MRSA – Emerging Therapeutic & Screening Approaches
Staphylococcus aureus is a gram positive, commensal bacteria found in normal human flora on the skin and mucous membranes. The commensal nature of this organism results in colonisation of around half of the general population, rising to around 80% in populations of healthcare workers, hospitalised patients and the immunocompromised1. However, given the opportunity to colonise internal tissues or the bloodstream, S. aureus infection can cause serious disease. Skin conditions caused by S. aureus include impetigo, scalded skin syndrome, boils, and abscesses. Examples of more serious conditions include meningitis, pneumonia, endocarditis, bacteraemia, and sepsis2.
Antimicrobial resistance (AMR) has, and continues to be, one of the largest threats to global health. In 2019, it is estimated that 1.27 million deaths globally were directly attributed to AMR, based on the drug-susceptible counterfactual, with only ischaemic heart disease and stroke accounting for more deaths in that year1. Figure 1 shows a global distribution map of MRSA isolates from the data of this comprehensive study. Methicillin-resistant Staphylococcus aureus (MRSA) was first identified only one year after the introduction of the penicillin-like antibiotic, methicillin3. While methicillin is no longer used in clinical practice, the term MRSA is used to encompass resistance to commercially available antibiotics such as β-lactams3. For many years, much work has gone into seeking novel therapies to combat drug-resistant bacteria, however, the indiscriminate overuse of antibiotics seen around the world, along with other factors, continues to contribute to the rise in AMR.
Identification of drug-resistant strains of bacteria is crucial to allow for characterisation of the pathogen and correct treatment of the infection. Classical evaluation consists of a routine culture to verify a diagnosis based on presenting symptoms. However, this can be a time consuming and laborious process which may delay diagnosis and treatment of a potentially fatal infection1.
Methicillin-Resistant Staphylococcus aureus
Methicillin is of a class of antibiotics known as β-lactams which bind to the penicillin binding protein (PBP) of the bacteria. PBP is responsible for crosslinking between N-acetylmuramic acid and N-acetylglucosamine which forms the architecture of the bacterial cell wall. When β-lactams bind to the PBP, a build-up of peptidoglycan precursors triggers autolytic digestion of peptidoglycan, facilitated by hydrolase. This reduction in peptidoglycans results in the loss of the integrity of the bacterial cell wall and ultimately culminates in cell damage caused by high internal osmotic pressure.
While methicillin has lost its clinical utility due to the emergent resistance, MRSA is used to describe S. aureus which displays resistance to penicillin-like antibiotics such as amoxicillin and oxacillin, as well as other forms of commercially available antibiotics like macrolides, tetracyclines, and fluroquinolones4. A meta-analysis by Dadashi et al., showed that 43% of S. aureus isolates where methicillin-resistant, exhibiting the prevalence of MRSA5.
Transmission is possible from direct contact with an infected individual or through contact with fomites2. MRSA infections can be categorised as either community acquired infections (CA-MRSA), or hospital acquired infections (HA-MRSA). While rates of HA-MRSA have fallen over the last ten years, this decrease in infection rates has not translated to CA-MRSA6. This is evidence of the requirement for quicker, easier testing in community settings to identify those infected by MRSA and to trigger the initiation of isolation and treatment.
While the pathophysiology of MRSA will largely depend on the causative strain of bacteria, collectively, S. aureus is the most common bacterial infection in humans and may result in infections of varying severity including1:
- Infective endocarditis
- Skin and soft tissue infections
- Septic arthritis
- Prosthetic device infections
- Pulmonary infections
- Toxic shock syndrome
Development of resistance and resistance mechanisms
Antimicrobial resistance arises from a combination of mechanisms. Genetic mutations are crucial in the development of resistance mechanisms. These genetic mutations must favour the survival of the mutated gene and the advantage of AMR mechanisms to the survival of bacteria cannot be understated. Regarding MRSA, S. aureus can gain resistance through horizontal gene transfer mediated by plasmids, mutations in chromosomal genes or mobile genetic elements4. Methicillin-susceptible Staphylococcus aureus (MSSA) gains the staphylococcal cassette chromosome (SCCmec) gene, a gene containing mecA, which is responsible for some of the resistance mechanisms displayed by MRSA4. The collection of antibiotics the bacteria gains resistance to, will depend on the SCCmec gene type.
The first mechanism of resistance is the expression of β-lactamase which functions to degrade β-lactams, ultimately resulting in loss of function of the antibiotic. This enzyme hydrolyses β-lactam ions in the periplasmic space, denaturing the antibiotic before it can interact with bacteria3. The mecA gene encodes the protein penicillin-binding protein 2a (PBP-2a), a type of PBP which has lower affinity for β-lactams, as well as other penicillin-like antibiotics due its conformation, meaning that the presence of these antimicrobial agents does not confer a loss of structure in the bacterial cell wall1.
One study conducted by Hosseini et al., investigated resistance mechanisms in MRSA and showed that all multidrug resistance MRSA strains displayed biofilm formation as part of its resistance strategy7. Biofilms induce resistance to high concentrations and a large variety of antimicrobial agents and help regulate anti-bacterial immune responses. Biofilm formation is mediated by the protein, polysaccharide intercellular adhesin (PIA). Furthermore, MRSA strains which display biofilm formation are associated with more severe and more virulent infections7.
Current and Emerging Therapeutic Strategies
Other types of antibiotics have been used to treat MRSA infections over the years. Vancomycin has been used to combat infections resistant to penicillin-like antibiotics as they display a different mode of action. Vancomycin inhibits peptidoglycan synthesis by forming hydrogen bonds within the structure of peptidoglycan precursors2. While this strategy has proven effective for past 50 years, more and more strains are displaying vancomycin resistance in addition to resistance to penicillin-like antibiotics8. One study by Deyno et al., estimates the prevalence of vancomycin-resistant S. aureus in Ethiopia to be around 11% 4. Daptomycin is another antibiotic which has been shown to be effective in MRSA treatment. This cyclic lipopeptide binds to the bacterial membrane, resulting in cell death9.
Due to the decreasing number of available, effective antibiotics, novel therapeutic strategies are required to combat MRSA infection. One of the most promising approaches uses antimicrobial peptides (AMPs). AMPs are naturally occurring molecules of the innate immune system and have one of two mechanisms of action: membranolytic action and non-membranolytic action. AMPs normally consist of and amphipathic or cationic structure, between 5-50 amino acids long. Naturally occurring AMPs have been used as a model to develop synthetic AMPs, designed to neutralise the limitations of natural AMPs boasting an improved half-life and improved antimicrobial properties3. Membrane disruptive AMPs can be further categorised by mechanism of action. The first is the Toroidal-pore model in which AMPs form vertical pores in the bacterial membrane causing a change in conformation of the lipid head. Next is the Barrel-stave mode, in which AMPs bind to the bacterial membrane and aggregate before breaching the cell wall causing uncontrolled cell movement, resulting in cell death3. Finally, in the carpet model, the membrane is destroyed in a detergent-like action where the AMPS arrange on the cell membrane with their hydrophobic part facing the phospholipid bilayer, altering the surface tension of the membrane. This eventually results in the formation of micelles and the destruction of the bacterial membrane3.
Non-membrane disruptive AMPs require much more investigation; however, it is accepted that these AMPs enter the cell, reacting with important intracellular components inhibiting protein and nucleic acid synthesis, cell division and protease activity3.
Silver nanoparticles (AgNPs) exhibit broad spectrum antimicrobial properties through various mechanisms of action. These nanosized particles boast increased antimicrobial properties due to an increased surface area per volume ratio. The first mechanism of action to note is AgNPs direct adhesion to the bacterial membrane, which alters the structural integrity of the membrane, allowing the AgNPs to penetrate the cell, wreaking havoc on the intracellular components until it loses the ability to carry out essential cellular processes3.
Once the AgNPs aggregate on the bacterial surface, the difference in electrostatic charge, driven by the positive charge displayed by the AgNPs and negatively charged bacteria, pit formation occurs on the cell surface, inhibiting vital cellular movement, resulting in cell death3. AgNPs may also inhibit protein synthesis by denaturing ribosomes and directly interacting with DNA. This interaction can cause denaturing of the DNA helix and ultimately result in cell death3. Finally, AgNPs can induce the production of reactive oxygen species (ROS) and free radicals. The molecules cause irreversible cell damage to the bacteria3.
While AMPs and AgNPs each possess individual limitations such as toxicity and instability, studies show that a combination of these therapeutic strategies can overcome these issues, stabilising the antimicrobial agents to their respective target sites3.
Screening, Testing & Evaluation
Classical determination of MRSA and other bacterial infections consists of obtaining a patient sample and growing colonies from the patient sample in culture. These cultures can then be investigated under a microscope and characterised, allowing diagnosis and the initiation of treatment. Whilst effective, these methods are time consuming and laborious, taking up to three days for cultures to develop, somewhat limiting their utility for the diagnosis of potentially fatal infections.
New molecular rapid PCR microbiology techniques aid in the identification of bacterial strains through a three-step process involving extraction, amplification, and detection. These new methods allow for timely identification of infectious strains and AMR characterisation. Specific genes or sections of gene which are responsible for AMR can be detected, helping to achieve strain characterisation and aid physicians in prescribing the correct treatment plan. These methods improve test turnaround times to around one to two days and help to reduce the risk of costly human error and contamination.
Bosch Vivalytic MRSA/SA is an automated qualitative in vitro diagnostic test based on real-time PCR for the detection and differentiation of methicillin-resistant Staphylococcus aureus (MRSA) and Methicillin-sensitive Staphylococcus aureus (MSSA) DNA from human nasal- or oropharyngeal swabs to aid in the diagnosis of MRSA infection of symptomatic or asymptomatic individuals, providing results in less than 1 hour.
Without MRSA screening, many MRSA colonised patients remain unnoticed in hospitals and will not be isolated. Without Isolation many of these patients transfer the pathogen to at least one other patient during their hospital admission. PCR based screening is associated with high precision and fast time to results and is often used for early decisions on isolation and hygiene measures.
This POCT system provides fast, accurate characterisation of MRSA/SA strains while minimising the required user steps and reducing the need for expensive laboratory equipment helping physicians implement timely and effective treatments.
- Methicillin-resistant Staphylococcus aureus
- Methicillin-sensitive Staphylococcus aureus
Specific Gene Targets:
- SCCmec/orfX junction
Some of the other benefits of this test include:
- Multiple sample types – Data shows that for approx. 13% of MRSA carriers, the pathogen is only located in the throat. Therefore, using throat swabs significantly increases the sensitivity of detection by approx. 26%.
- Broad MRSA Range – mecA or mecC are the genes responsible for resistance to β-lactam antibiotics. mecA/meC is part of the mobile genetic element Staphylococcal cassette chromosome mec (SCCmec). Vivalytic MRSA/SA can detect mecA as well as mecC and a broad variety of SCCmec elements which help to reduce false negative results.
- Fast time-to-result – Provides quick results in less than 1hr allowing quick decisions on therapies. Traditional culture time-to-result is 48-72hrs and laboratory PCR is 12-24hrs.
- This highly automated system minimises the user steps required to achieve a result while limiting the requirement for expensive lab equipment and sample transportation. Vivalytic MRSA/SA POCT test allow the implementation of treatment as soon as 1hr after sample collection.
- Murray CJ, Ikuta KS, Sharara F, et al. Global Burden of Bacterial Antimicrobial Resistance in 2019: A Systematic Analysis. The Lancet. 2022;399(10325):629-655. doi:https://doi.org/10.1016/S0140-6736(21)02724-0
- Nandhini P, Kumar P, Mickymaray S, Alothaim AS, Somasundaram J, Rajan M. Recent Developments in Methicillin-Resistant Staphylococcus aureus (MRSA) Treatment: A Review. Antibiotics. 2022;11(5):606. doi:https://doi.org/10.3390/antibiotics11050606
- Masimen MAA, Harun NA, Maulidiani M, Ismail WIW. Overcoming Methicillin-Resistance Staphylococcus aureus (MRSA) Using Antimicrobial Peptides-Silver Nanoparticles. Antibiotics. 2022;11(7):951. doi:https://doi.org/10.3390/antibiotics11070951
- Liu WT, Chen EZ, Yang L, et al. Emerging resistance mechanisms for 4 types of common anti-MRSA antibiotics in Staphylococcus aureus: A comprehensive review. Microbial Pathogenesis. 2021;156:104915. doi:https://doi.org/10.1016/j.micpath.2021.104915
- Dadashi M, Nasiri MJ, Fallah F, et al. Methicillin-resistant Staphylococcus aureus (MRSA) in Iran: A systematic review and meta-analysis. Journal of Global Antimicrobial Resistance. 2018;12:96-103. doi:https://doi.org/10.1016/j.jgar.2017.09.006
- Kourtis AP, Hatfield K, Baggs J, et al. Vital Signs: Epidemiology and Recent Trends in Methicillin-Resistant and in Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections — United States. MMWR Morbidity and Mortality Weekly Report. 2019;68(9):214-219. doi:https://doi.org/10.15585/mmwr.mm6809e1
- Hosseini M, Shapouri Moghaddam A, Derakhshan S, et al. Correlation Between Biofilm Formation and Antibiotic Resistance in MRSA and MSSA Isolated from Clinical Samples in Iran: A Systematic Review and Meta-Analysis. Microbial Drug Resistance. Published online March 10, 2020. doi:https://doi.org/10.1089/mdr.2020.0001
- Verma R, Verma SK, Rakesh KP, et al. Pyrazole-based analogs as potential antibacterial agents against methicillin-resistance staphylococcus aureus (MRSA) and its SAR elucidation. European Journal of Medicinal Chemistry. 2021;212:113134. doi:https://doi.org/10.1016/j.ejmech.2020.113134
- Deyno S, Fekadu S, Astatkie A. Resistance of Staphylococcus aureus to antimicrobial agents in Ethiopia: a meta-analysis. Antimicrobial Resistance & Infection Control. 2017;6(1). doi:https://doi.org/10.1186/s13756-017-0243-7
Diagnosing UTI Complications in Mothers and Newborns
Urinary tract infections (UTIs) are one of the most common bacterial infections that occur in humans. Over 50% of women become infected with a UTI at least once in their lives, with up to 10% of women suffering from yearly infections5. Recurrence rates are high in UTIs, almost 50% of women who contract a UTI experience reinfection or relapse within one year of the initial infection5. Men are four times less likely to contract a UTI due to a longer urethra seen in men when compared with women.
Infections occur in the urinary organs and structures which can be categorized by the site of infection: cystitis (bladder), pyelonephritis (kidney) and bacteriuria (urine)5. So-called, uncomplicated UTIs are sited only in the bladder, however, UTIs are highly likely to cause secondary infections, commonly in the kidneys. Pyelonephritis has been shown to result in renal scarring and in some cases, subsequent renal failure2. There are various species of bacteria responsible for UTIs, which have different mechanisms of infection and virulence. However, most species have surface adhesins which function like hooks, attaching the bacteria to the urothelial mucosal surface, and colonizing the bladder. From here, the bacteria can ascend the ureters, reaching the kidney and causing secondary infections2.
Under normal conditions, the innate immune system actions an inflammatory response to the infection site. However, some species of bacteria that cause UTI can inhibit or delay the immune response resulting in secondary infections in the ureters and kidneys where the risk of severe renal defects is considerable, and the bacteria have direct access to the bloodstream2.
Common symptoms of UTI include:
- Frequent urination
- Painful urination
- Incomplete voiding of the bladder
- Pelvic, back, and/or abdominal pain
- Nausea and/or vomiting
Antibiotic therapies are effective and aim to facilitate the immune response and inhibit the spread of the infection to the kidneys and upper urinary tract. Although these treatments are usually effective, antimicrobial resistance (AMR) has become a global crisis encompassing all medical disciplines3. This resistance to antibiotics can occur through several mechanisms such as dysregulation of protein expression, structural modifications, and mutations to name a few11.
Bacteria are capable of some level of intrinsic resistance, or insensitivity, to antibiotics through the production of various enzymes designed to degrade the drug or inhibit its mechanism11. Mutations found in the genome of bacterial species are often responsible for the resistance they display. These mutations commonly alter the bacterial binding sites used by antibiotics, therefore inhibiting their action. Some bacteria produce enzymes, which alter the chemical structure of the antibiotic, again, inhibiting them from binding to the antibiotic. Other examples include horizontal gene transfer and biofilm formation10.
One study reported in 2019, that AMR was the twelfth leading cause of death when compared with a susceptible infection counterfactual9. The same study went on to show that AMR had the highest mortality rate in low to middle-income countries providing evidence that AMR is an even bigger problem in the most impoverished parts of the world. New techniques such as CRISPR-Cas9 and antibiotic re-sensitization methods are at the forefront of the fight against AMR, however, the scale of the problem warrants taking all possible action to elevate the risk posed by AMR8.
UTI During Pregnancy
UTIs are a common occurrence in pregnancy with one hospital reporting over 15% of pregnant women being diagnosed with some form of UTI4. Diagnosis can usually be confirmed by a bacterial growth of over 105 counts/ml in urine4, 12, 13. Many hormonal and anatomical changes occur in a woman’s body during pregnancy that create favorable conditions for UTI. Firstly, the glomerular filtration rate is altered, causing an increase in glucose concentration and pH of the urine3. The urethral dilation, smooth muscle relaxation, enlarged mechanical compression of the uterus, and increased plasma volume result in lower urinary concentration and increased bladder size leading to urinary tract reflux and urine stagnation. These conditions are favorable for the proliferation of bacterial infections1.
Diagnosis of UTIs in pregnant women can be complicated. For example, the increased frequency of urination experienced could also be caused by additional pressure placed on the woman’s bladder by the baby, or the abdominal pain indicative of a UTI could be interpreted as Braxton Hicks contractions and vice versa3. There are several established risk factors associated with UTI in pregnancy including advanced maternal age, diabetes, sickle cell anemia, history of UTI, urinary tract abnormalities, and various immunodeficiencies3. Other reports claim that UTI in pregnancy is more common in women with hypothyroidism and women who are carrying their first child4.
Bacterial Species Responsible for UTI
There are a multitude of bacterial species responsible for UTIs, the most common is Escherichia coli (E. coli), followed by group B streptococcus (GBS), enterococcus, and Klebsiella pneumonia. Escherichia coli infections are categorized as either enteric or extraintestinal (ExPEC). Of the latter, there are two main culprits: neonatal meningitis E. coli (NMEC) and uropathogenic E. coli (UPEC)2. These infections can exist in the gut and spread, colonizing other parts of the host such as the blood or central nervous system, causing other potentially severe infections. Of these strains, UPEC is responsible for around 80% of both symptomatic and asymptomatic UTIs. UPEC strains have been associated with acute renal damage and are thought to encourage bacterial growth and persistence by inhibiting or delaying the innate immune response2.
Maternal and Perinatal UTI Complications
UTI complications in mothers and children have long been debated. However, there is sufficient evidence to support several prognostic claims. Preterm delivery is a major complication associated with UTI and has been well studied. Preterm neonates face a high risk of fatality with up to 1 million babies dying every year due to premature labor6. Those that survive are at risk of developing one or more of the following health defects1:
- Lung problems
- Heart Disease
- Hearing loss
- Visual impairment
- Learning disabilities
- Behavioral problems
- Cerebral palsy
The risk of preterm birth in women who suffered from a single UTI was increased when compared to women who had no infection during their pregnancy but recurrent UTIs did not increase the risk3. Risk of low birth weight has been shown to increase by 50% in women who suffered symptomatic UTIs compared to those who remained uninfected throughout their pregnancy; this risk can be mitigated through antibiotic therapy. The same treatments did not show any significant ameliorative effects on preterm birth4. Women who contract a UTI during pregnancy are also at a higher risk of various conditions such as preeclampsia, postpartum endometritis, sepsis1, hypertensive disorders, anemia and amnionitis4.
Asymptomatic UTIs, also known as asymptomatic bacteriuria (ASB), are not known to cause as drastic primary effects on pregnancy as seen with symptomatic infections. Despite this, ASB can spread and colonize in the kidneys. At this point, pyelonephritis is likely to occur, increasing the risk of severe renal scarring4 and advanced risk of preterm birth3. In these cases, it is common to treat the patient with antibiotics to reduce the risk of a secondary, symptomatic infection. While these treatments are effective at limiting the progression of the infection, overuse of antibiotics is a primary factor contributing to antimicrobial resistance4.
Screening and Treating UTI Complications
Women who are not pregnant and show no risk factors can be tested for UTI through a simple urine dipstick. The presence of leukocyte and absence of nitrite can be considered a positive UTI diagnosis. However, where complications are likely, a urine culture is required. Cultures can be carried out on blood or MacConkey agar and require preservation of the sample in boric acid, or in a refrigerator, for 24 hours prior to testing. This culture can then be isolated and used to identify the strain of bacteria causing the infection7.
Species identification is imperative in maternal UTIs. Different species have different levels of sensitivity to the various antibiotics available. E. coli, for example, shows 93% sensitivity to Nitrofurantoin but is only 86% sensitive to Fosfomycin. Selection of the correct treatment can ameliorate symptoms rapidly and reduce the possible complications for both mother and baby4. Many species of bacteria known to be responsible for UTIs have displayed resistance to antibiotics. Group B streptococcus has been shown to be 42% resistant to clindamycin4. The selection of antibiotics available to clinicians treating maternal UTI are already limited as many antibiotics have been associated with increased risk of miscarriage and birth defects independent of UTI1.
With the patient in mind, Randox provides clinicians with both laboratory and near patient testing solutions. Bringing to the market, to help eliminate distress and improve testing turnaround times, the Randox Urinary Tract Infection Array. It has the ability to detect 30 bacterial, fungal, and associated antibiotic resistance markers from a single urine sample in under four hours. This multiplex diagnostic tool can help detect specific bacterial and fungal strains known to cause UTI allowing laboratories to confidently diagnose patients in a timely manner, aiding with targeted treatments and helping to reduce risk of complications.
The Ongoing UTI Battle
Maternal UTI is a very common problem resulting in many fatalities and morbidities worldwide. It is crucial to identify and characterize these infections to limit the negative effects seen to both mothers and their children. Quick and efficient screening is paramount in the battle against bacteria to allow the prescription of targeted treatment. While antibiotics are often an effective weapon against UTIs, care should be taken when prescribing these treatments to pregnant women due to the potential adverse effects that have been reported. Furthermore, unnecessary treatments using antibiotics should be avoided at all costs due to the increasingly serious issue of antimicrobial resistance.
1.Eslami V, Belin S, Sany T, Ghavami V, Peyman N. The relationship of health literacy with preventative behaviours of urinary tract infection in pregnant women. Journal of Health Literacy. 2022;6(4):22-31. doi:https://doi.org/10.22038/jhl.2021.59768.1183
2.Bien J, Sokolova O, Bozko P. Role of Uropathogenic Escherichia coli Virulence Factors in Development of Urinary Tract Infection and Kidney Damage. International Journal of Nephrology. Published online 2012:1-15. doi:https://doi.org/10.1155/2012/681473
3.Werter DE, Kazemier BM, van Leeuwen E, et al. Diagnostic work-up of urinary tract infections in pregnancy: study protocol of a prospective cohort study. BMJ Open. 2022;12(9):e063813. doi:https://doi.org/10.1136/bmjopen-2022-063813
4.Balachandran L, Jacob L, Al Awadhi R, et al. Urinary Tract Infection in Pregnancy and Its Effects on Maternal and Perinatal Outcome: A Retrospective Study. Cureus. 2022;14(1). doi:https://doi.org/10.7759/cureus.21500
5.Bono MJ, Reygaert WC. Urinary Tract Infection. Nih.gov. Published 2018. https://www.ncbi.nlm.nih.gov/books/NBK470195/
6.World Health Organization. Preterm birth. Who.int. Published February 19, 2018. Accessed February 8, 2023. https://www.who.int/news-room/fact-sheets/detail/preterm-birth
7.Sinawe H, Casadesus D. Urine Culture. PubMed. Published 2021. https://www.ncbi.nlm.nih.gov/books/NBK557569/
8.Schrader SM, Botella H, Vaubourgeix J. Reframing antimicrobial resistance as a continuous spectrum of manifestations. Current Opinion in Microbiology. 2023;72:102259. doi:https://doi.org/10.1016/j.mib.2022.102259
9.Murray CJ, Ikuta KS, Sharara F, et al. Global Burden of Bacterial Antimicrobial Resistance in 2019: A Systematic Analysis. The Lancet. 2022;399(10325):629-655. doi:https://doi.org/10.1016/S0140-6736(21)02724-0
10.Ali J, Rafiq QA, Ratcliffe E. Antimicrobial resistance mechanisms and potential synthetic treatments. Future Science OA. 2018;4(4):FSO290. doi:https://doi.org/10.4155/fsoa-2017-0109
11.Nelson DW, Moore JE, Rao JR. Antimicrobial resistance (AMR): significance to food quality and safety. Food Quality and Safety. 2019;3(1):15-22. doi:https://doi.org/10.1093/fqsafe/fyz003
12.Myers AL. Curbside Consultation in Pediatric Infectious Disease : 49 Clinical Questions. Slack; 2012:4.
13.Oie S, Kamiya A, Hironaga K, Koshiro A. Microbial contamination of enteral feeding solution and its prevention. American Journal of Infection Control. 1993;21(1):34-38. doi:https://doi.org/10.1016/0196-6553(93)90205-i
7. Sinawe H, Casadesus D. Urine Culture. PubMed. Published 2021. https://www.ncbi.nlm.nih.gov/books/NBK557569/
It’s World Antimicrobial Awareness week!
Antimicrobial resistance occurs when bacteria, viruses, fungi, and parasites resist the effects of medications, making common infections harder to treat and increasing the risk of disease spread, severe illness and death. As a result of drug resistance, antibiotics and other antimicrobial medicines become ineffective and infections become increasingly difficult or impossible to treat.
Randox want to take part in the global campaign that is celebrated annually to improve awareness and understanding of Antimicrobial. We have interviewed one of our Molecular specialists, Dr Dwaine Vance on how our revolutionary Randox products aid in the fight against AMR.
What threat does AMR present to the health care environment?
In a worse-case scenario the increasingly worrying levels of AMR globally will have a significant negative effect on healthcare. Without effective antimicrobials to treat a wide arrange of infectious diseases, people will be more likely to get ill, be unresponsive to medications, which in turn will result in longer hospital stays, increased economic burden, lower levels of quality of life and ultimately poorer prognosis including elevated levels of morbidity and mortality.
How does Randox help in the fight against AMR?
Randox have developed and continue to develop infectious disease tests to detect a wide-range infectious disease. Randox have also included resistance gene markers within these molecular-based PCR tests to determine if an infection is sensitive or resistance to certain antimicrobials.
In addition to diagnostic tests, Randox also supply quality control materials such as third-party molecular controls and external quality assessment schemes that are used in molecular microbiology laboratories to ensure their PCR tests are working accurately and robustly. This means that labs can provide the correct information to clinicians that is vitally important to determine what antibiotic therapy is prescribed to the patient.
Can you tell us about any exciting developments in Randox?
Randox are continuously investing and reinvesting in our Molecular Research and Development departments. We have recently released a molecular point of care test that can discriminate between MRSA and MSSA. This means that sufficient isolation and correct primary treatment can be provided to the patient in a timelier fashion. We are in the process of releasing a UTI test that can detect over 20 UTI-related bacterial infections. In addition to these pathogens, this test also determines if the pathogens detected are resistant to commonly used antibiotics such as Trimethoprim or Vancomycin.
Furthermore, Randox are releasing an immunoassay-based point of care machine called the VerasSTAT, which includes tests for CRP and MxA biomarkers. These biomarkers are released into the bloodstream during infection as part of the body’s immune response. CRP and MxA can assist the clinician in determining if an infection is of bacterial or viral origin.
What measures do you think we can take to prevent the spread of AMR?
Improved personal hygiene and sanitation will reduce transmission of infectious diseases within the global population. The development of more innovative and more easily accessible antibiotics, as well as improved antibiotic stewardship within clinical settings will also help slow down the alarming rates of AMR globally. Most importantly, the creation of new syndromic style testing panels, like the tests currently provided by Randox will undoubtedly improve the clinical outcome for patients who are have an infectious disease.
We are urging the public to help raise awareness of antimicrobial resistance. Randox is committed to the ongoing development of products and services as well as our research into numerous disease areas to improve health worldwide.
Rapid PCR MRSA/SA testing now available on Vivalytic
Providing a quick diagnosis of methicillin resistant at the point of the care, the latest addition to the Vivalytic portfolio of tests, not only provides rapid RT-PCR results in 53 minutes but differentiates whether the bacterial strain is methicillin-resistant (MRSA) or methicillin-sensitive (MSAA) which promotes targeted therapy.
MRSA is a major multi-resistant nosocomial pathogen worldwide with the WHO estimating that the mortality rate of patient infection rates is around 50% higher compared with patients who have been infected by non-resistant Staphylococcus aureus strains.1 Moreover, the extensive period of hospitalisation, morbidity, and the associated medical costs increase significantly with an MRSA infection.2
Introducing MRSA to the vivalytic portfolio can provide high quality answers, anywhere and anytime improving patient pathways and the need for care. Significantly, introducing rapid MRSA screening at both ward level, emergency settings and before hospital elective surgery procedures allow for an effective response to identifying whether the bacteria strain is methicillin-sensitive (MSSA) or -resistant.
Making a point to care, the rapid essence and speed of Vivalytic not only showcase technology but the ability to contribute to current health risks by preventing contamination, breaking the chain of infection, and again fighting the silent pandemic of antimicrobial resistance (AMR) & superbugs.
The treatment on the front line today looks at increasing empirical antibiotic prescribing and increasing drug-resistant outbreaks. AMR is growing rapidly, with superbugs threatening the ability to treat common infectious diseases appropriately. The COVID-19 pandemic has elevated concerns over AMR and antibiotic-associated adverse events, with surges in antibiotic prescribing, hospitalisations, and drug-resistant bacterial transmissions.
Speed is key here – since the result of diagnostics with culture sampling, which is the current traditional method for MRSA testing is only available after one to three days, this PCR test for the point of care is ideal as an additional tool when speed is of the essence.
Few points to note about the current Vivalytic panel for MRSA/SA detection:
- By using one single cartridge, the Vivalytic MRSA/SA test detects and differentiates between MRSA and MSSA DNA to aid in the diagnosis of MRSA infection in a speedy manner so that appropriate antibiotic treatment can be applied, and complications prevented.
- Detection Method: Real-Time PCR
- Result Time: 53 minutes
- Sample Volume: 600 μl
- Sample Type: Nasal- or oropharyngeal swab sample
|DETECTABLE DNA PATHOGENS:||SPECIFIC GENE TARGETS:|
|Methicillin-resistant Staphylococcus aureus (MRSA)||SCCmec/orfX junction|
|Methicillin-sensitive Staphylococcus aureus (MSSA)||mecA/ mecC, SA422|
Making this happen, The MRSA/SA rapid test on Vivalytic by Bosch, a point of care platform brought to the market by Randox Laboratories. The Vivalytic system is a fully automated, cartridge-based platform capable of both Hi-Plex and Lo-Plex infectious disease testing. Each easy-to-use cartridge contains all necessary reagents, is fully-sealed to minimise risk and can be conveniently stored at room temperature.
The Vivalytic consolidates the full molecular workflow into a small benchtop platform, capable of extraction, PCR amplification and detection. It follows an easy 4 step process from sample entry to results and with the gold standard PCR testing. With most up to date technology, the Vivalytic has wireless connectivity, with no peripherals required, making a unique space saving and hygienic solution. Handling and utilisation are simple and medical professionals require only minimal training.
Identification and Differentiation of Viral and Bacterial Respiratory Infection to Guide Antibiotic Stewardship
The development of point-of-care testing is critical in the identification and differentiation between bacterial and viral respiratory infections. Defining the indications of infection to improve antibiotic stewardship, ensures that patients are protected from unnecessary antibiotic use and antibiotic resistance. It has been shown that particular protein biomarkers, such as myxovirus resistance protein (MxA) and C-reactive protein (CRP), differentiate infections between bacterial and viral. Using point-of-care platforms, such as Randox’s VeraSTAT, for detection of these protein biomarkers may provide more rapid and cost-effective discriminating tools.
The treatment of bacterial and viral infections can differ significantly, however people are often treated with empirical antibiotics due to a lack of paid and accurate testing. Although early intervention of infection is urgent, current diagnostic methods are either time intensive or inaccurate. The challenges clinicians are faced with in the differentiation of viral or bacterial respiratory infection can lead to delayed diagnosis, misappropriation of antibiotics and increased healthcare costs.
MxA protein has the potential to greatly enhance the rapid detection of viral respiratory infections as it increases significantly when there is actuate viral infection. CRP is the dominant acute phase protein often used to guide treatment of a bacterial infection or inflammation associated with tissue injury, inflammatory disorders, and associated diseases.
CRP & MxA together, allow clinicians to make appropriate decisions in supporting antimicrobial stewardship and guide the appropriate use of antibiotics, saving time performing unnecessary tests, providing unnecessary treatment which missing the opportunity to provide the right treatment in a timely manner.
The Randox VeraSTAT is a simple, accurate, portable point of care device which delivers rapid results via the use of patented cathodic electrochemiluminescence technology (C-ECL). Designed with the aim of offering users the next generation of rapid diagnosis, the VeraSTAT eliminates the requirement to send samples to a laboratory and instead returns results in as little as 6 minutes.
- Eliminates delays in sending samples to the lab and facilitate immediate decision making at the point of care.
- Lightweight, portable and convenient, the Randox VeraSTAT can be used in a variety of locations to deliver results as required, such as a GP surgery or Emergency Department.
- Intuitive user interface guides the operator through the entire testing process.
- All necessary reagents are conveniently included in each single use, sealed cassette with no preparation required. All necessary consumables are supplied with the kit.
- The Randox VeraSTAT allows for results to be exported via Bluetooth connectivity.
- Flexible test menu comprising of a range of immunoassay, protein, inflammatory, diabetes & infectious disease markers.
Novel testing approaches identifying the type of infection at the point of care are essential in accurately guiding appropriate antibiotic treatment. Although these tests can’t determine what type of viral or bacterial infection a patient has, it will determine whether the infection is viral or bacterial, further testing is then carried out to determine what type of pathogen the patient has via PCR – the gold standard. The ability to distinguish between viral and bacterial infections is the most effective guide for clinical decision making and is an innovative tool for antibiotic stewardship.
1 – Fleming-Dutra K.E., Hersh A.L., Shapiro D.J. Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits, 2010–2011. JAMA. 2016;315:1864–1873. doi: 10.1001/jama.2016.4151.
2 – Cals JW, Hopstaken RM, Butler CC, Hood K, Severens JL, Dinant GJ. Improving management of patients with acute cough by C-reactive protein point of care testing and communication training (IMPAC3T): study protocol of a cluster randomised controlled trial. BMC Fam Pract. 2007;8:15.
3- New report calls for urgent action to avert antimicrobial resistance crisis [Internet]. World Health Organization. World Health Organization; 2019
4 – Hutchings MI, Truman AW, Wilkinson B. Antibiotics: past, present and future. Curr Opin Microbiol. (2019) 51:72–80. doi: 10.1016/j.mib.2019.10.008