Obstructive uropathy includes: calculi at any level of the urinary tract; prostatic hypertrophy; cancer of the prostate, bladder, or uterus; external compression by uterine or other tumors; neurogenic bladder; and congenital abnormalities. Any of these conditions may be associated with a complicated UTI. An obstruction above the bladder can lead to renal pelvic dilatation and hydronephrosis with subsequent pressure atrophy of renal cortical tissue. When an infection does occur in the setting of partial or complete obstruction, the clearance of an infection is more difficult because drainage may be limited, antibiotic penetration might decrease, and host responses may be impaired.

Obstruction of the urinary tract may be acute or chronic, unilateral or bilateral, and complete or incomplete. Acute obstruction of the upper urinary tract may be associated with retroperitoneal or flank pain, especially if calculi are present. Obstruction at the bladder level increases the risk of infection by decreasing the effect of micturition on reducing bacterial inocula as well as allowing for the multiplication of bacteria to the degree that mucosal antibacterial and other host factors are overwhelmed or inactivated. An obstruction at higher levels of the urinary tract may predispose the patient to infection because dilatation and pressure necrosis may decrease defense mechanisms in the kidney and may allow disseminating hematogenous bacteria to alight and form a nidus of infection in the renal cortex or medulla. Also, once the normal architecture of the urinary tract has been damaged, whether as a result of reflux or obstruction, bacteria that lack the virulence factors necessary to cause renal infection in the absence of structural lesions may be responsible for serious upper tract infection once introduced into the kidney.

The treatment of urinary infections in the face of obstructive uropathy or stone disease usually requires antibiotic therapy for a longer duration than that for uncomplicated infections; treatment may be required for up to 6 weeks. Obviously, correction of the obstruction and removal of calculi are important adjunctive measures. In general, a 6-week course of a bactericidal antibiotic that achieves adequate concentration in renal tissue and bladder urine is recommended. Depending on the organism and susceptibility testing results, intravenous or oral therapy can be used; for example, a fluoroquinolone or a β-lactam antibiotic. Susceptibility testing is particularly important given the increased frequency of antibiotic-resistant bacteria in complicated urinary tract infections.¹ Special consideration is needed in the
face of staghorn calculi, which often form in the presence of urease-producing organisms such as Proteus spp. Once the organism has been eradicated with a long course of antibiotics, “prophylactic” or “suppressive” therapy can be given with low-dose trimethoprim-sulfamethoxazole, daily or every other day, or with a combination of trimethoprim and a methenamine compound. Nephrolithiasis is considered in more detail in Chapter 20.

The distal third of the urethra is normally colonized with perineal and skin flora. Instrumentation for any reason may introduce these organisms into the bladder. In the presence of an indwelling catheter, bacteria can ascend from the periurethral area along the mucous sheath that develops between the urethral mucosa and the latex rubber catheter.² Although several techniques have been introduced to prevent urinary infection in chronically catheterized patients, such as closed sterile drainage, continuous irrigation through a three-way catheter with antibiotic or acetic acid, and systemic antibiotic prophylaxis, all patients with prolonged urinary catheter drainage ultimately become colonized with high counts of bacteria (from 2 to about 21 days).

Catheter-associated bacteriuria and catheter-associated urinary tract infections (CA-UTIs) are the most common infection acquired in hospitals and long-term care facilities (LTCF);³ elderly patients are at greatest risk. Over 40% of nosocomial infections originate in the urinary tract and Escherichia coli is responsible for most of these infections, followed by Enterococcus spp., Pseudomonas aeruginosa, and Candida spp.³,⁴,⁵ Bacteremia, an important sequela of complicated UTIs, develops in about 4% of patients with indwelling bladder catheter-associated urinary infections, and case-fatality rates of 13% to 30% have been reported for these bacteremic nosocomial urinary infections.³,⁵,⁶

Catheter-associated nosocomial UTIs (CA-UTI) have been described in a study of 1,497 patients. These infections were more frequent in women (23.2%) than men (8.9%). They were unimicrobial in 94% and polymicrobial (primarily with enterococci and gram-negative bacilli) in 6%. The distribution of single isolates in these patients included gram-negative bacilli in 34%, enterococci or staphylococci in 27%, and Candida spp. in 27%. Patients with CA-UTIs only rarely have symptoms (<10%) in the face of infections and pyuria, and they may not have peripheral leukocytosis.⁷,⁸ Catheters left in place without bona fide medical necessity often contribute to nosocomial infections and are accompanied by an increase in associated antibiotic costs.⁹

Environmental factors may relate to the nosocomial acquisition of bacteriuria in catheterized patients. Prevalent bacteria in the hospital colonize patients, or the patient’s endogenous flora may enter the urinary collecting system or drainage bag. Within 24 to 48 hours they may be found in the bladder, and they increase to high colony counts over the subsequent 48 hours.¹⁰,¹¹ Bacteria may attach to the luminal surface of the catheter in association with the production of a mucoid biofilm, and this may predispose the patient to urinary infection or catheter blockage and obstruction.⁷,¹⁰

Urea splitting bacteria may lead to mucosal encrustations and encrusted cystitis and pyelitis. Corynebacterium group D₂ also have been implicated.¹² There is often a history of a prior urologic procedure or chronic illness, including immune compromise or renal transplantation. Patients may describe symptoms of cystitis, dysuria, gross hematuria, passage of encrusted debris, often with complaints of an ammonia odor to the urine. Failure to diagnose this condition can lead to renal impairment or ureteric obstruction and loss of renal graft as a result of infection, renal abscess, or obstructive uropathy. Treatment consists of antibiotics. The glycopeptides vancomycin and teicoplanin have in vitro activity against Corynebacterium group D₂, which are frequently resistant to fluoroquinolone antibiotics (>50%).
Additional treatment includes acidification of urine as well as chemolysis and the removal of infected calcified plaques that contain the organisms.¹²

Some caution is warranted in interpreting the results of cultures of material obtained from urinary collection devices. Several populations of bacteria may grow within the catheter and include planktonic bacteria in the urine and surface bacteria associated with the bacterial biofilm.¹³ Bacteria may be cultured from catheter lumen encrustations when bladder urine might be sterile.¹⁴ Because bladder urine is normally sterile, Garibaldi and associates¹⁵ suggested that the presence of 100 or more organisms per milliliter should be considered as evidence of a positive urine culture in a catheterized patient. These authors demonstrated that breaks in the catheter-collecting system junction were associated with an early acquisition of bacteriuria. Current guidelines from the Infectious Diseases Society of America (IDSA) suggest that infection is likely in the presence of compatible signs and symptoms and an indwelling catheter if the bacterial counts of one or more organisms are equal to or greater than 10³ CFU per milliliter.³

Condom catheters are the usual alternatives to indwelling bladder catheters in incontinent male patients without obstructive uropathy. Although associated with fewer infectious complications, at least one outbreak implicated these devices in 64 geriatric patients, 40 (63%) of whom had asymptomatic infections, frequently with mechanical obstruction of urine flow including kinking of the outlet, or blockage of flow by adhesive devices with associated penile cyanosis and ulceration. These problems may lead to urinary stasis, bacteriuria, and bladder wall distention, all of which may predispose a patient to complicated urinary infections.¹⁶

Treatment of catheter-associated urinary infections depends on the clinical setting. In general, asymptomatic bacteriuria in catheterized patients is not treated. In patients with catheters in place for the long term, there is some risk of dissemination of bladder bacteriuria to the blood during manipulation of the urinary tract as during catheter changes (generally done to minimize concretions and obstruction). Antimicrobial agents have not been shown to prevent catheter associated UTIs in persons with long-term indwelling urethral catheters.³ Preventive strategies that avoid antibiotics are needed for these patients. We occasionally advocate treating the colonizing bacteria 8 to 24 hours prior to the catheter change, with a single dose of a bactericidal antibiotic based on susceptibility testing of the organisms (e.g., a quinolone or an aminoglycoside). This topic is extensively reviewed in the new IDSA guidelines,³ and they do not support antibiotics at catheter replacement.

Interventional attempts to decrease the incidence of nosocomial UTIs using a silver-alloy, hydrogel-coated latex urinary catheter have been compared with standard silicone-coated latex catheters.¹⁷ In older studies, silver-coated catheters significantly reduced the rates of bacteriuria in male surgical patients not receiving antibiotics.¹⁸ In the more recent study,¹⁷ silver-coated catheters were associated with a 32% decrease in the infection risk in male patients. Infection rates in females were similar in both catheter groups. In addition to a decrease in nosocomial infection rates, significant savings on hospitalization and other infectionrelated costs were described. Another study estimated that economic consequences of nosocomial symptomatic UTIs can reach over US$650 and catheter-related bacteriuria over US$2,800 per incident.¹⁹ A study by Rupp et al.²⁰ demonstrated additional cost savings with the silver-alloy hydrogen-coated urinary catheters and also showed a decline in nosocomial UTIs. No evidence of silver-resistant urinary pathogens was found.

Symptomatic urinary infections or urosepsis in the presence of an indwelling catheter is best treated with rapidly bactericidal antibiotics such as an aminoglycoside, a fluoroquinolone, or a β-lactam-aminoglycoside combination based on antimicrobial susceptibility testing.¹ Bacteremia is usually easily cleared, but eradication of the urinary infecting organism may be difficult in the continued presence of the catheter. Guidelines for the prevention and management of catheter-related urinary infections have been updated recently.³

Complicated infections within or associated with isolated renal cysts, autosomal dominant polycystic renal disease (ADPKD), or acquired renal cystic disease (three or more renal cysts or cystic involvement of >25% of renal mass in the absence of autosomal dominant polycystic kidney disease) remain important diagnostic and therapeutic challenges.²¹

Patients with polycystic kidney disease may develop typical infections of the urinary bladder and ascending pyelonephritis with renal parenchymal involvement as well as infection within the renal cysts themselves.²² The presence of polycystic kidney disease is associated with a 50% to 70% lifetime risk of some form of UTI.²³ In an autopsy study of 23 patients with polycystic kidney disease, 13 (56%) had findings consistent with pyelonephritis.²⁴ It may be difficult to implicate infection as a cause of hematuria or flank pain in patients with cystic abnormalities of the kidney because these symptoms may be present in the absence of infection.²⁵ Also, pyuria (≥10 leukocytes/high-power field) may be present in more than 40% of patients with polycystic kidney disease, with or without other symptoms suggestive of urinary tract infection; however, infection is documented in only about 10% of these patients.²⁶ Findings suggestive of a UTI in the presence of cystic renal disease include positive blood cultures, leukocytosis, fever, and lower GU tract symptoms such as dysuria. Negative urine cultures do not exclude infection of a renal cyst.

In a classic review of renal infections in patients with polycystic kidney disease, Sklar and associates²⁵ described
four types of infections according to anatomic involvement: (1) localized infected cyst (pyocyst), (2) pyonephrosis (intrarenal abscess associated with ureteral obstruction), (3) acute bacterial interstitial nephritis, and (4) perinephric abscess. Clinical findings may vary with the anatomic location of bacterial infections in these patients.

The diagnosis of complicated UTIs in patients with renal cystic disease is usually based on the results of clinical examination, laboratory testing, and diagnostic imaging. Radiologic evaluation with plain radiography, ultrasound, computed tomography (CT), and gallium imaging has been used to determine the presence and location of infection.²⁵ Gallium imaging may show uptake within the kidney, but it does not provide specific information to determine whether an abscess or an infected cyst is present. CT may be necessary to define pyocysts but CT scans are not optimal in distinguishing infected from noninfected cysts. Plain radiography may be useful if calculi are contributing to the clinical presentation. Renal ultrasonography also may identify calculi and can differentiate hydronephrosis from pyonephrosis and perinephric abscess. Recent studies suggest that positron emission tomography (PET) scanning and diffusion-weighted magnetic resonance imaging (MRI) might be useful in differentiating infected from noninfected cysts.²¹,²⁷ The percutaneous drainage of infected cysts in adult polycystic kidney disease has been described, as has laparoscopic cyst decortication using transperitoneal or retroperitoneal access.²⁸,²⁹

When cysts are infected, the Enterobacteriaceae (especially E. coli, Klebsiella spp., and Proteus spp.) and P. aeruginosa are most frequently implicated, with Staphylococcus aureus, Salmonella spp., Streptococcus spp., Corynebacterium spp., and others isolated less frequently.²¹,³⁰ A gas producing Clostridium perfringens infection in a renal cyst has been reported in a patient with ADPKD.³¹

Attempts should be made to isolate the infecting organism from the blood, urine, or cyst drainage. Appropriate treatment of infections in patients with polycystic kidney disease depends on the use of antibiotics that are able to concentrate within the infected cysts in addition to providing bactericidal activity against the infecting organism. Aminoglycosides, penicillins, and cephalosporins have relatively poor penetration into renal cysts, although pH, cyst physiology, and histology may affect the diffusion.³² These antibiotics are relatively lipophobic and do not diffuse across cyst epithelial layers. Lipophilic agents such as clindamycin, chloramphenicol, macrolides, metronidazole, and trimethoprim are able to penetrate and accumulate within cysts, but they may or may not be active against the infecting organisms.³³ Fluoroquinolone antibiotics such as ciprofloxacin accumulate in cystic fluid, and they have been used successfully to treat infected renal cysts.³⁴,³⁵ Because most of the causative organisms in infected cysts are facultative gram-negative bacilli with presumed fluoroquinolone susceptibility, these agents may still be quite useful clinically. Oral therapy is acceptable unless patients are septic. Infection in multiple cysts has been associated with sepsis and may require surgical intervention (nephrectomy) in rare cases.³⁶ Intravenous therapy should be used in bacteremic patients and in patients with decreased gastrointestinal (GI) quinolone absorption (e.g., antacid use). Antibiotic choice should be based on pharmacology and antibiotic susceptibility testing given the increased incidence of antibiotic resistance among gram-negative bacilli.¹

Urinary diversions are performed to reroute urine in patients with obstructive uropathy from many causes—urinary bladder carcinoma or prostatic or gynecologic malignancies—and in
patients with congenital abnormalities, neurologic disorders, and pelvic trauma. Although intermittent catheterization may be preferable in some patients with neurogenic bladder dysfunction (e.g., multiple sclerosis, paraplegia), the creation of a ureteroileal conduit is a popular alternative to achieve control of urine excretion. This procedure does not carry the associated metabolic and electrolyte complications seen with jejunal bypass procedures. The surgical construction of an ileal loop conduit is associated with few serious complications and a low mortality rate.

Infectious complications have been well described in pediatric and adult populations, and an increased incidence of infections has been noted when the ureteric component becomes obstructed; pyelonephritis may result. Renal calculi are encountered frequently after urinary diversion and are often caused by urea-splitting organisms such as P. mirabilis and Proteus morganii. The urease produced by these organisms splits urea to form an alkaline pH, and the solubility product constant for calcium and phosphate is exceeded with the resultant precipitation of crystals, which form the nidus for renal stones.⁴³,⁴⁴ Newer diversion procedures have been introduced (such as orthotopic urinary diversion or the neobladder) and also carry a risk of urinary infection.⁴⁵

Recommendations for the management of these patients include aggressive control of the infection using bactericidal drugs active against urea-splitting organisms and acidification of the urine or avoidance of alkaline urinary pH, which encourages stone formation. The detection of urinary infection in these patients is difficult because the ileal loops are almost always colonized. Asymptomatic bacteriuria in the presence of a ureteroileal conduit should not be treated and prophylactic antibiotics are not recommended; this is less clear with orthotopic diversions.⁴⁵ However, positive urine cultures associated with physical findings of fever, chills, and flank pain should prompt the initiation of appropriate bactericidal antibiotics directed against gram-negative enteric rods including Proteus spp. Aminoglycosides, fluoroquinolones, third- or fourth-generation cephalosporins, carbapenems, and penicillin-β-lactamase inhibitor combinations (e.g., ampicillin-sulbactam, piperacillin-tazobactam, ticarcillin-clavulanate) may be useful in this setting. When susceptibilities are known, specific therapy can be instituted. Septic complications often lead to failure of ileal diversions.⁴⁶

Acute and recurrent UTIs in the presence of abnormalities of urachal development with patent urachal remnants may be difficult to diagnose. Four primary developmental defects exist and present with varying signs and symptoms: patent urachus, umbilical urachal sinus, vesicourachal diverticulum, and urachal cyst.⁵⁴ Umbilical urachal sinuses and urachal cysts are only rarely infected and many urachal cysts are found incidentally during surgery or radiographic studies. Although most patent urachal remnants in adults are undetected and asymptomatic, umbilical urachal sinuses occasionally may be infected and present with purulent umbilical drainage or periumbilical erythema. These infections may present as infraumbilical abdominal wall abscesses or with contiguous involvement of the peritoneal cavity with an enteric fistula. Adult and pediatric cases have been reviewed.⁵⁴,⁵⁵,⁵⁶

A vesicourachal diverticula may present with recurrent urinary infections, and urethral discharge, pneumaturia, and a suprapubic mass also may be found. Imaging studies may help make the diagnosis, but often cystoscopy may be necessary, especially if the diverticulum is associated with malignant transformation of the remnant. The organisms that infect the vesicourachal diverticula include E. coli and other Enterobacteriaceae, S. aureus, Enterococcus spp., and Actinomyces spp.⁵⁴,⁵⁷

Many factors that predispose the diabetic patient to infections in the urinary tract have been described. Diabetes mellitus is putatively associated with an increased risk of these infections as a result of poorly controlled plasma glucose concentrations, which in turn may impair granulocyte function and cell-mediated immunity. Also, the neurologic dysfunction associated with diabetic neuropathy may result in a neurogenic bladder with incomplete bladder emptying, urinary stasis, and retention. The increased likelihood of urethral instrumentation may predispose these patients to infection, as may diabetic microangiopathy, which can contribute to local ischemia and impaired host defenses.⁵⁸,⁵⁹

Table 25.2 lists the manifestations of UTIs in patients with diabetes mellitus. Asymptomatic bacteriuria has been described as occurring two to four times more frequently in diabetic women⁵⁹,⁶⁰ and as being more prevalent in diabetic women than men.⁶¹ Although the treatment of asymptomatic bacteriuria in diabetic women reduced the duration of long-term bacteriuria, recolonization occurred after most treatment regimens.⁶² A recent study in type 1 diabetic women suggested that sexual activity is more likely to be a risk factor for cystitis and pyelonephritis than diabetes control or complications.⁶³ In one recent small series, the distribution of responsible pathogens was similar among diabetic and nondiabetic patients, as was the frequency of infection with antibiotic-resistant organisms.⁶⁴ Bacteriuria in diabetic patients may be associated with a disproportionate risk of infection in the upper urinary tract and kidneys, and one study reported that upper tract infection could be documented in 79% of diabetic women with asymptomatic bacteriuria.⁶⁰ Other renal parenchymal complications of UTIs in diabetic patients include pyelonephritis, emphysematous pyelonephritis, papillary necrosis, and perinephric abscesses; these conditions should be considered in the evaluation of nonresponse to appropriate antibiotic therapy for urinary infections in diabetic patients.

Diabetic patients with urinary infections are more likely to be bacteremic or uroseptic than are nondiabetic patients.⁶⁵ These patients are also more likely to develop acute pyelonephritis at a fivefold greater risk than nondiabetic patients.⁶⁶ Diabetic patients with serious systemic signs of urinary infections should be studied with abdominal radiography to detect renal emphysematous pyelonephritis. Ultrasound or CT scans should be performed if an obstruction or an abscess is suspected. The urinary tract is implicated as the source of bacteremia more frequently in diabetic than in nondiabetic patients.⁶⁵ Postmenopausal women with diabetes are at a higher risk of a UTI and this is related to the duration of diabetes and insulin dependence.⁶⁷ Type 2 diabetic women with histories of UTIs (especially upper UTIs) are at increased risk for renal scarring and damage, as demonstrated by renal cortex scans.⁶⁸ Most of the bacteria responsible for urosepsis in diabetics are gram-negative rods, with E. coli and Klebsiella spp. accounting for about 70%. Notably, Klebsiella spp. are isolated frequently in diabetic patients with bacteremic urinary infections, and a large proportion of these patients have indwelling urinary bladder catheters.