Acute pyelonephritis is defined as inflammation of the kidney and renal pelvis, and its diagnosis is usually made clinically.
Presentation and Findings
Patients with acute pyelonephritis present with chills, fever, and costovertebral angle tenderness. They often have accompanying lower-tract symptoms such as dysuria, frequency, and urgency. Sepsis may occur, with 20–30% of all systemic sepsis resulting from a urine infection. Urinalysis commonly demonstrates the presence of WBCs and red blood cells in the urine. Leukocytosis, increased erythrocyte sedimentation, and elevated levels of C-reactive protein are commonly seen on blood analysis. Bacteria are cultured from the urine when the culture is obtained before antibiotic treatment is instituted. E. coli is the most common causative organism, accounting for 80% of the cases. Klebsiella, Proteus, Enterobacter, Pseudomonas, Serratia, and Citrobacter spp. account for the remaining cases. Of the gram-positive bacteria, Streptococcus faecalis and S. aureus can be important causes of pyelonephritis. In reproductive-age women, sexual activity and patient and family history of UTI are associated with an increased risk of developing pyelonephritis. Diabetes and urinary incontinence also independently increase this risk (Scholes et al, 2005).
Contrast-enhanced computed tomography (CT) scans can accurately demonstrate findings, confirming the diagnosis of pyelonephritis (Dacher et al, 1993). Acute bacterial infection causes constriction of peripheral arterioles and reduces perfusion of the affected renal segments. Perfusion defects, which can be segmental, multifocal, or diffuse, are seen as areas of reduced signal density (Figure 14–2). Renal enlargement, attenuated parenchyma, and a compressed collecting system are other characteristic findings on CT scan. However, CT scan is not necessary unless the diagnosis is unclear or the patient is not responding to therapy. Radionuclide study with 99mTc-dimercaptosuccinic acid is equally sensitive in detecting the perfusion defects of pyelonephritis (Levtchenko et al, 2001). In patients with acute pyelonephritis, renal ultrasonography is important to rule out concurrent urinary tract obstruction but cannot reliably detect inflammation or infection of the kidney.
Acute pyelonephritis. Computed tomography scan with intravenous contrast demonstrates a perfusion defect (white arrow) and enlargement of the affected kidney.
The management of acute pyelonephritis depends on the severity of the infection (Ghiro et al, 2002; Nickel, 2001). In patients who have toxicity because of associated septicemia, hospitalization is warranted. Approximately 10–30% of all adult patients with acute pyelonephritis require hospitalization, with incidence of 11.7 per 10,000 for women and 2.4 per 10,000 for men (Brown et al, 2005). Empiric therapy with intravenous ampicillin and aminoglycosides is effective against a broad range of uropathogens, including enterococci and Pseudomonas species. Alternatively, amoxicillin with clavulanic acid or a third-generation cephalosporin can be used. In a recent study of community-acquired UTIs in children hospitalized in a tertiary center (Marcus et al, 2005), it was noted that 40% of the culture-proved UTIs were caused by non–E. coli pathogens. Non–E. coli infections were more commonly found in males who had renal abnormalities and who had received antibiotic therapy in the prior month. Non–E. coli uropathogens were often resistant to cephalosporins and aminoglycosides. About 19% of the patients were initially treated with inappropriate empiric intravenous antibiotics. Fever from acute pyelonephritis may persist for several days despite appropriate therapy. Parenteral therapy should be maintained until the patient defervesces. If bacteremia is present, parenteral therapy should be continued for an additional 7–10 days and then the patient should be switched to oral treatment for 10–14 days. In patients who are not severely ill, outpatient treatment with oral antibiotics is appropriate. For adults, treatment with fluoroquinolones or TMP–SMX is well tolerated and effective. Therapy should continue for 10–14 days. Some patients in whom acute pyelonephritis develops will require follow-up radiologic examination such as voiding cystourethrogram or cystoscopy.
Emphysematous pyelonephritis is a necrotizing infection characterized by the presence of gas within the renal parenchyma or perinephric tissue. About 80–90% of patients with emphysematous pyelonephritis have diabetes; the rest of the cases are associated with urinary tract obstruction from calculi or papillary necrosis (Shokeir et al, 1997; Tseng et al, 2005).
Presentation and Findings
Patients with emphysematous pyelonephritis present with fever, flank pain, and vomiting that fails initial management with parenteral antibiotics (Tang et al, 2001). Pneumaturia may be present. Bacteria most frequently cultured from the urine include E. coli, Klebsiella pneumoniae, and Enterobacter cloacae.
The diagnosis of emphysematous pyelonephritis is made after radiographic examination. Gas overlying the affected kidney may be seen on a plain abdominal radiograph [kidneys, ureters, bladder (KUB)]. CT scan is much more sensitive in detecting the presence of gas in the renal parenchyma than renal ultrasonography.
In the management of emphysematous pyelonephritis, prompt control of blood glucose and relief of urinary obstruction are essential, in addition to fluid resuscitation and parenteral antibiotics. The mortality rate is 11–54% (Michaeli et al, 1984). Poor prognostic factors include high serum creatinine level, low platelet count, and the presence of renal/perirenal fluid in association with a bubbly/loculated gas pattern or gas in the collecting system (Wan et al, 1998). In combination with medical treatment, percutaneous drainage appears to be helpful in accelerating resolution of the infection and minimizing the morbidity and mortality of the infection (Chen et al, 1997). Nephrectomy may be required if there is no function in the affected kidney. About 3–4 weeks of parenteral antibiotic therapy is usually required.
Chronic pyelonephritis results from repeated renal infection, which leads to scarring, atrophy of the kidney, and subsequent renal insufficiency. The diagnosis is made by radiologic or pathologic examination rather than from clinical presentation.
Presentation and Findings
Many individuals with chronic pyelonephritis have no symptoms, but they may have a history of frequent UTIs. In children, there is a strong correlation between renal scarring and recurrent UTIs (Wennerstrom et al, 2000). The developing kidney appears to be very susceptible to damage, and this susceptibility appears to be age dependent. Renal scarring induced by UTIs is rarely seen in adult kidneys. Because patients with chronic pyelonephritis are often asymptomatic, the diagnosis is made incidentally when radiologic investigation is initiated to evaluate for the complications associated with renal insufficiency, such as hypertension, visual impairments, headaches, fatigue, and polyuria. In these patients, urinalysis may show leukocytes or proteinuria but is likely to be normal. Serum creatinine levels reflect the severity of the renal impairment. Urine cultures are only positive when there is an active infection.
Intravenous pyelogram or CT scan can readily demonstrate a small and atrophic kidney on the affected side. Focal coarse renal scarring with clubbing of the underlying calyx is characteristic. Ultrasonography similarly can demonstrate these findings. Dimercaptosuccinic acid (DMSA) is the best imaging modality to look for renal scarring (Figures 14–3A and B; Stoller and Kogan, 1986). Areas of scarring can be seen as photopenic areas.
Chronic pyelonephritis. Multiple parenchymal defects (white and black arrows) are seen on DMSA scan (A), suggestive of scarring from recurrent infection. Voiding cystourethrogram (B) revealed high-grade reflux in this patient.
The management of chronic pyelonephritis is somewhat limited because renal damage incurred by chronic pyelonephritis is not reversible. Eliminating recurrent UTIs and identifying and correcting any underlying anatomic or functional urinary problems such as obstruction or urolithiasis can prevent further renal damage. In children, evaluation for vesicoureteral reflux with a voiding cystourethrogram is important to eliminate a risk factor for recurrent pyelonephritis and renal scarring. Long-term use of continuous prophylactic antibiotic therapy may be required to limit recurrent UTIs and renal scarring. Rarely, removal of the affected kidney may be necessary due to hypertension or having a large stone burden in a nonfunctioning kidney.
Renal abscesses result from a severe infection that leads to liquefaction of renal tissue; this area is subsequently sequestered, forming an abscess. They can rupture out into the perinephric space, forming perinephric abscesses. When the abscesses extend beyond the Gerota's fascia, paranephric abscesses develop. Historically, most renal/perinephric abscesses result from hematogenous spread of staphylococci, in particular from infected skin lesions. Patients with diabetes, those undergoing hemodialysis, or intravenous drug abusers were at high risk for developing renal abscesses. With the development of effective antibiotics and better management of diseases such as diabetes and renal failure, renal/perinephric abscesses due to gram-positive bacteria are less prevalent; those caused by E. coli or Proteus species are becoming more common (Merimsky and Feldman, 1981; Thorley et al, 1974). Abscesses that form in the renal cortex are likely to arise from hematogenous spread, whereas those in the corticomedullary junction are caused from gram-negative bacteria in conjunction with some other underlying urinary tract abnormalities, such as stones or obstruction.
Presentation and Findings
The most common presenting symptoms in patients with renal/perinephric abscesses include fever, flank or abdominal pain, chills, and dysuria. Many of the symptoms have lasted for more than 2 weeks. A flank mass may be palpated in some patients. Urinalysis usually demonstrates WBCs; however, it may be normal in approximately 25% of the cases (Thorley et al, 1974). Urine cultures only identify the causative organisms in about one-third of cases and blood cultures in only about half of cases (Edelstein and McCabe, 1988).
Renal abscesses can be accurately detected using ultrasonography or CT scans. There is a wide range of ultrasonographic findings ranging from an anechoic mass within or displacing the kidney to an echogenic fluid collection that tends to blend with the normally echogenic fat within Gerota's fascia (Corriere and Sandler, 1982). With high sensitivity, CT scans can demonstrate an enlarged kidney with focal areas of hypoattenuation early on during the course of the infection. Once the inflammatory wall forms around the fluid collection, the abscess appears as a mass with a rim of contrast enhancement, the “ring” sign (Figure 14–4). CT scans may also demonstrate thickening of Gerota's fascia, stranding of the perinephric fat, or obliteration of the surrounding soft-tissue planes (Dalla Palma et al, 1999). Intravenous pyelogram and kidneys, ureter, and bladder tests are less sensitive tests in detecting renal/perinephric abscesses, with results being normal in about 20% of the cases (Thorley et al, 1974).
Renal abscess. CT scan with intravenous contrast demonstrates a large perinephric fluid collection with rim enhancement (white arrow). The parenchyma defect in the right kidney is suggestive of pyelonephritis.
The appropriate management of renal abscess first must include appropriate antibiotic therapy. Because it is often very difficult to identify the correct causative organisms from the urine or blood, empiric therapy with broad-spectrum antibiotics (ampicillin or vancomycin in combination with an aminoglycoside or third-generation cephalosporin) is usually recommended. If the patient does not respond within 48 hours of treatment, percutaneous drainage under CT scan or ultrasound guidance is indicated (Siegel et al, 1996). The drained fluid should be cultured for the causative organisms. If the abscess still does not resolve, then open surgical drainage or nephrectomy may be necessary. Follow-up imaging is needed to confirm resolution of the abscesses. These patients will also require evaluation for underlying urinary tract abnormalities such as stone or obstruction after the infection has resolved.
Xanthogranulomatous pyelonephritis (XGP) is a form of chronic bacterial infection of the kidney. The affected kidney is almost always hydronephrotic and obstructed. In most cases, XGP occurs unilaterally. Severe inflammation and necrosis obliterate the kidney parenchyma. Characteristically, foamy lipid-laden histiocytes (xanthoma cells) are present and may be mistaken for renal clear cell carcinoma (Iskandar et al, 1993; Lorentzen and Nielsen, 1980).
Presentation and Findings
Patients with XGP commonly present with flank pain, fever, chills, and persistent bacteriuria. A history of urolithiasis is present in about 35% of the patients (Malek and Elder, 1978). On physical examination, a flank mass can often be palpated. Urinalysis commonly demonstrates WBCs and protein. Serum blood analysis reveals anemia and may show hepatic dysfunction in approximately 50% of the patients (Malek and Elder, 1978). Because XGP primarily occurs unilaterally, azotemia or renal failure is not often seen (Goodman et al, 1979). E. coli or Proteus species are commonly cultured from the urine. However, one-third of patients with XGP have no growth in their urine, most likely because they have recently received antibiotic therapy. Approximately 10% of the patients with XGP have mixed organisms or anaerobic bacteria identified in their urine. Culture of the affected renal tissue can reliably identify the causative organism.
CT scan is the most reliable method in imaging patients suspected of having XGP. It usually demonstrates a large heterogeneous, reniform mass. The renal parenchyma is often marked with multiple water-density lesions, representing dilated calyces or abscesses (Figures 14–5A and B; Goldman et al, 1984). On contrast-enhanced images, these lesions will have a prominent blush peripherally, while the central areas, which are filled with pus and debris, do not enhance. An area of central calcification surrounded by a contracted pelvis may also be seen (Eastham et al, 1994). The inflammatory process may be seen extending to the perinephric fat, the retroperitoneum, and adjacent organs such as the psoas muscle, spleen, colon, or the great vessels. Because of the association of urolithiasis and XGP, renal calculi may be seen (Parsons, 1993). Renal ultrasonography can also be used in performing imaging on patients with XGP (Tiu et al, 2001). It usually reveals an enlarged kidney with a large central echogenic area and anechoic parenchyma. However, ultrasonography does not provide comparable anatomic details with those obtained from CT scan. It is not uncommon for XGP to be misdiagnosed as a renal tumor because of their similar appearances on radiologic imaging (Zorzos et al, 2002).
Xanthogranulomatous pyelonephritis. A: CT scan demonstrates a large heterogeneous left kidney, with dilated calyces and areas filled with lipid-laden macrophages. Xanthogranulomatous pyelonephritis is often associated with the presence of renal stones. B: Pathology specimen better demonstrated the pockets of intraparenchymal abscesses and deposition of macrophages (arrows). PNS, percutaneous nephrostomy.
The management of XGP is dependent on accurate diagnosis. In some cases, XGP is misdiagnosed as a renal tumor. A nephrectomy is performed and a diagnosis is made pathologically. In those in whom a diagnosis of XGP is suspected, kidney-sparing surgery such as a partial nephrectomy is indicated. However, when the infection is extensive, a nephrectomy with excision of all involved tissue is warranted. There are reported cases of treating XGP with antibiotic therapy alone (Brown et al, 1996) or in combination with percutaneous drainage; however, these treatments are not likely to be curative in most patients and may lead to complications such as renal cutaneous fistula.
Pyonephrosis refers to bacterial infection of a hydronephrotic, obstructed kidney, which leads to suppurative destruction of the renal parenchyma and potential loss of renal function. Because of the extent of the infection and the presence of urinary obstruction, sepsis may rapidly ensue, requiring rapid diagnosis and management.
Presentation and Findings
Patients with pyonephrosis are usually very ill, with high fever, chills, and flank pain. Lower tract symptoms are not usually present. Bacteriuria and pyuria may not be present when there is complete obstruction of the affected kidney.
Imaging with renal ultrasonography can be performed to rapidly diagnose pyonephrosis. Ultrasonographic findings include persistent echoes in the inferior portion of the collecting system, fluid–debris level with dependent echoes that shift with positional changes (Figure 14–6), strong echoes with acoustic shadowing from air in the collecting system, and weak echoes throughout a dilated collecting system. Renal or ureteral calculi may also be identified on ultrasonography.
Pyonephrosis. Ultrasonography demonstrates fluid–debris level (white arrow) within the dilated renal pelvis.
Management of pyonephrosis includes immediate institution of antibiotic therapy and drainage of the infected collecting system. Broad-spectrum antimicrobials are indicated to prevent sepsis while the causative organism is being identified; antibiotics should be started before manipulation of the urinary tract. Performing drainage of the obstruction through the lower urinary tract (such as using a ureteral stent) should be reserved for patients who are not septic. Extensive manipulation may rapidly induce sepsis and toxemia. In the ill patient, drainage of the collecting system with a percutaneous nephrostomy tube is preferable. Once the infection is treated, additional imaging evaluation is required to identify the cause of the urinary obstruction, such as urolithiasis or ureteropelvic junction obstruction.
Acute cystitis refers to urinary infection of the lower urinary tract, principally the bladder. Acute cystitis more commonly affects women than men. The primary mode of infection is ascending from the periurethral/vaginal and fecal flora. The diagnosis is made clinically. In children, the distinction between upper and lower UTI is important. In general, those in whom acute cystitis developed do not usually require any extensive radiologic investigation (such as a voiding cystourethrogram), but those in whom pyelonephritis developed do (American Academy of Pediatrics, 1999).
Presentation and Findings
Patients with acute cystitis present with irritative voiding symptoms such as dysuria, frequency, and urgency. Low back and suprapubic pain, hematuria, and cloudy/foul-smelling urine are also common symptoms. Fever and systemic symptoms are rare. Typically, urinalysis demonstrates WBCs in the urine, and hematuria may be present. Urine culture is required to confirm the diagnosis and identify the causative organism. However, when the clinical picture and urinalysis are highly suggestive of the diagnosis of acute cystitis, urine culture may not be needed. E. coli causes most of the acute cystitis. Other gram-negative (Klebsiella and Proteus spp.) and gram-positive (S. saprophyticus and enterococci) bacteria are uncommon pathogens (Gupta et al, 1999a). Diabetes and lifetime history of UTI are risk factors for acute cystitis. Of interest, the use of oral or vaginal estrogen was not protective in postmenopausal women with recurrent acute cystitis (Jackson et al, 2004).
In uncomplicated infection of the bladder, radiologic evaluation is often not necessary.
Management for acute cystitis consists of a short course of oral antibiotics (reviewed by Falagas et al, 2009). TMP–SMX, nitrofurantoin, and fluoroquinolones have excellent activity against most pathogens that cause cystitis. TMP–SMX and nitrofurantoin are less expensive and thus are recommended for the treatment of uncomplicated cystitis (Huang and Stafford, 2002). However, it is estimated that resistance to TMP–SMX by E. coli isolates causing uncomplicated acute cystitis is approximately 20%, compared with <2% to nitrofurantoin (Gupta et al, 1999a). In adults and children, the duration of treatment is usually limited to 3–5 days (Abrahamsson et al, 2002; Naber, 1999). Longer therapy is not indicated. Single-dose therapy for the treatment of recurrent cystitis/UTI appears to be less effective (Philbrick, 1986); however, fluoroquinolones with long half-lives (fleroxacin, pefloxacin, and rufloxacin) may be suitable for single-dose therapy (Naber, 1999). Resistance to penicillins and aminopenicillins is high and thus they are not recommended for treatment.
Presentation and Findings
Recurrent cystitis/UTI is caused either by bacterial persistence or reinfection with another organism. Identification of the cause of the recurrent infection is important, because the management of bacterial persistence and reinfection are distinct. If bacterial persistence is the cause of recurrent UTI, the removal of the infected source is often curative, whereas preventative therapy is effective in treating reinfection.
When bacterial persistence is the suspected cause, radiologic imaging is indicated. Ultrasonography can be obtained to provide a screening evaluation of the genitourinary tract. More detailed assessment with intravenous pyelogram, cystoscopy, and CT scans may occasionally be necessary. In patients who have frequent, recurrent UTI, bacterial localization studies and more extensive radiologic evaluation (such as retrograde pyelograms) are warranted. When bacterial reinfection is the suspected cause of recurrent cystitis, the patient should be carefully evaluated for evidence of vesicovaginal or vesicoenteric fistula. Otherwise, radiologic examination is often not necessary in these patients.
Management of recurrent cystitis, again, depends on its cause. Surgical removal of the infected source (such as urinary calculi) is needed to treat bacterial persistence. Similarly, fistulas need to be repaired surgically to prevent bacterial reinfection. In most cases of bacterial reinfection, medical management with prophylactic antibiotics is indicated. Low-dose continuous prophylactic antibiotic has been shown to reduce the recurrences of UTI by 95% compared with placebo or historical controls (Mangiarotti et al, 2000; Nicolle and Ronald, 1987). Alternatively, intermittent self-start antibiotic therapy can be used in treating recurrent cystitis in some women. Motivated patients self-identify episodes of infection on the basis of their symptoms and treat themselves with a single dose of antibiotics such as TMP–SMX. This regimen has been shown to be effective and economical in selected patients (Pfau and Sacks, 1993; Raz et al, 1991). When the recurrent cystitis/UTI is related to sexual activity, frequent emptying of the bladder and a single dose of antibiotic taken after sexual intercourse can significantly reduce the incidence of recurrent infection (Pfau and Sacks, 1994). Alternatives to antibiotic therapy in the treatment of recurrent cystitis/UTI include intravaginal estriol (Raz and Stamm, 1993), lactobacillus vaginal suppositories (Reid and Burton, 2002), and cranberry juice taken orally (Lowe and Fagelman, 2001).
Malakoplakia is an uncommon inflammatory disease of the bladder that can also affect other parts of the urinary tract, including the ureters and kidneys (Stanton and Maxted, 1981). In the bladder, it manifests as plaques or nodules made of large histiocytes (von Hansemann cells) with laminar inclusion bodies (Michaelis–Gutmann bodies) (McClure et al, 1981).
Presentation and Findings
Malakoplakia more commonly affects women than men (Stanton and Maxted, 1981) and is associated with a history of UTI. Patients with malakoplakia often have chronic illness or are immunosuppressed. In patients with malakoplakia of the bladder, irritative voiding symptoms (urgency and frequency) and hematuria are common (Curran, 1987). When the disease affects the ureter or kidney, the patient may present with fever, flank pain, or flank mass. When it affects both kidneys, signs or symptoms of azotemia or renal failure may be present (Dobyan et al, 1993). Treatment with fluoroquinolone has significantly decreased the mortality rate associated with renal malakoplakia (Tam et al, 2003).
Radiologic imaging with ultrasonography or CT may demonstrate a mass in the bladder and evidence of obstruction if the disease extends to the ureter (Vas et al, 1985). When the disease involves the kidney, focal or diffuse, hypodense, parenchymal masses may be seen on CT imaging (Frederic et al, 1981). It is often difficult to distinguish malakoplakia from malignancy (transitional cell or renal cell carcinoma) with radiologic imaging. The diagnosis is often established after biopsy.
Management of malakoplakia primarily consists of antibiotic therapy, in particular those that produce high intracellular levels. Consequently, TMP–SMX and fluoroquinolones are recommended in the treatment of malakoplakia. Bethanecol and ascorbic acid, which enhance phagolysosomal activity, may have some benefits (Stanton and Maxted, 1981; Trujillo-Santos et al, 1999). In patients with malakoplakia limited to the lower urinary tract, antibiotic therapy alone is usually sufficient. However, when malakoplakia involves the ureter or kidney, surgical excision may be needed in addition to the antibiotic therapy (Dasgupta et al, 1999; Long and Althausen, 1989). The prognosis is poor and the mortality rate is high in patients who have bilateral renal involvement, regardless of treatment.
Acute Bacterial Prostatitis
Acute bacterial prostatitis refers to inflammation of the prostate associated with a UTI. It is thought that infection results from ascending urethral infection or reflux of infected urine from the bladder into the prostatic ducts. In response to bacterial invasion, leukocytes (polymorphonuclear leukocytes, lymphocytes, plasma cells, and macrophages) are seen within and surrounding the acini of the prostate. Edema and hyperemia of the prostatic stroma frequently develop. With prolonged infection, variable degree of necrosis and abscess formation can occur.
Presentation and Findings
Acute bacterial prostatitis is uncommon in prepubertal boys but frequently affects adult men. It is the most common urologic diagnosis in men younger than 50 years (Collins et al, 1998). Patients with acute bacterial prostatitis usually present with an abrupt onset of constitutional (fever, chills, malaise, arthralgia, myalgia, lower back/rectal/perineal pain) and urinary symptoms (frequency, urgency, dysuria). They may also present with urinary retention due to swelling of the prostate. Digital rectal examination reveals tender, enlarged glands that are irregular and warm. Urinalysis usually demonstrates WBCs and occasionally hematuria. Serum blood analysis typically demonstrates leukocytosis. Prostate-specific antigen levels are often elevated. The diagnosis of prostatitis is made with microscopic examination and culture of the prostatic expressate and culture of urine obtained before and after prostate massage. In patients with acute prostatitis, fluid from the prostate massage often contains leukocytes with fat-laden macrophages. However, at the onset of acute prostatitis, prostatic massage is usually not suggested because the prostate is quite tender and the massage may lead to bacteremia. Similarly, urethral catheterization should be avoided. Culture of urine and prostate expressate usually identifies a single organism, but occasionally, polymicrobial infection may occur. E. coli is the most common causative organism in patients with acute prostatitis. Other gram-negative bacteria (Proteus, Klebsiella, Enterobacter, Pseudomonas, and Serratia spp.) and enterococci are less frequent pathogens. Anaerobic and other gram-positive bacteria are rarely a cause of acute prostatitis (Roberts et al, 1997b).
Radiologic imaging is rarely indicated in patients with acute prostatitis. Bladder ultrasonography may be useful in determining the amount of residual urine. Transrectal ultrasonography is indicated only in patients who do not respond to conventional therapy.
Treatment with antibiotics is essential in the management of acute prostatitis. Empiric therapy directed against gram-negative bacteria and enterococci should be instituted immediately while awaiting the culture results. Trimethoprim and fluoroquinolones have high drug penetration into prostatic tissue and are recommended for 4–6 weeks (Wagenlehner et al, 2005). The long duration of antibiotic treatment is to allow complete sterilization of the prostatic tissue to prevent complications such as chronic prostatitis and abscess formation (Childs, 1992; Nickel, 2000). Patients who have sepsis, are immunocompromised or in acute urinary retention, or have significant medical comorbidities would benefit from hospitalization and treatment with parenteral antibiotics. Ampicillin and an aminoglycoside provide effective therapy against both gram-negative bacteria and enterococci. Patients with urinary retention secondary to acute prostatitis should be managed with a suprapubic catheter because transurethral catheterization or instrumentation is contraindicated.
Chronic Bacterial Prostatitis
In contrast to the acute form, chronic bacterial prostatitis has a more insidious onset, characterized by relapsing, recurrent UTI caused by the persistence of pathogen in the prostatic fluid despite antibiotic therapy.
Presentation and Findings
Most patients with chronic bacterial prostatitis typically present with dysuria, urgency, frequency, nocturia, and low back/perineal pain. These patients usually are afebrile and not uncommonly have a history of recurrent or relapsing UTI, urethritis, or epididymitis caused by the same organism (Nickel and Moon, 2005). Others are asymptomatic, but the diagnosis is made after investigation for bacteriuria. In patients with chronic bacterial prostatitis, digital rectal examination of the prostate is often normal; occasionally, tenderness, firmness, or prostatic calculi may be found on examination. Urinalysis demonstrates a variable degree of WBCs and bacteria in the urine, depending on the extent of the disease. Serum blood analysis normally does not show any evidence of leukocytosis. Prostate-specific antigen levels may be elevated. Diagnosis is made after identification of bacteria from prostate expressate or urine specimen after a prostatic massage, using the four-cup test (Table 14–8). The causative organisms are similar to those of acute bacterial prostatitis. It is currently believed that other gram-positive bacteria, Mycoplasma, Ureaplasma, and Chlamydia spp. are not causative pathogens in chronic bacterial prostatitis.
Table 14–8. Technique of Localization Cultures (Four-Cup Test) for the Diagnosis of Prostatitis. ||Download (.pdf)
Table 14–8. Technique of Localization Cultures (Four-Cup Test) for the Diagnosis of Prostatitis.
- Require that the patient has a full bladder
- Retract foreskin of uncircumcised men
- Clean glans with soap/water or povidone-iodine
- Collect first 10 mL of voided urine (VB1)
- Discard the next 100 mL
- Collect the next 10 mL of voided urine (VB2)
- Massage prostate and collect prostate expressate (EPS)
- Collect first 10 mL of voided urine after massage (VB3)
- Immediate culture and microscopic examination of all specimen
- All specimens <103 CFU/mL → not bacterial prostatitis
- VB3 or EPS >10× CFU of VB1 → chronic bacterial prostatitis
- VB1 > other specimens → urethritis or specimen contamination
- All specimens >103 CFU/mL → treat for UTI and repeat test
- Sensitivity of the test may not be high (Lipsky, 1999)
- Time consuming and expensive
- Voided specimen before and after prostate massage (Nickel, 1997)
Radiologic imaging is rarely indicated in patients with chronic prostatitis. Transrectal ultrasonography is only indicated if a prostatic abscess is suspected.
Antibiotic therapy is similar to that for acute bacterial prostatitis (Bjerklund Johansen et al, 1998). Interestingly, the presence of leukocytes or bacteria in the urine and prostatic massage does not predict antibiotic response in patients with chronic prostatitis (Nickel et al, 2001). In patients with chronic bacterial prostatitis, the duration of antibiotic therapy may be 3–4 months. Using fluoroquinolones, some patients may respond after 4–6 weeks of treatment. The addition of an alpha-blocker and anti-inflammatory agents to antibiotic therapy has been shown to reduce symptom recurrences (Barbalias et al, 1998; Murphy et al, 2009). Despite maximal therapy, cure is not often achieved due to poor penetration of antibiotic into prostatic tissue and relative isolation of the bacterial foci within the prostate. Third-line agents include 5α-reductase inhibitors, glycosaminoglycans, quercetin, cernilton (CN-009), and saw palmetto. When recurrent episodes of infection occur despite antibiotic therapy, suppressive antibiotic (TMP–SMX 1 single-strength tablet daily, nitrofurantoin 100 mg daily, or ciprofloxacin 250 mg daily) may be used (Meares, 1987). Transurethral resection of the prostate has been used to treat patients with refractory disease; however, the success rate has been variable and this approach is not generally recommended (Barnes et al, 1982).
Granulomatous prostatitis is an uncommon form of prostatitis. It can result from bacterial, viral, or fungal infection, the use of bacillus Calmette-Guérin therapy (Rischmann et al, 2000), malakoplakia, or systemic granulomatous diseases affecting the prostate. Two-thirds of the cases have no specific cause. There are two distinct forms of nonspecific granulomatous prostatitis: noneosinophilic and eosinophilic. The former represents an abnormal tissue response to extravasated prostatic fluid (O'Dea et al, 1977). The latter is a more severe, allergic response of the prostate to some unknown antigen.
Presentation and Findings
Patients with granulomatous prostatitis often present acutely, with fever, chills, and obstructive/irritative voiding symptoms. Some may present with urinary retention. Patients with eosinophilic granulomatous prostatitis are severely ill and have high fevers. Digital rectal examination in patients with granulomatous prostatitis demonstrates a hard, indurated, and fixed prostate, which is difficult to distinguish from prostate carcinoma. Urinalysis and culture do not show any evidence of bacterial infection. Serum blood analysis typically demonstrates leukocytosis; marked eosinophilia is often seen in patients with eosinophilic granulomatous prostatitis. The diagnosis is made after biopsy of the prostate.
Some patients respond to antibiotic therapy, corticosteroids, and temporary bladder drainage. Those with eosinophilic granulomatous prostatitis dramatically response to corticosteroids (Ohkawa et al, 2001). Transurethral resection of the prostate may be required in patients who do not respond to treatment and have significant outlet obstruction.
Most cases of prostatic abscess result from complications of acute bacterial prostatitis that were inadequately or inappropriately treated. Prostatic abscesses are often seen in patients with diabetes; those receiving chronic dialysis; or patients who are immunocompromised, undergoing urethral instrumentation, or who have chronic indwelling catheters.
Presentation and Findings
Patients with prostatic abscess present with similar symptoms to those with acute bacterial prostatitis. Typically, these patients were treated for acute bacterial prostatitis previously and had a good initial response to treatment with antibiotics. However, their symptoms recurred during treatment, suggesting development of prostatic abscesses. On digital rectal examination, the prostate is usually tender and swollen. Fluctuance is only seen in 16% of patients with prostatic abscess (Weinberger et al, 1988).
Imaging with transrectal ultrasonography (Figure 14–7) or pelvic CT scan is crucial for diagnosis and treatment.
Prostatic abscess. Transrectal ultrasonography demonstrates hypoechoic lesions (black and white arrows) in the prostate consistent with abscesses.
Antibiotic therapy in conjunction with drainage of the abscess is required. Transrectal ultrasonography or CT scan can be used to direct transrectal drainage of the abscess (Barozzi et al, 1998). Transurethral resection and drainage may be required if transrectal drainage is inadequate. When properly diagnosed and treated, most cases of prostatic abscess resolve without significant sequelae (Weinberger et al, 1988).
Infection/inflammation of the urethra can be categorized into those types caused by Neisseria gonorrhoeae and by other organisms (Chlamydia trachomatis, Ureaplasma urealyticum, Trichomonas vaginalis, and herpes simplex virus) (Dixon et al, 2002). Most cases are acquired during sexual intercourse.
Presentation and Findings
Patients with urethritis may present with urethral discharge and dysuria. The amount of discharge may vary significantly, from profuse to scant amounts. Obstructive voiding symptoms are primarily present in patients with recurrent infection, in whom urethral strictures subsequently develop. It is important to note that approximately 40% of patients with gonococcal urethritis are asymptomatic (John and Donald, 1978). The diagnosis is made from examination and culture of the urethra. It is important to obtain the specimen from within the urethra, rather than from just the discharge. Approximately 30% of men infected with N. gonorrhoeae will have concomitant infection with C. trachomatis.
Retrograde urethrogram is indicated only in patients with recurrent infection and obstructive voiding symptoms. Most patients with uncomplicated urethritis do not require any radiologic imaging.
Pathogen-directed antibiotic therapy is required. In patients with gonococcal urethritis, ceftriaxone (250 mg intramuscularly) or fluoroquinolones (ciprofloxacin 250 mg) (David et al, 2000) or norfloxacin (800 mg) may be used. For patients with nongonococcal urethritis, treatment is with tetracycline or erythromycin (500 mg four times daily) or doxycycline (100 mg twice daily) for 7–14 days (O'Mahony, 1999). However, the most essential component of treatment is prevention. Sexual partners of the affected patients should be treated, and protective sexual practices (such as using condoms) are recommended.
Causes of Epididymitis/Orchitis
Infection and inflammation of the epididymis most often result from an ascending infection from the lower urinary tract. The infection in the epididymis may spread to involve the testis. Most cases of epididymitis/orchitis in men younger than 35 years are due to sexually transmitted organisms (N. gonorrhoeae and C. trachomatis); those in children and older men are due to urinary pathogens such as E. coli. Other causes of epididymitis/orchitis in young children are due to a postinfectious inflammatory reaction to pathogens such as mycoplasma pneumoniae, enteroviruses, and adenoviruses, which often follows a more benign course. In homosexual men who practice anal intercourse, E. coli and other coliform bacteria are common causative organisms.
Presentation and Findings
Patients with epididymitis/orchitis present with severe scrotal pain that may radiate to the groin or flank. Scrotal enlargement due to the inflammation of the epididymis/testis or a reactive hydrocele may develop rapidly. Other symptoms of urethritis, cystitis, or prostatitis may be present before or concurrent with the onset of scrotal pain. On physical examination, an enlarged and red scrotum is present, and it is often difficult to distinguish the epididymis from the testis during the acute infection. A thickened spermatic cord can occasionally be palpated. Urinalysis typically demonstrates WBCs and bacteria in the urine or urethral discharge. Serum blood analysis often reveals leukocytosis.
Frequently, it is difficult to distinguish epididymitis from acute testicular torsion based on the history and physical examination alone (Petrack and Hafeez, 1992). Scrotal Doppler ultrasonography or radionuclide scanning can be used to confirm the diagnosis (Paltiel et al, 1998). The presence of blood flow in the testis on Doppler ultrasonography or uptake of the tracers into the center of the testis on radionuclide scanning rules out torsion. On scrotal ultrasonography, patients with epididymitis/orchitis commonly have an enlarged epididymis or testis with increased blood flow. A reactive hydrocele may also be seen. Prepubertal children who are diagnosed with epididymitis will require radiologic investigation for urinary tract anomalies such as reflux or ureteral ectopia (Likitnukul et al, 1987). Postpubertal children who are diagnosed with epididymitis should be educated about sexually transmitted diseases and safe sexual practices.
Oral antibiotic treatment is directed against specific causative organisms, as mentioned in the previous sections on urethritis and UTI. In addition, bed rest, scrotal elevation, and the use of nonsteroidal anti-inflammatory agents are helpful in reducing the duration of the symptoms. In patients with epididymitis/orchitis caused by sexually transmitted organisms, treatment of their sexual partners is recommended to prevent reinfection. For patients with sepsis or severe infection, hospitalization and parenteral antibiotic therapy may be needed. Open drainage is indicated in cases in which an abscess develops. Occasionally, patients with chronic, relapsing epididymitis and scrotal pain may require epididymectomy/orchiectomy for relief of their symptoms.
With pregnancy, there are anatomic and physiologic changes to the urinary tract due to compression by the gravid uterus and alterations in the hormonal milieu. Renal length increases approximately by 1 cm during normal pregnancy as a result of increased vascular and interstitial volume (Waltzer, 1981). The glomerular filtration rate increases by 30–50%, most likely secondary to the increase in cardiac output (Waltzer, 1981). Typically, there is significant ureteral dilation with resultant urinary stasis during the second and third trimesters of gestation. This hydroureter is attributed to the smooth muscle–relaxing effects of progesterone and the mechanical compression of the ureters by the uterus at the level of the pelvic brim (Waltzer, 1981). The bladder is also affected, both physically and physiologically. The enlarged uterus displaces the bladder superiorly and anteriorly. The bladder becomes hyperemic, and its capacity is increased, most likely due to the effects of progesterone (Waltzer, 1981).
Because of these changes in the urinary tract during normal pregnancy, bacteriuria is a clinically relevant finding in pregnant women. It is estimated that the prevalence of bacteriuria is 4–6% (Sweet, 1977), which is not significantly different from that in nonpregnant women of comparable age. Interestingly, approximately 30% of those who have bacteriuria on screening evaluation later have pyelonephritis, compared with only 1–2% in those who do not have bacteriuria (Sweet, 1977). Treatment of bacteriuria decreases the incidence of pyelonephritis during pregnancy to approximately 3% (Christensen, 2000; Sweet, 1977). A history of previous UTIs and low socioeconomic status are risk factors for bacteriuria in pregnancy (Schnarr and Smaill, 2008).
Overall, the incidence of acute bacterial pyelonephritis is 1–4% in pregnant women (Gilstrap et al, 1981; Wing, 1998). About 60–70% of the episodes of pyelonephritis occur during the second and third trimesters of pregnancy, when urinary stasis is the greatest. In 10–20%, recurrent episodes of pyelonephritis develop before delivery (Gilstrap et al, 1981). Significant maternal risk factors include diabetes and history of UTI. When left untreated, pyelonephritis during pregnancy is associated with a high rate of infant prematurity and its associated perinatal mortality (Locksmith and Duff, 2001; McGregor and French, 1998; Schieve et al, 1994). It remains unclear whether treated pyelonephritis during pregnancy has any effects on the developing fetus (Gilstrap and Ramin, 2001).
Consequently, it is recommended that women be screened for bacteriuria during pregnancy to prevent the development of pyelonephritis. A voided urine specimen should be obtained at the first prenatal visit and at 16 weeks of gestation (Stenqvist et al, 1989). For asymptomatic individuals, significant bacteriuria is defined as two voided urine cultures with >105 CFU/mL of a single organism. For symptomatic pregnant women, >103 CFU/mL is considered to be significant (Rubin et al, 1992). Pregnant women who are found to have bacteriuria should be treated with penicillins, oral cephalosporins (Christensen, 2000; Wing et al, 1999), or fosfomycin trometamol (Minassian et al, 1998). Table 14–9 lists the antibiotics and their effects on pregnancy. However, amoxicillin is not recommended because of the rate of bacterial resistance (Hart et al, 2001). A 3-day course is suggested, although single-dose therapy may be effective in some patients (Tincello and Richmond, 1998). Repeat urine culture to document eradication of bacteriuria is necessary in all patients. Patients with acute bacterial pyelonephritis should be treated with parenteral cephalosporins, penicillins with beta-lactamase inhibitors, or monobactams (Rubin et al, 1992). Periodic surveillance urine culture is recommended because many of these women will have recurrent episodes of pyelonephritis.
Table 14–9. Antibiotics and Their Effects on Pregnancy. ||Download (.pdf)
Table 14–9. Antibiotics and Their Effects on Pregnancy.
Side effects on the developing fetus
Interferes with neural tube development
Dysplasia and discoloration of teeth and bones
Hemolysis and G6PD deficiency
Interferes with cartilage formation
UTI in Patients with Human Immunodeficiency Virus or Acquired Immunodeficiency Syndrome
Human immunodeficiency virus (HIV) alters the normal host defense against bacterial infection. When the CD4 lymphocyte count falls to <200 per mm3, the risk of bacterial and opportunistic UTI increases dramatically (Evans et al, 1995; Hoepelman et al, 1992). In addition, antiretroviral medications used to treat HIV (eg, zidovudine) can further suppress normal immune response and increase the risk of UTI in these patients.
Hoepelman et al (1992) obtained urine cultures from HIV-positive men prospectively and when they had symptoms suggestive of a UTI. They observed that positive urine cultures were identified in 30% of HIV-infected men with CD4 < 200 per mm3 and in 11% with CD4 = 200–500 per mm3, while none with CD4 > 500 per mm3 had evidence of a urine infection. Gugino et al (1998) similarly observed that the incidence of bacteriuria in asymptomatic HIV-infected women was the same as that in uninfected women. Causative organisms include common uropathogens such as E. coli and Klebsiella and Enterococcus spp. Urinary infection with S. aureus and Pseudomonas aeruginosa is more common in HIV-infected patients (Schonwald et al, 1999). Because of the common prophylactic use of TMP–SMX to prevent Pneumocystis carinii pneumonia in AIDS patients, the incidence of UTI in this group is decreased. However, when a UTI develops in these patients, the infecting organism is typically resistant to TMP–SMX (van Dooyeweert et al, 1996).
In HIV patients, the incidence of bacterial prostatitis is approximately 3% and it is 14% in patients with AIDS, compared with 1–2% in noninfected men of similar age (Leport et al, 1989). Causative organisms include common prostatitis pathogens such as E. coli and Proteus spp. and other less common organisms such as Salmonella typhi, S. aureus, P. aeruginosa, and N. gonorrhoeae (Staiman and Lowe, 1995). Prolonged treatment (4–6 weeks) with fluoroquinolones may be necessary because of a high risk of reinfection and lower immunity status in these patients. Prostatic abscess is more common in patients with AIDS compared with that in the general population (Staiman and Lowe, 1995; Trauzzi et al, 1994). Causative organisms include E. coli and other gram-negative bacteria or opportunistic fungus or mycobacterial infection (Lee et al, 2001). Effective drainage and prolonged antimicrobial or antifungal therapy are needed.
Epididymitis and Urethritis
In HIV-infected men, epididymitis may be caused by N. gonorrhoeae and C. trachomatis. However, infection by coliform bacteria such as E. coli is more common, especially in patients having unprotected anal intercourse (Berger et al, 1987). In HIV-infected patients with suppurative or antibiotic-resistant epididymitis, infection with fungi or mycobacteria should be considered (Desmond et al, 1993). In HIV-infected men who present with urethritis, treatment for both Chlamydia and N. gonorrhoeae is indicated even when gonococcus is isolated only from culture. Due to increased viral shedding with genital infections, it is recommended that HIV-infected patients abstain from sexual intercourse until 7 days after treatment is completed.
Infection by Uncommon Organisms
Urinary infection with Mycobacterium species can develop in HIV-infected patients. The kidneys are first infected and the infection spreads to the lower urinary tract. In patients with AIDS, it is estimated that 6–23% have renal tuberculosis (Marques et al, 1996). M. tuberculosis is the most common pathogen, with Mycobacterium avium and Mycobacterium intracellulare being less common (Sepkowitz et al, 1995). In HIV-infected patients who present with irritative/obstructive voiding symptoms but have no evidence of bacterial infection on culture, infection of the lower urinary tract by Mycobacterium species should be considered. Treatment with at least two antituberculosis agents is needed for 6–9 months.
UTIs in Patients with Diabetes Mellitus
UTIs are more common and tend to have more complicated course in patients with diabetes mellitus (reviewed by Chen et al, 2009). There is a two- to fivefold increase in the incidence of acute pyelonephritis in diabetic patients compared with nondiabetic patients. Complications such as emphysematous pyelonephritis and renal and perirenal abscesses are more frequently seen in the diabetic patients (Williams and Schaeffer, 2004). Interestingly, the mortality and risk of hospitalization for UTI were not increased in patients with diabetes; however, the length of hospitalization may be prolonged. Asymptomatic bacteriuria occurs in diabetic women more commonly than in nondiabetics. It is associated with an increased risk of UTI among patients with type-2 diabetes. However, treatment of asymptomatic bacteriuria with antimicrobial therapy has not been shown to reduce symptomatic UTIs, pyelonephritis, or hospitalization for UTI (Ooi et al, 2004).
The risk for UTI correlated with the degree of glycemia as measured by HBA1c. Autonomic neuropathy resulting in dysfunctional voiding and urinary retention can prevent bacterial clearance through micturition and thereby promoting bacterial growth. Defects in the local urinary cytokine secretions and an increased adherence of the microorganisms to the uroepithelial cells are also potential mechanisms that may contribute to the increased prevalence of both asymptomatic and symptomatic bacteriuria in these patients (Hoepelman et al, 2003; Nicolle, 2005). No relationship between specific uropathogen prevalence and diabetes status have been found; however, diabetic patients with asymptomatic bacteriuria are more likely to be infected with by Klebsiella and Enterococcus than by E. coli.
Although resistant bacteria are more frequently found in diabetic patients with UTI, empiric treatment with antibiotic therapy for a diabetic patient with complicated UTIs is similar to that of the nondiabetic patient. One important exception is that staphylococcal infection is not uncommon in the diabetic patients and can lead to urinary tract sepsis. This should be considered especially when a diabetic patient presents with a renal carbuncle. Oral outpatient therapy is not recommended for the diabetic patient with a complicated UTI. Treatment with TMP–SMX should be avoided if possible, because it can potentiate the hypoglycemic effects of the oral hypoglycemic drugs. Fluoroquinolones are safe and effective (ie, low resistance) in the treatment of diabetic patients with complicated UTIs (Williams and Schaeffer, 2004).