PHARMACOTHERAPY III PHCY 510 University of Nizwa College of Pharmacy and Nursing School of Pharmacy PHARMACOTHERAPY III PHCY 510 Lecture 7 Infectious Diseases “Urinary Tract Infections” Dr. Sabin Thomas, M. Pharm. Ph. D. Assistant Professor in Pharmacy Practice School of Pharmacy, CPN University of Nizwa

Course Outcome Upon completion of this lecture the students will be able to Describe the etiology, clinical presentation (signs and symptoms, diagnosis), diagnosis, treatment strategies, and follow up of Urinary tract infections. Individualize the antimicrobial treatments for UTI patients.

Infection of the bladder (cystitis) and kidney (pyelonephritis) are the most frequently involved. Complicated UTI can be acute or chronic and occur with metabolic, functional, or structural abnormalities of the urinary tract or kidneys. Metabolic factors include diabetes mellitus, renal failure and kidney transplantation. Functional abnormalities include neurogenic bladder and vesicoureteral reflux (backward flow of urine from the bladder into the kidneys). Structural abnormalities like stones, tumors, catheters, stents. Urosepsis is a serious condition in which the bacterial species found within the urinary tract and in the blood.

Etiology/Microbiology Enteric bacteria are the most common organisms causing urinary tract infections. UTI is prevalent in females because the urethra in women is shorter and closer to the anus. E coli is the most common causative organism (80%). In uncomplicated cystitis and pyelonephritis in women, Staphylococcus saprophyticus (coagulase-negative) is the next most common causative organism. In complicated UTI, common organisms are Candida spp., Pseudomonas aeruginosa and Enterococci.

Risk Factors Risk factors for UTI due to S. saprophyticus include use of spermicide- coated condoms, young age, previous UTI, and multiple sexual partners. Lower estrogen levels in postmenopausal women Pregnancy‐induced changes, such as decreased peristalsis and dilation of the ureter, allow bacteria easier access Neurogenic bladder (lack of bladder control), and glucosuria in diabetics Obstruction of the ureters by stones, strictures, or tumors also increases susceptibility to pyelonephritis.

Pathophysiology Organisms enter urinary tract via ascending route from the urethra. Vaginal colonization with potential urinary pathogens is an important intermediate step that gain entry to urethra and bladder. Chronic or intermittent bacteriuria may remain asymptomatic if organisms are not able to adhere to and invade bladder mucosa. Mucosal cells release chemokines that attract neutrophils to the affected tissues. With the onset of this local inflammatory response, the patient may experience symptoms of infection. Systemic responses such as fever or leukocytosis rarely occur with uncomplicated cystitis.

Signs and Symptoms Acute, uncomplicated cystitis occurs in young patients with pain or burning on urination (dysuria), frequent voiding of small amounts of urine (frequency), and needing to urinate immediately (urgency). On positive dipstick or urinalysis, nearly all patients will have pyuria and 40% will have hematuria. In acute uncomplicated pyelonephritis: fever, chills, nausea, vomiting, loin pain, tenderness, weakness, malaise, or headache.

Urine bacterial counts of 104 CFU (colony‐forming units per mL) = diagnosis of acute pyelonephritis. The clinical presentation of complicated UTIs may include the dysuria, frequency, and urgency, headache, temperature instability, and irritability. For patients with known or suspected complicated UTIs, a urinalysis, urine culture, blood count, and serum creatinine should be performed. Colony counts are usually 105 CFU or more per mL

Nosocomial UTI The majority of nosocomial UTIs are associated with urinary catheters. Symptoms are confusion and fever. The incidence of bacteriuria among catheterized patients increases with time at a rate of 6% per day of catheterization. For patients who have symptoms, a urinalysis and culture of urine and blood should be obtained. Antimicrobial treatment of catheter‐associated UTI has high failure and relapse rates. Removing the catheter increases cure rates

Treatment Antimicrobials currently considered first‐line treatment are cotrimoxazole, trimethoprim, or fluoroquinolones. Fluoroquinolones are relatively contraindicated in young children and pregnant women due to reports of cartilage abnormalities. The oral first‐generation cephalosporins and nitrofurantoin have higher relapse and reinfection rates. Gentamicin has long demonstrated clinical efficacy, but the risk of renal toxicity and ototoxicity have limited its use.

P. mirabilis, Klebsiella pneumoniae Condition Usual Pathogens Mitigating Circumstances Recommended Empirical Treatment Acute uncomplicated cystitis in women E. coli, S. saprophyticus, P. mirabilis, Klebsiella pneumoniae None Locations with high TMP/SMX E. Coli resistance Diabetes, symptoms for 7 days, recent UTI, age 65 yr Pregnancy 3-day regimen: oral TMP/SMX, trimethoprim, fluoroquinolone; 7-day regimen: nitrofurantoin 3-day regimen: oral ciprofloxacin, levofloxacin, gatifloxacin, ofloxacin, norfloxacin; 7-day regimen: nitrofurantoin Consider 7-day regimen: oral TMP/SMX, trimethoprim, ciprofloxacin, levofloxacin, gatifloxacin, ofloxacin, or norfloxacin Consider 7-day regimen: oral amoxicillin, nitrofurantoin, cefpodoxime proxetil, or trimethoprim

Mild to moderate illness, no nausea or vomiting— Condition Usual Pathogens Mitigating Circumstances Recommended Empirical Treatment Acute uncomplicated pyelonephritis in women E. coli, P. mirabilis, K. pneumoniae, S. saprophyticus Mild to moderate illness, no nausea or vomiting— outpatient therapy Severe illness–hospitalization Required Pregnancy–hospitalization recommended Oral TMP/SMX (if organism is susceptible), ciprofloxacin, ofloxacin for 7–10 days Parenteral extended-spectrum cephalosporin, ciprofloxacin, levofloxacin, gatifloxacin, or gentamicin (with or without ampicillin) until fever is gone; then oral TMP/SMX / fluoroquinolone as per culture results for 10–14 days. Parenteral extended-spectrum cephalosporin, gentamicin (with or without ampicillin),

E. coli, Proteus spp., Klebsiella spp., Pseudomonas spp., Condition Usual Pathogens Mitigating Circumstances Recommended Empirical Treatment Complicated UTI E. coli, Proteus spp., Klebsiella spp., Pseudomonas spp., Serratia spp., enterococci, Staphylococci Mild to moderate illness, no nausea or vomiting— outpatient therapy Severe illness or possible urosepsis—hospitalization Required Oral ciprofloxacin, levofloxacin, gatifloxacin, or ofloxacin for 7–10 days Parenteral ampicillin and gentamicin,fluoroquinolone, ceftriaxone, aztreonam until fever is gone; then oral TMP/SMX, ciprofloxacin, levofloxacin, gatifloxacin, ofloxacin as per culture results for 10–14 days

Treatment Goals & Patient Education Eradicate pathogenic strains of bacteria or fungi from the urinary tract and resolve or alleviate associated symptoms. Achieve successful clinical outcome with a treatment regimen that is effective, of less ADRs and low cost. Ciprofloxacin 125 mg has been shown to be as effective as a single‐dose postcoital prophylaxis. Prevent recurrent infection by prophylaxis and through patient education.

Photosensitivity reactions are common with co‐trimoxazole as well as with some fluoroquinolones, Patients should be cautioned about sun exposure and the use of sunscreens. Patients prescribed ciprofloxacin should be warned to avoid taking iron or other minerals / antacids at the same time to prevent treatment failure from decreased absorption.