Chapter 56. Urinary Tract Infections

• All patients with severe urosepsis requiring admission to the intensive care unit should have immediate imaging of the urinary tract preferably by computed tomography with contrast because suppurative complications are common and require drainage as a priority.
• Percutaneous drainage can be used to drain definitively or stabilize temporarily a patient with suppurative complications.
• Empiric antimicrobial therapy for acute complicated urosepsis should include two agents with activity against gram-negative bacilli, such as a combination of ciprofloxacin or piperacillin/tazobactam with an aminoglycoside, until the pathogen is isolated and antimicrobial sensitivities are known.
• Urinary catheters are associated with a high incidence, 1% to 5% per day, of bacteriuria. Patients are also predisposed to candiduria, especially those receiving broad-spectrum antibacterial therapy.
• Asymptomatic bacteriuria should be treated in all patients before instrumentation of the urinary tract to avoid the development of gram-negative bacteremia.
• The continued usefulness of a urinary catheter needs to be reassessed on a regular basis, and removal in selected awake stable patients needs to be considered.
• Treatment of bacteriuria without local signs of infection should be considered only in patients with fever or sepsis after exclusion of other potential causes of infection.

At the beginning of the 21st century, urinary tract infection (UTI) remains one of the commonest nosocomial infections, giving rise to prolonged hospitalization and additional cost. Eighty percent of nosocomial UTIs follow urinary catheterization, bacteremia arises in 1% to 3% of these, and the attributed mortality rate is then 13%.1 Community-acquired pyelonephritis occasionally causes sepsis syndrome, especially when it arises in an obstructed urinary tract or when the host defense is compromised by poorly controlled diabetes. Urinary tract infection is thus an important initiating event for admission to the intensive care unit (ICU). Because of the almost universal insertion of urinary catheters in critically ill patients, UTI is a common sequel of intensive care and ranks in the top four of ICU-acquired infections. Bacteriuria, acquired through urinary catheterization in the ICU, constitutes a reservoir of resistant pathogens, which occasionally gives rise to epidemic spread of infection within the hospital.

Bacteriuria simply means the presence of bacteria in the urine. Significant bacteriuria implies the presence of at least 105 organisms per milliliter by a quantitative method. However, a count of at least 102 aerobic gram-negative organisms per milliliter from a woman with pyuria and symptoms of lower UTI represents true infection.2 Low-level bacteriuria (or candiduria) of any quantity in a hospitalized, catheterized patient rapidly advances to significant bacteriuria, provided the patient is not receiving antimicrobial agents to which the organism is susceptible.3,4 Thus, any level of bacteriuria in a catheterized ICU patient is worthy of consideration as a cause of sepsis.

Pyuria, the presence of white blood cells in urine, is commonly measured by counting the number of cells per microscopic high-power field in a centrifuged urine specimen. Using the criterion of five cells per microscopic high-powered field, pyuria, when present, is a reliable indicator of UTI, especially when cells greatly exceed this number. However, the sensitivity is not high, and the absence of such pyuria does not reliably exclude UTI. When measured with a counting chamber, using a criterion of more than 10 cells per microliter, a sensitivity of 96% is achieved for symptomatic UTIs.5

Microbiology

Most (80% to 90%) of community-acquired UTIs in females are caused by Escherichia coli.6Staphylococcus saprophyticus is the second most common pathogen but rarely gives rise to sepsis and ICU admission. It remains fully susceptible to most antimicrobial agents used for UTI, including ampicillin and trimethoprim-sulfamethoxazole. Other Enterobacteriaceae (e.g., Proteus species, Klebsiella species, and Enterobacter species), Enterococcus species, and Pseudomonas aeruginosa account for only a small residual minority. In men Escherichia coli is also the commonest community-acquired urinary pathogen, but Enterococcus species and other Enterobacteriaceae are more commonly encountered.

For men and women, the spectrum of pathogens changes when UTI is acquired in the hospital environment. Escherichia coli (47%), Enterococcus species (13%), Klebsiella (11%), Pseudomonas aeruginosa (8%), Proteus mirabilis (5%), Enterobacter species (4%), and Citrobacter species (3%) together account for 91% of hospital-acquired bacterial UTIs, in a rank order that is consistent internationally.7 In the ICU the spectrum shifts, with Enterococcus species (24%) and Candida albicans (21%) dominating and E. coli accounting for only 15%.8 This predominance of more resistant species reflects the more widespread use of broad-spectrum antimicrobial agents and the nearly universal use of urinary catheters in ICUs.

Enterococcus species are an increasing concern as a cause of nosocomial UTI and bacteremia in the ICU. A Spanish prospective multicenter observational study of 21,979 ICU admissions between 1997 and 2001 found that 223 patients had 239 infections involving Enterococcus species, 14.3% of which were UTIs.9 In ICUs the proportion of enterococci resistant to vancomycin is increasing but varies geographically. These isolates may also exhibit resistance to ampicillin and high-level aminoglycoside.10 A retrospective study in one tertiary care center found a rate of vancomycin-resistant enterococci (VRE) bacteriuria of 23 per 10,000 admissions. Of 107 positive cultures, there were 13 symptomatic UTIs, two associated with bacteremia and one associated with death.11 Most are Enterococcus faecium and are sensitive to linezolid, nitrofurantoin, and chloramphenicol.12 Infection with VRE usually occurs in patients with significantly compromised host defenses and serious comorbidities, and this magnifies the importance of early effective antimicrobial treatment.13

VRE may serve as a reservoir of resistant genes for Staphylococcus aureus. Transfer of the VanA gene has occurred clinically, giving rise to vancomycin-resistant S. aureus invasive infection.14 Isolation of S. aureus in a urine culture is uncommon and should always raise the possibility of seeding of the urinary tract through the bloodstream. Such patients should be reviewed for evidence of vascular cannula infections (“line sepsis”), endocarditis, osteomyelitis, and pneumonia. Multiple or single cortical renal abscesses (renal carbuncle) may be present.

Persistent or relapsing bacteriuria caused by Proteus mirabilis should prompt a search for a staghorn calculus. Chronic bacteriuria due to Corynebacterium urealyticum may be also associated with alkaline urine and renal stones. This organism is fastidious and commonly resistant to most antimicrobial agents other than vancomycin.15

Infection with less common nosocomial urinary pathogens may arise, sometimes in outbreaks, depending on local antimicrobial usage patterns. These include K. pneumoniae and E. coli with extended-spectrum β-lactamase resistant to cephalosporins and most other antimicrobial classes other than carbapenems16 and Stenotrophomonas (Xanthomonas) maltophilia, resistant to carbapenems, cephalosporins, and aminoglycosides.17 UTI secondary to Shiga toxin-producing E. coli has rarely presented with hemolytic-uremic syndrome in children and adults, sometimes accompanied by bacteremia.18

Pathogenesis

Women with recurrent UTIs often have vaginal and periurethral cells to which E. coli adhere more readily as compared to controls. Most E. coli implicated in UTIs have several virulence factors, which include diverse adhesins, siderophores, toxins, polysaccharide coatings, and other properties that assist the bacteria in avoiding or subverting host defenses, injuring or invading host cells and tissues, and stimulating a noxious inflammatory response. Thus, certain strains are “selected out” of the fecal floral that are capable of causing UTI (uropathogenic E. coli).19 These various factors allow adhesion to periurethral cells, multiplication in the bladder, ascent of the ureters, and invasion of renal tissue in patients with anatomically normal urinary tracts. In contrast, those E. coli causing UTIs in patients with reflux nephropathy or obstruction are not specifically uropathogenic.19

Tamm-Horsfall protein, secreted by the loop of Henle, contains mannose residues that bind to type 1 fimbriae on E. coli and aggregate the organism preventing uroepithelial attachment and ascent against the urinary flow.20 Voiding of the bladder is another important host defense mechanism. Vesicoureteric reflux frustrates this defense and allows establishment of upper UTI. The medulla and papillae of the kidney are prone to infection because of hyperosmolality and low blood flow. During pyelonephritis, an acute inflammatory exudate develops that limits infection but contributes to scarring.19

Diagnosis

Acute pyelonephritis is a syndrome of fever with evidence of renal inflammation, such as costovertebral angle tenderness or flank pain. There are often signs of systemic toxicity and sometimes bacteremia. However, silent pyelonephritis is present in up to 33% of patients with clinical cystitis in primary care settings and may be latent for long periods. Patients with spinal cord injury are especially prone to silent, complicated, life-threatening pyelonephritis associated with urinary obstruction due to calculi and often will have fever with nonspecific abdominal discomfort, increased spasms, and autonomic dysreflexia.

Patients requiring ICU admission sometimes will have been admitted to the ward with a classic history of acute pyelonephritis. Subsequent deterioration should prompt a search for a urinary tract obstruction, such as calculus or renal papillary necrosis, or for a suppurative focus in or around the kidney (intrarenal or perinephric abscess, see below). Alternatively, such deterioration may arise if the urinary pathogen is resistant to the chosen empiric antimicrobial regimen. Features that suggest obstruction include classic renal colic, severe costovertebral angle tenderness, or a palpable kidney due to hydronephrosis.

At presentation, Gram stain of a drop of unspun urine can provide rapid, specific information. It may show gram-negative bacilli, gram-positive cocci in clumps, gram-positive cocci in chains, large gram-positive yeasts, or, much less often, a polymicrobial pattern. The stain can be valuable for distinguishing the less common etiologies (S. aureus, Enterococcus species, Candida species, and polymicrobial anaerobic) from the aerobic gram-negative bacilli that comprise the vast majority of pathogens.

A urine culture should always be obtained before therapy, if necessary, urinary catheterization. The culture identifies the infecting organism unless the patient has received prior antimicrobial agents or has complete obstruction or a perinephric abscess. Blood cultures also should be obtained because patients may have concomitant bacteremia. Renal function should be assessed, although acute renal failure caused directly by pyelonephritis is rare.21 If present, it is usually due to acute tubular necrosis due to sepsis or to drug toxicity.

Antimicrobial Therapy

A wide variety of regimens has been shown to be effective as empiric therapy of acute pyelonephritis. These include an aminoglycoside combined with ampicillin, trimethoprim-sulfamethoxazole alone, third-generation cephalosporins, extended-spectrum penicillins combined with β-lactam inhibitors, carbapenems, monobactams, and quinolones. All of these are excreted through the kidneys, with the exception of moxifloxacin and gemifloxacin. The choice of the initial antimicrobial regimen for a patient with severe urosepsis hinges primarily on the absolute necessity of covering the pathogen while awaiting definitive culture and sensitivity data at 24 to 48 hours. This has become increasingly difficult with the evolution of resistance to most antimicrobial classes. An initial combination of two agents effective against aerobic gram-negative bacilli is therefore appropriate in a septic patient with UTI, with consideration given to anti-enterococcal activity and to the risk of toxicity. The prevalence of resistance to a given agent will vary geographically and evolve with time. Such rates are invariably higher for nosocomial isolates and in patients with a prior history of antimicrobial exposure. In patients with a higher risk of aminoglycoside toxicity, such as those with prior renal impairment, liver dysfunction, advanced age, shock, or oliguria, consideration should be given to a non-aminoglycoside regimen or to a limitation to a single dose to cover the first 24 hours.

Historically, a combination of an aminoglycoside and ampicillin provided cost-effective, empiric coverage against most aerobic gram-negative bacilli and enterococci. However, in many geographic locations, greater than 50% of E. coli and most other Enterobacteriaceae are now ampicillin resistant. The addition of a β-lactamase inhibitor, such as clavulanic acid or sulbactam, eliminates the resistance in many cases. Similarly, resistance rates in uropathogens to trimethoprim-sulfamethoxazole are growing, with an excess of 20% of isolates resistant in many areas in North America and even higher rates in Latin America and Europe.7 A combination of a quinolone with an aminoglycoside offers initial double coverage against aerobic gram-negative bacilli but will not reliably cover enterococci because an increasing proportion has become quinolone resistant. Alternatively, piperacillin-tazobactam or ticarcillin-clavulanic acid will cover most aerobic-gram negative bacilli and enterococcal species. An aminoglycoside also can be added for double coverage until sensitivity data emerge. A third-generation cephalosporin will be active against most gram-negative bacilli but will have no activity against enterococci.

Once the organism is isolated and identified, then the antimicrobial regimen should be promptly adjusted to a single agent with the least toxicity and cost. Once fever has resolved and the patient can tolerate oral agents, an oral regimen can be started. Acute pyelonephritis requires 10 to 14 days of antimicrobial therapy. Cell wall synthesis inhibitors, such as the β-lactams, may have a higher relapse rate after completion of therapy. The hypertonic renal medulla may allow residual bacteria to survive as L forms (cell wall–deficient protoplasts).22,23  Trimethoprim alone, trimethoprim-sulfamethoxazole, or a quinolone is preferred as oral therapy.

The optimal treatment for VRE is not known and should be chosen in consultation with an infectious diseases physician. Case reports of success and failure of treatment of difficult infections due to VRE have been published, in addition to noncomparative series with large numbers of patients. Treatment options include chloramphenicol (which may not be suitable for UTI because it is not excreted in the urine), tetracycline, high-dose ampicillin or ampicillin-sulbactam, and nitrofurantoin (for lower UTI). Newer agents (linezolid and quinupristin-dalfopristin) have been approved, and additional agents are likely to emerge in the next few years.10

Imaging

Contrast-enhanced computed tomography (CT) is currently the initial study of choice for most patients with urosepsis. For patients in whom renal calculi may be present, the study should also include noncontrast images through the kidneys. CT scanning more accurately defines the anatomy of the renal parenchyma than ultrasound and gives a clear cross-sectional view of the surrounding anatomy. Helical scanning technology has greatly increased the quality and usefulness of the information CT provides. CT scan can more readily distinguish complications of upper UTI such as cortical abscess, acute focal bacterial nephritis (AFBN), and perinephric abscess. Accurate placement of percutaneous drains into suppurative collections may require CT scanning to delineate all structures precisely.24,25

Ultrasound can be technically inadequate because of obesity, overlying bowel gas, subcutaneous emphysema, wounds, or dressings. Although it has the advantage of being portable, the results depend on the skill and persistence of the operator. It will reliably diagnose most causes of obstruction and perinephric collections. Ultrasound may be chosen as the initial investigation for patients with severe urosepsis, when transport out of the ICU is hazardous or there are significant concerns about the risk of contrast induced nephrotoxicity. Intravenous urography currently has little or no role because helical CT scan is superior at demonstrating the collecting system and early papillary necrosis at a reversible phase and other lesions, such as tuberculosis and renal scarring due to childhood reflux nephropathy.26

Retrograde urography in conjunction with cystoscopy may be useful at demonstrating the anatomy of the collecting system in a nonexcreting kidney. Different adverse effects rarely result from the passage of the ureteral catheters or stents, including hemorrhage, perforation, or septicemia. However, this procedure may permit relief of obstruction by passage of a stent or manipulation of a calculus.

Human kidneys consist of five to 11 lobes (usually eight), each of which contains a conical medullary pyramid whose apex converges into a renal papilla projecting into a calyx. Each pyramid is capped by cortical tissue to form a renal lobe and is separated from other lobes by a renal column containing the interlobar arteries and veins.27 With the advent of CT scanning, there has been increasing recognition of AFBN.28 This is analogous to lobar pneumonia because the abnormalities are limited to one or more renal lobes. Patients manifest the usual features of acute pyelonephritis but do not respond with defervescence within 48 hours, thereby prompting investigation for obstruction or suppurative focus. Ultrasound may be normal or may visualize a solid, hypoechoic, poorly defined mass without evidence of liquefaction. Noncontrast CT scanning is frequently normal, but with intravenous contrast enhancement, the nephrogram invariably shows one or more wedge-shaped areas of decreased density. Such lesions may be demonstrated in a significant proportion of patients with acute pyelonephritis. The differential diagnosis of AFBN includes neoplasm, evolving renal infarct, and abscess. Demonstration of enhancing tissue within the mass on delayed CT images excludes cancer and abscess. AFBN usually resolves with antimicrobial therapy, but scarring and atrophy may result. Histopathology shows intense polymorphonuclear leukocyte infiltration without liquefaction, so needle aspiration or percutaneous drainage is not indicated. Escherichia coli is the most common organism isolated from patients with AFBN.28,29

Renal Abscess

AFBN may progress to suppuration, especially when associated with obstruction. The abscess may drain spontaneously into the calyxes or may rupture through the renal capsule to form a perinephric abscess. The usual pathogens are Enterobacteriaceae (E. coli, K. pneumoniae, and Proteus species). These organisms, which arise by the ascending route, are now commoner than cortical abscess arising from hematogenous spread. The latter was the commonest form of renal suppurative infection before the antibiotic era and usually resulted from S. aureus. Patients at high risk for staphylococcal septicemia, such as intravenous drug users, may present with renal cortical abscess, with or without other features of invasive staphylococcal infection, such as right-side endocarditis or multiple lung abscesses.

The clinical features of either form of renal abscess can be initially subtle. The patient often has chills, fever, and back or abdominal pain. Costovertebral angle tenderness, a flank mass, or involuntary guarding of the upper lumbar and paraspinal muscles may suggest the diagnosis. Prominent abdominal features such as nausea, vomiting, and abdominal guarding may suggest another intra-abdominal cause.

Ultrasound usually demonstrates an ovoid mass of decreased attenuation within the parenchyma. This may initially mimic AFBN, a cyst, or a tumor. Dependent echoes changing with position represent shifting debris within the abscess cavity. Gas within the abscess can be present. Definitive characterization of fluid within the mass is done by demonstration of enhanced transmission of the beam through the mass and refraction of the beam at the fluid–solid interface. The presence of debris within a cyst or an abscess is a strong indication of infection. CT shows a distinctly marginated low-attenuation (0 to 20 Hounsfield units) mass that fails to enhance. Sharp demarcation is demonstrated between the mass and the surrounding normally enhancing renal tissue. There may be a surrounding rim of increased enhancement (the ring sign). CT is more sensitive than ultrasound for small lesions (<2 cm in diameter) and for gas. Because hemorrhage within a cyst or necrotic debris within a tumor occasionally can mimic an abscess, confirmation by aspiration or nuclear medicine scanning is desirable. Alternatively, serial scanning until resolution while the patient is receiving antimicrobial therapy may suffice.

The classic therapy of intrarenal abscess is incision and drainage with a nephrectomy, if necessary, for larger abscesses. It is now clear that a trial of intravenous antimicrobial therapy will succeed in most patients once microbial etiology is established by urine, blood, or aspirate culture. Close monitoring of the response, including disappearance of fever and leukocytosis and diminution of size as assessed by ultrasound or CT, is necessary. Percutaneous drainage using ultrasound or CT guidance is another alternative to surgery and should be tried as initial therapy when the abscess cavity is large.30

Emphysematous Pyelonephritis

Emphysematous pyelonephritis is a fulminant disorder, historically associated with a mortality rate of 80%. The patient typically presents acutely with features of pyelonephritis and severe sepsis with or without multiorgan failure. Gas formation occurs in the renal parenchyma and surrounding tissues due to mixed acid fermentation of glucose by Enterobacteriaceae, which forms hydrogen and carbon dioxide. Most patients have uncontrolled diabetes mellitus and some have obstruction of the urinary tract. Escherichia coli accounts for the majority of pathogens, with most of the rest being due to Klebsiella species.31 Strict anaerobes have not been reported, but optimal anaerobic isolation techniques may not have been applied in all studies. Pathology demonstrates extensive necrotizing pyelonephritis with abscess formation and papillary necrosis. Poor perfusion is present in most cases due to infarction, vascular thrombosis, arteriosclerosis, and/or glomerulosclerosis.31

Plain radiographs may show diffuse mottling of the parenchyma as an early sign. More advanced cases show extensive bubbles in the parenchyma and a gas crescent surrounding the kidney within the perinephric space. Ultrasound and CT are much more sensitive than plain films at detecting gas. CT identifies the gas clearly and unambiguously. Ultrasound identifies gas by the artifacts produced. Artifacts include an intense band of echoes distant to the gas and “dirty shadowing” distally with poorly defined margins and many echoes. This must be distinguished from the shadows associated with calculi, which produce “clean shadows” with sharply defined margins.24

Case reports published before 1982 associated surgical intervention within 48 hours and antimicrobial therapy with improved outcome. Although relief of obstruction was sometimes sufficient, nephrectomy was frequently necessary. The possible involvement of the contralateral kidney was a concern. More recent reports have suggested that a combination of antimicrobial agents, ICU support, including tight control of hyperglycemia, and percutaneous drainage guided by modern imaging techniques is successful in most cases, with nephrectomy reserved for a minority (18% mortality rate in a series of 46 cases).31

Perinephric Abscess, Pyonephrosis, and Pyocystis

The perinephric space, containing the kidney, renal fat pad, and adrenal gland, is conical and opens inferiorly to the pelvis. In most cases, it communicates to the contralateral perinephric space anterior to the aorta and inferior vena cava. Bridging septae exist within it, which act as lamellar barriers against the spread of infection or hematoma. Multiple loculations may arise, causing difficulty with percutaneous drainage.32

Most cases of perinephric abscess occur secondary to pyelonephritis caused by Enterobacteriaceae (E. coli, K. pneumoniae, and Proteus species). However, a minority is bacteremic in origin due to S. aureus or pyogenic streptococci. Polymicrobial infection involving anaerobic bacteria also occurs. There have been rare reports of perinephric abscess due to Candida and Aspergillus species. Many patients have associated renal obstruction or diabetes mellitus. Perinephric abscess is usually confined by the renal fascia, but additional spread to adjacent structures and spaces can occur.

Initial descriptions of perinephric abscess emphasized its insidious nature, delay in diagnosis, and 50% mortality rate.33 Most patients have fever and chills. Other features may include weight loss, nausea, vomiting, dysuria, flank pain, abdominal pain, pleuritic chest pain, and pain in the thigh or groin. Symptoms usually last at least 2 weeks and sometimes persist for months.34 The patient may present for investigation of fever of unknown origin. Other patients are given an initial diagnosis of acute pyelonephritis. Flank mass or renal tenderness will be present in most patients.

With the ready availability of ultrasound and CT, the diagnosis is now made sooner. Ultrasound demonstrates fluid that may contain debris or gas. CT shows loculated collections with decreased attenuation (0 to 20 Hounsfield units). The abscess wall may show increased attenuation after intravenous injection of contrast material. Thickening of the renal fascia (Gerota fascia) and unilateral enlargement of the kidney or psoas muscle may also be seen. The diagnosis can be confirmed by ultrasound-guided aspiration of pus. Most patients can be treated by a combination of antimicrobial agents and percutaneous drainage. Empiric antimicrobial therapy should be directed at mixed anaerobes and S. aureus, in addition to the usual aerobic gram-negative bacilli.24,30,34

Pyonephrosis arises when infection develops proximal to an obstructed hydronephrotic kidney. Unilateral loss of renal function is present, as is infection of the renal parenchyma. Occasionally gas may form; if so, the prognosis is much better than with emphysematous pyelonephritis. The clinical presentation is similar to perinephric abscess and may be insidious. Initial investigations should include a plain abdominal radiograph to look for calculi. Ultrasound will show a distended upper urinary tract. Specific features of pyonephrosis that allow distinction from simple hydronephrosis include sedimented echoes and dispersed internal echoes within the dilated collecting system. These findings are present in a minority of patients with pyonephrosis.35 In a septic patient with hydronephrosis, direct aspiration is indicated. CT is more sensitive for detecting radiolucent calculi and will establish whether there is accompanying infection in the tissues around the kidney. Once the diagnosis is made, a nephrostomy tube should be inserted, which usually suffices to drain the infection.

Pyocystis (pus in the urinary bladder) with or without gas-forming organisms can present with sepsis, lower urinary tract signs, and pneumaturia. Patients with chronic oliguria on dialysis or those who have had diversion of urine away from the bladder (e.g., ileal conduit) are especially predisposed. Antimicrobial therapy and bladder irrigations may be sufficient therapy, but necrosis of the bladder wall as demonstrated by gas in the muscular layers on CT will require surgical resection.36,37

Infected Cysts

Dependent debris can be demonstrated in a renal cyst by ultrasound or CT and suggests infection. However, absence of such a finding does not exclude a pyocyst. Aspiration of cyst fluid for Gram stain and culture establishes the diagnosis. Assessment is much more problematic in polycystic renal disease. Pyocysts may arise from ascending infection or by hematogenous seeding. In the presence of uremia, systemic responses to infection, such as fever and leukocytosis, are often blunted. Infected cysts may manifest as persistent sepsis unresponsive to intravenous antimicrobial agents. Ultrasound or CT frequently fails to distinguish an infected cyst from the rest of the polycystic kidney. Delineation of the infected cyst as the cause may require white blood cell scanning, magnetic resonance imaging, or positron emission tomography,38,39 followed by percutaneous drainage of the particular cyst. Alternatively, unilateral nephrectomy can be carried out with preservation of the uninfected kidney. A trial of antimicrobial therapy should be carried out first if the patient is stable. Lipophilic agents, such as trimethoprim-sulfamethoxazole, ciprofloxacin or ofloxacin, are more likely to succeed. Lipophobic agents such as β-lactams and aminoglycosides penetrate cysts poorly, if at all.40

Urinary Tract Infection Due to Candida

By microscopic examination, Candida species are readily recognized as gram-positive, ovoid, unicellular forms and grow readily on routine culture systems. Quantitative methods are commonly applied in urine; 104 colony-forming units per milliliter, especially when associated with pyuria, should be regarded as indicating at least infection of the bladder and possibly the upper tract.

Disseminated invasive candidiasis may originate in the urinary tract or secondarily seed it. Widespread microabscesses often form in the kidney and in other parenchymal organs. The skin, bones, spleen, eyes, liver, endocardium, myocardium, and central nervous system are typical sites of seeding, but the kidneys are almost universally involved. Renal failure may develop from bilateral renal infection. Neutropenia, loss of mucous membrane integrity due to chemotherapy, burns, steroid use, diabetes mellitus, total parenteral nutrition, and upper gastrointestinal tract surgery predispose to invasive candidiasis. Overgrowth on superficial tissues such as skin, mucous membranes, and the gastrointestinal tract frequently precedes invasion and is often associated with prolonged broad-spectrum antibacterial therapy. Although there may be extensive tissue involvement, direct proof of such deep candida infection is frequently lacking. Blood cultures are positive in only 50% of cases.41

Primary infection of the kidneys by Candida is generally associated with an indwelling urinary catheter, broad-spectrum antibacterial agents, and an obstructed urinary tract. Candiduria confined to the bladder is usually present for a variable period before renal infection. Persistent candiduria should be assumed to reflect renal infection if the patient has any of the predispositions listed above, is receiving broad-spectrum antibacterial therapy, and continues to have features of sepsis such as fever or leukocytosis. A search should be made for specific features of disseminated candidiasis such as white “cotton wool” exudates in the retina and nodular skin lesions. Unilateral or bilateral hydronephrosis should raise suspicion of a fungus ball. Microscopic examination of the urinary sediment may show Candida casts.42 A careful evaluation of these clinical and laboratory data should allow selection of those patients who require early empiric antifungal therapy.

Renal or disseminated infection requires systemic amphotericin B therapy with its attendant toxicities or fluconazole.43 Outcome is superior if intravenous catheters are removed on or before the first day of therapy.41 Amphotericin B carries a significant risk of nephrotoxicity; fluconazole is not active against many non-Albicans species. However fluconazole may overcome such resistance in the urine by its high urinary levels.44 To date, there are no clinical trials validating the efficacy of other agents, such as the less nephrotoxic lipid formulations of amphotericin B, 5-flucytosine, voriconazole, and caspofungin in the treatment of ascending Candida pyelonephritis or renal candidiasis. Concern has been raised that the structure of lipid formulations of amphotericin B could impair their urinary excretion. Caspofungin and voriconazole are metabolized through the liver with little urinary excretion. 5-Flucytosine is excreted in high concentration in urine, but resistance can develop rapidly when used alone.

Hydronephrosis due to a fungus ball should be relieved by a percutaneous nephrostomy tube. Irrigation of the ureter with an amphotericin B solution is effective in some cases. Lack of response radiologically should prompt surgical excision.

A more commonly encountered situation is that of the stable ICU patient who has persistent candiduria. For many individuals, this is a benign condition, which resolves spontaneously or after withdrawal of the urinary catheter. Asymptomatic patients with candiduria should receive treatment if they have undergone transplantation, are neutropenic, or are about to undergo invasive urologic procedures. Amphotericin B washouts, although effective, have been largely abandoned because they are labor intensive and require the continuation of a catheter.44,45

Prostatic Infections

Acute bacterial prostatitis rarely causes sepsis requiring ICU admission. It presents with high fever and urgency, frequency, dysuria, difficulty voiding or acute retention of urine, with suprapubic or perineal pain.46 Rectal examination demonstrates a tender and swollen prostate. Gram-negative bacilli are the most frequent pathogens, and E. faecalis may also be responsible.

Because of the intense inflammatory response in acute bacterial prostatitis, most antimicrobial agents cross the prostatic epithelium effectively. Rarely, a patient with acute prostatitis may develop chronic infection, so we recommend continuing with an oral antimicrobial agent that penetrates the prostatic acini well, such as trimethoprim alone, trimethoprim-sulfamethoxazole, ciprofloxacin, or ofloxacin, for a total of 6 weeks in an attempt to eradicate the organisms from the prostate. Prostatic abscess, if present, can be confirmed by transrectal ultrasonography or CT. Transurethral resection of the prostate and unroofing or perineal aspiration of pus guided by transrectal ultrasonography usually provide adequate drainage.46

Catheter-Associated Bacteriuria

Before the 1960s, urinary catheters had “open” drainage systems, with a significant bacteriuria prevalence of 95% within 4 days of continuous use. The principal route of acquisition was intraluminal. The widespread introduction of closed urinary drainage systems has significantly reduced these high rates to 10% to 27% in various studies. The prevalence of catheter-associated bacteriuria is time-dependent. One percent of patients will acquire bacteriuria from single “in-out” catheterizations.47 The per-day risk of developing bacteriuria has varied from 1% to 5%, with lower figures reported in the ICU setting, but with a higher prevalence of resistant pathogens.8,48,49 Other factors associated with a higher prevalence of catheter-associated bacteriuria include advancing age and female sex.8 Systemic antimicrobial agents initially protect against catheter-associated bacteriuria. Subsequently, organisms manifesting extensive antimicrobial resistance become prevalent, such as enterococci, coagulase-negative staphylococci, Candida species, and Pseudomonas species. Disconnections of the collecting tube–catheter junction are associated with a two- to threefold increase in bacteriuria. Samples should always be taken by aspiration of urine through the distal catheter or collection port, after local disinfection.

Ascent of bacteria to the bladder occurs predominantly outside the lumen when a closed drainage system is used. The space between the catheter and the urethral mucous membrane is filled by a variable amount of fluid, mucus, and inflammatory exudate. This is static and lacks inhibitory factors against bacterial proliferation. A progressive multiplication of organisms originating from the meatus occurs, which accounts for the time-dependent acquisition and for the higher rates associated with the female urethra.50

In a small minority of patients, the organism originates from the collecting bag and ascends intraluminally. Contamination of the collecting bag can occur in association with disconnections of the distal catheter or during emptying of the bag near the drainage port. Organisms have been carried on the hands of personnel or in the collecting urinal from one source patient to the collecting bags of others. Thus, intraluminal spread is the mechanism associated with most epidemics of catheter-associated bacteriuria.51

Catheterization of the bladder is unavoidable in most patients in the ICU. Indications include the monitoring of urine output in patients with shock, hemodynamic instability, or polyuric renal failure and the relief of lower urinary tract obstruction. Catheterization should not be used routinely, to avoid incontinence and contamination of the perineal skin. The almost universal use of urinary catheters in most ICUs can be reduced by early withdrawal of catheters in selected patients. These include alert and stable patients who can maintain continence, patients with anuric renal failure for whom once-a-day catheterization will suffice, and male patients with an intact voiding mechanism who can be managed with condom drainage.1 Intermittent catheterization can be used in stable patients with neurogenic bladders and in some patients with disturbed consciousness. The necessity for the catheter should be frequently questioned and a trial of removal attempted when feasible. Once in place, there is no need for regular scheduled replacements of the catheter, which can be left indefinitely provided it is functioning well and there are no encrustations.52 Bacteremia can arise with instrumentation, including passage of a new urinary catheter. Bacteriuria should be treated in a catheterized patient before instrumentation of the urinary tract. Catheter-associated bacteriuria is generally asymptomatic. Treatment is sometimes justified to relieve symptoms of cystitis, especially in the patient in whom removal of the catheter is imminent. Short-course treatments will work well once the catheter has been removed.53

Studies of recent technical innovations to reduce catheter-associated bacteriuria have shown equivocal results. These include urinary catheters impregnated with nitrofurazone or minocycline and rifampin or coated with a silver alloy-hydrogel. Conflicting opinions exist concerning their efficacy and cost effectiveness. We do not recommend them at this time.49,54