MRSA ā Emerging Therapeutic & Screening Approaches
MRSA ā 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:
- Bacteraemia
- Infective endocarditis
- Skin and soft tissue infections
- Osteomyelitis
- Septic arthritis
- Prosthetic device infections
- Pulmonary infections
- Gastroenteritis
- Meningitis
- Toxic shock syndrome
- UTIs
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.
Vivalytic MRSA/SA
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.
Detectable Pathogens:
- Methicillin-resistant Staphylococcus aureus
- Methicillin-sensitive Staphylococcus aureus
Specific Gene Targets:
- SCCmec/orfX junction
- MecA/MecC
- SA422
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.
References
- 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
Lipoprotein (a) Awareness Day 2023
Randox are raising awareness for Lipoprotein(a), we want to drive awareness on tests that are available to you to decrease the risk of stroke, heart attack or other heart diseases!
Lp(a) is a risk factor for atherosclerosis and related diseases including CHD and stroke. It is increasingly recognised as the strongest known genetic risk factor for premature coronary artery disease.
Identifying any possible health conditions that would relate to early signs of stroke, heart attack or other heart diseases will allow you to make any decisions on an appropriate diet, lifestyle changes and early treatment to reduce your risk of further problems.
Benefits of the Randox Lp(a) assay
WHO/IFCC Reference Material
Dedicated Five-Point Calibrator Available
Excellent Correlation
Excellent Precision
Liquid Ready-To-Use
Available in nmol/L
Applications Available-on Roche, Abbott, Beckman, and more.
The biggest challenge that exists surrounding Lp(a) measurement is the heterogeneity of the apo(a) isoforms, resulting in the underestimation or overestimation of Lp(a) concentrations. In immunoassays, the variable numbers of repeated KIV-2 units in Lp(a) act as multiple epitopes. This is where standardisation across calibrators is vital. Unless the calibrants do have the same range of isoforms as test samples, those with higher numbers of the KIV-2 repeat, will represent with an overestimation in Lp(a) concentrations and those with smaller numbers of the KIV-2 repeat, will represent with an underestimation. The smaller isoforms are strongly associated with higher Lp(a) concentrations. Lack of standardisation of the calibrant would result in an underestimation of Lp(a) associated CVD risk. It is important to note that an Lp(a) immunoassay employing isoform insensitive antibodies does not exist.
How can Randox help?
Randox Sales Reps are experts in their fields and are available to discuss your specific requirements.
Simply send us an email by clicking the link below and we will get in touch!
THE 2023 RANDOX GRAND NATIONAL TROPHY IS REVEALED
THE 2023 RANDOX GRAND NATIONAL TROPHY IS REVEALED
Sunday 19th March
Elizabeth Moran of Randox, who designed the trophy, said: “It was a wonderfully creative challenge to design this year’s trophy, reflecting both this national, iconic sporting event and Randox’s innovation within healthcare, and I think we got it just right.”
During the Randox Grand National Festival (Thursday 13th April – Friday 15th April inclusive), the trophy as well as trophies from previous Randox Grand Nationals, can be viewed in trophy marquee next to the Red Rum Garden at Aintree Racecourse.
World Kidney Day 2023
World Kidney Day 2023
“Kidney health for all – Preparing for the unexpected, supporting the vulnerable”
Thursday 09th March
Chronic Kidney Disease (CKD) is considered a leading cause of global mortality with an overall global prevalence rate of around 13%1. This figure rises to 15% in the US2 and the statistics show that these rates are likely to continue this upward trend3. CKD is defined as damage to the kidneys which affects its ability to correctly filter bodily fluids which ultimately results in renal replacement therapy in the form of dialysis or transplantation4. This sustained or chronic damage of the kidney encourages kidney fibrosis and loss of structure. The early stages of CKD are generally asymptomatic with symptoms beginning to manifest in stages 4 and 5. These symptoms include nausea & vomiting, fatigue & weakness, oliguria, chest pain, hypertension, to name a few4.
World Kidney Day is an annual, global campaign spearheaded by the International Society of Nephrology (ISN) and the International Federation of Kidney Foundations – World Kidney Alliance (IFKF – WKA) which intends to raise awareness of how critical our kidneys are and to limit the prevalence and impact of kidney disease5. This year’s focus is “Kidney health for all – preparing for the unexpected, supporting the vulnerable.”
It is no surprise that patients suffering from noncommunicable diseases (NCDs) such as CKD were subject to worse prognosis during the COVID-19 pandemic6 due to prioritising of ongoing complex care over acute patient care7. But a pandemic is only one circumstance, albeit a major one, which can affect the ability of hospitals and laboratories to uphold their normal testing capacity. For example, natural disasters can make it impossible for people to reach facilities for testing or treatment7. Similar situations could arise at a more local level such as road closures, power outages or public transport strikes which have the potential to delay diagnosis or treatment.
To this end, laboratories should look to introduce novel and effective methods for testing under adverse conditions. Rapid testing will be imperative to help achieve these goals and promote fast test turnaround times and accurate diagnosis. The Randox CKD Arrays, in conjunction with the Randox Evidence Investigator, allow for simultaneous and quantitative detection of multiple serum biomarkers of kidney damage-related analytes allowing diagnosis at a much earlier stage than traditional creatinine tests.
Utilising patented Biochip Technology, the Randox CKD arrays could improve patient risk stratification whilst monitoring the effectiveness of treatment. Diagnosis of CKD at early stages will allow earlier intervention for the treatment of kidney disease, and the prevention of further kidney damage. The utility of this test cannot be overstated. In adverse circumstances, the Randox Evidence Investigator could permit diagnosis of CKD and determination of CKD severity at the site of the patient, helping prepare for the unexpected and support the vulnerable.
More information of CKD and other kidney related conditions can be found at: Homepage – World Kidney Day
References
Bibliography
-
Lv JC, Zhang LX. Prevalence and Disease Burden of Chronic Kidney Disease. Advances in Experimental Medicine and Biology. 2019;1165:3-15. doi:https://doi.org/10.1007/978-981-13-8871-2_1
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Centers for Disease Control and Prevention. Chronic Kidney Disease in the United States, 2021. US Department of Health and Human Services; 2021. https://www.cdc.gov/kidneydisease/pdf/Chronic-Kidney-Disease-in-the-US-2021-h.pdf
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Kovesdy CP. Epidemiology of chronic kidney disease: an update 2022. Kidney International Supplements. 2022;12(1):7-11. doi:https://doi.org/10.1016/j.kisu.2021.11.003
-
Vaidya SR, Aeddula NR. Chronic renal failure. Nih.gov. Published 2019. https://www.ncbi.nlm.nih.gov/books/NBK535404/
-
International Society of Nephrology. Homepage. World Kidney Day. Published 2023. https://www.worldkidneyday.org/
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Nikoloski Z, Alqunaibet AM, Alfawaz RA, et al. Covid-19 and non-communicable diseases: evidence from a systematic literature review. BMC Public Health. 2021;21(1). doi:https://doi.org/10.1186/s12889-021-11116-w
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Hsiao LL, Shah KM, Liew A, et al. Kidney health for all: preparedness for the unexpected in supporting the vulnerable. Kidney International. 2023;103(3):436-443. doi:https://doi.org/10.1016/j.kint.2022.12.013
For more information, please contact Market@randox.com
Diagnosing UTI Complications in Mothers and Newborns
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
- Haematuria
- Lethargy
- Nausea and/or vomiting
- Fever
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
- Diabetes
- 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.
References
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.
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Free Health Testing For Sandwell Residents As Council Partner With Randox Health To Detect Early Warning Signs of Serious Illness
Sandwell Council partners with Randox Health to launch free health checks service
Sandwell Council initiative places prevention at the centre of healthcare
Thousands of eligible Sandwell residents are being offered diagnostic NHS Health Checks to detect any early signs of diabetes, heart and kidney disease and hypertension.
The early identification of individuals with the potential to develop these conditions will enable the NHS to intervene and, in many cases, prevent the onset of potentially life-changing and life-threatening illnesses.
In a pioneering initiative, the Sandwell tests and online self-assessment provision will be provided by a partnership comprising the council’s Healthy Sandwell team, the NHS and diagnostics company Randox Health – whose tests and clinics will be used to facilitate the innovative testing. Tests and clinics will be available for Sandwell residents in both Sandwell and, if convenient, in Birmingham.
The awarding of the contract to Randox Health to provide the tests follows an open tender process by Sandwell Council. The company has demonstrated success in providing 17 million PCR tests to NHS Test and Trace during the Covid-19 pandemic, helping prevent thousands of hospitalisations and deaths in the UK.
Free tests will be offered to Sandwell residents aged between 40 and 74 who have not previously suffered coronary heart disease, strokes, diabetes or kidney disease. Each will, in the next few weeks, begin receiving letters inviting them to the 20-minute NHS check, with branding from Randox, Healthy Sandwell and the NHS. The letter will include a link to the Randox website through which the tests can be booked.
Sandwell residents who have not yet received a GP letter and believe they are eligible can visit the Randox website https://nhshealthcheck.randox.com, take an eligibility check and then book their own appointment.
Tests will be carried out by specially trained staff at a number of community pop-up clinics in locations in Sandwell such as leisure centres and community spaces, aiming to reach those most at risk of having an undiagnosed serious illness.
Tests for Sandwell residents will also be available at Randox Health’s Birmingham Clinic (39-40 High Street, B4 7SL).
Test results will be made available to GPs for inclusion on patient medical records through Health Diagnostics Ltd, a third-party provider. Randox will hold none of the data from the test results.
Not only will the testing programme enable prevention and mitigation through the early identification of serious illness, it will also allow lifestyle modification on issues including smoking, alcohol and weight management.
Councillor Suzanne Hartwell, Sandwell Council’s Cabinet Member for Adults, Social Care & Health, said:
David Ferguson, Chief Operating Officer for Randox Health said:
Editors Notes
1. Sandwell Council
Sandwell Council will participate in the partnership through Healthy Sandwell, which is part of the council’s Public Health team. Healthy Sandwell provides a range of services to support local people to make positive lifestyle changes, such as quitting smoking or losing weight. Further information: https://www.healthysandwell.co.uk/
2. Randox Health
Established in 1982, Randox is the largest healthcare diagnostics company from the UK and Ireland.
Undertaking research, development, manufacture and distribution of innovative laboratory tests and analysers, Randox provides 15% of all worldwide cholesterol tests and 10% of all clinical chemistry tests. More than 5% of the world’s population (over 370 million people) receive medical diagnosis using Randox products each year.
Randox Health focuses on the provision of timely and accurate testing to identify risk to health, improve clinical diagnoses and promote preventative healthcare; aiming to achieve better healthcare outcomes whilst reducing the burden on clinical services.
In early 2020 Randox recognised the threat from COVID-19 and quickly developed a test to accurately identify the virus. Testing at scale commenced within weeks to support the UK’s National Testing Programme and private clients. Randox has processed more than 25 million gold-standard PCR tests for the National Testing Programme and private COVID testing for travel.
Randox Health is clear that better diagnostics are unquestionably critical to future improvements within healthcare and is committed to remaining at the forefront of that field.
Its growing network of High Street clinics now operate in 20 locations around the UK and Ireland, including Birmingham.
Randox Laboratories and Roquefort Therapeutics Collaborate to Develop Midkine Cancer Antibodies
Randox and Roquefort Therapeutics collaborate to develop midkine cancer antibodies
Randox Laboratories collaborate with Roquefort Therapeutics, an LSE market listed biotech company, dedicated to developing first in class medicines in the high value, high growth oncology market. The partnership is focused on the field of medical diagnostics only, in relation to Roquefort’s Midkine antibody portfolio.
The collaboration Randox will allow to utilise Roquefort’s Midkine antibodies in the field of medical diagnostics. Randox will therefore engage with Roquefort in research programmes to identify new cancer diagnostics that will be treatable with the companies Midkine products.
Why this partnership is important?
Midkine is a herapin binding protein, known for being important in embryonic development. While normally undetected in healthy adults, it is often highly expressed in cancer, inflammatory conditions and autoimmune disorders. Extensive research has revealed that blocking Midkine with antibodies can help slow tumour growth, reduce metastasis and overcome treatment resistance.
Within the partnership, Randox focuses on medical diagnostics to detect cancers expressing Midkine, produce the diagnostics essential for clinical trials and help Roquefort Therapeutics remain focused on developing first in class oncology medicines.
Randox are highly committed to preventative healthcare through early and more accurate diagnostics therefore this partnership with Roquefort Therapeutics is vitally important. Early diagnosis significantly increases a patient’s chance of survival thus using medical diagnostics to identify patients with cancer expressing Midkine is essential to the development of first-in-class cancer medicines and the future of cancer treatments.
When talking about the partnership, Dr Peter Fitzgerald, Managing Director of Randox said
About Roquefort Therapeutics
Roquefort Therapeutics is a cancer focused biotech company developing first in class drugs in the high value and high growth oncology segment prior to partnering or selling to big pharma. Since listing in March 2021, Roquefort successfully acquired Lyramid Pty Ltd, a leader in the development of medicines for a new therapeutic target, Midkine and has since developed a leadership position in Midkine intellectual property.
Roquefort Therapeutics’ focused portfolio consists of four fully funded, novel patent protected, pre-clinical, anti-cancer medicines that include:
- Midkine antibodies with significant in vivo efficacy and toxicology studies
- Midkine RNA therapeutics with novel anti-cancer gene editing action
- MK cell therapy with direct NK-mediate anti-cancer action and
- SiRNA targeting novel STAT-6 target in solid tumour showing significant in VIVO efficacy.
For more information, please contact market@randox.com
Randox announces ‘Race against Dementia’ as partner charity for Randox Grand National Festival 2023
RANDOX ANNOUNCES ‘RACE AGAINST DEMENTIA’
AS PARTNER CHARITY FOR RANDOX GRAND NATIONAL FESTIVAL 2023
Thursday 16th February
Randox today announces that Race Against Dementia, a global charity founded by three-times Formula 1 World Champion Sir Jackie Stewart, OBE, as its charity partner for the Randox Grand National Festival 2023.
Today, across the globe, more than 55 million people are living with dementia, with someone new being diagnosed with the disease every three seconds. Unless a cure is found, it is estimated that one in three people born today will die with dementia.
Randox will support Race Against Dementia throughout the three-day Aintree festival, to highlight the impact of the disease and to raise funds for much needed research into its prevention and cure.
On Ladies Day (Friday 14th April), Randox’s sponsored race over the Grand National fences will be titled ‘The Randox Supports Race Against Dementia Topham Chase’, and there will be opportunities to reach out to both the racing public and, through the festival’s media coverage, to the nation.
The 2023 Festival will also enable a welcome return to Aintree for Sir Jackie, who raced at Aintree in the 1960s, at a time when Aintree was part of the Grand Prix circuit.
As a global diagnostics company, with over 40 years of experience and a focus on preventative healthcare, Randox and Race Against Dementia are natural partners.
In the pursuit of a cure for dementia, improved testing and diagnosis will both enhance patient management and greatly accelerate the race for treatment.
Dr Peter FitzGerald, Managing Director of Randox said:
“Randox is proud to partner with Race Against Dementia as our nominated charity for 2023.
“We understand the importance of taking action early regarding current and future health. As a global market leader within the clinical diagnostics field, it was an obvious choice for Randox to partner with a similarly ambitious organisation. Race Against Dementia is a cause very close to many of our hearts.”
Sir Jackie Stewart OBE, Founder of Race Against Dementia, said:
“Race Against Dementia is delighted to be supported by Randox Laboratories in our race to find a cure for dementia.
“It is a great privilege to partner with an organisation which is an active innovator and is supporting our mission to accelerate the progress of dementia research.
“We are confident that working together with Randox will help to raise funds that will allow us to break new ground in the search for a cure or prevention of dementia.
“On a personal front, I have raced at Aintree before – it is a pleasure to be back, with another ‘race’ in mind.”
Dickon White, Regional Director, The Jockey Club North West, said:
“We are proud to support Race Against Dementia at the Grand National Festival and extend our thanks to Randox for helping to bring this partnership to fruition.
“Being staged over the famous Grand National fences, the Randox Supports Race Against Dementia Topham Chase should prove a very suitable vehicle for helping to publicise the vital work of Race Against Dementia.”
About Randox Laboratories
With over 40 years of diagnostic experience, Randox is globally recognised as being at the forefront of diagnostic capability and understands the importance of comprehensive and reliable research.
Past research and development has identified key proteins associated with Alzheimer’s disease risk, stratifying at-risk populations, for early identification and assisting with clinical research.
Randox has recently made significant investment to deliver preventative, personalised testing packages across the nation and has opened over 20 new Randox Health clinics. Randox Health clinics focus on the provision of cost-effective, timely and accurate testing to identify risk to health, improve clinical diagnoses and promote preventative healthcare.
About Race Against Dementia
Race Against Dementia is a global charity, founded by Sir Jackie Stewart, OBE, to fund pioneering research into the prevention and cure of dementia.
RAD supports a number of Early Career Researchers in the UK, US, Australia, Europe and South Africa in order to accelerate dementia research.
RAD’s vision is a breakthrough in the prevention or treatment of dementia with the greatest of urgency.
For more information, please contact Market@randox.com
International Day of Women and Girls in Science!
International Day of Women and Girls in Science!
On Saturday 11th February, we are celebrating International day of Women and girls in Science! This day is an opportunity to celebrate and promote equal access to science for women and girls.
Why this Day is Important
The purpose of International Day of Women and Girls in Science (IDGWS) is to bring everyone forward for sustainable and fair development in society. The international day allows us to celebrate women’s achievements in science and places the necessary focus on ensuring girls are equally equipped with the skills necessary to enter a career in STEM.
This year commences the 8th year of International Day of Women and Girls in Science and aims to particularly focus on the role of women and girls in science in relation to the Sustainable Development Goals (SDGs). As Gender equality has always been a fundamental issue for the United Nations, the empowerment of women and girls will make a vital contribution, not only to economic development, but also across all the Goals of the 2030 Agenda for Sustainable Development. In doing so the IDWGS aims to connect women and girls in science to the international community, strengthening connections to science, society and the development of strategies aimed towards the future.
*Click the individual photographs for their full interview*
International Day of Women and Girls in Science!
International Day of Women and Girls in Science!
On Saturday 11th February, we are celebrating International day of Women and girls in Science! This day is an opportunity to celebrate and promote equal access to science for women and girls.
Ahead of the 11th, we have interviewed five influential Women who fulfil STEM based roles across Randox Laboratories. They have shared their experiences and thoughts on Women and girls in the science industry.
Our fifth interview is with Marketing Manager, Lynsey Adams.
Why did you pursue a career in STEM?
I have always been interested in biology and what makes us unique. For that reason, I chose to study Genetics at Queens University Belfast. I have been lucky enough to work in the life sciences industry ever since.
What is your role in Randox and how long have you worked in the company for?
When I first came to Randox 15 years ago, I started off in Technical Support. I then progressed into the Marketing department and worked my way up to where I am today, to be the Head of Marketing. My role predominantly involves Marketing our scientific product ranges as well as B2C product offerings and sponsorships. Having a background in science has helped me to excel in my Marketing role and I am fortunate to be able to have the opportunity to do both the things that I enjoy and am passionate about.
What change have you seen for women in science over the years?
There has been an increase of women in STEM in general, whether that be more females studying STEM related subjects at university or exploring a career in STEM. Throughout the years, I have been privileged to work with so many females in managerial and authoritative roles within Randox.
Have you found it harder or any different going into your career in science as a woman?
Throughout the years I have been fortunate enough to have female teachers and lecturers provide crucial STEM related education who encourage females to pursue a career in STEM. During my working career I have experienced the same opportunities as other colleagues and seen an increase in women exceling in science.
How do you think we can encourage more women to go into the science industry?
Awareness of the varied career paths available within STEM related industries would be beneficial. The availability of work experience, placement, apprenticeship and graduate programmes like those offered at Randox helps to expose both males and females to the many exciting opportunities in the field.
If you have one piece of advice as a woman starting out the STEM industry, what would it be?
STEM is an equal playing field, so have confidence in your own ability and intelligence to get to where you want to be.
For more information, please contact Market@randox.com