Antibiotics for Urinary Tract Infection (UTI)
What are urinary tract infections?
Urinary tract infections (UTIs) are extremely common bacterial infections worldwide, affecting approximately 150 million people each year. These infections are caused by bacteria invading the urinary system, which includes the kidneys, ureters, bladder and urethra. Although men can also suffer from UTIs, the incidence is significantly higher in women, with approximately 50 to 60 percent of women experiencing at least one such infection during their lifetime. E. coli is the most common cause of UTI, accounting for 80%-90% of all UTI cases. It usually resides in the gastrointestinal tract and can travel up the urinary tract to cause infection. In addition, less common bacteria such as Klebsiella, Proteus and coagulase-negative Staphylococcus can also cause urinary tract infections.
The clinical manifestations of urinary tract infections vary depending on the specific site of infection. An infection limited to the bladder, cystitis, often presents with a strong desire to urinate, a burning sensation while urinating, and cloudy urine. If the infection spreads to the kidneys and pyelonephritis develops, more serious symptoms may occur, including fever, lower back pain and nausea. Untreated, such infections can lead to kidney damage.
Importance of antibiotics in UTI treatment
Antibiotics are a class of agents used to kill or inhibit the growth of bacteria and are highly effective to treat a variety of bacterial infections, including urinary tract infections. In the absence of antibiotic treatment, it is often difficult for the body's own immune system to eliminate infection, especially in the face of E. coli, which can firmly adhere to the urinary tract mucosa. Therefore, timely use of antibiotics not only helps to quickly relieve symptoms, but also effectively stops the infection from spreading to the kidneys or entering the bloodstream, thereby avoiding the occurrence of serious complications such as kidney scarring, kidney abscess, or sepsis.
The standard treatment regimen for urinary tract infections usually consists of a short course of antibiotics lasting 3 to 7 days for cases without complications. When you need to choose the right antibiotic, it is necessary to consider many factors such as bacterial resistance, patient's allergy history and individual health status.
Antibiotic for UTI at BOC Sciences
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How do UTI antibiotics work ?
Antibiotics disrupt key life processes of bacteria through different mechanisms of action, which in turn lead to the death of pathogens or inhibit their growth. These mechanisms include interfering with the synthesis of bacterial cell walls, blocking the DNA replication process, or inhibiting protein synthesis. Because these processes are critical to bacterial survival, their impairment effectively prevents bacterial proliferation and encourages the body's immune system to clear the infection.
Best antibiotic for UTI in females
UTIs are particularly common in females, with nearly half of all women experiencing at least one UTI in their lifetime. The higher susceptibility in females is largely due to anatomical factors, including a shorter urethra and the proximity of the urethra to the vagina and rectum, which facilitates bacterial transfer. Selecting the best antibiotic for treating UTIs in women requires considering several key factors, such as the severity of the infection, patient-specific characteristics, and the local patterns of antibiotic resistance.
While many antibiotics are available for treating UTIs, the most effective ones vary depending on whether the infection is complicated or uncomplicated. For uncomplicated UTIs, where the infection is confined to the bladder, first-line treatments often include:
Nitrofurantoin: Commonly used for uncomplicated UTIs, nitrofurantoin is highly effective against E. coli, the bacteria responsible for most UTIs. It is favored due to its minimal impact on gut bacteria, which reduces the risk of antibiotic resistance. Nitrofurantoin is also well-tolerated in women and typically prescribed for 5-7 days.
Trimethoprim-sulfamethoxazole (TMP-SMX): This antibiotic combination has been a standard UTI treatment for years. This is the first choice for the treatment of E. coli and other common UTI pathogens, but resistance to TMP-SMX has increased, making it less effective in some regions. Therefore, it is only used when resistance rates are below 20%.
Fosfomycin: Fosfomycin is an attractive option for women due to its one-time dosing and efficacy against multidrug-resistant bacteria, including E. coli. It is often used in patients who cannot tolerate other antibiotics or when resistance to first-line treatments is a concern.
Cephalexin for UTI: This first-generation cephalosporin is another popular choice, particularly for pregnant women or patients with mild penicillin allergies. It targets the bacterial cell wall, making it an effective and safe choice for uncomplicated UTIs in women.
There is no single "best" antibiotic for all cases of UTIs in women. The most suitable choice depends on the individual's health status, the bacteria causing the infection, and regional resistance trends.
During pregnancy, due to the increase of estrogen secretion, the microflora around the urethra changes and local immunity decreases, coupled with the reduction of ureteral smooth muscle tension and the weakening of peristalsis, increasing the risk of urinary tract infection. In late pregnancy, uterine enlargement can press on the ureter and bladder, resulting in poor urine flow, slow urine flow or the formation of mild water, which is also conducive to bacterial invasion and reproduction and disease, these factors can increase the incidence of urinary tract infections during pregnancy. In general, nitrofurantoin and fosfomycin are highly effective for uncomplicated infections, while cephalexin is preferred in pregnant women.
Emerging strategies to reduce antibiotic resistance
World Health Organization consider antibiotic resistance to be one of the most pressing public health threats of the 21st century. Over the past 30 years, UroPathogenic Escherichia coli (UPEC) has developed resistance to the conventional antibiotics used to treat UTI, which include beta-lactam and carbapenems, fluoroquinolones, polymyxins, and aminoglycosides. The overuse, misuse and suboptimal infection prevention practices of antibiotics have accelerated resistance to antibiotics in UPEC. UPEC from China, India, and Vietnam have been reported to be up to 70% resistant to fluoroquinolones, and nearly 60% of UPEC strains express broad-spectrum beta lactamase. In countries such as Australia, Canada and the United States, the rate of resistance to fluoroquinolones or third-generation cephalosporins is 10-15% and rising.
New strategies to reduce antibiotic resistance are emerging, including new approaches to target antimicrobial drug delivery, nanoparticles, antimicrobial peptides (AMPs), small molecules, phages, immune regulation, hormone therapy, and microbiome manipulation.
Antimicrobial drug delivery
Targeted antimicrobial drug delivery is an area worth exploring. New delivery methods for UTI treatment are currently being designed to deliver high concentrations of antibiotics to the source of infection, target the urothelium, and maintain drug delivery.
Microvesicle
Ultrasonic microvesicles are an attractive way to deliver antibacterial drugs to the bladder. A microbubble is a small gas-filled bubble stabilized by a polymer or surfactant coating that can serve as a delivery carrier for hydrophobic drugs. Originally designed as a contrast agent for ultrasound, microvesicles have the potential to expand into targeted drug delivery for UTI. When exposed to ultrasound, the microbubbles oscillate in response to incoming pressure waves. Under low pressure and high frequency, the microbubbles can be directed to the target tissue. At high pressures and low frequencies, the microbubbles collapse and deliver their cargo. The movement of microvesicles under the action of ultrasound can not only release drugs, but also promote the adhesion and penetration of drugs in surrounding tissues. As a proof-of-concept study, gentamicin-modified microvesicles with liposomes safely cleared UPEC in a human bladder organoid model.
Mucosal adhesives
Mucosal adhesives can be synthetic or naturally occurring molecules containing hydrophilic polymers that covalently bind to urothelial glycosylated proteins, allowing them and the drugs they carry to maintain contact with the bladder wall, thereby enhancing drug retention within the bladder. By dissolving the antibiotics together during the formulation process, the antibiotics can be embedded in the mucosal adhesive. Many biomolecules, including chitosan, carbomer, and hydrogels, have shown promise as mucosal adhesives in preclinical models. They enhance the penetration of drugs into the urothelium, while also providing protection for damaged surface tissue in the bladder. For example, chitosan adhesion nanoparticles, derived from the natural polysaccharide chitin, can seal methoprene, adhere to the bladder of pigs, and maintain the long-term release of antibiotics at high concentrations under urinary stream.
Nanoparticles
Nanoparticles have the potential to enhance the stability and solubility of packaged goods, improve the delivery of drugs to tissues or target cells, and provide synergistic combinatorial chemistry because of their inherent antimicrobial effects. Nanoparticles are complex three-dimensional structures up to 1,000 nm in diameter that can be made from natural or synthetic materials, inorganic materials, or lipids. Research on nanoparticles is still in the preclinical stage, but in the field of urinary tract infections, current evidence suggests that nanobiotics improve urothelial penetration compared to conventional antibiotics, thereby having the ability to target intracellular UPEC reservoirs and reduce recurrent infections.
Antimicrobial peptide (AMPs)
AMP is promising for the treatment of antibiotic-resistant bacteria. AMPs are evolutionarily conserved peptides expressed in plants, insects, and lower and higher order vertebrates. Individual AMPs vary in structure and function, but they are primarily cationic, amphoteric peptides composed of fewer than 100 amino acids. The antibacterial activity of AMPs is related to its net charge, amphiphilicity, hydrophobicity and secondary structure. A great deal of research work is being done to explore how these biochemical signatures can be manipulated to improve the therapeutic index of peptides while minimizing potential cytotoxic effects. AMPs primarily kill bacteria by disrupting bacterial membranes leading to cell lysis and death, or by inhibiting bacterial transcription or translation through transmicrobial membrane transport. Preclinical evidence suggests that AMPs can be used as monotherapy, in combination with antibiotics or other AMPs to obtain synergistic activity, or packaged with antibacterial carriers (such as nanoparticles) to kill urogenic bacteria and destroy UPEC biofilms.
Small molecule
Preclinical data have advanced our understanding of how urinary tract pathogens use pili to bind to and invade host cells, and this understanding has led to the development of synthetic compounds, called pili fungicides and mannosides, that inhibit pili activity to reduce bacterial attachment or invasion. Preclinical evidence suggests that trichomicides prevent UPEC from attaching to urothelial cells, thereby preventing the establishment of infection. Mannoside is an FimH receptor analogue that binds FimH (FIMI adhesion type 1) with high affinity and blocks its binding to mannosylated receptors on the surface of urinary tract epithelium. Mannoside has oral bioavailability, is effective against drug-resistant UPEC, prevents bladder and kidney colonization, and can effectively treat and prevent UTI.
Bacteriophage
Bacteriophages are viruses that infect bacterial cells and promote bacterial dissolution. Intravesical phage therapy after kidney and prostate surgery has been evaluated clinically and has been shown to prevent bacterial infections with no reported adverse effects. In a double-blind clinical trial, in patients undergoing transurethral prostatectomy, intracavical phage therapy for UTI was no less effective than conventional antibiotic therapy.
Immunity and immune regulation
Vaccination is another strategy aimed at reducing antibiotic exposure. There are currently four vaccines available in Europe and Canada for the treatment of urinary tract infections: Urovac, Uro-Vaxom, ExPEC4V and Uromune. These vaccines use a combination of whole, heat-treated killed bacteria, bacterial extracts or immunogenic antigens.
Hormones
Hormones influence UTI defense, and numerous data confirm the value of estrogen in the treatment and prevention of UTI. After menopause, falling estrogen levels can cause changes in vaginal and urethral tissue, making it more susceptible to colonization by urinary tract pathogens. Evidence suggests that estrogen therapy, whether taken orally, topically, or intravaginally, can help restore genitourinary tissue health in postmenopausal women and reduce the risk of recurrent urinary tract infections. Estrogen therapy improves vaginal epithelial integrity, increases vaginal pH, enhances local immune response, and promotes the growth of beneficial vaginal flora, which together help reduce the risk of urinary tract infections.
Reference
- Simoni, A., et al. Current and emerging strategies to curb antibiotic-resistant urinary tract infections. Nature Reviews Urology. 2024: 1-16.
