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
- 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.
02 March 2021
The Global Economic Burden of STIs & The Impact of the COVID-19 Pandemic on Sexual Health Whitepaper Download
Sexual Health encompasses; genito-urinary medicine, sexually transmitted infections (STIs), HIV, contraception, psychosexual medicine, abortion services, teenage pregnancy and sexual and reproductive health. It is delivered in various settings, providing care across specialised services as well as through primary and third sector organisations.
Sexual and reproductive health is a fundamental public health issue and is clearly recognised by the World Health Organisation (WHO). This whitepaper focuses on the profound impact of sexually transmitted infections (STIs) worldwide with WHO reporting that more than 1 million STIs are acquired every day (WHO, 2020).
The whitepaper discusses issues such as antimicrobial resistance, in particular gonorrhoea, and the challenges faced in a social and public concept due to the COVID-19 pandemic.
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The global crisis of antimicrobial resistance is never far from the headlines. As part of World Amicrobial Awareness Week, we’ve been discussing the dangers and importantly the work being done to combat this growing threat.
There’s a very simple reason why we must all do what we can to tackle AMR. This year it’s thought 700,000 people died from drug resistant illnesses such as bacterial infections, malaria, HIV/Aids or tuberculosis. Experts warn that by 2050, this figure will rise to 10million.
Randox’s aim is to revolutionise global healthcare and we are committed to combating the threat of antibiotic resistance. We have a number of tests on the market that can help the fight against AMR, strengthen consumer confidence and ensure quality and safety for a number of different industries. So to round off this week, we spoke to two of our experts at Randox: Business Development Manager, Dr Mary Jo Kurth, and Molecular Diagnostics Manager, Dr Martin Crockard.
70% GP’s have been reported to prescribe antibiotics when they don’t know whether the infection is caused by the virus or bacteria.
At the frontline of the battle to curb AMR are the GPs but they’re not able to access the latest technology which can help them. Dr Mary Jo Kurth said, “In the current GP setting, diagnostic testing to determine whether a respiratory infection is bacterial or viral is unavailable, and therefore doctors often have to guess – or feel pressurised into prescribing antibiotics because patients demand it. However antibiotics only work to treat bacterial infections and are useless in treating infections that are caused by viruses.
“The consequences are severe. Medical procedures like organ transplantation and cancer chemotherapy need antibiotics to prevent and treat the bacterial infections that can be caused by the treatment. Without effective antibiotics, even routine operations could become high risk procedures if serious infections can’t be treated. The hard won victories against infectious diseases of the last fifty years will be jeopardized.”
Our Biosciences division have developed a test that can rapidly detect and identify the cause of 22 respiratory infections, in both the upper and lower respiratory tract, and therefore subsequently determine if an antibiotic is required as well as then identify the most effective antibiotic to take. Additionally our Confidante kit – the world’s first over-the-counter home sexual health test – can detect ten of the most common STIs with one patient sample and deliver accurate and reliable results securely and discreetly within one week. This takes the guesswork out of antibiotic prescription and could go a long way in fighting the antibiotic resistance crisis.
Dr Martin Crockard said, “Identifying the specific cause of illnesses provides opportunities to tailor treatment, reducing antibiotic misuse. Not all infections respond to antibiotics, however a multiplex approach which identifies bacterial, viral or fungal pathogens encourages improved clinical decision-making, refining treatment, leading to enhanced patient care.
“The molecular group here at Randox are developing a range of multiplex infection detection arrays to identify specific infection agents, allowing more appropriate use of antibiotics to improve patient care and reduce the onset of antibiotic resistance.”
In addition to tackling AMR via medical settings, there is work that can be done to deal with it in our food. Randox Food Diagnostics offer a comprehensive range of diagnostic solutions to allow for the detection and quantification of antibiotic residues within animal and food products. With validation across a range of matrices Randox Food allows producers to ensure their products are free from antibiotic residues.
As consumer awareness develops so does the need for antibiotic screening within agriculture and food production. Guaranteeing an antibiotic-free product strengthens consumer confidence and ensures food integrity on a global scale. Randox Food offers the Evidence Investigator matched with biochip array technology to provide the end user with fast, reliable results to ensure antibiotic free produce.
The UK Government recently commissioned a two year review into the crisis. Led by Lord Jim O’Neill, the final report outlined a new system of ‘market entry rewards’ worth $1.6 billion to the successful developer of a new antibiotic, which meets a prospectively-defined criteria of ‘unmet need’. Developers of alternative therapies aimed at tackling areas where there is unmet need due to rising AMR would also be eligible for these rewards. Such rewards would be paid after a successful product comes to market.
Chief Medical Officer, Dame Sally Davies said, “Antimicrobial resistance poses a catastrophic threat. If we don’t act now, any one of us could go into hospital in 20 years for minor surgery and die because of an ordinary infection that can’t be treated by antibiotics. That’s why governments and organisations across the world, including the World Health Organization and G8, need to take this seriously.
“This is not just about government action. We need to encourage more innovation in the development of antibiotics – over the past two decades there has been a discovery void around antibiotics, meaning diseases have evolved faster than the drugs to treat them.”
AMR will not go away on its own. It requires complex and comprehensive action across many sectors.
If you are interested in finding out more information, please visit randox.com
To coincide with the start of World Antibiotic Awareness Week the UK Government is being urged to ban excessive use of antibiotics in farming by a group of leading doctors, according to The Daily Telegraph.
Made up of 12 royal medical colleges, the British Medical Association and the Faculty of Public Health, the group say that the UK should “use the opportunity afforded by Brexit to lead the world in banning” preventative prescription of medicines on animals.
A decision made by the European Parliament earlier this year to ban mass agricultural medication has not yet been ratified by member states or the European Commission.
A Department of Environment, Food and Rural Affairs’ spokesman told the newspaper that dealing with AMR is a “top priority” though the paper notes it ‘stopped short of promising a ban.’
In 2015 McDonalds set itself a two year deadline to stop its US restaurants buying chicken raised with human antibiotics. It led to one of the US’s leading meat producers – Tyson Foods – promising to end the practice by September 2017 – which is, as The Guardian stated, “one of the most aggressive timelines yet set by an American poultry company.” The company’s CEO Donnie Smith told the newspaper: “We have found as we have reduced the level of antibiotics we use, whether it’s human use or vet-only, our cost has actually gone down. A lot of the ways we’ve been able to accomplish this is by working with our farmers on better husbandry practices. If this millennial mum wants a no-antibiotic ever..nugget we better supply that.”
Farmers Weekly reported this month on a Danish Crown initiative launched in 2015 whereby pig farmers attach an antibiotics-free tag to piglets at the neonatal stage. It’s removed at any point if antibiotic treatment is deemed necessary. It claims that although early farm trials suggest a production fall of up to 2.5 piglet per sow per year, the “premium covers additional costs if 35% or more piglets carry the tag to the slaughterhouse.”
Pig farmer Stine Mikkelsen carried out a major review of hygiene and health on her farm to reduce antimicrobial use to boost revenue by £11.25 per pig. She says that although production is down and labour costs did increase, it “feels good” to farm in this way. She told the newspaper, “I am very motivated to do something about it – it’s a hard route to take but I have a good feeling about this system.”
Randox Food Diagnostics is working with global leaders in the food industry to tackle antibiotic resistance and safeguard their use for both human and veterinary treatment.
Using a dedicated research and development team, Randox have the ability to respond rapidly to emerging new drugs of abuse and regulations in relation to food and animal safety, with sixty-five new residue drug targets are currently in development to keep up with the ever changing market of food safety. Randox Food Diagnostics are ensuring that all residue screening laboratories requirements are met by providing reliable food safety screening on a global scale.
On top of the food safety product range Randox Food also offer a range of analysers, reagents and test kits for use throughout the winemaking process to ensure quality is maintained in every bottle.
For more information on what we do, please visit: www.randoxfood.com
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