Biotechnology Fights HAI

Biotechnology Fights HAI

Nosocomial infections, or as they are now more commonly called, hospital-acquired infections (HAIs), are exactly what the more modern latter nomenclature implies: illnesses that are most commonly acquired in hospital settings. Those that are frequently encountered include bloodstream infections, pneumonias, urinary tract infections, surgical site infections, and gastroenterological conditions. Staphylococcus aureus, one of the most common nosocomial pathogens, causes skin lesions and could even lead to necrotizing fasciitis. The bloodstream infections increase risk of developing sepsis, another major problem that hospitals face.

 The pathogens that cause these illnesses vary; while most are bacterial, some are viral and fungal. Genera like Staphylococcus (especially S. aureus), Streptococcus, and Mycobacterium are most notoriously associated with hospital-acquired infections, as is Clostridium difficile; some of the other disease agents include Pseudomonas æruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia, Escherichia, Legionella, Klebsiella, the fungal Candida genus (especially C. albicans), norovirus, rotavirus, and cytomegalovirus.

 Most of the bacterial pathogens have several things in common. Many are opportunistic – that is, they are normally commensal or even symbiotic organisms found among the gut flora or other mucosa throughout the body, but if the balance of organisms is disrupted (usually through antibiotics), these organisms become dominant and pathogenic, leading to illness. Preventing these organisms from colonizing and taking over the gut flora is the principle rationale for the increase in popularity of probiotics, be they encapsulated or dietary supplements.

 HAI-associated pathogens tend to have multiple mechanisms of resistance to antibiotic treatments, both genomic and structural in nature. For instance, A. baumannii possess pathogenicity islands – two or more adjacent genes in a genome that confer improved virulence – called AbaR-type resistance that facilitate horizontal gene transfer, which passes genes from one organism to another that encode for antibiotic resistance, without the individual’s reproduction. Many bacterial pathogens’ cellular membranes are dotted with efflux pumps, which will pump antibiotic molecules out of the cytoplasm as soon as they are detected; others produce enzymes like carbapenemase and β-lactamase that cleave and deactivate antibiotics. Another defense mechanism is the production of biofilms, which allow pathogens to survive on artificial surfaces for extended periods of time, preventing large molecules from entering the cells or preventing the organisms from desiccating. Others, like C. difficile, produce spores that are protective against heat and alcohol or other germicidal substances.

 The most common attributes among HAI pathogens are, of course, the environment in which they are most commonly encountered and risk factors of contracting their infections. They are most commonly associated with invasive devices like IV and urinary catheters, tracheotomy tubes, and ventilators, with open wounds, surgical sites, and other areas of trauma like severe burns, or with immunosuppressant treatment administered to patients with organ and tissue transplants. As is usually the case, the very young, the elderly, and those with compromised immunity are at highest risk, as are diabetic patients, and women who have recently given birth or experienced a miscarriage.

 In addition to mounting antibiotic resistance, an issue that clinicians face when diagnosing HAIs is that many of them share similar symptomatologies with other bacterial infections, including fever or chills, nausea, muscle aches or rash. Likewise, gastroenterological illnesses and pneumonias have multiple pathological causes. A number of biotechnology firms are producing molecular diagnostics that detect many of the pathogens associated with these illnesses, with some of them dedicated entirely to nosocomial infections. We at Kalorama Information have profile these companies in our Molecular Point-of-Care Markets report, a new edition of which will be released in the coming weeks.

  • The GenomEra CDX system, produced by Abacus Diagnostica Oy, is found more often in hospitals than in POC sites because the system’s assays are so directed for HAI and sepsis testing. The platform has a whole host of tests designed for the detection of such pathogens, including norovirus, difficile, and S. pneumoniæ; there are multiple diagnostics for methicillin-resistant S. aureus (MRSA) alone, with variants for nasal swab, culture plate, blood culture, and multiple site swab.
  • Becton Dickinson’s BD MAX is designed to compete in the HAI testing market, with assays available for difficile, Campylobacter, enteroinvasive E. coli (EIEC), norovirus, rotavirus, Salmonella, and three MRSA assays. BD is currently developing a panel for carbepenem-resistant organisms, and produces a research use only (RUO) assay for carbepenem-resistant Enterobacteriaceæ (CRE).
  • The BioFire FilmArray by bioMérieux has multiplex diagnostic panels for gastrointestinal and bloodstream infections. The former detects difficile, Campylobacter, norovirus, rotavirus, and Salmonella; the latter targets Acinetobacter, Candida species, Enterococcus, P. æruginosa, S. aureus, as well as genes that confer drug resistance.
  • Installations of Cepheid’s GeneXpert system have been driven in part by the company’s pathogen-testing applications, especially for MRSA and difficile. Cepheid released an updated version of the MRSA assay (MRSA NxG) that can perform MRSA surveillance testing in 45 minutes. Additional assays include norovirus, carbapenem resistance genes, vancomycin resistance in Enterococcus, and an assay that targets the HAI-specific C. difficile Epidemic 027 strain.
  • Coris Bioconcept produces immunochromatographic dipsticks and cassettes for pathogens including difficile and rotavirus, and qPCR kits for genes (mexA and mexX) that encode proteins for efflux pumps in P. æruginosa.
  • The LiDiA diagnostic platform by DNA Electronics, slated for launch this year, is dedicated primarily to sepsis and HAI pathology, with the first cartridge-based test designed to detect bacterial and fungal infections associated with bloodstream infections; DNAe anticipates LiDiA to be placed principally in hospitals.
  • DxNA produces an S. aureus test for its CE-marked, cartridge-based GeneSTAT, that detects strains both resistant and sensitive to methicillin.
  • Greiner Bio-One’s Genspeed R2 is dedicated entirely to nosocomial infections, with four CE-IVD tests on the market. Genspeed MRSA detects not only aureus, but also S. epidermidis and S. hæmolyticus, as well as mecA and mecC genes. Genspeed C. diff OneStep detects the C. difficile GDH antigen as well as the entero-, cyto- and binary toxins the bacteria produce. Genspeed Superbug targets over 70 carbepenemase variants, and Genspeed VanABC Plus is a single-tube multiplex assay for transmissible and non-transmissible vancomycin resistance genes.
  • iCubate produces RUO assays including a Gram-positive Bacteria cassette that detects many HAI-associated pathogens, as well as a fully purpose-built HAI cassette that targets baumannii, Escherichia coli, E. fæcalis, E. fæcium, Enterobacter cloacæ, P. æruginosa, Proteus mirabilis, S. aureus, five Candida species, and detects methicillin resistance.
  • Nanosphere’s Verigene system detects nucleic acids and proteins from numerous HAI-associated pathogens in Gram-positive and -negative, Enteric pathogen, and C. difficile tests. Targets include Campylobacter, Enterobacter, Escherichia, Klebsiella, Pseudomonas, Salmonella, Shigella, Staphylococcus, Streptococcus, and Vibrio species, among many others.
  • Users of Oxford Nanopore’s MinION have used the diminutive sequencing platform for clinical research or surveillance of æruginosa strains, sequencing Salmonella from an outbreak at a UK hospital, and rapid drug resistance detection in S. aureus.