarding indication. The rest of the off-label was not supported by the existing guidelines. 60 (65.2%) pediatric patients had at least one AMA. There were 73 prescriptions, 31 (42.5%) off-label. AMAs were most frequently prescribed off-label regarding indication (19), dose (12), and age (2). Institutional guidelines justified 3 off-label cases regarding indication and 1 regarding dose. ESCMID guidelines justified no off-label in children. The lack of guidelines was the leading cause of the off-label AMAs use in children. Conclusion One-third of AMAs are prescribed off-label regarding SmPC by ID specialists. However, institutional and international guidelines can justify part of this use. Disclosures All Authors: No reported disclosures.