Medical Device-Associated Healthcare Infections: Sterilization and the Potential of Novel Biological Approaches to Ensure Patient Safety

Abstract

Healthcare-associated infections caused by multi-drug-resistant pathogens are increasing globally, and current antimicrobial options have limited efficacy against these robust species. The WHO details the critically important bacterial and fungal species that are often associated with medical device HAIs. The effective sterilization of medical devices plays a key role in preventing infectious disease morbidity and mortality. A lack of adherence to protocol and limitations associated with each sterilization modality, however, allows for the incidence of disease. Furthermore, issues relating to carcinogenic emissions from ethylene oxide gas (EtO) have motivated the EPA to propose limiting EtO use or seeking alternative sterilization methods for medical devices. The Food and Drug Administration supports the sterilization of healthcare products using low-temperature VH2O2 as an alternative to EtO. With advances in biomaterial and medical devices and the increasing use of combination products, current sterilization modalities are becoming limited. Novel approaches to disinfection and sterilization of medical devices, biomaterials, and therapeutics are warranted to safeguard public health. Bacteriophages, endolysins, and antimicrobial peptides are considered promising options for the prophylactic and meta-phylactic control of infectious diseases. This timely review discusses the application of these biologics as antimicrobial agents against critically important WHO pathogens, including ESKAPE bacterial species.

Hospital Acquired Sepsis, Disease Prevalence, and Recent Advances in Sepsis Mitigation

“…Interestingly, the diversity of the resident GIT microbiota is disrupted in sepsis patients with a dysbiosis of key Firmicute and Bacteroide species, which have an impact on the immune response of the host, epithelial barrier function, and production of key regulatory molecules such as short chain fatty acids [9,36]. The relationship between the host GIT microbiota and numerous disease states has been well established [9,33]. antibiotic therapy [19] Corticosteroids in patients in septic shock who require vasopressor therapy [19] 40% in ICUs and ca.…”

“…Similar to AMPs, phages have large scale production, formulation, stability and pharmacokinetic issues which must be overcome before systemic application can be achieved [114]. Resistance to AMPs is not common Large-scale synthesis is costly Can be used in synergy to antibiotics Downstream processing and formulation considerations Cathelicidin AMPs, e.g., LL-37 have LPS neutralising action [119] Half-life, stability, and enzymatic degradation in vivo [9] Amenable to post-translational modification and genetic engineering [114] Limited in vivo studies on sepsis control Promote proteolysis of bacterial toxins [117] Binding to serum proteins in vivo may hinder bioavailability [114] LL-37 influences chemokine gene expression [124] LL-37 results in haemolytic damage at MIC range [9] Phage's Potent, selective, and specifically target species [132] Large-scale production and formulation issues [9] Self-limiting once pathogen is cleared Bacterial resistance may develop [114] Can be applied as a phage cocktail [133] Immune system clearance of phages may reduce activity in vivo [9] Effective against MDR species [133] Stability and storage issues [9] Biocompatible for patient use [9,132] Phage may transmit AMR genes [131] May regulate inflammatory responses in vivo [135] Phage may transmit genes coding for toxins [9] Limited impact on patient microbiota Risk of cytokine storm in patient; needs investigating [138]…”

“…Sepsis resulting from the LPS toxin is associated with cardiovascular failure, organ damage and organ failure in patients [ 10 ]. Contact between immune cells and these PAMPs triggers pro- and anti-inflammatory processes, which result in the dysregulation of the innate and acquired immune systems and may lead to excessive inflammation, immune suppression, and a loss of immune homeostasis [ 9 ]. Damage-associated molecular patterns (DAMPs) include cellular proteins, nucleic acids, nuclear lipids, cytoplasm, mitochondria, and endogenous granules of the host that are also active in sepsis [ 24 ].…”

“…day 5, secondary infection and a reduced immune capacity contribute to deaths after 20 days [ 12 , 34 , 35 ]. Interestingly, the diversity of the resident GIT microbiota is disrupted in sepsis patients with a dysbiosis of key Firmicute and Bacteroide species, which have an impact on the immune response of the host, epithelial barrier function, and production of key regulatory molecules such as short chain fatty acids [ 9 , 36 ]. The relationship between the host GIT microbiota and numerous disease states has been well established [ 9 , 33 ].…”

“…Studies show that sepsis associated with GNB is more severe than that of GPB, with increased levels of inflammatory components [ 3 ]. Furthermore, the LPS toxin of E. coli has a greater immunogenic potential than that which is excreted by other GNB [ 9 ]. Studies describe the LPS concentration released by ESBL E. coli following exposure to the bactericidal antibiotic, ceftazidime, in a dose-dependent manner [ 10 ].…”