Frequency of bloodstream infections caused by six key antibiotic-resistant pathogens for prioritization of research and discovery of new therapies in Europe: a systematic review.

BACKGROUND: To prioritize healthcare investments, ranking of infections caused by antibiotic-resistant bacteria should be based on accurate incidence data. OBJECTIVES: We performed a systematic review to estimate frequency measures of antimicrobial resistance for six key bacteria causing bloodstream infections (BSI) in European countries. DATA SOURCES: We searched PubMed, Web of Science, Embase databases, and the ECRAID-Base Epidemiological-Network platform. STUDY ELIGIBILITY CRITERIA: We included studies and surveillance systems assessing resistance-percentage, prevalence, or incidence-density of BSI because of carbapenem-resistant Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli, third-generation cephalosporins-resistant E. coli and K. pneumoniae, vancomycin-resistant Enterococcus faecium, and methicillin-resistant Staphylococcus aureus. METHODS: Reviewers independently assessed published data and evaluated study quality with the modified Joanna Briggs Institute critical appraisal tool. Pooled estimates were determined using random effects meta-analysis. Consistency of data was assessed using random effects meta-regression (Wald test, p > 0.05). RESULTS: We identified 271 studies and 52 surveillance systems from 32 European countries. Forty-five studies (16%) reported on BSI, including 180 frequency measures most commonly as resistance-percentage (88, 48.9%). Among 309 frequency measures extracted from 24 (46%) surveillance systems, 278 (89%) were resistance-percentages. Frequency measures of methicillin-resistant S. aureus and vancomycin-resistant E. faecium BSI were more frequently reported from Southern Europe and Western Europe (80%), whereas carbapenem-resistant P. aeruginosa BSI from Northern Europe and Western Europe (88%). Highest resistance-percentages were detected for carbapenem-resistant A. baumannii (66% in Central Eastern Europe) and carbapenem-resistant K. pneumoniae (62.8% in Southern Europe). Pooled estimates showed lower resistance-percentages in community versus healthcare-associated infections and in children versus adults. Estimates from studies and surveillance systems were mostly consistent among European regions. The included data was of medium quality. DISCUSSION: Pathogen-specific frequency measures of antimicrobial resistance in BSI are insufficient to inform antibiotic stewardship and research and development strategies. Improving data collection and standardization of frequency measures is urgently needed.

EPI-Net One Health reporting guideline for antimicrobial consumption and resistance surveillance data: a Delphi approach.

Strategic and standardised approaches to analysis and reporting of surveillance data are essential to inform antimicrobial resistance (AMR) mitigation measures, including antibiotic policies. Targeted guidance on linking full-scale AMR and antimicrobial consumption (AMC)/antimicrobial residues (AR) surveillance data from the human, animal, and environmental sectors is currently needed. This paper describes the initiative whereby a multidisciplinary panel of experts (56 from 20 countries-52 high income, 4 upper middle or lower income), representing all three sectors, elaborated proposals for structuring and reporting full-scale AMR and AMC/AR surveillance data across the three sectors. An evidence-supported, modified Delphi approach was adopted to reach consensus among the experts for dissemination frequency, language, and overall structure of reporting; core elements and metrics for AMC/AR data; core elements and metrics for AMR data. The recommendations can support multisectoral national and regional plans on antimicrobials policy to reduce resistance rates applying a One Health approach.

Surveillance of Antifungal Resistance in Candidemia Fails to Inform Antifungal Stewardship in European Countries.

BACKGROUND: The increasing burden of candidemia and the emergence of resistance, especially among non-Candida albicans strains, represent a new threat for public health. We aimed to assess the status of surveillance and to identify publicly accessible resistance data in Candida spp. blood isolates from surveillance systems and epidemiological studies in 28 European and 4 European Free Trade Association member states. METHODS: A systematic review of national and international surveillance networks, from 2015 to 2020, and peer-reviewed epidemiological surveillance studies, from 2005 to 2020, lasting for at least 12 consecutive months and with at least two centers involved, was completed to assess reporting of resistance to amphotericin B, azoles, and echinocandins in C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, and C. auris. RESULTS: Only 5 (Austria, Italy, Norway, Spain, and United Kingdom) of 32 countries provided resistance data for Candida spp blood isolates. Among 322 surveillance studies identified, 19 were included from Belgium, Denmark, Iceland, Italy, Portugal, Spain, Sweden, Switzerland, and United Kingdom. C. albicans and C. glabrata were the most monitored species, followed by C. parapsilosis and C. tropicalis. C. krusei was not included in any national surveillance system; 13 studies assessed resistance. No surveillance system or study reported resistance for C. auris. Fluconazole, voriconazole, caspofungin, and amphotericin B resistance in C. albicans, C. glabrata, and C. parapsilosis were the most common drug-species combination monitored. Quality of surveillance data was poor, with only two surveillance systems reporting microbiological methods and clinical data. High heterogeneity was observed in modalities of reporting, data collection, and definitions. CONCLUSION: Surveillance of antifungal resistance in Candida spp blood-isolates is fragmented and heterogeneous, delaying the application of a translational approach to the threat of antifungal resistance and the identification of proper targets for antifungal stewardship activities. International efforts are needed to implement antifungal resistance surveillance programs in order to adequately monitor antifungal resistance.

Linking antimicrobial resistance surveillance to antibiotic policy in healthcare settings: the COMBACTE-Magnet EPI-Net COACH project.

OBJECTIVES: To systematically summarize the evidence on how to collect, analyse and report antimicrobial resistance (AMR) surveillance data to inform antimicrobial stewardship (AMS) teams providing guidance on empirical antibiotic treatment in healthcare settings. METHODS: The research group identified 10 key questions about the link between AMR surveillance and AMS using a checklist of 9 elements for good practice in health research priority settings and a modified 3D combined approach matrix, and conducted a systematic review of published original studies and guidelines on the link between AMR surveillance and AMS. RESULTS: The questions identified focused on AMS team composition; minimum infrastructure requirements for AMR surveillance; organisms, samples and susceptibility patterns to report; data stratification strategies; reporting frequency; resistance thresholds to drive empirical therapy; surveillance in high-risk hospital units, long-term care, outpatient and veterinary settings; and surveillance data from other countries. Twenty guidelines and seven original studies on the implementation of AMR surveillance as part of an AMS programme were included in the literature review. CONCLUSIONS: The evidence summarized in this review provides a useful basis for a more integrated process of developing procedures to report AMR surveillance data to drive AMS interventions. These procedures should be extended to settings outside the acute-care institutions, such as long-term care, outpatient and veterinary. Without proper AMR surveillance, implementation of AMS policies cannot contribute effectively to the fight against MDR pathogens and may even worsen the burden of adverse events from such interventions.

White Paper: Bridging the gap between surveillance data and antimicrobial stewardship in the animal sector-practical guidance from the JPIAMR ARCH and COMBACTE-MAGNET EPI-Net networks.

BACKGROUND: The JPIAMR ARCH and COMBACTE-MAGNET EPI-Net networks have joined efforts to formulate a set of target actions to link the surveillance of antimicrobial usage (AMU) and antimicrobial resistance (AMR) with antimicrobial stewardship (AMS) activities in four different settings. This White Paper focuses on the veterinary setting and embraces the One Health approach. METHODS: A review of the literature was carried out addressing research questions in three areas: AMS leadership and accountability; AMU surveillance and AMS; and AMR surveillance and AMS. Consensus on target actions was reached through a RAND-modified Delphi process involving over 40 experts in infectious diseases, clinical microbiology, AMS, veterinary medicine and public health, from 18 countries. RESULTS/DISCUSSION: Forty-six target actions were developed and qualified as essential or desirable. Essential actions included the setup of AMS teams in all veterinary settings, building government-supported AMS programmes and following specific requirements on the production, collection and communication of AMU and AMR data. Activities of AMS teams should be tailored to the local situation and capacities, and be linked to local or national surveillance systems and infection control programmes. Several research priorities were also identified, such as the need to develop more clinical breakpoints in veterinary medicine. CONCLUSIONS: This White Paper offers a practical tool to veterinary practitioners and policy makers to improve AMS in the One Health approach, thanks to surveillance data generated in the veterinary setting. This work may also be useful to medical doctors wishing to better understand the specificities of the veterinary setting and facilitate cross-sectoral collaborations.

Real-time PCR assay for detection of Staphylococcus aureus, Panton-Valentine Leucocidin and Methicillin Resistance directly from clinical samples.

Rapid detection of Methicillin Resistant Staphylococcus aureus (MRSA) is an important concern for both treatment and implementation of infection control policies. The present study provides an 'in house' real-time PCR assay to detect directly nuc, pvl, and mecA genes. The assay is able to perform identification of MRSA, Methicillin-Sensitive S. aureus, Methicillin-Resistant Coagulase Negative Staphylococci and the Panton-Valentine leukocidin virulence gene from rectal and pharyngeal swab samples in a screening context. We found an analytical sensitivity of this current Triplex PCR assay of 514 CFU/mL. Analytical specificity was tested with different Gram-positive and Gram-negative species and yielded no false-positive PCR signal. The sensitivity and specificity of the Triplex Real Time PCR were both 100% for these targets when compared with the culture and conventional methods. This assay is readily adaptable for routine use in a microbiology laboratory, as it will enable the implementation of timely and properly guided therapy and infection control strategies.

Duplex real-time polymerase chain reaction assay for the detection of human KIPyV and WUPyV in nasopharyngeal aspirate pediatric samples.

In this study, we describe a duplex real-time PCR assay for the simultaneous detection of KIPyV and WUPyV polyomaviruses based on TaqMan probes. This assay detected 500 copies/mL both for KIPyV and WUPyV in 100% of tested positive samples. We assessed this technique on 482 nasopharyngeal aspirate specimens from hospitalized pediatric patients with respiratory symptoms, previously analyzed with commercial multiplex assay for 16 major respiratory viruses. Our assay detected KIPyV genome in 15 out of 482 samples (3.1%) and WUPyV genome in 24 out of 482 samples (4.9%), respectively, and in three samples the coinfection of the two viruses was found. Interestingly, 29 out of 36 of samples with KIPyV and/or WUPyV infection exhibited a co-infection with one or more respiratory viruses confirming that KIPyV and WUPyV were often detected in association to other viral infections. Of note, KIPyV and WUPyV were detected singularly in 4 out of 15 cases and 3 out of 24 cases, respectively, suggesting a possible direct role of these viruses in the respiratory diseases. In conclusion, this method could be taken into account as an alternative technical approach to detect KIPyV and/or WUPyV in respiratory samples for epidemiological and diagnostic analyses.