UTI Anti-Infectives PDF

# Urinary Tract Anti-Infectives / Urinary Tract Anti-Infective Agents / Urinary Antiseptics ## By Dr. Md Azizur Rahman - Associate Professor (J) - Department of Pharmaceutical Chemistry - Faculty of Pharmacy - Integral University, Lucknow, Uttar Pradesh, India ## Introduction to Urinary Tract Infe...

# Urinary Tract Anti-Infectives / Urinary Tract Anti-Infective Agents / Urinary Antiseptics ## By Dr. Md Azizur Rahman - Associate Professor (J) - Department of Pharmaceutical Chemistry - Faculty of Pharmacy - Integral University, Lucknow, Uttar Pradesh, India ## Introduction to Urinary Tract Infection (UTI) - Most UTIs are caused by Gram-negative bacteria, especially coliforms. - Acute infection involves a single organism, E.coli. - Chronic and recurrent infections by mixed infections. - Bacteria gets into urine through the urethra and travels up into the urinary bladder. - About 60% of women (due to shorter urethras than men) and 12% of men will have at least one UTI during their lifetime. - One-way flow of urine helps prevent infections. ## Symptoms of UTI - Red and irritated bladder and urethra cause pain in the lower abdomen pelvic area and even lower back. - Urinating more often. - Burning or pain when urinating. - Urine smells bad and is cloudy. - Kidney infections often cause fevers and upper back pain - usually on one side or the other, nausea, and vomiting. - Kidney infections can be a life-threatening health issue if not treated. ## Diagnosis of UTI - Urine examined under a microscope for bacteria or WBC. - Urine culture to detect and identify bacteria and yeast in the urine. - Fevers and symptoms of a UTI. - Ultrasound or CT scan to check the urinary tract. ## Treatment of UTI - Women have simple UTIs, while the UTIs in men and children should be thought of as complicated UTI. - Simple UTI or lower UTI: 3-day course of an antibiotic. - Drink plenty of liquids, especially around the time of a UTI. - Complicated UTI / Upper UTI: Longer course of antibiotics is given, started IV, then oral for upto 2 weeks. - Drink plenty of liquids, especially around the time of a UTI. ## Urinary Tract Anti-Infective Agents - Are highly active against most of the Gram-negative pathogens including Pseudomonas aeruginosa and Enterobacteria. - Some AMAs when taken orally, are concentrated in the renal tubules. So, they are used to treat infections of the urinary tract as UTI anti-infectives or urinary antiseptics. - It is advisable to select a drug which does not disrupt normal gut flora. - If recurrencies are frequent, chronic suppressive treatment with sulphonamides, cotromoxazole, nitrofurantoin, methenamine, cephalexin or norfloxacin may be given. ### Antimicrobial Regimens for Acute UTI (all given orally for 3-5 days) 1. Norfloxacin 400 mg 12 hourly 2. Ciprofloxacin 250 mg 12 hourly 3. Cotrimoxazole 960 mg 12 hourly 4. Cephalexin 250 mg 6 hourly 5. Cefpodoxime proxetil 200 mg 12 hourly 6. Amoxicillin + clavulanic acid (500 + 125 mg) 8 hourly 7. Nitrofurantoin 50 mg 8 hourly or 100 mg 12 hourly x 5-7 days * For upper UTI, the same drugs may be given for 10-14 days. Nitrofurantoin is not suitable for pyelonephritis. ### Favourable Urinary pH for Antimicrobial Action | Acidic | Alkaline | pH inumaterial | |---|---|---| | Nitrofurantoin | Cotrimoxazole | Chloramphenicol| | Methenamine| Aminoglycosides| Ampicillin| | Tetracyclines| (Gentamicin, etc.) | Colistin| | Cloxacillin | Cephalosporins | | | | Fluoroquinolones | | ## Classification Chemical classification of synthetic antibacterial agents includes: 1. Sulfonamides: eg. Sulfadiazine, Sulfathiazole, Sulfacetamide. 2. Quinolones: - First generation quinolones: eg. Nalidixic acid, Cinoxacin. - Fluoroquinolones (2nd, 3rd, 4th generation quinolones): - 1st generation FQs: Norfloxacin, Ciprofloxacin, Ofloxacin, Pefloxacin - 2nd generation FQs: Levofloxacin, Lomefloxacin, Gatifloxacin, Sparfloxacin, Moxifloxacin. 3. Nitrofurans: eg. Nitrofurazone, Furazolidone, Nitrofurantoin. 4. Methenamine and its salts: eg. Methenamine mandelate, Methenamine hippurate. ## II. Quinolones - The quinolone antibacterial comprise a group of synthetic substances possessing a common N-1-alkylated-3-carboxy-4-one ring fused to another aromatic ring. ### Nalidixic Acid (Gramoneg, Negadix) - 1-Ethyl-1,4-dihydro-7-methyl-4-oxo­-1,8-naphthyridin-3-carboxylic acid. - Use: It is particularly effective against Gram-negative bacteria that causes urinary tract infection. ### Norfloxacin (Norbactin, Norflox) - 1-Ethyl-6-fluoro-1,4-dihydro-4-oxo­-7-(1-piperazinyl)-3-quinoline carboxylic acid - Use: It is indicated for the treatment of urinary tract infections caused by E. coli, K. pneumoniae and P. mirabilis, indole-positive Proteus spp. including P. vulgaris, P. aeruginosa, S. aureus and S. epidermidis and group-D Streptococci. ### Ciprofloxacin (Cifran, Ciplox, Cipride) - 1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo­-7-(1-piperazinyl)-3-quinoline carboxylic acid - Use: It is a very effective drug for the treatment of urinary tract infection. - Newest fluoroquinolone like Levofloxacin are active against Streptococcus pneumonia. - Fluoroquinolones are used to treat upper and lower respiratory infections, gonorrhea, bacterial gastroenteritis, skin and soft tissue infections. ## III. Nitro Furans ### Nitrofurantoin - Lemon-yellow powder - Wide antibacterial spectrum both against Gram +ve & Gram -ve, E.coli & enterococci. - Primarily bacteriostatic but bactericidal at high concentration and in acidic urine. - Used in treatment of uncomplicated UTI & long term suppressive therapy, mainly against E.coli. - Urine of patients taking it turns dark brown on air exposure. - MOA: Bacteria reduces nitrofurantoin more rapidly than mammalian cells, thus it is selective to bacteria, and generates reactive intermediates which damage DNA. - Adverse effects: Nausea, gastric pain, diarrhoea, peripheral neuritis, haemolytic anemia, liver damage, lung fibrosis. ## (iv) Methenamine and its salts: eg. Methenamine, Methenamine mandelate, Methenamine hippurate. - Methenamines are of value for chronic suppressive treatment of UTI. It is most useful against E.coli, S.aureus, & S.epidermidis. - MOA: The compound decomposes in H₂O in acidic urine to generate formaldehyde which inhibits all bacteria: - N4(CH2)6 + 6H₂O + H+ →4NH4+ + 6HCHO (Methenamine) (acidic urine) (formaldehyde) - Organic acids like mandelic acid, hippuric acid or ascorbic acid are used to decrease urine pH to 5.5. - Administered as enteric coated tablets to prevent gastritis & decomposition in gastric juice. ### Methenamine hippurate - Methenamines are of value for chronic suppressive treatment of UTI. It is most useful against E.coli, S.aureus, & S.epidermidis. - MOA: The compound decomposes in H₂O in acidic urine to generate formaldehyde which inhibits all bacteria: - N4(CH2)6 + 6H₂O + H+ →4NH4+ + 6HCHO (Methenamine) (acidic urine) (formaldehyde) - Organic acids like mandelic acid, hippuric acid or ascorbic acid are used to decrease urine pH to 5.5. - Administered as enteric coated tablets to prevent gastritis & decomposition in gastric juice.