Urinary Tract Infections Lobna A AlJuffali,MSc Fall 2010 Urinary Tract Infection (UTI) Most common bacterial infections in humans: 7million office visits per year 1 million hospitalizations 15-20% of women will have a UTI during their lifetime. From ages 1 to 50,UTIs predominantly occur in women After 50 men are affected because of prostate problems. Definition defined as the presence of microorganism in the urine that cannot be accounted for by contamination. The organisms have the potential to invade the tissues of the urinary tract and adjacent structures. The presence of bacteria is termed bacteriuria fungi in the urine is termed or funguria Anatomy of UTS Classification based on anatomic site Lower tract infections include cystitis (bladder) urethritis (urethra) prostatitis (prostate gland) epididymitis. Upper tract infections (such as pyelonephritis) involve the kidney and are referred to as pyelonephritis. Uncomplicated UTIs Are not associated with structural or neurologic abnormalities that may interfere with the normal flow of urine or the voiding mechanism. Include acute cystitis and pyelonephritis in healthy individuals They have the lowest risk of complications or treatment failure. Complicated UTIs Can be acute or chronic are the result of a predisposing lesion of the urinary tract such as: Metabolic factors: Renal Failure Diabetes Mellitus Kidney transplantation Functional abnormalities: neurologic al bladder. Structural abnormality a congenital abnormality distortion of the urinary tract, a stone indwelling catheter prostatic hypertrophy Obstruction Recurrent UTIs Recurrent UTIs are characterized by multiple symptomatic episodes with asymptomatic periods occurring between these episodes. These infections are either due to reinfection or to relapse. Reinfections are caused by a different organism and account for the majority of recurrent UTIs. Relapse represents the development of repeated infections caused by the same initial organism. Occur within 2-4 weeks after treatment has ended. Persistent infections Asymptomatic bacteriuria is a common finding, particularly among those 65 years of age and older when there is signiﬁcant bacteriuria >105 bacteria/mL of urine in the absence of symptoms. Patients with infection usually have more than 105 bacteria/mL of urine, although as many as one-third of women with symptomatic infection have less than 105 bacteria/mL. Symptomatic abacteriuria or acute urethral syndrome consists of symptoms of frequency and dysuria in the absence of signiﬁcant bacteriuria. This syndrome is commonly associated with Chlamydia infections. Signiﬁcant bacteriuria is a term used to distinguish the presence of microorganisms that represent true infection versus contamination of the urine as it passes through the distal urethra prior to collection. Criteria for defining significant bacteriuria ≥ 102 CFU coliforms/ml or ≥ 105 CFU noncoliforms/ml in a symptomatic female ≥ 103 CFU bacteria/ml in a symptomatic male ≥ 105 CFU bacteria/ml in asymptomatic individuals on two consecutive specimens Any growth of bacteria on suprapubic catheterization in symptomatic patient ≥ 102 CFU bacteria/ml in catheterized patient Pathopysiology The bacteria causing UTIs usually originate from bowel flora of the host. Bacteria are then believed to enter the bladder from the urethra. Once in the bladder, the organisms multiply quickly and can ascend the ureters to the kidney. UTIs can be acquired via three possible routes: 1. 2. 3. The ascending, Hematogenous Lymphatic pathways. In females, the short length of the urethra and proximity to the perirectal area make colonization of the urethra likely. Patients who are unable to void urine completely are at greater risk of developing UTIs and frequently have recurrent infections. Three factors determine the development of UTI: the size of the inoculum 2. virulence of the microorganism 3. competency of the natural host defense mechanisms. 1. Virulence Factor Of Bacteria Their ability to adhere to urinary epithelial cells by fimbriae, resulting in colonization of the urinary tract, bladder infections, and pyelonephritis. Hemolysin, a cytotoxic protein produced by bacteria that lyses a wide range of cells including erythrocytes, polymorphonuclear leukocytes, and monocytes Aerobactin, which facilitates the binding and uptake of iron by Escherichia coli MICROBIOLOGY Community-acquired Infections (%) nosocomial infections (%) E. Coli 73 E. coli, 31 Staphylococcus saprophyticus 13 Pseudomonas aeruginosa 10 10 P.Mirabils 5 Other gram negtive bacilli Klebsiella pneumoniae 4 Klebsiella pneumoniae 9 Enterococci 2 Staphylococci 6 P.Mirabils 5 Enterococci 2 Fungi 14 Candidaspp. (critically ill and chronically catheterized patient). MICROBIOLOGY • The majority of UTIs are caused by a single organism; however, in patients with stones, indwelling urinary catheters, or chronic renal abscesses, multiple organisms may be isolated. E.COLI Predisposing Factors Age Female gender Diabetes mellitus Pregnancy Immunosuppression Urinary tract instruments Urinary tract obstruction Renal disease; renal transplantation Neurological dysfunction Clinical presentation Symptoms alone are unreliable for the diagnosis of bacterial UTIs. The key to the diagnosis of a UTI is the ability to demonstrate significant numbers of microorganisms present in an appropriate urine specimen to distinguish contamination from infection. Elderly patients frequently do not experience specific urinary symptoms, but they will present with altered mental status, change in eating habits, or GI symptoms. Signs and symptoms Lower UTI: Dysuria, urgency, frequency, nocturia, suprapubic heaviness Gross hematuria Upper UTI: Flank pain, fever, nausea, vomiting, malaise Physical examination Upper UTI: Costovertebral tenderness Laboratory tests Bacteriuria Pyuria (white blood cell count >10/mm) Nitrite-positive urine (with nitrite reducers (E. coli).) Leukocyte esterase-positive urine (pyuria). Antibody-coated bacteria (upper UTI) Laboratory tests A standard urinalysis should be obtained in the initial assessment of a patient. Microscopic examination of the urine should be performed by preparation of a Gram stain of unspun or centrifuged urine. The most reliable method of diagnosing UTIs is by quantitative urine culture. DESIRED OUTCOME The goals of treatment for UTIs are to prevent or treat systemic consequences of infection, eradicate the invading organism, and prevent recurrence of infection. GENERAL PRINCIPLES The management of a patient with a UTI includes initial evaluation selection of an antibacterial agent and duration of therapy, and follow-up evaluation. GENERAL PRINCIPLES The initial selection of an antimicrobial agent for the treatment of UTI is primarily based: on the severity of the presenting signs and symptoms, the site of infection, and whether the infection is determined to be complicated or uncomplicated PHARMACOLOGIC TREATMENT The ability to eradicate bacteria from the urinary tract is directly related to the sensitivity of the organism and the achievable concentration of the antimicrobial agent in the urine. The therapeutic management of UTIs is best accomplished by first categorizing the type of infection: acute uncomplicated cystitis, symptomatic abacteriuria, asymptomatic bacteriuria, complicated UTIs, recurrent infections, or prostatitis. Acute Uncomplicated Cystitis These infections are predominantly caused by E. coli, and antimicrobial therapy should be directed against this organism initially. Other causes include S. saprophyticus and occasionally K. pneumoniae and Proteus mirabilis. Acute Uncomplicated Cystitis Short-course therapy (3-day therapy) with trimethoprim– sulfamethoxazole or a fluoroquinolone (e.g., ciprofloxacin, levofloxacin, or norfloxacin) is superior to single-dose therapy for uncomplicated infection and should be the treatment of choice. Amoxicillin or sulfonamides are not recommended because of the high incidence of resistant E. coli. Follow-up urine cultures are not necessary in patients who respond. If sulfa allergy nitrofuranton 100 mg PO bid x 5 days Symptomatic Abacteriuria Single-dose or short-course therapy with trimethoprim– sulfamethoxazole has been used effectively, and prolonged courses of therapy are not necessary for the majority of patients. If single-dose or short-course therapy is ineffective, a culture should be obtained. If the patient reports recent sexual activity, therapy for Chlamydia trachomatis should be considered azithromycin 1 g as a single dose doxycycline 100 mg twice daily for 7 days. Asymptomatic Bacteriuria The management of asymptomatic bacteriuria depends on the age of the patient and, if female, whether she is pregnant. In children, treatment should consist of conventional courses of therapy, as described for symptomatic infections. In the nonpregnant female, therapy is controversial; however, it appears that treatment has little effect on the natural course of infections. Most clinicians feel that asymptomatic bacteriuria in the elderly is a benign disease and may not warrant treatment. The presence of bacteriuria can be confirmed by culture if treatment is considered. Uncomplicated Pyelonephritis FQ for 2 weeks managed in outpatient setting Trimethoprim-sulfamethoxazole Complicated Urinary Tract Infections Acute Pyelonephritis The presentation of high-grade fever (greater than 38.3°C [100.9°F]) and severe flank pain should be treated as acute pyelonephritis, and aggressive management is warranted. Severely ill patients with pyelonephritis should be hospitalized and IV drugs administered initially. The duration for treatment is 14 days At the time of presentation, a Gram stain of the urine should be performed, along with urinalysis, culture, and sensitivities. Complicated Urinary Tract Infections Acute Pyelonephritis Gram stain reveals grampositive cocci, Streptococcus faecalis • ampicillin. • Amoxicillin or Amoxicillincalvulanic acid 14 days • IV FQ, an aminoglycoside with or without ampicillin, In the seriously ill patient • or an extended-spectrum cephalosporin with or without an aminoglycoside. • 14 days If the patient has been hospitalized in the last 6 months, has a urinary catheter, or is in a nursing home, • P. aeruginosa and enterococci infection, as well as multiply-resistant organisms, should be considered. • ceftazidime, ticarcillin-clavulanic acid, piperacillin, aztreonam, meropenem, or imipenem, in combination with an aminoglycoside, is recommended. Complicated Urinary Tract Infections Acute Pyelonephritis If the patient responds to initial combination therapy, the aminoglycoside may be discontinued after 3 days. Follow-up urine cultures should be obtained 2 weeks after the completion of therapy to ensure a satisfactory response and to detect possible relapse. Urinary Tract Infections in Males The conventional view is that therapy in males requires prolonged treatment A urine culture should be obtained before treatment, because the cause of infection in men is not as predictable as in women. If gram-negative bacteria are presumed, trimethoprim–sulfamethoxazole or a fluoroquinolone is a preferred agent. Initial therapy is for 10 to 14days. For recurrent infections in males, cure rates are much higher with a 6-week regimen of trimethoprim–sulfamethoxazole. Recurrent Infections Recurrent episodes of UTI (reinfections and relapses) account for a significant portion of all UTIs. Relapses: Assess for pharmacologic reason for treatment failure. Treat longer 2-6 weeks If relapse occurs after 6 weeks of treatment, urologic examination should be performed, and therapy for 6 months or even longer may be considered. Reinfection: Reinfection 2 or less UTI in a year 3 or more UTI in a year Related to sexual activity 3 or more UTI in a year Not related to sexual activity 3 day treatment regimen Postintercourse prophylaxis with TMP/SMZ SS, cephalexin 250 mg Nitrofurantoin 50100mg Daily or 3 times a wk TMP/SMZ SS, Nitrofurantoin 50100mg Norfloxacin 200 mg cephalexin 250 mg 6 months Urinary Tract Infection in Pregnancy In patients with significant bacteriuria, symptomatic or asymptomatic, treatment is recommended in order to avoid possible complications during the pregnancy. Therapy should consist of an agent with a relatively low adverse-effect potential (a sulfonamide, cephalexin, amoxicillin, amoxicillin/clavulanate, nitrofurantoin) administered for 7 days. Antibiotics to avoid in Pregnancy Tetracyclines should be avoided because of teratogenic effects sulfonamides should not be administered during the third trimester because of the possible development of kernicterus and hyperbilirubinemia. fluoroquinolones should not be given because of their potential to inhibit cartilage and bone development in the newborn. Catheterized Patients When bacteriuria occurs in the asymptomatic, short-term catheterized patient (less than 30 days), the use of systemic antibiotic therapy should be withheld and the catheter removed as soon as possible. If the patient becomes symptomatic, the catheter should again be removed, and treatment as described for complicated infections should be started. The use of prophylactic systemic antibiotics in patients with short-term catheterization reduces the incidence of infection over the first 4 to 7 days. In long-term catheterized patients, however, antibiotics only postpone the development of bacteriuria and lead to emergence of resistant organisms. Prostatitis P. aeruginosa, Proteus spp.,K. pneumoniae, E. coli. Treatment 1. Trimethoprim–sulfamethoxazole × 4–6 weeks 2. Quinolone× 4–6 weeks Acute prostatitis may require IV therapy initially The conversion to an oral antibiotic can be considere dafter the patient is afebrile for 48 hours or after 3 to 5 days of intravenous therapy. The total course of antibiotic therapy should be 4-6weeks Chronic prostatitis may require longer treatment periods (6 to 12 weeks) or surgery Management of UTIs in females. Management of UTIs in males.