Nosocomial Pathogens and Antibiotic Resistance

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Antimicrobial Agents and Resistance".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 27604

Special Issue Editors


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Guest Editor
1. TOXRUN—Toxicology Research Unit, University Institute of Health Sciences, CESPU, CRL, 4585-116 Gandra, Portugal
2. UCIBIO-Applied Molecular Biosciences Unit, Laboratory of Microbiology, Department of Biological Sciences, REQUIMTE Faculty of Pharmacy, University of Porto, Porto, Portugal
Interests: antimicrobial resistance and infectious diseases; molecular and genomic epidemiology of bacterial pathogens under a one health approach; forensic microbiology
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Guest Editor
Division of Nosocomial Pathogens and Antibiotic Resistances, Department of Infectious Diseases, Robert Koch Institute, National Reference Centre for Staphylococci and Enterococci, Wernigerode Branch, 38855 Wernigerode, Germany
Interests: nosocomial pathogens; AMR; typing; genomics; enterococci; Klebsiella

Special Issue Information

Dear Colleagues,

Healthcare-associated infections caused by antimicrobial-resistant (AMR) bacteria are increasingly hard to treat, threatening our progress in healthcare and life expectancy, and generating a tremendous social and economic impact worldwide. In general, challenges in patient treatment and public health vary largely between low and middle-income countries (LMIC) and industrialized countries. However, a few aspects are similarly independent of climate, geographic origin, ethnic affiliation and quality and quantity of medical care. AMR is one of these key challenges to health care all over the world, although the foci might be different in the different world regions also in relation to age, gender, access to health care and underlying diseases. AMR in industrialized countries is rather an issue in intensive care with severely ill patients in relation to invasive treatment and high antibiotic pressure. Successfully treated but colonized patients may transmit the AMR problem into other hospitals, long-term care facilities and ambulatory care. AMR in LMIC spans the entire range from intensive, stationary and ambulatory care through One-Health-oriented scenarios and wild animal, food animal and environmental reservoirs.

With this Special Issue, we offer the opportunity to submit papers on all aspects of nosocomial, bacterial pathogen and antibiotic resistance. We also cover aspects of One-Health-oriented AMR issues with a direct link to nosocomial bacterial pathogens such as mcr-mediated colistin resistance in Enterobacterales and optrA-, cfr- and poxtA-mediated linezolid resistance in Gram-positive pathogens, to give two examples.   

Prof. Dr. Ana R. Freitas
Prof. Dr. Guido Werner
Guest Editors

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Keywords

  • genomics
  • hypervirulence and resistance
  • healthcare pathogens
  • One Health and AMR

Published Papers (10 papers)

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Editorial

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5 pages, 207 KiB  
Editorial
Nosocomial Pathogens and Antimicrobial Resistance: Modern Challenges and Future Opportunities
by Ana R. Freitas and Guido Werner
Microorganisms 2023, 11(7), 1685; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms11071685 - 28 Jun 2023
Cited by 3 | Viewed by 1082
Abstract
Antimicrobial resistance (AMR) has become a critical global health emergency in the 21st century, with the greatest burden in resource-limited settings [...] Full article
(This article belongs to the Special Issue Nosocomial Pathogens and Antibiotic Resistance)

Research

Jump to: Editorial, Review

13 pages, 955 KiB  
Article
Controlling an Unprecedented Outbreak with Vancomycin-Resistant Enterococcus faecium in Germany, October 2015 to November 2019
by Jennifer K. Bender, Julia Hermes, Lutz T. Zabel, Sebastian Haller, Nadja Mürter, Hans-Peter Blank, Guido Werner, Ingo Hüttner and Tim Eckmanns
Microorganisms 2022, 10(8), 1603; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10081603 - 09 Aug 2022
Cited by 8 | Viewed by 2075
Abstract
Hospital outbreaks with vancomycin-resistant enterococci (VRE) pose a serious health threat and a challenge to infection prevention and control (IPC). We herein report on a VRE outbreak of unprecedented extent in Southern Germany (October 2015–November 2019). We used descriptive epidemiology and whole-genome sequencing [...] Read more.
Hospital outbreaks with vancomycin-resistant enterococci (VRE) pose a serious health threat and a challenge to infection prevention and control (IPC). We herein report on a VRE outbreak of unprecedented extent in Southern Germany (October 2015–November 2019). We used descriptive epidemiology and whole-genome sequencing (WGS) for a detailed outbreak investigation. Of the 2905 cases, 2776 (95.3%) were colonized, whereas from 127 (3.7%), VRE could be isolated from otherwise sterile body fluids or sites unlikely for enterococci colonization. Cases had a median age of 78 years (IQR 68–84) and 1339/2905 (46%) were female. The majority of isolates sequenced belonged to the clonal lineage ST80/CT1013 (212/397, 53%). Nosocomial transmission was observed as well as the constant import of VRE into the hospital. Extensive IPC measures were implemented and terminated the outbreak in late 2019, eventually. Our study shows that the combination of epidemiological and genomic analyses is indispensable for comprehensive outbreak investigations. The adaptation of IPC measures to these findings, their timely implementation, and strict execution also allow containment of large VRE outbreaks in hospital settings. Full article
(This article belongs to the Special Issue Nosocomial Pathogens and Antibiotic Resistance)
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18 pages, 1746 KiB  
Article
New Variants of Pseudomonas aeruginosa High-Risk Clone ST233 Associated with an Outbreak in a Mexican Paediatric Hospital
by Pamela Aguilar-Rodea, Elia L. Estrada-Javier, Verónica Jiménez-Rojas, Uriel Gomez-Ramirez, Carolina G. Nolasco-Romero, Gerardo E. Rodea, Benjamín Antonio Rodríguez-Espino, Sandra Mendoza-Elizalde, Cesar Arellano, Beatriz López-Marcelino, Daniela de la Rosa Zamboni, Ana Estela Gamiño-Arroyo, Rosalia Mora-Suárez, Margarita Torres García, Isabel Franco Hernández, Israel Parra-Ortega, Guillermina Campos-Valdez, Norma Velázquez-Guadarrama and Irma Rosas-Pérez
Microorganisms 2022, 10(8), 1533; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10081533 - 29 Jul 2022
Cited by 4 | Viewed by 2166
Abstract
Recent multidrug resistance in Pseudomonas aeruginosa has favoured the adaptation and dissemination of worldwide high-risk strains. In June 2018, 15 P. aeruginosa strains isolated from patients and a contaminated multi-dose meropenem vial were characterized to assess their association to an outbreak in a [...] Read more.
Recent multidrug resistance in Pseudomonas aeruginosa has favoured the adaptation and dissemination of worldwide high-risk strains. In June 2018, 15 P. aeruginosa strains isolated from patients and a contaminated multi-dose meropenem vial were characterized to assess their association to an outbreak in a Mexican paediatric hospital. The strains were characterized by antibiotic susceptibility profiling, virulence factors’ production, and biofilm formation. The clonal relationship among isolates was determined with pulse-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) sequencing. Repressor genes for the MexAB-OprM efflux pump were sequenced for haplotype identification. Of the strains, 60% were profiled as extensively drug-resistant (XDR), 33% as multidrug-resistant (MDR), and 6.6% were classified as sensitive (S). All strains presented intermediate resistance to colistin, and 80% were sensitive to aztreonam. Pyoverdine was the most produced virulence factor. The PFGE technique was performed for the identification of the outbreak, revealing eight strains with the same electrophoretic pattern. ST235 and ten new sequence types (STs) were identified, all closely related to ST233. ST3241 predominated in 26.66% of the strains. Twenty-five synonymous and seventeen nonsynonymous substitutions were identified in the regulatory genes of the MexAB-OprM efflux pump, and nalC was the most variable gene. Six different haplotypes were identified. Strains from the outbreak were metallo-β-lactamases and phylogenetically related to the high-risk clone ST233. Full article
(This article belongs to the Special Issue Nosocomial Pathogens and Antibiotic Resistance)
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8 pages, 704 KiB  
Article
First Cases of Candida auris in a Referral Intensive Care Unit in Piedmont Region, Italy
by Silvia Corcione, Giorgia Montrucchio, Nour Shbaklo, Ilaria De Benedetto, Gabriele Sales, Martina Cedrone, Davide Vita, Cristina Costa, Susanna Zozzoli, Teresa Zaccaria, Carlo Silvestre, Rossana Cavallo, Luca Brazzi and Francesco Giuseppe De Rosa
Microorganisms 2022, 10(8), 1521; https://doi.org/10.3390/microorganisms10081521 - 27 Jul 2022
Cited by 8 | Viewed by 1730
Abstract
Candida auris is an emerging healthcare-associated infection that can easily cause dissemination in hospitals through colonizing the skin and contaminating environmental surfaces, especially in Intensive Care Units (ICU). Difficulties with identification of this organism, uncertainty about routes of transmission and antifungals resistance have [...] Read more.
Candida auris is an emerging healthcare-associated infection that can easily cause dissemination in hospitals through colonizing the skin and contaminating environmental surfaces, especially in Intensive Care Units (ICU). Difficulties with identification of this organism, uncertainty about routes of transmission and antifungals resistance have impacted significantly outbreak detection and management. Here, we describe our experience with colonization/infection of C. auris among critically ill patients, admitted to a referral ICU of a University Hospital, in a transitional period (July 2021–March 2022) between management of non-COVID-19 and COVID-19 patients due to the reconversion of the ICU between two waves. A total of 8 patients presented colonization from C. auris, and two of them developed invasive infection from C. auris. The fungal pathogen was cultured from different sites: the skin (7 isolates), urine (2), respiratory tract (1), blood (1). The median time from admission to first detection is 24 days with 100% of patients requiring mechanical ventilation. All 8 patients received broad-spectrum antibiotic therapy for bacterial infections before identification of C. auris; 62.5% of the patients had prior antifungal exposure; 87.5% received steroids; 37.5% patients used immunomodulatory; and 75% had severe COVID-19 illness prior to C. auris identification. Only two cases (25%) were treated with antifungals as C. auris infections (1 patient for suspected UTI; 1 patient with candidemia). Infection control measures, including rapid microbiological identification, contact isolation, screening of contacts, antisepsis of colonized patients, dedicated equipment, cleaning and disinfection of the environment and subsequent follow-up sampling, remain essential in critically ill patients. Our experience highlights the importance of establishing a multidisciplinary model and bundling of practices for preventing C. auris’ spread. Full article
(This article belongs to the Special Issue Nosocomial Pathogens and Antibiotic Resistance)
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11 pages, 1111 KiB  
Article
Antimicrobial Resistance and Antimicrobial Activity of Staphylococcus lugdunensis Obtained from Two Spanish Hospitals
by Rosa Fernández-Fernández, Carmen Lozano, Laura Ruiz-Ripa, Beatriz Robredo, José Manuel Azcona-Gutiérrez, Carla Andrea Alonso, Carmen Aspiroz, Myriam Zarazaga and Carmen Torres
Microorganisms 2022, 10(8), 1480; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10081480 - 22 Jul 2022
Cited by 7 | Viewed by 1631
Abstract
Staphylococcus lugdunensis is a coagulase-negative-staphylococci (CoNS) that lately has gained special attention in public health as a human pathogen and also as a bacteriocin-producer bacteria. In this study, we characterized 56 S. lugdunensis isolates recovered from human samples in two Spanish hospitals. Antimicrobial [...] Read more.
Staphylococcus lugdunensis is a coagulase-negative-staphylococci (CoNS) that lately has gained special attention in public health as a human pathogen and also as a bacteriocin-producer bacteria. In this study, we characterized 56 S. lugdunensis isolates recovered from human samples in two Spanish hospitals. Antimicrobial susceptibility testing was performed and antimicrobial resistance and virulence genotypes were determined. Antimicrobial activity (AA) production was evaluated by the spot-on-lawn method against 37 indicator bacteria, including multidrug-resistant (MDR) isolates, and the presence of the lugD gene coding for lugdunin bacteriocin was analyzed by PCR. The antibiotic resistance detected was as follows (% resistance/genes detected): penicillin (44.6%/blaZ), oxacillin (1.8%/mecA on SCCmec-V), erythromycin-clindamycin inducible (7.1%/erm(C), msrA), tetracycline (5.3%/tetK), gentamicin and/or tobramycin (3.6%/ant(4′)-Ia, acc(6′)-aph(2″)), and fosfomycin (21.4%). A MDR phenotype was detected in 5% of isolates. Twenty-one of the S. lugdunensis isolates showed susceptibility to all 20 antibiotics tested (37.5%). The screening for AA revealed 23 antimicrobial producer (AP) isolates with relevant inhibition against coagulase-positive-staphylococci (CoPS), including both methicillin-susceptible and –resistant S. aureus. The lugD gene was detected in 84% of the 56 S. lugdunensis isolates. All of the AP S. lugdunensis isolates (n = 23) carried the lugD gene and it was also detected in 24 of the non-AP isolates, suggesting different gene expression levels. One of the AP isolates stood out due to its high antimicrobial activity against more than 70% of the indicator bacteria tested, so it will be further characterized at genomic and proteomic level. Full article
(This article belongs to the Special Issue Nosocomial Pathogens and Antibiotic Resistance)
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13 pages, 1419 KiB  
Article
High-Resolution Genotyping Unveils Identical Ampicillin-Resistant Enterococcus faecium Strains in Different Sources and Countries: A One Health Approach
by Ana R. Freitas, Ana P. Tedim, Ana C. Almeida-Santos, Bárbara Duarte, Houyem Elghaieb, Mohamed S. Abbassi, Abdennaceur Hassen, Carla Novais and Luísa Peixe
Microorganisms 2022, 10(3), 632; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10030632 - 16 Mar 2022
Cited by 6 | Viewed by 2356
Abstract
Multidrug-resistant (MDR) Enterococcus faecium (Efm) infections continue to increase worldwide, although epidemiological studies remain scarce in lower middle-income countries. We aimed to explore which strains circulate in E. faecium causing human infections in Tunisian healthcare institutions in order to compare them [...] Read more.
Multidrug-resistant (MDR) Enterococcus faecium (Efm) infections continue to increase worldwide, although epidemiological studies remain scarce in lower middle-income countries. We aimed to explore which strains circulate in E. faecium causing human infections in Tunisian healthcare institutions in order to compare them with strains from non-human sources of the same country and finally to position them within the global E. faecium epidemiology by genomic analysis. Antibiotic susceptibility testing was performed and transfer of vancomycin-vanA and ampicillin-pbp5 resistance was performed by conjugation. WGS-Illumina was performed on Tunisian strains, and these genomes were compared with Efm genomes from other regions present in the GenBank/NCBI database (n = 10,701 Efm genomes available May 2021). A comparison of phenotypes with those predicted by the recent ResFinder 4.1-CGE webtool unveiled a concordance of 88%, with discordant cases being discussed. cgMLST revealed three clusters [ST18/CT222 (n = 13), ST17/CT948 strains (n = 6), and ST203/CT184 (n = 3)], including isolates from clinical, healthy-human, retail meat, and/or environmental sources in different countries over large time spans (10–12 years). Isolates within each cluster showed similar antibiotic resistance, bacteriocin, and virulence genetic patterns. pbp5-AmpR was transferred by VanA-AmpR-ST80 (clinical) and AmpR-ST17-Efm (bovine meat). Identical chromosomal pbp5-platforms carrying metabolic/virulence genes were identified between ST17/ST18 strains of clinical, farm animal, and retail meat sources. The overall results emphasize the role of high-resolution genotyping as provided by WGS in depicting the dispersal of MDR-Efm strains carrying relevant adaptive traits across different hosts/regions and the need of a One Health task force to curtail their spread. Full article
(This article belongs to the Special Issue Nosocomial Pathogens and Antibiotic Resistance)
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10 pages, 296 KiB  
Communication
High Frequency of the EMRSA-15 Clone (ST22-MRSA-IV) in Hospital Wastewater
by Vanessa Silva, Jessica Ribeiro, Jaqueline Rocha, Célia M. Manaia, Adriana Silva, José Eduardo Pereira, Luís Maltez, José Luis Capelo, Gilberto Igrejas and Patrícia Poeta
Microorganisms 2022, 10(1), 147; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10010147 - 11 Jan 2022
Cited by 12 | Viewed by 2201
Abstract
Hospital wastewaters often carry multidrug-resistant bacteria and priority pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA). Pathogens and antibiotic resistance genes present in wastewaters may reach the natural environment facilitating their spread. Thus, we aimed to isolate MRSA from wastewater of 3 hospitals located [...] Read more.
Hospital wastewaters often carry multidrug-resistant bacteria and priority pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA). Pathogens and antibiotic resistance genes present in wastewaters may reach the natural environment facilitating their spread. Thus, we aimed to isolate MRSA from wastewater of 3 hospitals located in the north of Portugal and to characterize the isolates regarding the antimicrobial resistance and genetic lineages. A total of 96 wastewater samples were collected over six months. The water was filtered, and the filtration membrane was immersed in BHI broth supplemented with 6.5% of NaCl and incubated. The inoculum was streaked in ORSAB agar plates for MRSA isolation. The isolates susceptibility testing was performed against 14 antimicrobial agents. The presence of resistance and virulence genes was accessed by PCR. Molecular typing was performed in all isolates. From the 96 samples, 28 (29.2%) were MRSA-positive. Most isolates had a multidrug-resistant profile and carried the mecA, blaZ, aac(6′)-Ie-aph(2″)-Ia, aph(3′)-IIIa, ermA, ermB, ermC, tetL, tetM, dfrA dfrG and catpC221 genes. Most of the isolates were ascribed to the immune evasion cluster (IEC) type B. The isolates belonged to ST22-IV, ST8-IV and ST105-II and spa-types t747, t1302, t19963, t6966, t020, t008 and tOur study shows that MRSA can be found over time in hospital wastewater. The wastewater treatment processes can reduce the MRSA load. The great majority of the isolates belonged to ST22 and spa-type t747 which suggests the fitness of these genetic lineages in hospital effluents. Full article
(This article belongs to the Special Issue Nosocomial Pathogens and Antibiotic Resistance)
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9 pages, 2358 KiB  
Article
Molecular Epidemiology of Vancomycin-Resistant Enterococci Bloodstream Infections in Germany: A Population-Based Prospective Longitudinal Study
by Carlos L. Correa-Martínez, Annette Jurke, Janne Schmitz, Frieder Schaumburg, Stefanie Kampmeier and Alexander Mellmann
Microorganisms 2022, 10(1), 130; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10010130 - 08 Jan 2022
Cited by 8 | Viewed by 1797
Abstract
Vancomycin-resistant enterococci (VRE) pose a public health challenge worldwide. While VRE bloodstream infections (VREBI) increase in Germany and Europe, population-based molecular data are scarce. We aimed to analyze the molecular epidemiology, demographic aspects, and geographical distribution of VREBI in the German Federal State [...] Read more.
Vancomycin-resistant enterococci (VRE) pose a public health challenge worldwide. While VRE bloodstream infections (VREBI) increase in Germany and Europe, population-based molecular data are scarce. We aimed to analyze the molecular epidemiology, demographic aspects, and geographical distribution of VREBI in the German Federal State of North-Rhine–Westphalia (NRW), located in the German–Dutch–Belgian border area, representing over 20% of Germany’s population. VREBI isolates were collected from hospitals across NRW between 2016 and 2019. Demographic data were gathered and anonymized upon sample collection. Multilocus sequence typing (MLST) and identification of glycopeptide resistance were carried out. Epidemiological analysis and geographical mapping were performed. Single VREBI isolates from 755 patients were analyzed. In total, 38.9% were female, and 80.0% were aged ≥ 60 years. The VREBI incidence per 100,000 inhabitants nearly tripled, from 0.52 (2016) to 1.48 (2019), particularly in male patients aged ≥ 50 years. The proportion of vanB reached 83% (n = 202/243) in 2018, overtaking vanA as the predominant glycopeptide resistance determinant, detected in close relation with ST117 isolates. The proportion of MLST sequence type (ST) 117 peaked in 2018, at 78.2% (n = 190/243). The major role of these emerging strains in invasive infections in central Europe requires novel strategies for their diagnosis, treatment, and prevention. Full article
(This article belongs to the Special Issue Nosocomial Pathogens and Antibiotic Resistance)
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20 pages, 2286 KiB  
Article
Recovering Escherichia coli Plasmids in the Absence of Long-Read Sequencing Data
by Julian A. Paganini, Nienke L. Plantinga, Sergio Arredondo-Alonso, Rob J. L. Willems and Anita C. Schürch
Microorganisms 2021, 9(8), 1613; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9081613 - 28 Jul 2021
Cited by 8 | Viewed by 4600
Abstract
The incidence of infections caused by multidrug-resistant E. coli strains has risen in the past years. Antibiotic resistance in E. coli is often mediated by acquisition and maintenance of plasmids. The study of E. coli plasmid epidemiology and genomics often requires long-read sequencing [...] Read more.
The incidence of infections caused by multidrug-resistant E. coli strains has risen in the past years. Antibiotic resistance in E. coli is often mediated by acquisition and maintenance of plasmids. The study of E. coli plasmid epidemiology and genomics often requires long-read sequencing information, but recently a number of tools that allow plasmid prediction from short-read data have been developed. Here, we reviewed 25 available plasmid prediction tools and categorized them into binary plasmid/chromosome classification tools and plasmid reconstruction tools. We benchmarked six tools (MOB-suite, plasmidSPAdes, gplas, FishingForPlasmids, HyAsP and SCAPP) that aim to reliably reconstruct distinct plasmids, with a special focus on plasmids carrying antibiotic resistance genes (ARGs) such as extended-spectrum beta-lactamase genes. We found that two thirds (n = 425, 66.3%) of all plasmids were correctly reconstructed by at least one of the six tools, with a range of 92 (14.58%) to 317 (50.23%) correctly predicted plasmids. However, the majority of plasmids that carried antibiotic resistance genes (n = 85, 57.8%) could not be completely recovered as distinct plasmids by any of the tools. MOB-suite was the only tool that was able to correctly reconstruct the majority of plasmids (n = 317, 50.23%), and performed best at reconstructing large plasmids (n = 166, 46.37%) and ARG-plasmids (n = 41, 27.9%), but predictions frequently contained chromosome contamination (40%). In contrast, plasmidSPAdes reconstructed the highest fraction of plasmids smaller than 18 kbp (n = 168, 61.54%). Large ARG-plasmids, however, were frequently merged with sequences derived from distinct replicons. Available bioinformatic tools can provide valuable insight into E. coli plasmids, but also have important limitations. This work will serve as a guideline for selecting the most appropriate plasmid reconstruction tool for studies focusing on E. coli plasmids in the absence of long-read sequencing data. Full article
(This article belongs to the Special Issue Nosocomial Pathogens and Antibiotic Resistance)
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Review

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32 pages, 1479 KiB  
Review
Antimicrobial Resistance in the Global Health Network: Known Unknowns and Challenges for Efficient Responses in the 21st Century
by Teresa M. Coque, Rafael Cantón, Ana Elena Pérez-Cobas, Miguel D. Fernández-de-Bobadilla and Fernando Baquero
Microorganisms 2023, 11(4), 1050; https://doi.org/10.3390/microorganisms11041050 - 17 Apr 2023
Cited by 20 | Viewed by 6274
Abstract
Antimicrobial resistance (AMR) is one of the Global Health challenges of the 21st century. The inclusion of AMR on the global map parallels the scientific, technological, and organizational progress of the healthcare system and the socioeconomic changes of the last 100 years. Available [...] Read more.
Antimicrobial resistance (AMR) is one of the Global Health challenges of the 21st century. The inclusion of AMR on the global map parallels the scientific, technological, and organizational progress of the healthcare system and the socioeconomic changes of the last 100 years. Available knowledge about AMR has mostly come from large healthcare institutions in high-income countries and is scattered in studies across various fields, focused on patient safety (infectious diseases), transmission pathways and pathogen reservoirs (molecular epidemiology), the extent of the problem at a population level (public health), their management and cost (health economics), cultural issues (community psychology), and events associated with historical periods (history of science). However, there is little dialogue between the aspects that facilitate the development, spread, and evolution of AMR and various stakeholders (patients, clinicians, public health professionals, scientists, economic sectors, and funding agencies). This study consists of four complementary sections. The first reviews the socioeconomic factors that have contributed to building the current Global Healthcare system, the scientific framework in which AMR has traditionally been approached in such a system, and the novel scientific and organizational challenges of approaching AMR in the fourth globalization scenario. The second discusses the need to reframe AMR in the current public health and global health contexts. Given that the implementation of policies and guidelines are greatly influenced by AMR information from surveillance systems, in the third section, we review the unit of analysis (“the what” and “the who”) and the indicators (the “operational units of surveillance”) used in AMR and discuss the factors that affect the validity, reliability, and comparability of the information to be applied in various healthcare (primary, secondary, and tertiary), demographic, and economic contexts (local, regional, global, and inter-sectorial levels). Finally, we discuss the disparities and similarities between distinct stakeholders’ objectives and the gaps and challenges of combatting AMR at various levels. In summary, this is a comprehensive but not exhaustive revision of the known unknowns about how to analyze the heterogeneities of hosts, microbes, and hospital patches, the role of surrounding ecosystems, and the challenges they represent for surveillance, antimicrobial stewardship, and infection control programs, which are the traditional cornerstones for controlling AMR in human health. Full article
(This article belongs to the Special Issue Nosocomial Pathogens and Antibiotic Resistance)
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