A little bit about urinary tract infections

UTI: UA= pyuria + bacteriuria ± hematuria ± nitrites 

Urine Culture (from clean-catch midstream or straight-cath specimen): obtain culture only if symptoms

Significant bacterial counts: typically ≥ 10^5 CFU/ mL in women, ≥ 10^3 CFU/ mL in men or catheterized Pts. Counts may vary depending on dilution & stage of infxn; interpret in context of symptoms and host

Pyuria & urine culture = sterile pyuria → urethritis, nephritis, renal tuberculosis, foreign body

Blood cultures: obtain in febrile Pts; consider in complicated UTIs

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A few examples: is this a UTI? How would you treat?

Patient #1 -with foley in place

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Urine culture (from Foley) grew abundant (>=100,000 CFU/ml) ENTEROBACTER CLOACAE COMPLEX, IMIPENEM resistant (MIC 8), tetracycline MIC 2. Patient was stable, switched from imipenem (partially treated UTI) to doxycycline. Foley out.

Patient #2 – with ureteral stents in place

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Blood cultures grew Pan-S pseudomonas

Urine culture grew abundant (>=100,000 CFU/ml) NONENTERIC GRAM NEGATIVE RODS of 3 colony types – cefepime narrowed to ciprofloxacin. Stent removal deferred.

 

CAUTI: Because the presence of bacteria in a urine sample may represent contamination by bacteria colonizing the periurethral area in addition to bladder bacteriuria, thresholds for bacterial growth from a urine sample that is likely to represent true bladder bacteriuria in specific contexts have been suggested by various expert groups. The Infectious Diseases Society of America (IDSA) guidelines define catheter-associated bacteriuria as follows:

Symptomatic bacteriuria (urinary tract infection [UTI]) — Culture growth of ≥103 colony forming units (cfu)/mL of uropathogenic bacteria in the presence of symptoms or signs compatible with UTI without other identifiable source in a patient with indwelling urethral, indwelling suprapubic, or intermittent catheterization. Compatible symptoms include fever, suprapubic or costovertebral angle tenderness, and otherwise unexplained systemic symptoms such as altered mental status, hypotension, or evidence of a systemic inflammatory response syndrome.

Asymptomatic bacteriuria — Culture growth of ≥105 colony forming units (cfu)/mL of uropathogenic bacteria in the absence of symptoms compatible with UTI in a patient with indwelling urethral, indwelling suprapubic, or intermittent catheterization.

The diagnosis of a CAUTI is made by the finding of bacteriuria in a catheterized patient who has signs and symptoms that are consistent with UTI or systemic infection and are otherwise unexplained. A UTI diagnosed in a patient who had a catheter removed within the past 48 hours is also considered a catheter-associated UTI.

CAUTI

Because the symptoms and signs of catheter-associated UTI can be nonspecific, a fair amount of clinical judgment and individualization is required. As an example, although urine bacterial counts as low as 102 cfu/mL have been associated with UTI without catheterization, the vast majority of patients with catheter-associated UTI have counts ≥105 cfu/mL; thus it is reasonable to have a higher threshold for attributing nonspecific symptoms to a UTI in the setting of lower bacterial counts, particularly if the isolated organisms are not Enterobacteriaceae.

Certain findings, such as pyuria and the appearance or smell of the urine, should not be used to diagnose a UTI when found in isolation. Pyuria is frequently found in catheterized patients with bacteriuria, whether they have symptoms or not, and odorous or cloudy urine has not been demonstrated to be indicative of either bacteriuria or UTI. On the other hand, the absence of pyuria in a symptomatic catheterized patient suggests a diagnosis other than UTI.

Ideally urine samples for culture should be obtained by removing the indwelling catheter and obtaining a midstream specimen. If ongoing catheterization is needed, the catheter should be replaced prior to collecting a urine sample for culture, to avoid culturing bacteria present in the biofilm of the catheter but not in the bladder

Many systems have a “needleless” site that can be cleansed prior to specimen collection. If a sample is being collected without catheter removal, urine should be obtained from the port in the drainage system. For circumstances in which the above approaches are not possible, the culture should be obtained by separating the catheter from the drainage system. Although this approach is associated with some risk of introducing microbes into the closed system, culture results from urine collected from the drainage bag cannot be used to guide treatment.

In the setting of condom catheters, it can be difficult to distinguish true infection from skin and mucosal contamination. In these cases, a clean catch midstream specimen should be obtained, or urine should be collected from a freshly applied condom catheter after cleaning the glans

Presumptive Diagnosis of Urinary Tract Infection

Using the preferred definition of pyuria, which is at least 10 leukocytes/mm3 of midstream urine by counting chamber, the vast majority of patients with symptomatic or asymptomatic bacteriuria have pyuria. In fact, with symptomatic infection, most have hundreds of leukocytes per cubic millimeter. A less reliable method uses a urine specimen that is centrifuged for 5 minutes at 2000 rpm and then the sediment examined under high power. With this method, 5 to 10 leukocytes/high-power field in the sediment is the upper limit of normal. It should be emphasized that the finding of pyuria is nonspecific, and patients with pyuria may or may not have infection.145

The dipstick leukocyte esterase test is a rapid screening test for detecting pyuria and has largely replaced microscopic methods. Although the sensitivity and specificity are high for detecting more than 10 white blood cells/mm3 of urine (75% to 96% and 94% to 98%, respectively), a positive test by no means indicates UTI, and in patients with a negative leukocyte esterase test and UTI symptoms, a urine microscopic examination for pyuria or a urine culture should be considered.146,147

Microscopic or sometimes gross hematuria is occasionally seen in patients with UTI (i.e., hemorrhagic cystitis). 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. The ability to identify bacteria in the urine depends on whether the specimen has been centrifuged and on whether it has been stained with Gram or methylene blue stain (Table 74-4). Smaller numbers of bacteria can be detected microscopically in a stained than in an unstained specimen, and smaller numbers can be detected in centrifuged than in uncentrifuged urine. The presence of at least one bacterium per oil immersion field in a midstream, clean-catch, Gram-stained, uncentrifuged urine correlates with 105 bacteria/mL of urine or more. Because this titer is regarded to represent significant bacteriuria, Gram staining of an uncentrifuged specimen is an easy, rapid, and relatively reliable way to detect significant numbers of organisms. The absence of bacteria in several fields in a stained sedimented specimen indicates the probability of fewer than 104 bacteria/mL.

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.146False-negative test results are common, especially in the detection of low-count bacteriuria (102 to 103/mL and with certain bacterial species), but false-positive results are unusual. 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.148-150 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

General Considerations

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. Most patients with infection usually have at least 105 bacteria/mL in urine in the bladder, and therefore voided urine usually contains at least 105 bacteria/mL. Patients without infection have sterile bladder urine and, with proper collection, voided urine usually contains less than 104 bacteria/mL. However, it is important to remember that about one third of young women with cystitis have fewer than 105 bacteria/mL of urine (see later, “Urinary Tract Infection with Low Numbers of Organisms”). It is likely that a significant proportion of other patients with symptomatic and asymptomatic infection have fewer than 105bacteria/mL of urine. The Infectious Diseases Society of America consensus culture definition of cystitis for use in antibiotic treatment studies is 103 colony-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%).151 In more recent practice guidelines, 102 CFU/mL or more of a uropathogen was used.152 These concentrations of microorganisms can be identified by standard microbiologic techniques in most clinical laboratories.

Calibrated loops serve as a simple inexpensive way to examine the bacteriologic characteristics of urine specimens quantitatively. Platinum loops that deliver 0.01 and 0.001 mL are used to streak urine onto agar plates. After incubation at 37° C for 24 hours, the number of CFU is counted, and the total number of organisms originally present in the specimen is estimated by multiplying the colony count by 102 or 103, respectively. Other methods, such as the dip inoculum method, in which agar-coated glass slides or paddles are dipped into urine and then incubated, have excellent correlations with calibrated-loop techniques.

Acceptable methods for urine collection include (1) midstream clean catch, (2) catheterization, and (3) suprapubic aspiration. The clean-catch method is preferred for the routine collection of urine for culture. It avoids the risk of infection inherent in catheterization. The patient must be instructed in the proper technique of obtaining the urine; this is especially important for women. The woman should wash her hands, straddle the commode (facing the back of the commode), wash her vulva from front to back four times with four different sterile gauze pads soaked in green soap or another appropriate cleansing agent, and then rinse with two more sponges soaked in sterile distilled water. She should then spread her labia and void, discarding the first portion of urine and collecting the second. The urine should be processed immediately or, if refrigerated at 4° C, it can be cultured within 24 hours.

Some have challenged the need for cleansing or for using a midstream specimen from women when collecting urine for culture. Similar contamination rates were noted when midstream urine was collected after cleansing versus voiding into a container without cleansing.153

In men the prepuce should be retracted, and thereafter the technique is similar. In infants and small children, sterile bags can be used for urine collection, but contamination is common.154

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. When catheterization is performed, scrupulous aseptic technique should be observed.

The suprapubic aspiration method has been established as a safe technique for premature infants, neonates, children, adults, and even pregnant patients,94,154 but is rarely used. With this method, the patient refrains from voiding until the bladder can be percussed above the symphysis pubis, and suprapubic pressure causes the urge to void. After preparation of the skin, the bladder is then punctured above the symphysis pubis with a 22-gauge needle on a syringe; local anesthesia is not required. After the procedure, self-limited hematuria may be observed. 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.

If there are more than 105 bacteria/mL in a clean-catch urine specimen from an asymptomatic woman, there is an 80% probability that this represents true bacteriuria. If two different specimens demonstrate at least 105 of the same bacterium/mL, the probability increases to 95%. Thus, two clean-catch specimens should be obtained in an asymptomatic woman to confirm the diagnosis.127 When the number of bacteria/mL is between 104 and 105 in an asymptomatic woman, a confirmatory second specimen will contain 105 or more bacteria/mL in only 5% of cases. Thus, in asymptomatic women, 95% of the time 104 to 105 bacteria/mL represents contamination, with occasional infection manifested by fewer than 105 bacteria/mL of urine. In asymptomatic men, in whom contamination is less likely, 103 or more organisms/mL in one culture is suggestive of infection, and 105/mL defines bacteriuria.127 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.

These criteria apply only to the Enterobacteriaceae. Gram-positive organisms, fungi, and bacteria with fastidious growth requirements may not reach titers of 105/mL in patients with infection and may be in the 104 to 105/mL range. The organism recovered often helps distinguish contamination from true bacteriuria. Samples with counts of less than 104organisms/mL often contain saprophytic skin organisms, such as diphtheroids, Neisseria, and staphylococci. Pure growth of Enterobacteriaceae is uncommonly found in low-titer specimens but is present in over 90% of urine samples containing more than 105bacteria/mL. 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.

In patients with symptoms of UTI, one titer of 105 or more bacteria/mL of urine carries a 95% probability of true bacteriuria. With titers below 105/mL but in the presence of frequency, urgency, and dysuria, women have a 33% chance of having bacterial infection (see “Urinary Tract Infection with Low Numbers of Organisms” later). The presence of low numbers of Enterobacteriaceae (i.e., 102 to 105/mL) in such women correlates highly with infection. The presence of fewer than 102/mL Enterobacteriaceae is evidence against UTI. To further confuse the situation, a recent study demonstrated that in women with acute uncomplicated cystitis, enterococci and group B streptococci isolated from midstream urine were often not found in catheterized urine obtained at the same time.154a

Samples obtained by catheterization from noninfected patients are less likely to become contaminated. According to the guidelines, 102 CFU/mL or more is consistent with bacteriuria.127 Bladder urine obtained by suprapubic aspiration is either sterile or contains significant growth, even if bacterial numbers are below 105/mL. The practice of forcing fluids before the procedure tends to reduce numbers of organisms. In fact, almost 50% of suprapubic aspirates from infected patients contain fewer than 105 organisms/mL. However, small numbers of bacteria may be found in aspirated urine from presumably noninfected persons. This suggests that bladder urine may be occasionally contaminated from the urethra. For diagnosis with an indwelling catheter see Chapter 304.

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