LSP essay urinary tract infection What is UTI? UTI is a microbes infection that occurs at any part of your urinary system. Kidneys, ureters, bladder, and urethra are the components of the urinary system and it can be divided into two sections which are th PDF

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What is UTI?
UTI is a microbes infection that occurs at any part of your urinary system. Kidneys, ureters, bladder, and urethra are the components of the urinary system and it can be divided into two sections which are the upper and lower level of the urinary system. Urinary tract infection (U...

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What is UTI? UTI is a microbes infection that occurs at any part of your urinary system. Kidneys, ureters, bladder, and urethra are the components of the urinary system and it can be divided into two sections which are the upper and lower level of the urinary system. Urinary tract infection (UTI) usually occurs at the lower part of the urinary system. Most UTI cases involve bacteria, fungi and rare cases by viruses. Examples of bacteria that can be found in a person who has the UTI are Escherichia coli, Enterobacteria, Klebsiella, and Pseudomonas aeruginosa. All these types of microorganism can be called as uropathogen. Clinically, UTIs can be categorized as uncomplicated UTI or complicated UTI. Uncomplicated UTI – infection in a healthy, non-pregnant, pre-menopausal female patient with anatomically and functionally normal urinary tract Complicated UTI – infection associated with factors increasing colonization and decreasing efficacy of therapy Uncomplicated UTIs Uncomplicated urinary tract infections (UTIs) begin when uropathogens that reside in the gut contaminate the periurethral area (step 1) and are able to colonize the urethra. Subsequent migration to the bladder (step 2) and expression of pili and adhesins results in colonization and invasion of the superficial umbrella cells (step 3). Host inflammatory responses, including neutrophil infiltration (step 4), begin to clear extracellular bacteria. Some bacteria evade the immune system, either through host cell invasion or through morphological changes that result in resistance to neutrophils, and these bacteria undergo multiplication (step 5) and biofilm formation (step 6). These bacteria produce toxins and proteases that induce host cell damage (step 7), releasing essential nutrients that promote bacterial survival and ascension to the kidneys (step 8). Kidney colonization (step 9) results in bacterial toxin production and host tissue damage (step 10). If left untreated, UTIs can ultimately progress to bacteraemia if the pathogen crosses the tubular epithelial barrier in the kidneys (step 11).

Complicated UTIs Uropathogens that cause complicated UTIs follow the same initial steps as those described for uncomplicated infections, including periurethral colonization (step 1), progression to the urethra and migration to the bladder (step 2). However, in order for the pathogens to cause infection, the bladder must be compromised. The most common cause of a compromised bladder is catheterization. Owing to the robust immune response induced by catheterization (step 3), fibrinogen accumulates on the catheter, providing an ideal environment for the attachment of uropathogens that express fibrinogen-binding proteins. Infection induces neutrophil infiltration (step 4), but after their initial attachment to the fibrinogen-coated catheters, the bacteria multiply (step 5), form biofilms (step 6), promote epithelial damage (step 7) and can seed infection of the kidneys (steps 8 and 9), where toxin production induces tissue damage (step 10). If left untreated,

uropathogens that cause complicated UTIs can also progress to bacteraemia by crossing the tubular epithelial cell barrier (step 11).

Treatment for uncomplicated UTIs Antibiotics usually are the first line treatment for urinary tract infections that caused by bacteria. The common antibiotics that used to treat uncomplicated UTIs are trimethoprimsulfamethoxazole, also known as BACTRIM. the most commonly recommended therapeutics for UTIs BACTRIM has long been considered the standard of therapy for acute and recurrent urinary tract infections because of its activity against the uropathogens. Bactrim is a combination of two antimicrobial agents which are Sulfamethoxazole and Trimethoprim that is commonly used to treat urinary tract infection. Both Sulfamethoxazole and Trimethoprim are bacteriostatic, but the combination becomes bactericidal against many organisms by working synergistically. Basically, Trimethoprim and Sulfamethoxazole works at two separate steps of the bacterial folate metabolism, resulting in the inhibition of DNA synthesis. Sulfamethoxazole is a structural analogue of para-aminobenzoic acid (PABA). Sulfamethoxazole inhibits enzyme dihydropteroate synthase by competing with PABA for the binding site. This will block the biosynthesis of folate coenzyme and arrest the bacterial growth and cell division. Sulfamethoxazole has similar chemical features as PABA except that the COOH (carboxy) group is replaced with SO2NH2 (sulfonamide) moiety. Its amine group and aromatic ring can form hydrogen bond and Van der Waals interaction, respectively with active site of dihydropteroate synthase. The ionisation of SO2NH2 moiety at physiological pH allows Sulfamethoxazole to form a similar ionic bond with an active site. Trimethoprim in BACTRIM is an anti-folate agent that binds to dihydrofolate reductase and inhibits the reduction of dihydrofolic acid to tetrahydrofolic acid. Tetrahydrofolic acid is an essential precursor in the thymidine synthesis pathway. Interference with this pathway prevents bacterial DNA synthesis and eventually continued bacteria survival. Sequential blockade of bacterial folic acid synthesis by Bactrim. Together, the powerful combination blocks two important steps required for certain bacteria to make the proteins they need to survive.

Treatment for complicated UTIs Zosyn is the one of the most common and effective antibiotics that used to treat complicated UTI. Zosyn is an injectable combination of two antibiotics, which are piperacillin and tazobactam, with broad spectrum activity against an extended range of bacterial species.

Piperacillin is a β-lactam antibiotic under penicillin class. It inhibits the biosynthesis of peptidoglycan of the bacterial cell walls, weakens the cell wall and ultimately causes the bacterial cell wall to break. But, how it can break the cell wall? Piperacillin can break the cell wall of bacteria because it has a similar structure as Dalanine D-alanine. D-alanine D-alanine is the component of bacterial peptidoglycan. Thus, this enable it to compete with D-alanine D-alanine for binding site and bind to the active site of transpeptidase enzyme located inside the bacterial cell walls. Once bound, piperacillin is prone to get nucleophilic attack by serine of transpeptidase enzyme. Thus, transpeptidase will be unable to cross link the peptidoglycan chains. Eventually, bacterial cell wall synthesis is inhibited and this causing the bacteria undergo osmotic lysis and die. Tazobactam is a β-lactamase inhibitor. This is because piperacillin can be destroyed by an enzyme produced by β-lactamase enzyme produced by the bacteria. Tazobactam inhibits beta lactamase and prevents the enzymatic destruction of piperacillin by β-lactamase. Therefore, tazobactam is given with piperacillin to enhance the activity of piperacillin in eradicating bacterial infections.

Conclusion In short, type of medication and dose for UTIs patient is depends on whether their infection is complicated or uncomplicated. Complicated UTIs need to treated more carefully to serve patients with these infections and to avoid overuse and misuse of antibiotics that will ultimately result in more resistant infections in the future. Using the right antibiotic for the right duration is key. Practitioners should not hesitate to take advantage of infectious disease specialty services in these situations to help optimize antibiotic use....