Understanding UTI Diagnosis and Management

UTI diagnosis and management

Presumptive Diagnosis of Urinary Tract Infection Using the preferred definition of pyuria, which is at least 10 leukocytes/ mm3 of midstream urine , the vast majority of patients with symptomatic or asymptomatic bacteriuria have pyuria. It should be emphasized that the finding of pyuria is nonspecific, and patients with pyuria may or may not have infection.

Microscopic or sometimes gross hematuria is occasionally seen in patients with UTI. However, red blood cells may be indicative of other disorders, such as calculi, tumor, vasculitis, glomerulonephritis, and renal tuberculosis.

White cell casts in the presence of an acute infectious process are strong evidence for pyelonephritis, but the absence of white cell casts does not rule out upper tract infection. White cell casts can also be seen in renal disease in the absence of infection.

Proteinuria is a common although not universal finding in UTI. Most patients with UTI excrete less than 2 g of protein/24 hr; excretion of 3 g/24 hr or more suggests glomerular disease. Microscopic examination of a urine specimen for bacteria can be useful for the presumptive diagnosis of UTI.

A number of rapid indirect methods have been devised to detect bacteriuria for presumptive diagnosis. Most common are tests (e.g., dipstick) that detect the presence of urine nitrite, which is formed when bacteria reduce the nitrate that is normally present.

The sensitivity and specificity of screening tests for UTI, such as dipsticks, depends on the likelihood of infection in the group being studied (e.g., acutely symptomatic patients vs. those who are asymptomatic) and range widely. A negative leukocyte esterase test plus a negative nitrite test result are strongly predictive of the absence of UTI.

Diagnosis of Urinary Tract Infection by Culture Urine in the bladder is normally sterile. Because the urethra and periurethral areas are difficult to sterilize, even the most carefully collected specimens (including those obtained by catheterization) are frequently contaminated. By quantitating bacteria in midstream clean- voided urine, it is possible statistically to separate contamination from UTI

The Infectious Diseases Society of America consensus culture definition of cystitis for use in antibiotic treatment studies is 103colony- forming units (CFU)/mL or more of a uropathogen (sensitivity 90% and specificity 90%) and, for pyelonephritis, 104 CFU/mL or more (sensitivity 90% and specificity 90%). In more recent practice guidelines, 102 CFU/mL or more of a uropathogen was used.

Acceptable methods for urine collection include (1) midstream clean catch (2) catheterization (3) suprapubic aspiration. The clean-catch method is preferred for the routine collection of urine for culture.

In patients unable to cooperate, such as those with an altered sensorium or those who are unable to void for neurologic or urologic reasons, catheterization may be necessary.

Suprapubic aspiration may be indicated in special clinical situations such as with pediatric subjects, when urine is difficult to obtain. Another situation is the rare adult in whom infection is suspected, results obtained from more routine procedures have been confusing or equivocal, and diagnosis is critical.

False-positive cultures are caused by contamination or incubation of urine before processing. False-negative cultures may be caused by the use of antimicrobial agents, soap from the preparation falling into the urine, total obstruction below the infection, infection with a fastidious organism, renal tuberculosis, and diuresis.

The organism recovered often helps distinguish contamination from true bacteriuria. High colony counts containing more than one species of bacteria from the urine of asymptomatic persons often represent contamination but may be more significant in the presence of symptoms. Mixed infection occurs in about 5% of cases.

Urinary Tract Infection with Low Numbers of Organisms

Most women with an acute onset of frequency, urgency, or dysuria, or all of these, have UTI with 105 or more bacteria/mL of urine However, up to half are found to have fewer than 105 bacteria/ mL of urine, and the term urethral syndrome has been used to refer to this entity.

low-count bacteriuria may represent an early phase of urinary infection. The remaining women with the urethral syndrome, after excluding those with bacteria in the bladder and those with genital herpes infection or vaginitis, can be divided into two groups:

(1) those with pyuria from urethritis (e.g., caused by Chlamydia trachomatis, Neisseria gonorrhoeae, or Mycoplasma genitalium infection) (2) those without pyuria in whom all bacterial cultures are negative. The pathogenesis of this latter symptom complex is unknown, but various fastidious microorganisms and noninfectious factors (traumatic, psychological, allergic, and chemical) have been suggested as causes.

Although symptoms and the clinical settings cannot reliably distinguish between the causes of dysuria in women, they can be suggestive.

MANAGEMENT OF URINARY TRACT INFECTION

General Considerations All symptomatic UTI is usually treated. On the other hand, there has been no benefit demonstrated or currently postulated in the treatment of asymptomatic bacteriuria in any group outside of pregnant women, those who are to undergo traumatic genitourinary procedures associated with mucosal bleeding such as transurethral prostatectomy, and those who have recently had renal transplantation.

Nonantimicrobial Therapy and Prevention Hydration: Forcing fluids usually results in a rapid reduction of bacterial counts. Permanent loss of bacteriuria has been reported in a few patients with rapid hydration, but in most patients, the bacterial count returns to the original level when hydration is stopped (e.g., overnight).

Forcing fluids may also have some disadvantages: Increased fluid intake could theoretically result in increased vesicoureteral reflux and possibly The larger urine output results in dilution of antibacterial substances normally present in the urine and in lower urinary concentrations of antimicrobial agents. Water diuresis also decreases urinary acidification, which enhances the antibacterial activity of urine and certain antimicrobial agents.

Urinary pH: The antibacterial activity of urine results mainly from a high urea concentration and osmolality and is pH dependent, being higher at a lower pH. The urinary pH level affects the antibacterial activity of many chemotherapeutic agents used for the treatment of UTIs.

To acidify the urine, it is often necessary to modify the diet by restriction of agents that tend to alkalinize the urine (e.g., milk, fruit juices [except cranberry juice] Another major problem with acidification is that patients with renal insufficiency are unable to excrete an acid load and may become systemically acidotic when urinary acidification is attempted. It may be impossible to acidify urine infected with urea-splitting organisms such as Proteus spp. because of the production of ammonia from urea. Acidification for long-term antimicrobial therapy is frequently difficult to achieve

Analgesics: Urinary analgesics such as phenazopyridine hydrochloride (Pyridium) have little place in the routine management of symptomatic infections. The dysuria of UTI usually responds rapidly to antibacterial therapy and requires no local analgesia. If flank pain or dysuria is severe, systemic analgesics can be used. Analgesics such as phenazopyridine hydrochloride may be useful in the management of certain patients with dysuria but without infection.

Principles of Antimicrobial Therapy the agent should be chosen with the least toxicity and the least likelihood of affecting the normal flora of the vagina and gastrointestinal tract.

Response to Therapy If therapy is appropriate, clinical response should occur within 24 hours with treatment of cystitis. With pyelonephritis, response should occur by 48 to 96 hours. Lack of response by 72 hours should be an indication for imaging studies. There are four patterns of response of bacteriuria to antimicrobial therapy cure, persistence, relapse, and reinfection.

Quantitative bacterial counts in urine should decrease within 48 hours after the initiation of an antimicrobial agent to which the microorganism is sensitive in vitro. If titers do not decrease during this time, the therapy being given will almost invariably be unsuccessful.

Bacteriologic Cure This is defined as negative urine cultures on chemotherapy and during the follow-up period, usually 1 to 2 weeks.

Bacteriologic Persistence (1) persistence of significant bacteriuria after 48 hours of treatment (2) persistence of the infecting organism in low numbers in urine after 48 hours. Significant bacteriuria usually persists only if the urinary levels of the antimicrobial agent are below the concentration of the drug needed to inhibit the microorganism: a resistant organism, not taking the agent, insufficient dosage, poor intestinal absorption, or poor renal excretion, as in renal insufficiency

Persistence of the infecting microorganism in low titers in voided urine may mean persistence in the urinary tract or contamination from the urethra or vagina. Bladder puncture cultures would be necessary to evaluate the significance of low titers of bacteria obtained when the patient is receiving therapy, but this procedure is rarely indicated.

Sites of persistence in the urinary tract are the renal parenchyma, calculi, and prostate. Persistence in bladder cells is a theoretic possibility. The simplest way of determining the significance of persistence of the organism in low titers in the urinary tract is to obtain follow-up urine cultures after therapy has been stopped. Prompt relapse of significant bacteriuria usually follows persistence of the organism in the urinary tract.

Bacteriologic Relapse This usually occurs within 1 to 2 weeks after the cessation of chemotherapy and is often associated with renal infection, structural abnormalities of the urinary tract, or chronic bacterial prostatitis. Relapse indicates that the infecting microorganism has persisted in the urinary tract during therapy.

However, an apparent relapse can be related to reinfection (new infection) with the same microorganism. In spite of eradication from the urinary tract, the original infecting organism may still be present in the periurethral area, vagina, or intestine and then may cause a new infection.

Reinfection After initial sterilization of the urine, reinfection may occur during the administration of chemotherapy (also called superinfection) or at any time thereafter. Reinfection is easy to identify when there is a change in bacterial species. However, there may be reinfection with a different strain of the same species (usually E. coli) or even the same strain.

Considerations in Choice of Therapy With upper tract infection, agents that give antibacterial serum activity, such as fluoroquinolones, trimethoprim- sulfamethoxazole, -lactam antibiotics, and aminoglycosides, should be used. With lower tract infection, additional agents such as nitrofurantoin and oral fosfomycin can be used.

Amoxicillin and ampicillin can no longer be recommended as reliable agents because at least 35% of isolates from communityacquired UTI are now resistant to these agents. In parts of the United States and elsewhere in the world, E. coli resistance to trimethoprim- sulfamethoxazole has exceeded 20%, a level at which trimethoprim-sulfamethoxazole is no longer considered useful for empiric therapy.

Similarly, resistance to the fluoroquinolones is increasing among E. coli, and it is generally considered that when the level of resistance reaches 10%, fluoroquinolones may also become unsatisfactory for empiric therapy as a single agent. Nitrofurantoin and fosfomycin have maintained a high level of activity against E. coli to date.

There is evidence that cell wallactive agents (e.g., penicillins, cephalosporins) are not as effective in eradicating infection in the kidneys, or for that matter anywhere in the urinary tract, as trimethoprimsulfamethoxazole, fluoroquinolones, or aminoglycosides.

Classification and Antimicrobial Therapy for Different Groups

Infection in Children UTI in children younger than 3 months of age is usually caused by E. coli or Enterococcus faecalis. After obtaining urine (and if indicated blood) cultures, recommended empiric therapy is usually a -lactam antibiotic and aminoglycoside such as ampicillin and gentamicin intravenously. Therapy is modified, if necessary, on the basis of culture results. After response, therapy is changed to oral agents such as a -lactam or trimethoprim-sulfamethoxazole, on the basis of susceptibility studies, for a total period of 7 to 14 days.

After 3 months of age, IV therapy is used in seriously ill children as for those younger than 3 months; third-generation cephalosporins are a reasonable choice. Oral therapy with a -lactam such as a secondor third-generation cephalosporin or trimethoprim- sulfamethoxazole (pending cultures for definitive therapy) is recommended for those not seriously ill, 3 days for afebrile cases, and 7 to 14 days for febrile cases.

Prophylaxis with an antimicrobial agent following treatment for febrile UTI in infants and young children is controversial. it should probably be reserved for children with grade III or higher reflux with renal scarring.

Recommendations for imaging in infants and young children: those who are seriously ill, those with possible obstruction (e.g., poor urine flow, abdominal or bladder masses, elevated creatinine, lack of response to antibiotics), non E. coli organisms, and children with recurrent UTIs. In practice, many physicians obtain renal ultrasounds for most children after the first UTI to detect obstructive uropathy.

Acute Uncomplicated Pyelonephritis in Women All patients with pyelonephritis should have a urine culture with antimicrobial . Susceptibilities. Patients who are severely ill with pyelonephritis should be hospitalized and treated intravenously; the others can be treated orally if they are reliable, compliant, hemodynamically stable, and able to take oral therapy.

If a Gram stain of the urine is available, it will help direct therapy toward gram-negative bacilli, by far the most common causes of pyelonephritis, or gram-positive cocci (usually enterococci), but in the majority of cases the selection of antimicrobial therapy is empirical.

Oral Therapy: Although 14 days of therapy has classically been recommended for treatment of pyelonephritis, it has been demonstrated that 7 days of a fluoroquinolone and, with levofloxacin, 5 days of therapy is sufficient. For oral therapy, current international guidelines recommend a 7-day course of ciprofloxacin 500 mg twice daily or 1 g once daily or a 5-day course of levofloxacin 750 mg once daily if local fluoroquinolone resistance is under 10%.

When local resistance is greater than 10% fluoroquinolone, therapy should start with an initial, additional, single dose of a parenteral antibiotic such as a 1-g dose of ceftriaxone or a dose of an aminoglycoside to provide coverage while awaiting results of the urine culture. With use of any agent other than a fluoroquinolone, 14 days of therapy is generally recommended.

When a fluoroquinolone cannot be used, oral trimethoprimsulfamethoxazole (160/800 mg twice daily) is reasonable, but an initial injection of ceftriaxone or an aminoglycoside is recommended pending results of cultures. If an oral -lactam agent must be used, an initial dose of ceftriaxone or aminoglycoside should also be administered. Routine imaging studies are not required for women with acute uncomplicated pyelonephritis. Follow-up urine cultures are not indicated except in pregnancy.