Urinary Tract Infections (UTIs) and Prostatitis

1. Urinary Tract Infections (UTIs)and Prostatitis Pharm.D Balsam Alhasan

2. DEFINITION • Infections of the urinary tract represent a wide variety of clinical syndromes, including urethritis, cystitis, prostatitis, and pyelonephritis. • A urinary tract infection (UTI) is defined as the presence of microorganisms 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.

3. DEFINITION • Lower tract infections include cystitis (bladder), urethritis (urethra), prostatitis (prostate gland), and epididymitis. Upper tract infections (such as pyelonephritis) involve the kidney and are referred to as pyelonephritis.

4. DEFINITION • Uncomplicated UTIs are not associated with structural or neurologic abnormalities that may interfere with the normal flow of urine or the voiding mechanism. Complicated UTIs are the result of a predisposing lesion of the urinary tract such as a congenital abnormality or distortion of the urinary tract, a stone, indwelling catheter, prostatic hypertrophy, obstruction, or neurologic deficit that interferes with the normal flow of urine and urinary tract defenses.

5. DEFINITION • 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.

6. PATHOPHYSIOLOGY • The bacteria causing UTIs usually originate from bowel flora of the host. • UTIs can be acquired via three possible routes: the ascending, hematogenous, or lymphatic pathways.

7. PATHOPHYSIOLOGY • In females, the short length of the urethra and proximity to the perirectal area make colonization of the urethra likely. 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.

8. PATHOPHYSIOLOGY • Three factors determine the development of UTI: the size of the inoculum, virulence of the microorganism, and competency of the natural host defense mechanisms. • Patients who are unable to void urine completely are at greater risk of developing UTIs and frequently have recurrent infections.

9. PATHOPHYSIOLOGY • An important virulence factor of bacteria is their ability to adhere to urinary epithelial cells by fimbriae, resulting in colonization of the urinary tract, bladder infections, and pyelonephritis. Other virulence factors include hemolysin, a cytotoxic protein produced by bacteria that lyses a wide range of cells including erythrocytes, polymorphonuclear leukocytes, and monocytes; and aerobactin, which facilitates the binding and uptake of iron by Escherichia coli.

10. MICROBIOLOGY • The most common cause of uncomplicated UTIs is E. coli, accounting for more than 85% of community-acquired infections, followed by Staphylococcus Saprophyticus(coagulase-negative staphylococcus), accounting for 5% to 15%.

11. MICROBIOLOGY • The urinary pathogens in complicated or nosocomial infections may include E. coli , which accounts for less than 50% of these infections, Proteus spp., Klebsiellapneumoniae, Enterobacterspp., Pseudomonas aeruginosa, staphylococci, and enterococci.

12. MICROBIOLOGY • Candida spp. have become common causes of urinary infection in the critically ill and chronically catheterized patient. • 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.

13. CLINICAL PRESENTATION • The typical symptoms of lower and upper UTIs are presented in Table 50-1.

15. 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.

16. CLINICAL PRESENTATION • Elderly patients frequently do not experience specific urinary symptoms, but they will present with altered mental status, change in eating habits, or GI symptoms. • A standard urinalysis should be obtained in the initial assessment of a patient.

17. DIAGNOSIS: • Microscopic examination of the urine should be performed by preparation of a Gram stain of unspun or centrifuged urine. The presence of at least one organism per oil-immersion field in a properly collected uncentrifuged specimen correlates with more than 100,000 bacteria/mL of urine. • Criteria for defining significant bacteriuria are listed in Table 50-2.

18. DIAGNOSIS:

19. DIAGNOSIS: • The presence of pyuria (more than 10 white blood cells/mm 3) in a symptomatic patient correlates with significant bacteriuria. • The nitrite test can be used to detect the presence of nitrate-reducing bacteria in the urine (such as E. coli). The leukocyte esterase test is a rapid dipstick test to detect pyuria.

20. DIAGNOSIS: • The most reliable method of diagnosing UTIs is by quantitative urine culture. 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. • A method to detect upper UTI is the antibody-coated bacteria test, an immunofluorescentmethod that detects bacteria coated with immunoglobulin in freshly voided urine.

21. TREATMENT

22. 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.

23. 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. • 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.

24. 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.

25. PHARMACOLOGIC TREATMENT • Table 50-3 lists the most common agents used in the treatment of UTIs, along with comments concerning their general use.

29. THERAPEUTIC OPTIONS • Table 50-4 presents an overview of various therapeutic options for outpatient therapy for UTI.

32. TREATMENT REGIMENS • Table 50-5 describes empiric treatment regimens for selected clinical situations.

34. 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. saprophyticusand occasionally K. pneumoniaeand Proteus mirabilis.

35. Acute Uncomplicated Cystitis • Because the causative organisms and their susceptibilities are generally known, a cost-effective approach to management is recommended that includes a urinalysis and initiation of empiric therapy without a urine culture (Fig. 50-1).

37. Acute Uncomplicated Cystitis • Short-course therapy (3-day therapy) with trimethoprim–sulfamethoxazoleor 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.

38. Symptomatic Abacteriuria • Single-dose or short-course therapy with trimethoprim–sulfamethoxazolehas 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 or doxycycline 100 mg twice daily for 7 days).

39. 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.

40. Asymptomatic Bacteriuria • 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.

41. Complicated Urinary Tract Infections

42. 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. Milder cases may be managed with oral antibiotics in an outpatient setting.

43. Acute Pyelonephritis • At the time of presentation, a Gram stain of the urine should be performed, along with urinalysis, culture, and sensitivities. • In the mild to moderately symptomatic patient for whom oral therapy is considered, an effective agent should be administered for at least a 2-week period, although use of highly active agents for 7 to 10 days may be sufficient.

44. Acute Pyelonephritis • Oral antibiotics that have shown efficacy in this setting include trimethoprim–sulfamethoxazoleor fluoroquinolones. If a Gram stain reveals gram-positive cocci, Streptococcus faecalisshould be considered and treatment directed against this pathogen (ampicillin).

45. Acute Pyelonephritis • In the seriously ill patient, the traditional initial therapy has included an IV fluoroquinolone, an aminoglycoside with or without ampicillin, or an extended-spectrum cephalosporin with or without an aminoglycoside. • If the patient has been hospitalized in the last 6 months, has a urinary catheter, or is in a nursing home, the possibility of P. aeruginosaand enterococci infection, as well as multiply-resistant organisms, should be considered.

46. Acute Pyelonephritis • In this setting, ceftazidime, ticarcillin-clavulanic acid, piperacillin, aztreonam, meropenem, or imipenem, in combination with an aminoglycoside, is recommended. 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.

47. Urinary Tract Infections in Males • The conventional view is that therapy in males requires prolonged treatment (Fig. 50-2).

49. Therapeutic Options: • 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–sulfamethoxazoleor a fluoroquinoloneis a preferred agent. Initial therapy is for 10 to 14 days. For recurrent infections in males, cure rates are much higher with a 6-week regimen of trimethoprim–sulfamethoxazole.

50. Recurrent Infections • Recurrent episodes of UTI (reinfections and relapses) account for a significant portion of all UTIs. • These patients are most commonly women and can be divided into two groups: those with fewer than two or three episodes per year and those who develop more frequent infections.