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To reduce antimicrobial resistance (AMR), pathogen-specific AMR burden data are crucial to guide target selection for research and development of vaccines and monoclonal antibodies (mAbs). We identified knowledge gaps through previously conducted systematic reviews, which informed a Delphi expert consultation on future AMR research priorities and harmonisation strategies to support data-driven decision-making. Consensus (≥80% agreement) on importance and feasibility of research topics was achieved in two rounds, involving 24 of 39 and 19 of 24 invited experts, respectively. Priority pathogens and resistance profiles for future research were identified: third generation cephalosporin-resistant Klebsiella pneumoniae and Escherichia coli, for bloodstream and urinary tract infections, respectively, and meticillin-resistant Staphylococcus aureus for surgical-site infections. Prioritised high-risk populations included surgical, haemato-oncological and transplant patients. Mortality and resource use were prioritised as health-economic outcomes. The importance of age-stratified data and inclusion of a non-infected comparator group were highlighted. This agenda provides guidance for future research to fill knowledge gaps and support data-driven selection of target pathogens and populations for new preventive and treatment strategies, specifically vaccines and mAbs, to effectively address the AMR burden in Europe. These research priorities are also relevant to improve the evidence base for future AMR burden estimates.

Objective: Knowledge of the role of hospital conditions in SARS-CoV-2 transmission should inform strategies for the prevention of nosocomial spread of this pathogen and of similarly transmitted viruses. This study aimed to identify risk factors for nosocomial acquisition of SARS-CoV-2. Methods: We ran a nested case-control study with incidence density sampling among adult patients hospitalized for >7 days (August-December 2020). Patients testing positive for SARS-CoV-2 after the 7th day of hospitalization were defined as cases and matched with controls (1:4) by date of admission, hospitalization duration until index date, and type of department. Individual and contextual characteristics were gathered, including admission characteristics and exposures during the risk period. Conditional logistic regression was used to estimate the odds ratios (ORs) with respective 95% confidence intervals (CI) separately for probable (diagnosed on day 8-13) and definitive (diagnosed after day 14) nosocomial sets. Results: We identified 65 cases (31 probable; 34 definitive) and 219 controls. No individual characteristic was related to nosocomial acquisition of SARS-CoV-2. Contextual risk factors for nosocomial acquisition were staying in a non-refurbished room (probable nosocomial: OR = 3.6, 1.18-10.87), contact with roommates with newly diagnosed SARS-CoV-2 (probable nosocomial: OR = 9.9, 2.11-46.55; definitive nosocomial: OR = 3.4, 1.09-10.30), and contact with roommates with a first positive test 21-90 days before the beginning of contact (probable nosocomial: OR = 10.7, 1.97-57.7). Conclusions: Hospital conditions and contact with recently infected patients modulated nosocomial SARS-CoV-2 transmission. These results alert us to the importance of the physical context and of agile screening procedures to shorten contact with patients with recent infection.

Background: Surgical site infection (SSI) is an important cause of disease burden and healthcare costs. Fully manual surveillance is time-consuming and prone to subjectivity and inter-individual variability, which can be partly overcome by semi-automated surveillance. Algorithms used in orthopaedic SSI semi-automated surveillance have reported high sensitivity and important workload reduction. This study aimed to design and validate different algorithms to identify patients at high risk of SSI after hip or knee arthroplasty., Methods: Retrospective data from manual SSI surveillance between May 2015 and December 2017 were used as gold standard for validation. Knee and hip arthroplasty were included, patients were followed up for 90 days and European Centre for Disease Prevention and Control SSI classification was applied. Electronic health records data was used to generate different algorithms, considering combinations of the following variables: ≥1 positive culture, ≥ 3 microbiological requests, antimicrobial therapy ≥ 7 days, length of hospital stay ≥ 14 days, orthopaedics readmission, orthopaedics surgery and emergency department attendance. Sensitivity, specificity, negative and predictive value, and workload reduction were calculated., Results: In total 1631 surgical procedures were included, of which 67.5% (n = 1101) in women; patients' median age was 69 years (IQR 62 to 77) and median Charlson index 2 (IQR 1 to 3). Most surgeries were elective (92.5%; n = 1508) and half were hip arthroplasty (52.8%; n = 861). SSI incidence was 3.8% (n = 62), of which 64.5% were deep or organ/space infections. Positive culture was the single variable with highest sensitivity (64.5%), followed by orthopaedic reintervention (59.7%). Twenty-four algorithms presented 90.3% sensitivity for all SSI types and 100% for deep and organ/space SSI. Workload reduction ranged from 59.7 to 67.7%. The algorithm including ≥ 3 microbiological requests, length of hospital stay ≥ 14 days and emergency department attendance, was one of the best options in terms of sensitivity, workload reduction and feasibility for implementation., Conclusions: Different algorithms with high sensitivity to detect all types of SSI can be used in real life, tailored to clinical practice and data availability. Emergency department attendance can be an important variable to identify superficial SSI in semi-automated surveillance., (© 2024. The Author(s).)

Third-generation cephalosporins are widely used due to the convenient spectrum of activity, safety, and posology. However, they are associated with the emergence of multidrug-resistant organisms, which makes them important targets for antimicrobial stewardship interventions. We aimed to assess the appropriateness of empirical prescriptions of ceftriaxone in a tertiary hospital. This cross-sectional study analysed empirical ceftriaxone prescriptions in January and June 2021. Patients under other antimicrobials 48 h before admission were excluded. The quality of ceftriaxone prescription was assessed regarding the initial appropriateness, duration of inappropriate ceftriaxone therapy, and missed opportunities for de-escalation. Of 465 prescriptions, 46.5% were inappropriate. The ceftriaxone prescription was inappropriate in 95.7% of lower respiratory tract infections (LRTI) globally and in nearly 40% of urinary tract infections (UTI) in medical and intensive care departments. Intensive care, internal medicine, and palliative care departments showed the highest number of inappropriate ceftriaxone prescriptions and longer length of inappropriate ceftriaxone prescriptions compared to the hospital's average. Improvement of empirical ceftriaxone prescription in LRTI and urinary infections, adherence to local guidelines and de-escalation practices, and targeted interventions focusing on critical departments may significantly reduce the inappropriate empirical use of ceftriaxone.

Background: KPC-producing K pneumoniae (KPC-Kp) is a public health problem with important clinical and epidemiological implications. We describe an outbreak of KPC-Kp at vascular surgery and neurosurgery wards in a central hospital in Porto, Portugal., Methods: A case of KPC-Kp was considered to be a patient positive for KPC-Kp with strong epidemiological plausibility of having acquired this microorganism in the affected wards and/or with genetic relationship ≥92% between KPC-Kp isolates. Active surveillance cultures (ASCs) and real-time polymerase chain reaction were used for the detection of carbapenemase genes through rectal swab in a selected population. Molecular analysis was performed using pulsed-field gel electrophoresis at the National Reference Laboratory. Patient risk factors were collected from the electronic medical record system. Information regarding outbreak containment strategy was collected from the Infection Control Unit records., Results: Of the 16 cases, 11 (69%) were identified through active screening, representing 1.4% of the total 766 ASCs collected. The most frequent risk factors identified were previous admission (63%), antibiotic exposure in the past 6 months (50%), and immunodepression (44%). The length of stay until KPC-Kp detection was high (0-121 days, mean 35.6), as was the total length of stay (5-173 days, mean 56.6). Three patients (19%) were infected by KPC-Kp, 2 of whom died. One previously colonized patient died later because of KPC-Kp infection., Conclusions: Multifactorial strategy based on contact precautions (with patient and healthcare professional cohorts) and ASC, as well as Antibiotic Stewardship Program reinforcement, allowed to contain this KPC-Kp outbreak., Competing Interests: None., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of PBJ-Associação Porto Biomedical/Porto Biomedical Society. All rights reserved.)

Objectives: To assess whether electronic records data could improve the efficiency, exhaustiveness, and representativeness of SSI surveillance by selecting a group of high-risk patients for manual review., Methods: Colorectal surgeries (2016-2018) and cholecystectomies (2017-2018) were selected. Post-surgical antibiotic use, positive culture, C-reactive protein (CRP) values, body temperature, leukocyte count, surgical re-intervention, admission to the emergency room, and hospital readmission were retrieved. For representativeness, procedures registered in HAI-Net were compared with non-included procedures, and the validity of each variable (or combination) was tested considering the presence of SSI as the gold standard. The proportion of procedures flagged for manual review by each criterion was estimated., Results: Little more than 50% of procedures were included in HAI-Net (SSI risk: 10.6% for colorectal and 2.9% for cholecystectomies). Non-included procedures showed higher proportions of infection markers. Antibiotic use and CRP >100 mg/dl presented the highest sensitivity for both surgical groups, while antibiotic use achieved the highest positive predictive value in both groups (22% and 21%, respectively) and flagged fewer colorectal procedures (47.7%)., Conclusions: Current SSI surveillance has major limitations. Thus, the reported incidence seems unreliable and underestimated. Antibiotic use appears to be the best criterion to select a sub-sample of procedures for manual review, improving the exhaustiveness and efficiency of the system., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Antimicrobial resistance is a major public health threat. Antimicrobial stewardship (AMS) is one of the key strategies to overcome resistance, but robust evidence on the effect of specific interventions is lacking. We report an interrupted time series (ITS) analysis of a persuasive AMS intervention implemented during a KPC producing Klebsiella pneumoniae outbreak., Methods: A controlled ITS for carbapenem consumption, total antibiotic consumption and antibiotic-free days, between January 2012 and May 2018 was performed, using segmented regression analysis. The AMS intervention was implemented in the Vascular Surgery ward starting on April 2016 in the context of a KPC outbreak. The General Surgery ward was taken as a control group. Data were aggregated by month for both wards, including 51 pre-intervention and 26 intervention points., Results: The AMS intervention produced a level change in carbapenem consumption of - 11.14 DDDs/100 patient-days accompanied by a decreasing trend of total antibiotic consumption and stable rate of antibiotic-free days in Vascular Surgery ward. These differences were not apparent in the control group. No differences in mortality or readmission rates between pre-intervention and intervention periods were noticed in any of the groups., Conclusion: Persuasive AMS interventions on top of previously implemented restrictive interventions can reduce carbapenem consumption without increasing total antibiotic consumption. Starting persuasive AMS interventions in an outbreak setting does not compromise the sustainability of the intervention.

Ceftazidime/avibactam combines ceftazidime with a new beta-lactam that successfully that inhibits Amber Class A and D carbapenemases. We report a clinical case of a 61 year-old man with a carbapenemase-producing Klebsiella pneumoniae intra-abdominal infection after an elective abdominal hernia repair. The infection was successfully managed with multiple abdominal surgeries, drainage and combined antibiotic therapy with ceftazidime/avibactam plus tigecycline., Competing Interests: None., (© 2020 The Author(s).)

Objectives: To develop and validate a clinical model to identify patients admitted to hospital with community-acquired infection (CAI) caused by pathogens resistant to antimicrobials recommended in current CAI treatment guidelines., Methods: International prospective cohort study of consecutive patients admitted with bacterial infection. Logistic regression was used to associate risk factors with infection by a resistant organism. The final model was validated in an independent cohort., Results: There were 527 patients in the derivation and 89 in the validation cohort. Independent risk factors identified were: atherosclerosis with functional impairment (Karnofsky index <70) [adjusted OR (aOR) (95% CI) = 2.19 (1.41-3.40)]; previous invasive procedures [adjusted OR (95% CI) = 1.98 (1.28-3.05)]; previous colonization with an MDR organism (MDRO) [aOR (95% CI) = 2.67 (1.48-4.81)]; and previous antimicrobial therapy [aOR (95% CI) = 2.81 (1.81-4.38)]. The area under the receiver operating characteristics (AU-ROC) curve (95% CI) for the final model was 0.75 (0.70-0.79). For a predicted probability ≥22% the sensitivity of the model was 82%, with a negative predictive value of 85%. In the validation cohort the sensitivity of the model was 96%. Using this model, unnecessary broad-spectrum therapy would be recommended in 30% of cases whereas undertreatment would occur in only 6% of cases., Conclusions: For patients hospitalized with CAI and none of the following risk factors: atherosclerosis with functional impairment; previous invasive procedures; antimicrobial therapy; or MDRO colonization, CAI guidelines can safely be applied. Whereas, for those with some of these risk factors, particularly if more than one, alternative antimicrobial regimens should be considered., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: CD4 cell-count has been regarded as the key surrogate marker for prognostic staging and therapeutic monitoring of HIV-infected individuals. Our purpose was to assess the probability of maintaining a CD4 count >200 cells/μL in patients with continuous viral suppression and CD4 cell counts >200 cells/μL., Methods: Retrospective cohort study of HIV-infected patients, treatment naïve, who started antiretroviral therapy between 2007 and 2011. We estimated the probability of maintaining CD4 counts >200 cells/μL during continuous viral suppression using the Kaplan-Meier method. The hazard ratios of a CD4 count <200 cells/μL were estimated and compared using Cox proportional hazards regression., Results: 401 patients were included: 70.1% men; median age 37 years; 98.8% HIV-1 infected. The median duration of continuous viral suppression with CD4 counts >200 cells/μL was 40.5 months. Ninety-three percent of patients maintained CD4 counts ≥200 cells/μL during the period of continuous viral suppression. Compared with those with an initial CD4 count ≥350 cells/μL, patients with initial CD4 count <300 cells/μL had a significantly higher risk of a CD4 count <200 cells/μL. Patients with viral suppression and CD4 counts ≥350 cells/μL had a 97.1% probability of maintaining CD4 cell counts ≥200 cells/μL for 48 months., Conclusions: The probability of a CD4 count <200 cells/μL in an HIV-infected patient with viral suppression and CD4 ≥350 cells/μL was very low. These data suggests less frequent monitoring of CD4 counts in these patients., (Copyright © 2017. Published by Elsevier B.V.)

Background: Boosted protease inhibitors (PIs), including ritonavir-boosted atazanavir (ATV/r), are a recommended option for the initial treatment of HIV-1 infection based upon clinical trial data; however, long-term real-life clinical data are limited., Objective: We evaluated the long-term use of ATV/r as a component of antiretroviral combination therapy in the real-life setting in the REMAIN study., Methods: This was an observational cohort study conducted at sites across Germany, Portugal, and Spain. Retrospective historical and prospective longitudinal follow-up data were extracted every six months from medical records of HIV-infected treatment-naïve patients aged ≥ 18 years initiating a first-line ATV/r-containing regimen., Results: Eligible patients (n = 517) were followed up for a median of 3.4 years. The proportion remaining on ATV/r at 5 years was 51.5% with an estimated Kaplan-Meier median time to treatment discontinuation of 4.9 years. Principal reasons for discontinuation were adverse events (15.9%; 8.9% due to hyperbilirubinemia) and virologic failure (6.8%). The Kaplan-Meier probability of not having virologic failure (HIV-1 RNA < 50 copies/mL) was 0.79 (95% CI: 0.75, 0.83) at five years. No treatment-emergent major PI resistance occurred. ATV/r was generally well tolerated during long-term treatment with no significant changes in estimated glomerular filtration rate over five years., Conclusions: In a real-life clinical setting over five years, treatment-naïve patients with HIV-1 infection initiating an ATV/r-based regimen showed sustained virologic suppression, an overall treatment persistence rate of 51.5%, an absence of treatment-emergent major PI resistance mutations at virologic failure, a long-term safety profile consistent with that observed in clinical trials, and no significant decline in renal function.

Education is widely recognized as one of the cornerstones of successful antimicrobial stewardship programmes. There is evidence of important knowledge flaws around antimicrobial prescribing among both medical students and clinicians. Educational interventions improve antimicrobial prescribing, but traditional tools may be insufficient to deliver training to meet the complex demands of global healthcare professionals working across a diverse range of healthcare and resource settings. The educational solutions increasingly need to be timely, efficient, pragmatic, high quality, aligned to the needs of the professional in a specific context, sustainable and cost-effective. Online learning has been playing a growing role in education about antimicrobial stewardship and the recent phenomenon of massive open online courses (MOOCs) offers novel and additional opportunities to deliver relevant information to a wide range of people. Additional research on MOOCs as an educational approach is needed in order to define their effectiveness, sustainability and the best ways to achieve the intended results. Although the precise value of new online strategies such as MOOCs is ill defined, they certainly will have an important place in increasing awareness and improving antimicrobial prescribing., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Human nocardiosis, caused by Nocardia spp., an ubiquitous soil-borne bacteria, is a rare granulomatous disease close related to immune dysfunctions. Clinically can occur as an acute life-threatening disease, with lung, brain and skin being commonly affected. The infection was classically diagnosed in HIV infected persons, organ transplanted recipients and long term corticosteroid treated patients. Currently the widespread use of immunomodulators and immunossupressors in the treatment of inflammatory diseases changed this scenario. Our purpose is to review all published cases of nocardiosis in immunomodulated patients due to inflammatory diseases and describe clinical and laboratory findings. We reviewed the literature concerning human cases of nocardiosis published between 1980 and 2014 in peer reviewed journals. Eleven cases of nocardiosis associated with anti-tumor necrosis factor (TNF) prescription (9 related with infliximab and 2 with adalimumab) were identified; 7 patients had inflammatory bowel disease (IBD), 4 had rheumatological conditions; nocardia infection presented as cutaneous involvement in 3 patients, lung disease in 4 patients, hepatic in one and disseminated disease in 3 patients. From the 10 cases described in IBD patients 7 were associated with anti-TNF and 3 with steroids and azathioprine. In conclusion, nocardiosis requires high levels of clinical suspicion and experience of laboratory staff, in order to establish a timely diagnosis and by doing so avoid worst outcomes. Treatment for long periods tailored by the susceptibility of the isolated species whenever possible is essential. The safety of restarting immunomodulators or anti-TNF after the disease or the value of prophylaxis with cotrimoxazole is still debated.

Background: Nocardia species cause infections in both immunocompromised and otherwise immunocompetent patients, although the mechanisms defining susceptibility in the latter group are elusive. Anticytokine autoantibodies are an emerging cause of pathogen-specific susceptibility in previously healthy human immunodeficiency virus-uninfected adults, including anti-granulocyte macrophage colony-stimulating factor (GM-CSF) autoantibodies with cryptococcal meningitis., Methods: Plasma from patients with disseminated/extrapulmonary nocardiosis and healthy controls was screened for anticytokine autoantibodies using a particle-based approach. Autoantibody function was assessed by intranuclear staining for GM-CSF-induced STAT5 phosphorylation in normal cells incubated with either patient or normal plasma. GM-CSF-mediated cellular activation by Nocardia was assessed by staining for intracellular cytokine production and intranuclear STAT5 phosphorylation., Results: We identified neutralizing anti-GM-CSF autoantibodies in 5 of 7 patients studied with central nervous system nocardiosis and in no healthy controls (n = 14). GM-CSF production was induced by Nocardia in vitro, suggesting a causative role for anti-GM-CSF autoantibodies in Nocardia susceptibility and dissemination., Conclusions: In previously healthy adults with otherwise unexplained disseminated/extrapulmonary Nocardia infections, anti-GM-CSF autoantibodies should be considered. Their presence may suggest that these patients may be at risk for later development of pulmonary alveolar proteinosis or other opportunistic infections, and that patients may benefit from therapeutic GM-CSF administration., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.)