Critical Care Medicine

Urogenital Infections in the ICU (UTI, Cystitis, Pyelonephritis, Catheter-Associated UTI, Asymptomatic bacteriuria, ASB, Urosepsis)

Urogenital Infections in the ICU

Related Conditions

UTI, Cystitis, Pyelonephritis, Catheter-Associated UTI, Asymptomatic bacteriuria, ASB, Urosepsis

1. Description of the problem

What every clinician needs to know

Urogenital infections in patients in the intensive care unit (ICU) include urinary tract infection (UTI) and, in the male, prostatitis. The clinical spectrum of UTI includes asymptomatic bacteriuria and funguria, cystitis, pyelonephritis, and urosepsis with or without obstructive uropathy.

Urogenital infections in ICU patients may be community acquired or healthcare associated, the main difference being that hospital-acquired, especially ICU-acquired, UTIs are more likely to be caused by multiple antimicrobial-resistant uropathogens. The vast majority of UTIs in the ICU occur in patients with urinary catheters. Chronically catheterized patients admitted to the ICU with UTI from the community are also likely to have multiple-drug-resistant uropathogens. Candiduria is a common cause of urinary infection in ICU patients.

UTIs in ICU patients are generally considered to be complicated. A complicated UTI is defined as a UTI that occurs in a patient who has a condition that increases the risk for serious complications or treatment failure and may require urologic intervention. A listing of conditions that potentially complicate UTI in the ICU is shown in Table I.

Table I.

Some UTIs in ICU patients are uncomplicated. Thus, a young healthy woman admitted to the ICU with severe pyelonephritis may be considered to have uncomplicated UTI if she has no obvious underlying metabolic, anatomic or functional abnormality of the urinary tract.

Patients with complicated cystitis are not likely to require ICU care, but patients in the ICU for other reasons, especially those who are catheterized, may develop cystitis and require antimicrobial treatment. However, most patients admitted to the ICU for UTI and most patients who develop symptomatic UTI while they are in the ICU have pyelonephritis with or without bacteremia and/or urosepsis.

UTI complicated by sepsis is defined as the presence of UTI and at least two of the following: temperature greater than 38°C, heart rate greater than 90 beats per minute; respiratory rate greater than 20 per minute or PaCO2 less than 32 mm Hg; white blood count greater than 12,000 per mm3, less than 4000 per mm3, or greater than 10% band forms.

A recent guideline on the diagnosis, prevention, and treatment of catheter-associated UTI in adults has proposed standardization of the confusing terminology used in the UTI literature. The following definitions were proposed:

  • Significant bacteriuria is the quantitative level of bacteriuria consistent with true bladder bacteriuria, rather than contamination, based on growth from a urine specimen collected in a manner to minimize contamination and transported to the laboratory in a timely fashion to limit bacterial growth.

  • UTI refers to significant bacteriuria in a patient with symptoms or signs attributable to the urinary tract and no alternate source.

  • Asymptomatic bacteriuria (ASB) refers to significant bacteriuria in a patient without symptoms or signs attributable to the urinary tract.

  • Bacteriuria is a non-specific term that refers to UTI and ASB combined.

The vast majority of UTI in hospitalized patients are catheter associated, and bacteriuria in catheterized patients is the most common healthcare-associated infection, accounting for up to 40% of hospital-acquired infections and most of the 900,000 patients with nosocomial bacteriuria in US hospitals each year. UTI is occasionally diagnosed in the non-catheterized ICU patient.

Most catheter-associated episodes of bacteriuria occur in asymptomatic patients and do not require treatment. However, it is often difficult for ICU clinicians to determine whether signs or symptoms, usually a temperature spike, are due to bacteriuria in the catheterized patient with pyuria, and thus whether to treat for UTI.

Factors that complicate the assessment of whether a bacteriuric ICU patient has a symptomatic UTI include alteration in mental status, difficulty in communicating because of the presence of an endotracheal tube, or the patient's inability to sense the usual symptoms of cystitis (dysuria, frequency, urgency) because of the presence of a urinary catheter or neurogenic bladder. In practice, if no other cause for the fever can be identified, it is reasonable to assume it is related to the patient's bacteriuria and to treat accordingly.

In this regard, in the ICU clinicians must generally lower the threshold for what is considered to be appropriate use of antimicrobials and, thus, often use antimicrobials in a patient who has bacteriuria that is not clearly associated with signs or symptoms given that:

  • Most ICU patients are, by definition, severely ill and in a fragile state.

  • Most ICU patients cannot provide reliable information on whether UTI symptoms are present.

  • Pyuria and bacteriuria are nonspecific indicators of UTI in the catheterized patient.

However, ICU clinicians should do their best to try to avoid overuse of antimicrobials in catheterized patients to reduce selection pressure for antimicrobial resistance. In this regard, ICU patients who are afebrile and have no clinical findings suggestive of infection should not be evaluated for pyuria or bacteriuria with urinalysis or urine culture and, if such tests are performed and demonstrate bacteriuria with or without pyuria, should not be treated with antimicrobials. In addition, treatment durations should be limited to that recommended for UTI.

The issues faced by clinicians in assessing the importance of catheter-associated bacteriuria are also true for catheter-associated funguria, the vast majority of which is caused by Candidaspecies. In the ICU, fungal isolates account for one third of all urinary isolates.

ICU patients with UTI warrant a low threshold for performing imaging studies or urologic consultation to make sure there are no conditions present that would warrant urologic intervention, such as to relieve obstruction.

Clinical features

Symptoms and signs pointing to the urinary tract, such as dysuria, frequency, urgency, suprapubic pain, flank pain or costovertebral angle tenderness are strongly suggestive of UTI, but such symptoms and signs are present in only a small proportion of ICU patients with UTI, such as those who are non-catheterized or recently catheterized.

Moreover, alteration in mental status, difficulty in communicating because of an endotracheal tube, or inability to sense the usual symptoms of cystitis because of the presence of a urinary catheter or neurogenic bladder complicates the assessment of whether a bacteriuric patient has a symptomatic UTI.

In the catheterized patient, new costovertebral pain or tenderness, rigors, or onset of delirium generally warrant a urinalysis and urine culture and initiation of antimicrobial treatment. Some patients manifest atypical symptoms, including fatigue, irritability, nausea, headache, malaise, lethargy, and/or abdominal or back pain. Patients with spinal cord injury may manifest increased spasticity, autonomic dysreflexia, or a sense of unease in the setting of catheter-associated UTI. Some patients present with a sepsis syndrome with no focal symptoms.

A common problem confronting ICU clinicians is trying to determine whether a temperature spike is due to UTI in the catheterized patient who has pyuria and bacteriuria. A recent prospective study of newly catheterized patients who developed bacteriuria highlights the problems encountered in catheterized patients:

Only 8% of those patients who could respond to symptom assessment reported symptoms referable to the urinary tract, including pain, urgent urination, or dysuria, although bacteriuria and pyuria were present in most patients for many days.

There were no significant differences between catheterized patients with and those without bacteriuria with respect to signs or symptoms commonly associated with UTI (fever, dysuria, urgency, or flank pain) or with respect to leukocytosis.

In another large retrospective cohort study of critically ill trauma patients:

Neither fever nor leukocytosis was associated with catheter-associated bacteriuri. The authors concluded that there was an unnecessary emphasis on UTI as a source of fever and leukocytosis in patients hospitalized in the ICU.

Thus, for an ICU patient with an indwelling catheter, symptoms referable to the urinary tract often cannot be elicited from patients. Moreover, even if patients can respond to symptom assessment, pyuria, fever, or peripheral leukocytosis have little predictive value for the diagnosis of symptomatic UTI. In addition, foul smelling and/or cloudy urine, often interpreted as warranting antimicrobial treatment in catheterized patients with bacteriuria, have not been shown to have clinical significance in such patients and should not be used alone to determine when treatment is indicated.

Nevertheless, the diagnosis of UTI in ICU patients, and a subsequent decision to treat empirically with antimicrobials, is often made in the setting of fever, pyuria, and significant bacteriuria with no other discernable cause. This is appropriate in this population that, by definition, is generally much sicker than other hospitalized patients.

Some patients are either admitted to the ICU with more severe UTI or develop such infections while in the ICU. These complications are usually detected by imaging studies performed because of symptoms atypical for UTI, severe UTI symptoms and/or delayed response to treatment. Patients with diabetes mellitus are overrepresented in patients who develop these complications. Most patients have pyuria and bacteriuria (or candiduria), but these may not be present if the infection does not communicate with the collecting system.

Acute prostatitis

Acute prostatitis is associated with UTI symptoms and obstructive voiding symptoms, unless the patient is catheterized, fever and chills, and a tender and swollen prostate. Examination of the prostate is complicated by bacteriuria in some patients so caution must be exercised. It is likely that many men with catheter-associated UTI in the ICU have concomitant prostatitis, but the diagnosis is difficult to make.

Treatment directed at the UTI generally should suffice for treatment of the prostatitis, although if one suspects prostatitis, longer treatment regimens are recommended. Rarely, a prostatic abscess is detected on an imaging study performed because of typical prostatitis symptoms or because of a delayed response to treatmenf for UTI.

Renal abscess

Renal cortical and corticomedullary abscesses and perirenal abscesses are usually associated with fever, chills, back or abdominal pain and costovertebral angle pain and tenderness (Figure 1). Urinary symptoms and bacteriuria and pyuria are generally present unless the abscess does not communicate with the collecting system.

Figure 1.

Perirenal abscess

A renal cortical abscess is often caused by hematogenous spread of Staphylococcus aureus. A corticomedullary abscess usually results from ascending UTI in association with an underlying urinary tract abnormality, such as obstructive uropathy or vesicoureteral reflux, and is usually caused by Escherichia coliand other organisms found in complicated UTI. Perirenal abscess results from extension of a corticomedullary abscess through the renal capsule, by hematogenous spread, or spread from a contiguous infection, and aspiration may be necessary to ascertain the causative pathogen.

Small abscesses may be treated with antimicrobials alone, especially cortical abscesses, but drainage of pus is often required for corticomedullary and perirenal abscesses, and nephrectomy may be indicated in patients with extensive disease.

Papillary necrosis

Papillary necrosis (Figure 2) is a complication of pyelonephritis that is occasionally found in patients with diabetes, sickle cell disease, or urinary tract obstruction and results from ischemia in the renal papilllae. Patients usually present with pyelonephritis symptoms and may also have renal colic, renal insufficiency or failure, or urinary obstruction with severe urosepsis. The usual uropathogens are those commonly found in complicated UTI. Antimicrobial treatment is usually effective, but papillae obstructing the ureter may require removal or relief of obstruction.

Figure 2.

Acute pyelonephritis complicated by acute papillary necrosis

Emphysematous pyelonephritis

Emphysematous pyelonephritis (Figure 3) is a fulminant, necrotizing, life-threatening variant of acute pyelonephritis caused by gas-forming organisms, including E. coli, Klebsiellapneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis. Candida species can also cause emphysematous pyelonephritis. Up to 90% of cases occur in diabetic patients. Symptoms are similar to those with pyelonephritis, but dehydration and ketoacidosis are common. Patients usually have pyuria and bacteriuria.

Figure 3.

Emphysematous pyelonephritis

Gas is usually detected by a plain abdominal radiograph or ultrasound, but computed tomography (CT) can better localize the gas than ultrasound. It is important to accurately localize the gas as gas can occur in less serious infections, such as an infected obstructed collecting system or in a renal abscess.

In addition to broad-spectrum antimicrobials, percutaneous catheter drainage with relief of obstruction is indicated for those less severely ill and nephrectomy for those more severely ill or those with a delayed response to percutaneous catheter drainage. The mortality rate is high in those treated without surgical intervention.

Emphysematous pyelitis

Emphysematous pyelitis (Figure 4) is an infection caused by gas-forming organisms, including E coli, K pneumoniae, Enterobacter aerogenes, and P mirabiliswith gas localized to the renal collecting system. This condition is more benign that emphysematous pyelonephritis and antibiotic therapy alone appears to be sufficient. CT is the most reliable imaging study for diagnosis.

Figure 4.

Emphysematous pyelitis

Emphysematous cystitis

Emphysematous cystitis (Figure 5, Figure 6) is a severe manifestation of bladder infection produced by gas-forming organisms including E coli, E aerogenes,K pneumoniae, P mirabilis, and C albicans. Patients may complain of irritative symptoms, abdominal discomfort or pneumaturia, but it is often first considered after imaging studies have been done. It is associated with female sex, immunocompromised state, diabetes mellitus, urinary stasis, neurogenic bladder and in transplant recipients.

Figure 5.

Emphysematous cystitis

Figure 6.

Emphysematous cystitis

Patients with emphysematous cystitis are not as ill as those with pyelonephritis. Treatment is with parenteral antibiotics and bladder drainage.

Funguria cannot be distinguished from bacteriuria clinically, and as with catheter-associated bacteriuria, the clinical significance of catheter-associated funguria can be difficult to determine. There are no established colony count thresholds to help distinguish contamination from bladder infection as there are with bacteriuria, although, as with bacteriuria, even low quantitative counts in a specimen taken from a freshly placed catheter are likely to represent bladder infection.

Pyuria is common in catheterized patients, and its presence does not help in the decision as to whether to treat. Absence of pyuria suggests the infection is not invasive. Hematogenous dissemination is relatively much more likely to be the source of candiduria than with bacteriuria.

Ascending infection of the kidney and disseminated candidiasis are rarely associated with candiduria and are usually found in the setting of urinary tract obstruction or urologic manipulation.

Funguria may be associated with fever, fungus balls in the bladder or renal pelvis, renal or perirenal abscess, emphysematous pyelitis or pyelonephritis or papillary necrosis. As with bacterial infection, patients who develop such complications are often diabetic.

Key management points

Patients who have typical symptoms of UTI should be treated with antimicrobials that are tailored based on culture results. Asymptomatic bacteriuria, whether catheter-associated or not, does not warrant treatment in ICU patients since it has not been shown to reduce subsequent morbidity or mortality but it has been shown to select for antimicrobial-resistant uropathogens. However, it is usually not possible in an ICU patient to distinguish symptomatic UTI vs asymptomatic bacteriuria for the reasons expressed above.

Nevertheless, ICU patients with fever are usually started on empiric antibiotics after being pancultured, and bacteriuria, frequently present in the catheterized patient, is usually considered the likely source if no alternate source is found.

It is inappropriate, however, for ICU patients who are afebrile and who have no signs or symptoms of infection to be screened for and treated for ASB.

Likewise, asymptomatic candiduria usually does not require treatment since it often resolves spontaneously, morbidity is low, and treatment is often followed by rapid recurrence and selection for antimicrobial resistance. When possible, the underlying risk factor should be corrected, such as removing or changing the urinary catheter or stent or discontinuing antimicrobial therapy. Treatment of asymptomatic candiduria is recommended, however, for patients at high risk for dissemination, such as those with neutropenia, those about to undergo urologic procedures, or low birthweight infants.

Imaging studies, such as a renal ultrasound or abdominal CT, are indicated as feasible in an ICU patient who has sepsis complicating their UTI or a delayed clinical or microbiologic response to appropriate antimicrobial treatment in order to rule out a condition that requires urologic intervention. Patients with candiduria and systemic signs or symptoms should be evaluated for disseminated infection with imaging and blood cultures.

2. Emergency Management

Emergencies associated with UTI are usually detected by imaging studies in those patients who are very ill upon presentation or who have a delayed response to appropriate antimicrobial treatment.

UTI in the setting of obstructive uropathy is an emergency that warrants early antibiotics and immediate urologic consultation. This condition is suspected in the setting of fever and hydronephrosis as observed on imaging studies. Emergency management entails relief of the obstruction via catheterization or percutaneous nephrostomy.

Emphysematous pyelonephritis is a medical emergency that warrants early antibiotics and relief of obstructive uropathy if present. Patients with gas in the renal parenchyma without extension to the extrarenal space should undergo percutaneous catheter drainage. Patients with extension of gas or abscess to the extrarenal space should undergo percutaneous catheter drainage and possibly immediate nephrectomy, especially if thrombocytopenia, acute renal failure, impaired consciousness, or shock are present.

Immediate urologic consultation is indicated to determine the most appropriate surgical approach. Other conditions that warrant immediate urologic consultation for consideration of drainage or, in severe cases, nephrectomy, include large intrarenal or perirenal abscesses.

3. Diagnosis

UTI in ICU patients is usually considered when the patient has a fever. The diagnostic tests for UTI in such patients are the urinalysis, urine culture and blood culture.

The urinalysis is helpful in that absence of pyuria suggests a condition other than UTI is causing the patient's fever. On the other hand, the presence, absence or degree of pyuria in the catheterized patient cannot be used to distinguish catheter-associated ASB from UTI and, thus, whether treatment is indicated. The presence of pyuria is more useful in the non-catheterized patient as a clue that UTI may be present. The nitrite test has limited sensitivity and specificity and should not be relied on in clinical decision making.

Of note, pyuria (and bacteriuria) may be absent if the infection does not communicate with the collecting system, such as in the patient with obstructive uropathy, or if there is little or no urine output from an infected but poorly functioning kidney. Unexplained sepsis in a patient at risk for obstructive uropathy should prompt early imaging despite a normal urinalysis or culture.

It is very important to obtain a urine culture prior to initiation of empiric antimicrobials so that the presence of bacteriuria can be confirmed and so that treatment can be appropriately tailored (or discontinued) based on such results. Urine specimens for culture in catheterized patients should be obtained by sampling through the catheter port using aseptic technique or by puncturing the catheter tubing with a needle and syringe.

Blood cultures also should be obtained prior to antimicrobial treatment. Although positive blood cultures per se do not warrant a different approach or duration to antimicrobial therapy, bacteremia with the same organism as in the urine is strong evidence that the urinary tract is in fact the source of the patient's symptoms and may warrant earlier imaging studies.

Interpretation of urine culture results is based on the definitions of significant bacteriuria. Significant bacteriuria is defined as the quantitative level of bacteriuria consistent with true bladder bacteriuria, rather than contamination, based on growth from a urine culture, and its definition depends on the conditions of specimen collection.

In the symptomatic catheterized patient, almost any level of bacteriuria is likely to represent significant bacteriuria, but a quantitative count of greater than or equal to 103 cfu per mL is a reasonable compromise between sensitivity in detecting significant bacteriuria and the feasibility for the microbiology laboratory in quantifying uropathogens. It is important to appreciate that laboratories that report as positive only those urine specimens with greater than or equal to 104 or greater than or equal to 105 cfu per mL will underreport many UTIs.

In patients who have had an indwelling catheter for more than a week, it is recommended that a new catheter be placed prior to obtaining the urine culture if this is feasible, to increase the specificity of the culture results. Culture specimens should never be obtained from the drainage bag.

Although a clean-catch urine specimen in the symptomatic non-catheterized patient is more likely to be contaminated by periurethral flora (especially in women) compared with a catheter specimen, it is also reasonable to consider a quantitative count of greater than or equal to 103 cfu per mL as representing significant bacteriuria based on studies of paired voided and catheter urine specimen cultures in women with uncomplicated cystitis.

As with catheterized patients, laboratories that report as positive only those urine specimens with greater than or equal to 104 or greater than or equal to 105 cfu per mL will underreport many UTIs.

Although ASB should not routinely be screened for in catheterized or non-catheterized patients except in research studies and in selected clinical situations such as pregnancy and urologic surgery, a quantitative count of greater than or equal to 105 cfu per mL should be used as the definition to provide increased specificity.

Imaging studies should be considered in severely ill patients, in patients who have signs or symptoms suggestive of obstruction, stone, flank mass, or urosepsis, and in patients who have a delayed response to appropriate antimicrobial therapy.

The most effective imaging modality in adults is the contrast-enhanced CT as it has superior resolution and sensitivity in detecting renal abnormalities and perirenal abscess. Renal ultrasound is useful for detection of stones and abscesses and may be more readily accessible than CT, but it is less sensitive than CT for detection of many renal abnormalities. The role of magnetic resonance imaging for complicated UTI remains to be determined.

4. Specific Treatment

Antimicrobial treatment is indicated in any ICU patient with symptoms or signs of UTI. Patients with complicating conditions (Table I) who develop UTI in the community or while in the ICU should be empirically treated with broad-spectrum antimicrobials given the likelihood that the infecting uropathogen will manifest multiple drug resistances.

However, otherwise healthy women with acute uncomplicated pyelonephritis and no prior hospitalization or antibiotics for the past 6 months who are admitted to the ICU may be expected to be infected with uropathogens having a drug susceptibility profile reflective of that in community uropathogens and may be empirically treated with a less broad-spectrum antimicrobial.

Of concern, there are increasing reports worldwide of community-acquired uncomplicated UTIs that are caused by extended spectrum beta lactamase (ESBL)-producing uropathogens that are resistant to most of the antimicrobials usually used for UTI, including fluoroquinolones. Carbapenems are the drugs of choice for such uropathogens, although for uncomplicated cystitis in women, nitrofurantoin and fosfomycin trometamol are potentially effective.

Fortunately, ESBL-producing uropathogens remain uncommon causes of community UTI and generally do not warrant empiric carbapenem coverage when such patients are admitted to the hospital unless patients are known to have had previous infection with such strains. However, ESBL strains and those strains even more resistant, including carbapenem-resistant Enterobacteriaceae (CRE), are occasionally found colonizing or infecting the urinary tract of ICU patients.

Enterococcus is occasionally found in the catheterized patient with UTI, and some of the recommended empiric regimens, such as cefepime, are not effective again this organism. Vancomycin-resistant enterococci (VRE) is an uncommon cause of UTI in an ICU patient, and it does not warrant empiric coverage unless the patient is known to be colonized or previously infected with VRE.

Likewise, methicillin-resistant S aureus (MRSA) is an uncommon cause of UTI in the community or hospital, but it also is occasionally found to cause complicated UTI. A urine Gram stain may help the clinician determine whether a patient is infected with Enterococcus or S aureus and, thus, whether appropriate empiric coverage is warranted.

Practically speaking, however, the urine Gram stain is often of little use for evaluating ICU patients for UTI since vancomycin is almost always included in the empiric treatment regimens of an ICU patient presumed to be infected since the source of infection is usually not known with certainty.

An imaging study, such as a renal ultrasound or CT scan, should be performed in any ICU patient who is severely ill or who is known to have a potentially complicating condition such as those listed in Table I. Obstruction to urinary flow in the setting of infection is a potential urologic emergency and warrants early evaluation by the urologist and relief of the obstruction.

Likewise, renal or perirenal abscesses may need to be drained. Emphysematous pyelonephritis is a life-threatening condition and may need drainage or nephrectomy. Emphysematous pyelitis and emphysematous cystitis are more benign conditions and usually respond to appropriate antimicrobial treatment.

Antimicrobial treatment

The most effective antimicrobial and duration of treatment for UTI in ICU patients is not known, but most patients are cured with an antimicrobial regimen tailored to the susceptibility results. It is important to obtain a urinalysis, urine culture and blood culture prior to treatment, and to have a low threshold for imaging the urinary tract if response is delayed.

The choice for empiric antimicrobial regimen in the ICU patient must be informed by the patient's recent culture results when available. For example, if the patient is known to have recently had an ESBL-producing E coli in the urinary tract (or perhaps elsewhere), it is reasonable to use a carbapenem for empiric treatment. In addition, an ICU-specific antibiogram should be used, when available, to select an empiric regimen. Recommended empiric antimicrobial regimens for UTI in ICU patients are shown in Table II.

Table II.

The optimal duration of antibiotic treatment for catheter-associated UTI is not known. Reviews of complicated UTI have recommended treatment durations from 7 to 21 days. In the few treatment studies of catheter-associated UTI published in the literature, short-course regimens (3 days or less) were comparable to longer regimens in catheterized patients with mild infection.

A recent large study demonstrated almost identical clinical and microbiologic success rates in patients with acute pyelonephritis or complicated UTI (only 11% were catheterized) who were treated with a 5-day course of levofloxacin compared with a 10-day course of ciprofloxacin.

These data suggest that a 5-day regimen with levofloxacin (and probably with ciprofloxacin or other recommended antimicrobials) is likely to be sufficient in those patients who are less severely ill, such as a patient with complicated cystitis, are infected with uropathogens susceptible to the antibiotic used, and have a rapid response to treatment. A 7- to 10-day regimen is reasonable for most patients with complicated UTI, including catheter-associated UTI, in ICU patients whose clinical findings resolve within a few days of initiation of appropriate antimicrobial therapy.

A 10- to 14-day regimen is recommended in those patients who have a delayed response to therapy but no need by imaging studies for urologic intervention, and longer durations may be appropriate in those requiring surgical intervention and prolonged drainage.

It is not appropriate to extend antimicrobial treatment in the patient with UTI who received an appropriate antimicrobial (based on susceptibility test results) and who has no evidence of a urologic abnormality on imaging studies just because fever is persistent. One must continue to look for other causes of fever, but the UTI should have been adequately treated with treatment durations as recommended above.

Patients with UTI should respond relatively quickly to treatment if the uropathogen is susceptible to the antimicrobial being used and if there is no complicating factor (Table I) present. Thus, such patients should begin to defervesce and have improvement in other vital signs within 24 to 48 hours.

An imaging study is warranted if the patient, while on an appropriate antimicrobial regimen, does not have noticeable improvement in his/her clinical condition within 48 hours, if there is worsening in their condition at any time, or if blood cultures remain positive. If susceptibility test results are not available in the patient who is not improving but who has no demonstrable urologic abnormality on imaging studies, one should consider broadening the empiric antimicrobial regimen to cover a possible highly resistant uropathogen, such as an ESBL strain.

If there are no findings on the imaging study that explain the lack of a satisfactory response, further investigation for other possible sources of the patient's signs and symptoms should be initiated. As noted previously, pyuria and bacteriuria are nonspecific indicators of symptomatic UTI. In addition, a discussion with the radiologist may be helpful in deciding whether other imaging studies are warranted.

If imaging studies demonstrate urinary tract pathology that might explain the patient's poor response to treatment, urologic consultation is indicated.

5. Disease monitoring, follow-up and disposition

Patients with UTI should respond relatively quickly to treatment if the uropathogen is susceptible to the antimicrobial being used and if there is no complicating factor (Table I) present. Thus, such patients should begin to defervesce and have improvement in other vital signs within 24 to 48 hours.

In patients who have a satisfactory response to antimicrobial treatment, there is no reason to repeat the urinalysis or urine culture. Likewise, there is no reason to repeat the urinalysis or culture after treatment has been discontinued in patients who are clinically cured since ASB, if present, does not warrant treatment. While ASB in itself probably does not pose a risk to the patient, its presence is often the rationale for inappropriate re-institution of antimicrobial therapy in a hospitalized patient.

An imaging study that showed an abnormality in the urinary tract that did not require urologic intervention generally does not need to be repeated in patients who have a good clinical response to treatment. However, a repeat study may be warranted in patients who did require urologic intervention. This is usually determined by the urology consultant.

Pathophysiology

In the noncatheterized healthy patient, the usual origin of uropathogens is the fecal flora that colonizes the periurethral area and ascends via the urethra to the bladder and in some cases to the kidneys.

In healthy women, UTI risk is increased by factors that favor colonization of the periurethral area with uropathogens, such as spermicide use, antimicrobial use, and estrogen deficiency, and by sexual intercourse, which facilitates bacteria into the bladder. There is growing evidence that genetic determinants influence the risk of UTI.

Strains of E coli that cause symptomatic cystitis or pyelonephritis in the normal host are more likely to have certain virulence determinants, such as P fimbriae, compared with colonic strains and those causing ASB.

Almost all UTIs that occur in ICU patients are related to the presence of indwelling urinary catheters. Urinary catheters predispose to UTI by multiple mechanisms listed in Table III. Essentially, indwelling catheters bypass normal host defense mechanisms and allow uropathogenic bacteria from the patient's endogenous flora or from the hands of healthcare workers or the environment to ascend to the bladder.

Table III.

The catheters also enhance microbial colonization with biofilm formation. Biofilms protect bacteria from antimicrobials and the host immune response and facilitate transfer of antibiotic resistance genes.

Uropathogen virulence determinants that appear to be important in noncatheterized patients appear to be of much less importance in the pathogenesis of nosocomial UTIs.

Epidemiology

The vast majority of UTI in hospitalized patients are catheter-associated, and bacteriuria in catheterized patients is the most common healthcare-associated infection, accounting for up to 40% of hospital-acquired infections and most of the 900,000 patients with nosocomial bacteriuria in US hospitals each year.

In a large study of 205 medical-surgical ICUs, UTIs represented 23% of all reported infections, and 97% occurred in catheterized patients.

From 15% to 25% of patients in a general hospital have a urethral catheter inserted at some time during their stay, usually for only a few days, but often for much longer. However, it has been estimated that over 90% of patients sick enough to be admitted to an ICU for 2 or more days have an indwelling urinary catheter.

The incidence of bacteriuria associated with indwelling catheterization is 3% to 8% per day. In a recent study of ICU patients, bacteriuria occurred in 6.5% of patients with an incidence of 9.6 episodes per 1000 ICU days. Bacteriuria was more common in medical compared with surgical patients.

The duration of catheterization is the most important risk factor for the development of catheter-associated bacteriuria. Other risk factors associated with catheter-associated bacteriuria are listed in Table IV.

Table IV.

The risk of bacteremia from an episode of catheter-associated bacteriuria in hospitalized patients ranges from less than 1% to 4%, although the risk from catheter-associated ASB is probably much less. Studies suggest that approximately 15% of cases of nosocomial bacteremia are attributable to the urinary tract, and bacteriuria is the most common source of gram-negative bacteremia among hospitalized patients. However, in the ICU, nosocomial bacteriuria is the source for bacteremia in approximately 3% of cases (intravascular catheters are by far the most common source).

The effect of catheter-associated bacteriuria on mortality remains controversial, but the association noted in some studies is likely explained by confounding factors given that catheterized patients tend to be sicker and more functionally impaired.

Studies of catheter-associated ASB demonstrate no benefit of antimicrobial treatment and, instead, antimicrobial treatment selects for more antimicrobial-resistant uropathogens. Thus, guidelines recommend that asymptomatic patients should not be screened for ASB and that ASB, if detected by culture, should not be treated. Exceptions are pregnant women and patients undergoing urologic surgery.

Catheter-associated ASB has not been shown to have any significant adverse consequences per se, but it is not a benign condition, and efforts to prevent it are warranted because it probably predisposes to symptomatic infection (although the vast majority of episodes of ASB do not progress to symptomatic infection). Also, it is the source of many episodes of nosocomial bacteremia and comprises a large reservoir of antimicrobial-resistant uropathogens, particularly on critical care units, that can be the source of cross-infection.

Catheter-associated ASB is a common infection and is often treated inappropriately by well-meaning clinicians who have a low threshold for using antimicrobials, thus increasing the pressure for selection of antimicrobial resistant organisms in fragile patients. In the ICU, however, it is probably reasonable to have a lower threshold for treating patients with catheter-associated ASB since assessment of symptoms is often difficult and the risk of delaying treatment may be consequential.

Guidelines on the diagnosis, treatment and prevention of catheter-associated bacteriuria have been recently published by the Infectious Diseases Society of America. Strategies recommended and those not recommended to prevent catheter-associated bacteriuria are listed in Table V.

Table V.

Microbiology

Most catheterized ICU patients with bacteriuria grow a single uropathogen species, but the longer the catheter remains indwelling the more likely that polymicrobic bacteriuria will occur. Since bacteria growing in a catheter urine specimen represent bacteria present in the bladder as well as those shed from a catheter biofilm, it is optimal in those patients whose catheter has been in place for more than a week to collect the culture specimen from a freshly placed catheter when possible. This is often not feasible in an ICU patient.

In a freshly placed urinary catheter, polymicrobic flora cannot be assumed to represent contamination (as is the case with a voided specimen), and the empiric antimicrobial regimen may need to be tailored to the susceptibility pattern of more than one uropathogen.

E coli is the most common uropathogen in catheter-associated UTI, but it is relatively less common than in uncomplicated UTI, causing approximately one third of infections. The spectrum of uropathogens causing UTI in the ICU are shown in Table VI.

Table VI.

Of note, UTI organisms isolated from ICU patients, especially those in the ICU for several days, are much more likely to be multiple-drug-resistant compared with UTI organisms isolated from patients in the community. In the ICU, especially in patients with many co-morbidities, it is not uncommon to see highly resistant ESBL or CRE strains in the urinary tract.

Prognosis

The prognosis of complicated UTI in ICU patients is generally very good but outcomes may be compromised by multiple co-morbidities, presentation with or development of severe urosepsis, delayed optimal empiric antimicrobial treatment of UTI caused by a highly resistant uropathogen, or delayed diagnosis or optimal treatment of a serious renal infection, particularly emphysematous pyelonephritis or a large intrarenal or perirenal abscess.

Special considerations for nursing and allied health professionals.

NA

What's the evidence?

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(A guideline from the IDSA that reviews the clinical features, epidemiology, pathogenesis, diagnosis, prevention, and treatment of asymptomatic bacteriuria.)

Hooton, TM, Bradley, SF, Cardenas, DD. "Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America". Clin Infect Dis. vol. 50. 2010. pp. 625-63.

(An international guideline from the Infectious Disease Society of America that reviews the clinical features, epidemiology, pathogenesis, diagnosis, prevention, and treatment of catheter-associated UTI in adults.)

Hooton, TM, Mandell, GL, Bennett, JE, Dolin, R. "Nosocomial urinary tract infections". Principles and Practice of Infectious Disease. Churchill Livingstone Elsevier. 2009. pp. 3725-37.

(A review of the clinical features, epidemiology, pathogenesis, diagnosis, prevention, and treatment of catheter-associated UTI in adults)

Sobel, J, Kaye, D, Mandell, GL, Bennett, JE, Dolin, R. "Urinary tract infection". Principles and Practice of Infectious Disease. Churchill Livingstone Elsevier. 2009. pp. 957-85.

(A review of the clinical features, epidemiology, pathogenesis, diagnosis, prevention, and treatment of UTI.)

Bagshaw, SM, Laupland, KB. "Epidemiology of intensive care unit-acquired urinary tract infections". Curr Opin Infect Dis. vol. 19. 2006. pp. 67-71.

(A review of the occurrence, microbiology, risk factors for acquisition, and outcomes associated with intensive care unit-acquired UTI.)

Golob, JF, Claridge, JA, Sando, MJ. "Fever and leukocytosis in critically ill trauma patients: it's not the urine". Surg Infect (Larchmt). vol. 9. 2008. pp. 49-56.

(A review of trauma patients that looks at the problem of UTI diagnosis in patients with fever and leukocytosis.)

Tambyah, PA, Maki, DG. "Catheter-associated urinary tract infection is rarely symptomatic: a prospective study of 1,497 catheterized patients". Arch Intern Med. vol. 160. 2000. pp. 678-82.

(A large prospective study that addresses the epidemiology and clinical features associated with catheter-associated bacteriuria.)

Tambyah, PA. "Catheter-associated urinary tract infections: diagnosis and prophylaxis". Int J Antimicrob Agents. vol. 24 Suppl 1. 2004. pp. S44-S48.

(Diagnosis of catheter-associated UTI)

Tambyah, PA, Halvorson, KT, Maki, DG. "A prospective study of pathogenesis of catheter-associated urinary tract infections.". Mayo Clin Proc. vol. 74. 1999. pp. 131-36.

(Pathogenesis of catheter-associated UTI)

Tambyah, PA, Maki, DG. "The relationship between pyuria and infection in patients with indwelling urinary catheters: a prospective study of 761 patients". Arch Intern Med. vol. 160. 2000. pp. 673-77.

(Clinical manifestations and diagnosis)

Warren, JW. "Catheter-associated urinary tract infections". Infect Dis Clin North Am. vol. 11. 1997. pp. 609-22.

(A review of the clinical manifestations, epidemiology, diagnosis, and management of catheter-associated UTI)

Richards, MJ, Edwards, JR, Culver, DH, Gaynes, RP. "Nosocomial infections in combined medical-surgical intensive care units in the United States". Infect Control Hosp Epidemiol. vol. 21. 2000. pp. 510-5.

(A large study of the epidemiology of UTI in ICU in the United States.)

Richards, MJ, Edwards, JR, Culver, DH, Gaynes, RP. "Nosocomial infections in medical intensive care units in the United States". National Nosocomial Infections Surveillance System. Crit Care Med. vol. 27. 1999. pp. 887-92.

(Epidemiology of ICU UTIs)

Kaufman, CA. "Candiduria". Clin Infect Dis.. vol. 41. 2005. pp. S371-6.

(Review of clinical, epidemiology, diagnosis, treatment of candiduria)

Pappas, PG, Rex, JH, Sobel, JD. "Infectious Diseases Society of America. Guidelines for treatment of candidiasis". Clin Infect Dis. vol. 38. 2004. pp. 161-89.

(IDSA guideline on diagnosis, epidemiology, clinical, treatment of candidal infections)

Finer, G, Landau, D. "Pathogenesis of urinary tract infections with normal female anatomy". Lancet Infect Dis. vol. 4. 2004. pp. 631-5.

(Pathogenesis of UTI in normal female)

Kunin, CM, Douthitt, S, Dancing, J, Anderson, J, Moeschberger, M. "The association between the use of urinary catheters and morbidity and mortality among elderly patients in nursing homes". Am J Epidemiol. vol. 135. 1992. pp. 291-301.

(A study evaluating the association between catheter-associated bacteriuria and mortality)

Clec'h, C. Infect Control Hosp Epidemiol. vol. 28. 2007. pp. 1367-73.

(Evaluation of association between catheter-associated UTI and mortality in ICU patients)

Laupland, KB, Bagshaw, SM, Gregson, DB, Kirkpatrick, AW, Ross, T, Church, DL. "Intensive care unit-acquired urinary tract infections in a regional critical care system". Crit Care. vol. 9. 2005. pp. R60-5.

(Epidemiology of UTI in regional ICU system)

Bergqvist, D, Brönnestam, R, Hedelin, H, Ståhl, A. "The relevance of urinary sampling methods in patients with indwelling Foley catheters". Br J Urol. vol. 52. 1980. pp. 92-5.

(Diagnosis of catheter-associated UTI)

Jacobsen, SM, Stickler, DJ, Mobley, HL, Shirtliff, ME. "Complicated catheter-associated urinary tract infections due to Escherichia coli and Proteus mirabilis". Clin Microbiol Rev. vol. 21. 2008. pp. 26-9.

(Pathogenesis of catheter-associated UTIs)

Clec'h, C, Schwebel, C, Français, A. "Does catheter-associated urinary tract infection increase mortality in critically ill patients?". Infect Dis Clin North Am. vol. 17. 2003. pp. 261-78.

(Thorough review of virulence determinants in UTI)

Huang, WC, Wann, SR, Lin, SL. "Catheter-associated urinary tract infections in intensive care units can be reduced by prompting physicians to remove unnecessary catheters". Infect Control Hosp Epidemiol. vol. 25. 2004. pp. 974-8.

(Prevention of catheter-associated UTI)

Niël-Weise, BS, van den Broek, PJ. "Urinary catheter policies for short-term bladder drainage in adults". Cochrane Database Syst Rev. 2005. pp. CD004203.

(Review of catheter policies in short-term catheterized patients.)

Johnson, JR, Kuskowski, MA, Wilt, TJ. "Systematic review: antimicrobial urinary catheters to prevent catheter-associated urinary tract infection in hospitalized patients". Ann Intern Med. vol. 144. 2006. pp. 116-26.

(Review of antimicrobial coated catheters)

Stamm, WE, Hooton, TM. "Management of urinary tract infections in adults". N Engl J Med. vol. 329. 1993. pp. 1328-34.

(Review of clinical, diagnosis, epidemiology, treatment of UTI, including catheter-associated)

Raz, R, Schiller, D, Nicolle, LE. "Chronic indwelling catheter replacement before antimicrobial therapy for symptomatic urinary tract infection". J Urol. vol. 164. 2000. pp. 1254-8.

(Treatment of catheter-associated UTI)

Dow, G, Rao, P, Harding, G. "A prospective, randomized trial of 3 or 14 days of ciprofloxacin treatment for acute urinary tract infection in patients with spinal cord injury". Clin Infect Dis. vol. 39. 2004. pp. 658-64.

(Randomized treatment trial of catheter-associated UTI)

Peterson, J. Urology. vol. 71. 2008. pp. 17-22.

(Large randomized treatment trial of complicated UTI)

Lundstrom, T, Sobel, J. "Nosocomial candiduria: a review". Clin Infect Dis. vol. 32. 2001. pp. 1602-7.

(A review of clinical, diagnosis, epidemiology, treatment of nosocomial candiduria)
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