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Letter to the Editor| Volume 135, P206-207, May 2023

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A proposed classification system for opportunistic pathogens for improved healthcare infection prevention and control risk assessments

Published:March 20, 2023DOI:https://doi.org/10.1016/j.jhin.2023.03.008
      Sir,
      Healthcare-associated infections (HCAIs) are a major challenge for healthcare systems. Many micro-organisms responsible for HCAIs are considered to be opportunistic pathogens – defined as causing infection when outside of their normal ecological niche [
      • Graeventiz A.V.
      The role of opportunistic bacteria in human disease.
      ,
      • Brown S.P.
      • Cornforth D.M.
      • Mideo N.
      Evolution of virulence in opportunistic pathogens: generalism, plasticity, and control.
      ]. Such micro-organisms can often be found in the physical hospital environment, where contamination may persist and contribute to transmission [
      • Otter J.A.
      • Yezli S.
      • French G.L.
      The role played by contaminated surfaces in the transmission of nosocomial pathogens.
      ]. In order to effectively target infection prevention and control (IPC) practice designed to mitigate environmental microbial contamination, a clear risk assessment framework is required to guide interventions. As there is great variation between infection rates caused by organisms which typically colonize humans and those found in the clinical environment, the classification of many such microbes as opportunistic pathogens does not support risk assessment development. Therefore, a more nuanced classification system is required to help establish the risks posed to patients.
      Here, we propose a classification system for micro-organisms originating from the hospital environment and associated with HCAI based on reported incidence in the scientific literature. Literature searches were conducted via PubMed utilizing the search string (‘Species name’) AND (infections[MeSH]) [
      PubMed [Internet]..
      ]. Species were checked for synonyms through Taxonomy Browser; where species names have been historically changed, the string was modified to (‘Species name’) OR (‘Species name synonym’) AND (infections[MeSH]) [
      • Schoch C.L.
      • Ciufo S.
      • Domrachev M.
      • Hotton C.L.
      • Kannan S.
      • Khovanskaya R.
      • et al.
      NCBI Taxonomy: a comprehensive update on curation, resources and tools.
      ]. Only case reports, clinical studies, clinical trials, and letters reporting infections in humans were included, and no time limitation was implemented. Total academic reports for each search were enumerated and reporting incidences were classified (Table I). Searches were conducted for species typically regarded as opportunistic pathogens, species known to be detected in the clinical environment and species considered to be true pathogens in clinical practice for reference.
      Table ISummary of each reporting incidence categorization tier
      Total reports identifiedReporting incidence levelSpecies examples
      ≥1000Very highStaphylococcus aureus
      Human commensal organisms which are regarded as genuine pathogens when outside of their normal human environment.
      , Escherichia coli
      Human commensal organisms which are regarded as genuine pathogens when outside of their normal human environment.
      , Pseudomonas aeruginosa, Klebsiella pneumoniae
      Human commensal organisms which are regarded as genuine pathogens when outside of their normal human environment.
      , Clostridioides difficile
      Human commensal organisms which are regarded as genuine pathogens when outside of their normal human environment.
      , Enterococcus spp.
      Human commensal organisms which are regarded as genuine pathogens when outside of their normal human environment.
      , Enterobacter spp.
      Human commensal organisms which are regarded as genuine pathogens when outside of their normal human environment.
      , Staphylococcus epidermidis
      500–999HighAcinetobacter baumannii, Legionella pneumophila, Serratia marcescens, Proteus mirabilis
      100–499ModerateMycobacterium abscessus, Stenotrophomonas maltophilia, Burkholderia cepacia, Klebsiella oxytoca, Citrobacter freundii, Morganella morganii
      10–99LowStaphylococcus haemolyticus, Micrococcus luteus, Rhizobium radiobacter, Pantoea agglomerans, Corynebacterium jeikeium, Pseudomonas putida, Pseudomonas stutzeri, Staphylococcus capitis
      ≤9Very lowDermabacter hominis, Kocuria rhizophila, Acinetobacter johnsonii, Corynebacterium aurimucosum, Staphylococcus equorum, Brachybacterium muris
      Example organisms which group as either very high, high, moderate, low or very low reporting incidence are listed.
      a Human commensal organisms which are regarded as genuine pathogens when outside of their normal human environment.
      The classification results show that species that act as true pathogens are reported at a higher frequency compared with opportunists. S. aureus, E. coli, P. aeruginosa, K. pneumoniae, C. difficile, Enterococcus species, Enterobacter species, and S. epidermidis all grouped as very high reporting incidence. Other HCAI-associated species were identified as having high (e.g. S. marcescens, L. pneumophila, and P. mirabilis), moderate (e.g. M. abscessus, S. maltophilia, K. oxytoca), and low (e.g. coagulase-negative staphylococci (CoNS) species and C. jeikeium) reporting incidence, with C. jeikeium often being associated with HCAI in immunocompromised patients [
      • Pardo S.M.M.
      • Patel R.H.
      • Ramsakal A.
      • Greene J.
      Disseminated Corynebacterium jeikeium infection in cancer patients.
      ].
      In the examples listed, Enterobacter and Enterococcus species are included as genera instead of individual species as infections associated with them are often published in the literature at genus level only (for example as vancomycin-resistant enterococci). CoNS are included here at species level, despite being historically reported simply as a grouping. The grouping of CoNS is classified as very high reporting incidence in the proposed framework. As evidence has shown that different species of CoNS are associated with different infection burdens, it is therefore more appropriate to classify their infection incidence rates at species level [
      • Hitzenbichler F.
      • Simon M.
      • Salzberger B.
      • Hanses F.
      Clinical significance of coagulase-negative staphylococci other than S. epidermidis blood stream isolates at a tertiary care hospital.
      ].
      By determining the incidence of infections caused by opportunistic pathogens through reporting in the scientific literature, these micro-organisms can be numerically compared and classified. When taken in conjunction with other factors contributing to IPC risk assessments (e.g. the severity of infection caused, the environmental loading of a species, and the susceptibility of the surrounding patient population), the assigned classifications can contribute to an environmental IPC risk assessment framework. The use of such a framework would allow for more evidence-based and targeted IPC interventions relating to environmental microbial contamination.
      There are some limitations when classifying species in this manner. As there is no central reporting framework for all HCAI-causative organisms, the incidence of scientific reports discussing each species are enumerated instead. However, scientific report incidences may not reflect the true infection burden of each species, as publications may include multiple infections, outbreaks, or discuss therapies for infections. Equally, the use of scientific reports may produce bias towards historically well-documented HCAI-associated micro-organisms. Additionally, some species (e.g. individual CoNS species) may be under-reported due to issues with species-level identification [
      • Argemi X.
      • Riegel P.
      • Lavigne T.
      • Lefebvre N.
      • Grandpré N.
      • Hansmann Y.
      • et al.
      Implementation of matrix-assisted laser desorption ionization–time of flight mass spectrometry in routine clinical laboratories improves identification of coagulase-negative staphylococci and reveals the pathogenic role of Staphylococcus lugdunensis.
      ]. Despite these limitations, this approach based on the quantitative measure of reporting incidence allows infection control teams to better categorize such micro-organisms. This will support evidence-based infection control risk assessment development, improving patient safety within hospital spaces.

      Conflict of interest statement

      None declared.

      Funding source

      This work was funded by the Healthcare Infection Society Major Grant Scheme [MRG/2019/006].

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