17 - Urinary Tract Infections

Authors: Macfarlane, Michael T.

Title: Urology, 4th Edition

Copyright 2006 Lippincott Williams & Wilkins

> Table of Contents > Part Two - Selected Topics > Chapter 17 - Urinary Tract Infections

Chapter 17

Urinary Tract Infections

Urinary tract infections (UTIs) are common and potentially disabling. It is important to use the same terminology when referring to various types of infectious episodes. Bacteriuria is merely the presence of bacteria in the urine, whereas a UTI implies an inflammatory response to bacterial invasion of the tissues. Pyuria is the presence of white blood cells (WBCs) in the urine seen on microscopic urinalysis and is an indication of an inflammatory process.

Classification of Urinary Tract Infections

• First infection

• Unresolved bacteriuria during therapy (most commonly owing to a resistant organism)

• Recurrent UTIs:

  • Reinfection (>80%) recurrence from new organisms outside the urinary tract

  • Bacterial persistence (uncommon) recurrence from the same organism within the urinary tract despite sterilization of urine during therapy

Causes of Bacterial Persistence

• Infected stones

• Chronic bacterial prostatitis

• Unilateral infected atrophic kidney

• Vesicovaginal or intestinal fistulas

• Ureteral anomalies

• Infected diverticula

• Foreign bodies (stents, catheters)

• Infected urachal cyst

• Infected medullary sponge kidney

• Infected papillary necrosis

• Ureteral stump after nephrectomy

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Factors That Increase Risk of Complications from Urinary Tract Infections

• Urinary tract obstruction

• Infections from urea-splitting bacteria

• Diabetes mellitus

• Renal papillary necrosis

• Neurogenic bladders

• Pregnancy

• Congenital urinary tract anomalies

• Elderly patient with acute bacterial prostatitis

• Severe reflux in children younger than 4 years

• End-stage renal disease on hemodialysis

• Immunosuppression after a renal transplant

Upper Tract Infections

Acute Pyelonephritis

Acute pyelonephritis is associated with a clinical syndrome of chills, fever, and flank pain as a result of bacterial infection of the renal parenchyma and pelvis. It is usually associated with dysuria, pyuria, frequency, and urgency. The most common causative organisms are Escherichia coli, Klebsiella, Proteus, Enterobacter, Pseudomonas, Serratia, Citrobacter, occasionally Streptococcus fecalis, and rarely Staphylococcus aureus. Infection usually results from bacteria ascending from the lower urinary tract. Hematogenous infection occurs infrequently.

Workup

• Urinalysis (pyuria, bacteriuria, hematuria)

• Urine culture and sensitivity (before and during therapy)

• Complete blood count (CBC) (significant neutrophilic leukocytosis)

• Blood culture (frequently positive)

• Noncontrast CT of abdomen and pelvis or intravenous urography (IVU) (may show stones or obstruction)

• Renal ultrasound (stones, hydronephrosis, or abscess)

• Voiding cystourethrography (VCUG) (delay several weeks because transient reflux can often occur during an acute infection)

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Differential Diagnosis

Differential diagnosis includes pancreatitis, basal pneumonia, appendicitis, cholecystitis, diverticulitis, and pelvic inflammatory disease.

Management

In uncomplicated cases, outpatient management with an oral fluoroquinolone may be appropriate. In others, intravenous (IV) antibiotic therapy should be started without delay after cultures are sent. A quinolone or ampicillin [1 g IV every 6 hours (q6h)] and gentamicin or tobramycin [1.5 mg/kg IV every 8 hours (q8h)] are a good choice initially until culture and sensitivity results are available. Obstruction noted on imaging studies must be relieved. Fevers will often persist for 2 to 5 days despite sterile urine and antibiotic therapy. However, if the urine continues to show infection, reevaluation should be instituted to rule out obstruction, abscess, or inappropriate antibiotic selection. If symptoms have resolved after 2 to 5 days of IV antibiotics, the patient may be switched to oral (PO) medication for an additional 10 to 14 days.

Pyonephrosis

Pyonephrosis refers to a patient with acute pyelonephritis complicated by obstructed hydronephrosis. The IVU will show nonfunction or poor visualization of the involved kidney. Renal ultrasound or CT scan can usually make the diagnosis. Fifty percent of obstructed pyonephrotic kidneys are nonfunctioning. Obstruction should always be ruled out in pyelonephritis. Renal ultrasound is usually sufficient.

Management

IV antibiotics and immediate relief of obstruction by either a percutaneous nephrostomy or placement of a retrograde ureteral stent are mandatory.

Emphysematous Pyelonephritis

Emphysematous pyelonephritis is an acute necrotizing parenchymal and perirenal infection. It is a rare complication of acute pyelonephritis in which organisms (generally E. coli) ferment glucose to CO₂ and H₂O, producing gas in the renal parenchyma. The characteristic appearance of intraparenchymal gas on kidney, ureter, and bladder (KUB) study is diagnostic. Eighty percent of

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cases occur in poorly controlled insulin-dependent diabetics, and the rest occur in patients with obstruction. Prognosis is poor with a high mortality.

Management consists of IV antibiotics, relief of obstruction, and frequently nephrectomy.

Renal Abscess (Carbuncle)

Renal cortical or medullary abscesses typically arise from a focus of pyelonephritis (usually E. coli) or by hematogenous spread of S. aureus from a distant cutaneous infection, particularly in IV drug abusers. Patients present with chills, fever, and flank pain. Urinalysis may be normal in a staphylococcal renal abscess. CBC will show marked leukocytosis with a shift to the left.

Diagnosis

Renal ultrasound or computed tomography (CT) scan can usually make the diagnosis. Percutaneous needle aspiration of the mass will confirm the diagnosis.

Treatment

Initial therapy should be IV antibiotics. Staphylococcal abscesses should be treated with a -lactamase-resistant penicillin such as nafcillin. Ampicillin and gentamicin or third-generation cephalosporins are appropriate for a gram-negative abscess. Drainage by percutaneous aspiration or surgical incision may be necessary. Nephrectomy is rarely needed.

Perinephric Abscess

A perinephric abscess lies between the renal capsule and the perirenal (Gerota's) fascia. Rupture of an intrarenal abscess into the perirenal space is the most common etiology; however, hematogenous seeding from distant sites of infection occurs. The most common organisms are Proteus or E. coli (from an intrarenal abscess) and S. aureus (from distant infections). Mortality has been reported to be as high as 50%, mostly because of the difficulty in making a diagnosis. Diabetics and patients with polycystic kidneys on hemodialysis are particularly susceptible.

Diagnosis

Diagnosis is best made by renal ultrasound and CT scan aided by diagnostic needle aspiration.

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Treatment

The primary treatment of a perinephric abscess is percutaneous or surgical drainage. Antibiotics are needed to control sepsis. Nephrectomy may be indicated if the kidney is nonfunctioning or severely infected.

Chronic Pyelonephritis

Chronic pyelonephritis is a radiologic (IVU) or pathologic diagnosis referring to severe cortical scarring or the small, contracted, atrophic kidney. Etiology is unclear; however, chronic pyelonephritis appears to originate in childhood and is associated with recurrent bacteriuria and vesicoureteral reflux.

Xanthogranulomatous Pyelonephritis

Xanthogranulomatous pyelonephritis is an uncommon, atypical chronic renal parenchymal infection that is often misdiagnosed as a renal tumor. Etiology is unknown, but infection and obstruction are almost always present.

Presentation

Fever, chills, flank pain, and flank mass are typical. The IVU shows a renal mass in 60% and stones in 40% to 70%. CT scan often demonstrates a large renal mass with a central calcification. The involved kidney is often nonfunctioning. Persistent bacteriuria occurs in less than 50%, with Proteus and E. coli being the most frequent organisms. It can be difficult to differentiate from renal cell carcinoma; therefore, the diagnosis is often made at surgical exploration.

Treatment

Partial or total nephrectomy is the usual treatment.

Lower Tract Infections

Cystitis

Acute bacterial cystitis is an infection of the bladder with organisms that ascended from the urethra. Its hallmark symptoms include frequency, urgency, nocturia, and dysuria. Patients will often complain of low back or suprapubic pain. Fever is unusual.

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Urinalysis typically shows pyuria, bacteriuria, and hematuria. Urine cultures are positive, and E. coli is the usual pathogen. A persistent Proteus infection should suggest the possibility of an infected struvite stone.

Females have a higher incidence of cystitis, which increases throughout their lifetime. Recurrence is also high and is associated with coliform bacterial colonization of the urethra and vaginal vestibule.

Males are more likely to have other associated urinary problems (e.g., prostatitis, urethritis, strictures, or benign prostatic hyperplasia) that must be treated.

Children with a UTI, particularly infants, should have a thorough evaluation of the urinary tract, including VCUG and renal ultrasound. (VCUG should be postponed 4 to 6 weeks because incidental low-grade reflux is often observed during an acute infection.)

Treatment

Short course (3 days) or single-dose therapy has been shown to be as effective as 7 to 14 days of therapy in adult nondiabetic females and children with uncomplicated lower UTIs of less than 2 days' duration. Sulfonamides, trimethoprim-sulfamethoxazole (TMP-SMX), and nitrofurantoins are usually effective agents for initial therapy. Antibiotic choice should always be guided by sensitivity testing when available.

Pyocystitis

Pyocystitis is a collection of pus within the bladder. It most commonly occurs in dialysis patients with low or absent urine output. Patients present with fever, suprapubic pain, and a palpable mass. Pelvic ultrasound can help make the diagnosis; however, a strong suspicion would warrant a diagnostic bladder aspiration. Management involves draining the bladder and providing appropriate antibiotic coverage.

Emphysematous Cystitis

Emphysematous cystitis (cystitis emphysematosa) is a rare manifestation of UTI characterized by gas within the bladder or its muscular wall. It usually occurs in severe diabetics and is commonly caused by E. coli, Proteus, Pseudomonas, and rarely Clostridia. Certain strains of these bacteria have the potential to ferment glucose. Other causes of air in the bladder include

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instrumentation and colovesical fistulas. The radiographic picture on KUB is pathognomonic. Cystography will confirm the location of the gas in the bladder. Treatment includes appropriate antibiotic therapy, control of glucosuria, and relief of any outlet obstruction.

Urethritis in Males

Urethritis in males presents with urethral discharge, dysuria, and frequency. It is an infection acquired by inoculation of organisms into the urethra during sexual intercourse. It is classified as gonococcal or nongonococcal urethritis based on the causative pathogens.

Gonococcal Urethritis

Gonococcal urethritis is caused by an intracellular gram-negative diplococcus, Neisseria gonorrhoeae. It has a short incubation of 2 to 8 days and produces a purulent, yellowish discharge with dysuria.

Diagnosis

Diagnosis is based on a history of sexual contact, a purulent discharge with dysuria, and a positive Gram stain and/or culture. The specimen for culture and the Gram stain must be carefully taken from within the urethra using a calcium alginate (Calgiswab) urethrogenital swab at least 1 hour after the patient last voided. A modified Thayer-Martin culture medium should be directly inoculated.

Treatment

Treatment should not await culture results even if the Gram stain is negative when suspicion is high. Appropriate regimens would include ceftriaxone 125 mg intramuscularly (IM), ciprofloxacin 500 mg PO, or ofloxacin 400 mg PO. Chlamydia coverage is also achieved with azithromycin 1.0 g PO or doxycycline 100 mg PO bid for 7 days.

Nongonococcal Urethritis

Nongonococcal urethritis is believed to be the most common cause of urethritis in males, with Chlamydia trachomatis being the most important pathogen (40%). Other likely pathogens include Ureaplasma urealyticum (30%), Trichomonas vaginalis (5%), and Candida albicans. It has a prolonged incubation of 5 to 21 days and produces a mucoid, whitish discharge, with or without dysuria. The diagnosis of nongonococcal urethritis requires the exclusion of gonorrhea and the demonstration of urethritis (a Gram

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stain of urethral swab showing >4 polymorphonucleocytes per oil immersion field).

Treatment

Azithromycin 1 g PO in a single dose, doxycycline 100 mg PO twice a day (bid) for 7 days, or ofloxacin (Floxin) 300 mg PO bid for 7 days is appropriate for Chlamydia or Ureaplasma. If T. vaginalis is suspected, then metronidazole 2 g PO single dose or 250 mg PO three times a day (tid) for 7 days should be given.

Reiter's Syndrome

Reiter's syndrome is a rare complication of nongonococcal urethritis possibly owing to C. trachomatis. It can present with arthritis, conjunctivitis, balanitis circinata, or keratodermia blennorrhagia.

Urethritis in Females

Urethritis in females presents with frequency, dysuria, and often pyuria; however, the urine culture will show no growth. Vaginitis accounts for up to one third of these cases and must be diagnosed and treated appropriately. Gonorrhea or chlamydial infection will be responsible for urethritis in most other patients, despite the absence of a urethral discharge, and is treated as done so in males.

Vaginitis

Vaginitis often produces symptoms that mimic a bladder infection and, therefore, must be recognized so that appropriate treatment may be rendered. Normal vaginal discharge is clear, white, or gray, with a pH of less than 4.5, and rare leukocytes. The most common causes of adult vaginitis are Trichomonas, Candida, and nonspecific organisms.

Trichomonas Vaginitis

Trichomonas vaginitis is caused by a flagellated protozoan, T. vaginalis, and produces a thin, watery, yellowish-green, foamy malodorous discharge. Patients present with soreness, itching, and dysuria. The discharge may liberate a fishy odor with 10% potassium hydroxide (KOH), has a pH of greater than 4.5, and will show leukocytes and motile trichomonads. Trichomonas culture is positive.

Treatment

Use one dose of metronidazole (Flagyl) 2 g PO or 500 mg PO bid for 7 days. (Note: patients should abstain from drinking alcohol

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while on Flagyl.) In pregnancy, clotrimazole vaginal suppositories should be used.

Candida Vaginitis

Candida vaginitis (Monilia) is generally caused by C. albicans and produces a thick, white, cheesy, curd-like discharge. Mycotic or fungal vaginitis most often occurs in pregnancy and diabetes and in patients taking oral contraceptives or antibiotics, especially tetracycline. Patients present with intense itching and discharge that shows yeast-like buds and hyphae on 10% KOH preparation and has a pH of less than 4.5.

Treatment

Use miconazole or clotrimazole cream 200 mg intravaginally daily (qd) for 3 days in uncomplicated acute infections. Alternative therapy is one dose of fluconazole (Diflucan) 150 mg PO.

Prostatitis

NIH Classification System for Prostatitis Syndromes

Category I Acute Bacterial Prostatitis

Acute bacterial prostatitis presents with sudden onset of chills, high fever, and low back and perineal pain. Patients have frequency, urgency, dysuria, and varying degrees of bladder outlet obstruction. Generalized malaise with arthralgias and myalgias is common. The prostate is exquisitely tender and swollen on digital rectal examination. Prostate massage should not be performed. The organism (usually E. coli) can generally be cultured from the voided urine.

Treatment

A quinolone antibiotic such as ciprofloxacin (Cipro) 500 mg PO bid or levofloxacin (Levaquin) 500 mg PO qd is appropriate initial therapy. Patients should be treated for 4 to 6 weeks to prevent chronic infection. After 7 days of a quinolone, patients may be switched to TMP-SMX (Bactrim, Septra), 160 mg TMP and 800 mg SMX PO bid, for the remaining 3 to 5 weeks to keep cost down. Pathogen susceptibility should be checked from cultures. Bladder outlet obstruction must be managed appropriately.

Prostatic Abscess

Prostatic abscess is an uncommon complication of acute bacterial prostatitis. E. coli is thought to be responsible for 70% of cases; however, N. gonorrhoeae was the most common pathogen in the

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past. Patients present with acute retention, high fever, and a fluctuant prostate on rectal examination. Patients are frequently diabetic. CT scan of the pelvis or transrectal ultrasound can help make the diagnosis.

Treatment

Treatment consists of antibiotics and surgical drainage by transperineal aspiration under local anesthesia with a large bore needle. A transurethral resection of the prostate (TURP) or perineal incision is occasionally necessary.

Category II Chronic Bacterial Prostatitis

Chronic bacterial prostatitis has a variable presentation. It is caused by bacterial colonization of the prostatic ducts resulting in relapsing UTIs. Most patients present with lower urinary tract symptoms including frequency, urgency, and dysuria and some complaints of genital or perineal pain. Fever and chills are unusual. Recurring UTI caused by the same organism is the hallmark of chronic bacterial prostatitis. However, negative urine cultures do not exclude the diagnosis. Prostatic expressates show more than 10 WBCs per high power field (hpf) and macrophages containing fat (oval fat bodies). Prostatic calculi are often seen on plain films of the pelvis.

Treatment

A quinolone antibiotic such as ciprofloxacin (Cipro) 500 mg PO bid or levofloxacin (Levaquin) 500 mg PO qd is effective therapy. Patients should be treated for 4 to 6 weeks. Alternatively, TMP-SMX (Bactrim, Septra), 160 mg TMP and 800 mg SMX PO bid, is also effective. Patients with prostatic calculi that are unresponsive to antibiotic therapy may benefit from a radical TURP.

Category III Chronic Pelvic Pain Syndrome (CPPS)

The predominant symptom of CPPS is pain, usually in the perineum, suprapubic area, and penis. Pain with ejaculation is common, as is irritative and obstructive voiding symptoms including urgency, frequency, and hesitancy. Differentiation of subtypes IIIA from IIIB is the presence of inflammatory cells in the urine or expressed prostatic secretions (EPS).

Category IIIa Chronic Nonbacterial Prostatitis

Chronic nonbacterial prostatitis is the most common prostatitis syndrome and has no known etiology. Possible causes include as yet unidentified pathogenic organisms or an intraprostatic urinary reflux causing a chemical prostatitis. Evidence suggests spastic dysfunction of the bladder neck and prostatic urethra from incomplete relaxation during voiding. This is thought to cause the

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intraprostatic urinary reflux. Patients present with irritative voiding symptoms and also complain of genital or perineal pain. Prostatic expressates will be positive for inflammatory cells (>15 20 WBCs per hpf), similar to chronic bacterial prostatitis. However, patients with nonbacterial prostatitis will have negative cultures and no history of documented UTIs.

Treatment

-Blockers have become the most important agents in the management of chronic nonbacterial prostatitis with the discovery of bladder neck internal sphincter dyssynergia. Other symptomatic support includes antiinflammatory agents and hot sitz baths to help soothe painful symptomatic episodes. Patients are often given an initial round of antibiotics if there is confusion with chronic bacterial prostatitis.

Category IIIb Prostatodynia

Prostatodynia describes a syndrome distinguished from nonbacterial prostatitis only by normal prostatic expressates. Prostatodynia describes patients who present with symptoms suggesting prostatitis but have negative cultures, no history of UTIs, and negative prostatic expressates for inflammation. These males are generally age 20 to 45 years and complain predominantly of perineal or pelvic pain, often associated with sitting or activity. The cause is unknown.

Treatment

Management is identical to that for nonbacterial prostatitis.

Category IV Asymptomatic Inflammatory Prostatitis

Category IV prostatitis does not cause symptoms; however, evidence of prostatic inflammation is demonstrated microscopically in EPS or histologic specimens.

Epididymitis and Orchitis

Acute Epididymitis

Acute epididymitis is an infection of the epididymis acquired by retrograde spread of organisms down the vas from the urethra or bladder. Patients present with heaviness and a dull, aching discomfort in the affected hemiscrotum that can radiate up to the ipsilateral flank. The epididymis will be markedly swollen and exquisitely tender to touch, eventually becoming a warm, red, enlarged, scrotal mass, indistinguishable from the testis. Fever and chills may develop, and patients usually have pyuria and bacteriuria.

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Pathogens

In sexually active men younger than 35 years, C. trachomatis and N. gonorrhoeae are the most common organisms. In children and men older than 35 years, E. coli is the most common pathogen.

Diagnosis

Torsion of the testicle must always be ruled out. Torsion of the testicle is discussed in detail Chapter 10. The presence of epididymitis in children younger than 10 years is uncommon and should suggest urethral obstruction (e.g., stricture, valves, or meatal stenosis). Adult males are at risk of epididymitis from an indwelling Foley catheter and urethral instrumentation and after a TURP. Culture results are particularly important in this group. Sexually active males will usually have an accompanying urethritis. The diagnosis is usually made from history, physical examination, and positive urinalysis.

Treatment

Treatment should begin immediately. For sexually transmitted chlamydial or gonorrheal epididymitis, doxycycline 100 mg PO bid for 2 to 3 weeks or ofloxacin (Floxin) 300 mg PO bid is appropriate. For nonsexually transmitted episodes in older men and children TMP-SMX (Bactrim, Septra), 160 mg TMP and 800 mg SMX PO bid for 4 weeks, is recommended. Alternatively, a quinolone agent (ofloxacin or ciprofloxacin) is appropriate for both gram-negative and gonorrheal epididymitis. Antibiotic choices should be modified based on culture results. Management should include bedrest and scrotal elevation initially. Analgesics and a cord block with local anesthetic can provide considerable relief. Complete resolution of pain and swelling may take several weeks to months.

Abscess Formation

Abscess formation may complicate a prolonged episode of acute epididymitis. Fixation of the testis to the scrotal wall heralds such an event. An ultrasound should be obtained to confirm the presence of an abscess. Orchiectomy is usually indicated.

Chronic Epididymitis

Chronic epididymitis can be the result of several recurrent episodes of acute epididymitis producing chronic induration and pain. Treatment consists of long-term antibiotics or epididymectomy.

Orchitis

Orchitis is generally secondary to an extension of an associated epididymitis, producing an epididymo-orchitis. Treatment is identical to that for acute epididymitis.

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Mumps Orchitis

Mumps orchitis is a specific instance of metastatic infection to the testis during an episode of viral mumps, usually occurring 4 to 6 days after the appearance of parotitis. Treatment consists of symptomatic relief, including bedrest, scrotal elevation, and analgesics. Mumps orchitis usually resolves spontaneously in 7 to 10 days.

Genitourinary Tuberculosis

Pathogenesis

Genitourinary tuberculosis occurs secondary to prior pulmonary infection. Patients first inhale infected droplet nuclei that produce the primary lung infection, which manifests as a nonspecific bronchopneumonia and is often asymptomatic. Purified protein derivative (PPD) skin test will convert at this time, and the tubercle bacilli can become blood-borne, showering the kidney and occasionally the prostate. Renal infection progresses slowly, taking 15 to 20 years to destroy the kidney and producing little or no clinical disturbance until end stage. An abscess eventually invades a calyx, releasing WBCs and acid-fast bacteria (AFB) into the urine. Other genitourinary organ involvement occurs via this infected urine in most instances.

Presentation

Presentation is primarily that of irritative voiding symptoms with hematuria and sterile pyuria or tuberculous epididymitis unresponsive to antibiotics. Renal involvement is generally silent. The vas deferens may be thickened or beaded along with induration of the prostate or seminal vesicles. Vague generalized malaise, fatigue, and persistent low-grade fever or night sweats are characteristic. Patients will often give a prior history of pulmonary tuberculosis.

Diagnosis

Diagnosis is made by finding acid-fast bacteria in the urine or by urine cultures positive for Mycobacterium tuberculosis. Routine urine cultures are generally negative despite persistent pyuria. Workup should include CBC, chemistry panel, urinalysis, urine

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for acid-fast bacteria, urine for routine and tuberculosis culture, PPD skin test, chest radiograph, IVU, and cystoscopy. A negative tuberculin skin test makes diagnosis unlikely. An IV pyelogram may demonstrate the characteristic moth eaten appearance of the minor calyces.

Treatment

Use of a three-drug regimen is recommended for initial therapy: pyrazinamide 25 mg/kg body weight per day, isoniazid (INH) 300 mg PO qd, and rifampicin 450 mg PO qd for 4 months. Pyridoxine (vitamin B6) 25 mg/day should also be added to prevent the peripheral neuropathy occasionally seen with INH. Liver function tests should be monitored once a month when administering INH and rifampin. Streptomycin should be added if there is intense infection or severe bladder symptoms. Obstructive lesions in the kidney or ureters will require appropriate surgical therapy. Asymptomatic strictures in the lower third of the ureters may occur.

Fungal Infections (Mycoses)

Fungal infections of the urinary tract are almost exclusively caused by C. albicans and occur usually in patients with one or more predisposing conditions, including central venous catheters, surgical drains, broad-spectrum antibiotics, steroids, cytotoxic agents, renal transplantation, indwelling Foley catheters, diabetes mellitus, malignancy, chronic debilitating diseases, and pregnancy. Renal metastases in a systemic fungal infection are common, occurring in up to 90% of patients with disseminated candidiasis.

Candidiasis

C. albicans, a yeastlike fungus, is a normal inhabitant of the intestinal tract (mainly the colon and oral cavity) and the vagina. It occurs in a unicellular form and as long threadlike pseudomycelia. The normal bacterial flora usually suppress its level of growth. Infection to the urinary tract can occur by either hematogenous (lymphatic or blood-borne) or retrograde (from anus to urethra) spread. The threadlike pseudomycelia of Candida tend to cluster, forming small bezoars or fungus balls that can cause ureteral obstruction.

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Presentation

Presentation can range from asymptomatic candiduria or cystitis to pyelonephritis and septicemia. Pneumaturia can occur in diabetics because of fermentation of sugar in the urine.

Diagnosis

Diagnosis is based on positive cultures. Workup should include urinalysis, urine and blood cultures, IVU, and retrograde urograms if necessary. The urinary sediment will often make the diagnosis, showing yeast and mycelial forms. Urine specimens from females should be from a catheterized or aspirated sample. Bladder bezoars often produce a typical radiographic filling defect.

Treatment

Treatment should be based on the patient's total clinical picture and not just the presence of candiduria. Careful attention should be paid to controlling or eliminating any predisposing factors (i.e., remove or change central lines, drains, or Foley catheters; control diabetes; and eliminate broad-spectrum antibiotics). Fungus balls should be handled surgically as needed.

Asymptomatic Patients

The candiduria of asymptomatic patients will often resolve spontaneously. Treatment should be limited to controlling or eliminating any predisposing factors. Persistent candiduria warrants more aggressive treatment.

Candida Cystitis

Candida cystitis will usually respond to urinary alkalinization (pH 7.5) with sodium bicarbonate or bladder irrigation with amphotericin B (amphotericin B 50 100 mg in 1 L sterile water qd run over 12 24 hours via a three-way Foley catheter for 5 7 days). Alternatively, fluconazole (Diflucan) 200 mg PO qd for 10 days is effective.

Candida Vaginitis

Candida vaginitis can be treated with one 150-mg dose of fluconazole.

Seriously Ill Patients

Seriously ill patients should be started on immediate IV therapy with amphotericin B or fluconazole for 2 to 6 weeks. Monitor laboratory tests (CBC, chem-7, and liver function tests) every other day (qod). Amphotericin irrigation via cystostomy or nephrostomy tubes may be necessary.

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Actinomycosis

Actinomycosis is a chronic granulomatous disease caused by the organism Actinomyces israelii (A. bovis). The disease will occasionally involve the kidneys, bladder, or testes. Marked fibrosis and spontaneous fistulae are characteristic. Diagnosis can be made by microscopic demonstration of the organism as yellow bodies called sulfur granules; however, culture results are usually necessary. Treatment consists of IV penicillin (20 million units/day for 2 weeks) or oral ampicillin (1,500 mg/day for 4 months). Surgical removal of the involved organ is occasionally necessary.

Parasitic Diseases

Schistosomiasis (Bilharziasis)

Schistosoma haematobium is a trematode or blood fluke endemic throughout most of Africa and the Middle East. It produces disease by following a life cycle that includes humans and an intermediate host. An increased incidence of squamous cell carcinoma of the bladder has been associated with schistosomal infection of the bladder. Presentation is classically that of hematuria and dysuria. Late clinical manifestations include bladder ulcers, stone formation, and silent obstructive uropathy.

Filariasis

The parasitic nematodes, Wuchereria bancrofti and Brugia malayi, are filarial worms about 0.5 cm long that live in human lymphatics. They are endemic in most tropical countries, and spread is by mosquitoes. Urogenital disease is the result of lymphatic filarial obstruction by adult worms. The tail of the epididymis and the lower spermatic cord are among the most common localization sites, causing funiculoepididymitis and elephantiasis of the penis, scrotum, or extremities.

Echinococcosis

The tapeworm Echinococcus is a primary parasite of the dog, with sheep and cattle as intermediary hosts. It is a disease primarily found in Australia, Argentina, and the Middle East where sheep-herding is common. Echinococcus eggs are passed via feces to their accidental host, humans, where they principally cause disease in

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the liver. However, 3% of cases involve the kidney. Hydatid cysts undergoing slow, concentric growth over many years are the pathologic lesions. They present as a renal mass, often calcified on plain films, and may be asymptomatic or cause symptoms of dull flank pain. CT and IVU can make the diagnosis. Treatment is surgical excision; usually a nephrectomy is elected. Needle aspiration is unwise.

Antibiotics Commonly Used in Urology

The essence of treating an infectious disease is the isolation and identification of the pathogenic organism and determination of its sensitivity to antimicrobial agents. However, because of the necessary delay in obtaining these results, patients must be treated based on other less exacting clinical evidence. Therefore, it is fundamental to have a specific working knowledge of the various antibiotic choices available and an understanding of their mode of action and possible adverse side effects.

General Guidelines for Antibiotic Therapy

• Obtain all culture specimens before initiating therapy.

• Be alert to host deficiencies such as malnutrition, chronic alcoholism, renal failure, impaired circulation, and immunosuppression.

• Consider hospital-acquired bacterial resistances.

• Remove foreign materials, debride necrotic tissue, drain abscesses, and relieve obstruction.

• Use IV administration for serious infections, at least initially.

• Adjust antibiotic dosages as necessary for renal or hepatic dysfunction.

• Monitor therapy (i.e., temperature curve, WBC count, signs of inflammation, and follow-up cultures).

• Select agents based on their potential toxicity and the severity of the infection.

• Control antibiotic resistance:

  • Only use antibiotics when necessary.

  • Avoid use of newer agents when available agents are effective.

  • Wash hands after seeing each patient.

• Revise antibiotic choice to reflect culture and sensitivity results.

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Sulfonamides

Sulfonamides (SMX) act by inhibiting the uptake of paraaminobenzoic acid and thus inhibit the synthesis of tetrahydrofolic acid, necessary for subsequent DNA synthesis. Mammalian cells do not produce folic acid and, consequently, are unaffected. Sulfonamides are bacteriostatic on most routine coliform bacteria. Negative side effects include allergic reactions, rash, fever, renal and liver damage, blood dyscrasia, and vasculitis. Dosage is sulfisoxazole 2 to 4 g/day PO.

Trimethoprim

Trimethoprim (TMP) also inhibits synthesis of tetrahydrofolic acid by competitive inhibition of the enzyme dihydrofolate reductase. It is bacteriostatic for many common urinary pathogens such as E. coli, Proteus, Klebsiella, and Enterobacter. It is a good choice for urinary prophylaxis because of a low incidence of resistance (10%) when used this way. Negative side effects include rash, fever, and hematologic and gastrointestinal abnormalities. Dosage is 100 mg every 12 hours (q12h) PO.

Trimethoprim-Sulfamethoxazole (Bactrim, Septra)

TMP-SMX is a fixed dose combination of 80 mg TMP and 400 mg SMX that together is bactericidal for most common urinary pathogens. It is also available in a double-strength tablet of 160 mg TMP and 800 mg SMX. Negative side effects include rash, fever, gastrointestinal symptoms (nausea, vomiting, diarrhea), and blood dyscrasia. Dosage is two regular tablets q12h PO.

Penicillins

Penicillins inhibit bacterial cell wall synthesis (bactericidal) by irreversible binding of the -lactam ring to the enzyme transpeptidase. Bacterial resistance is observed in those bacteria (most often S. aureus) that produce -lactamase, an enzyme that breaks the -lactam ring. Penicillins are excreted intact by the kidneys (primarily tubular secretion). Probenecid blocks tubular secretion and therefore enhances serum levels. Negative side effects include allergic reactions, rash, diarrhea, and anaphylaxis.

• Natural penicillin penicillin G (benzyl penicillin) and penicillin V potassium

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• Synthetic penicillins ampicillin, amoxicillin, carbenicillin (Geocillin), and ticarcillin (Ticar)

• Synthetic -lactamase-resistant penicillins methicillin, oxacillin, cloxacillin, dicloxacillin, and nafcillin

Cephalosporins

Cephalosporins are also -lactam antibiotics like penicillin with a wide antibacterial spectrum and resistance to some -lactamase-producing bacteria. They are excreted in the urine mainly by tubular secretion. First-generation cephalosporins have good gram-positive activity, except with group D streptococci (enterococcus) and methicillin-resistant S. aureus, whereas second- and third-generation agents have increasing activity against gram-negatives with less gram-positive effectiveness. Negative side effects include allergic reactions, rash, fever, anaphylaxis, and synergistic toxicity with aminoglycosides. Cross-reactivity with penicillin-allergic patients occasionally occurs.

• First generation cephalothin (Keflin), cefazolin (Ancef, Kefzol), cephapirin (Cefadyl), cephradine (Velosef, Anspor), cephalexin (Keflex), and cefadroxil (Duricef)

• Second generation cefuroxime (Zinacef), cefaclor (Ceclor), and cefoxitin (Mefoxin)

• Third generation cefotaxime (Claforan), ceftizoxime (Cefizox), ceftriaxone (Rocephin), ceftazidime (Fortaz, Tazicef), and cefoperazone (Cefobid)

• Oral cephalosporins cephalexin (Keflex), cephradine (Velosef), cefadroxil (Duricef), and cefaclor (Ceclor)

Aminoglycosides

Aminoglycosides are a group of bactericidal antibiotics that act by inhibiting bacterial protein synthesis. They are active against most gram-negative urinary tract pathogens including E. coli, Enterobacter, Klebsiella, Proteus, Pseudomonas, and Serratia. The drug is excreted in the urine by glomerular filtration. Negative side effects include ototoxicity and nephrotoxicity (nonoliguric renal failure after 5 10 days of therapy). Nephrotoxicity is potentiated by hypovolemia, cephalosporins, and furosemide (Lasix). Serum levels should be monitored and adjusted for renal insufficiency. Peak levels (taken 30 60 minutes after infusion) should be in the range of 4 to 6 g/mL. Trough levels (taken just before the next dose) should be greater than 2 g/mL.

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Gentamicin or tobramycin is a good first choice for most serious gram-negative infections. Amikacin is effective for gentamicin- or tobramycin-resistant organisms.

Tetracyclines

Tetracyclines are bacteriostatic antibiotics that interfere with bacterial protein synthesis. Excretion in the urine is mainly by glomerular filtration. Negative side effects include allergic reactions, phototoxicity, nausea, vomiting, diarrhea, superinfections, hepatic toxicity, and staining of the teeth in children. Gastrointestinal absorption is decreased if taken with food [tetracycline, doxycycline (Vibramycin), and minocycline (Minocin)].

Erythromycin

Erythromycin is a macrolide antibiotic that inhibits bacterial protein synthesis. It is effective against Mycoplasma, Ureaplasma, and Chlamydia. Negative side effects include allergic reactions, cholestatic hepatitis, and epigastric distress. Dosage is 0.5 to 1.0 g q6h PO/IV.

Clindamycin (Cleocin)

Clindamycin inhibits bacterial protein synthesis and is effective against most gram-positive organisms and anaerobic infections, including Bacteroides fragilis. Negative side effects include gastrointestinal disturbances, mostly diarrhea and pseudomembranous enterocolitis secondary to Clostridium difficile. Dosage is 300 to 900 mg IV q6h (adjust dosage for hepatic dysfunction).

Vancomycin (Vancocin)

Vancomycin is a bactericidal antibiotic that inhibits cell wall synthesis. It is active against gram-positive bacteria and C. difficile and is excreted by the kidneys unchanged. Negative side effects include ototoxicity, fever, phlebitis, and nephrotoxicity. Dosage is 500 mg IV q12h (adjust dosage for renal insufficiency).

Metronidazole (Flagyl)

Metronidazole is a bactericidal antibiotic for anaerobic infections of gram-negative organisms, especially B. fragilis. It acts by

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inhibiting DNA synthesis. Other therapeutic uses include amebiasis, giardiasis, and vaginitis secondary to Trichomonas or Gardnerella. It is eliminated primarily by hepatic metabolism. Negative side effects include nausea, vomiting, diarrhea, neurologic symptoms, and a sulfiram (Antabuse)-like effect when taken with alcohol. Dosage is 500 mg PO tid.

Quinolones

The quinolones are a class of bactericidal antibiotics that inhibit bacterial DNA synthesis (DNA gyrase). They have a broad spectrum of coverage including most gram-negative and gram-positive organisms, particularly Pseudomonas and group D streptococcus. They should be reserved for patients with complicated UTIs unresponsive to other oral agents. Quinolones should not be used in children or pregnant females. Use of quinolones should generally be avoided or monitored in patients on warfarin (Coumadin).

Ciprofloxacin (Cipro)

Ciprofloxacin has increased activity against P. aeruginosa, Providencia rettgeri, Acinetobacter spp., and S. aureus and has better pharmacokinetic properties than norfloxacin. It can be given intravenously, as well as orally, on a twice-daily regimen. Negative side effects include skin rash, gastrointestinal complaints, headache, vertigo, and malaise. Potential drug interactions have been reported when used with other drugs that utilize the cytochrome P-450 enzyme system. Ciprofloxacin should be avoided in patients taking theophylline because of fatal reactions reported and patients on warfarin (Coumadin) because of increased INR. Dosage is 250 to 500 mg PO/IV bid.

Levofloxacin (Levaquin)

Levofloxacin is an L-isomer of ofloxacin with similar broad-spectrum coverage and bioavailability but with decreased side effects of ofloxacin. Dosage is 500 mg PO/IV qd.

Other Quinolones

Other quinolones include moxifloxacin (Avelox) and lomefloxacin (Maxaquin).

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Urinary Antiseptics

Nitrofurantoin (Macrobid)

Nitrofurantoin is a synthetic bacteriocidal agent only effective in the urine where therapeutic levels are achieved. Never use in treating tissue infections such as pyelonephritis or prostatitis. Many urinary pathogens are sensitive; however, Proteus and Pseudomonas are usually resistant. Nitrofurantoin is useful for the prophylaxis of recurrent lower UTIs. Resistant bacterial strains rarely emerge during long-term use. Negative side effects include gastrointestinal upset, hypersensitivity reactions, rashes, pulmonary infiltrates, and hemolytic anemia in glucose-6-phosphate dehydrogenase deficient patients. Dosage is 100 mg q12h PO.

Methenamine (Mandelate Mandelamine, Hippurate Hiprex)

Methenamine is a condensation product of formaldehyde and ammonia that releases the formaldehyde in acid urine. Its bacteriostatic property is only effective in acid urine (pH less than 6.0). Ascorbic acid (vitamin C) is often given to help acidify the urine. Methenamine is combined with mandelic acid or hippuric acid to promote an acid urine and to enhance its antibacterial effect. Chronic long-term suppression of UTIs is its only use. Negative side effects include gastrointestinal distress and crystalluria. Dosage is 1 g q6h (Mandelamine) and 1 g q12h (Hiprex) PO [ascorbic acid 0.5 to 2 g every 4 hours (q4h); titrate to urinary pH].

Antibiotic Prophylaxis

Wound Classification

• Clean respiratory, gastrointestinal, or genitourinary tracts not entered

• Clean contaminated respiratory, gastrointestinal, or genitourinary tracts entered without excessive contaminated spillage

• Contaminated area of nonpurulent inflammation entered or a major break in sterile technique

• Dirty trauma more than 4 hours old, gross pus, or a perforated viscus

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General Recommendations

• Culture urine before surgery.

• Sterilize urine before any elective surgery.

• Select an antibiotic that gives high urine and urinary tract tissue concentrations.

• Short-term prophylactic antibiotic regimens are preferred to minimize development of resistance (e.g., 24 48 hours).

• Patients with preoperative indwelling Foley catheters or mature nephrostomy tracts should receive prophylactic antibiotics.

• For an antibacterial agent to be effective, it must be present in the tissues at the time the incision is made, so start prophylaxis before incision (i.e., on-call).

• Patients with increased risk of infective complications (e.g., diabetics, renal failure, neurogenic bladder, and immunosuppressed patients) should receive prophylactic antibiotics.

Prophylaxis Recommended (Sterile Urine)

• Surgery involving the use of bowel an oral bowel preparation (i.e., erythromycin base and neomycin) and systemic antibiotics

• Penile prostheses or artificial urinary sphincters

• Transrectal needle biopsy (cleansing enema and systemic antibiotic)

• Patients at high risk for developing bacterial endocarditis (suspected congenital or acquired heart disease, prosthetic valves, prior history of infective endocarditis, ventriculoseptal patches, mitral valve prolapse, and transvenous pacemakers)

• Surgery of infected calculi

• TURP or transurethral resection of bladder tumors

Prophylaxis Against Reinfection

Oral antibiotic therapy can produce resistant strains in the fecal flora with subsequent resistant UTIs. The following agents have been demonstrated to be useful when long-term prophylactic therapy is indicated: TMP-SMX, nitrofurantoin, and TMP alone.

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Septic Shock

Septic shock is a condition characterized by abnormal circulatory function secondary to overwhelming infection. The urinary tract is a common site of origin. Gram-negative sepsis is most common with E. coli, accounting for about 20% of all cases. Mortality rate has been reported to be as high as 50%.

Pathophysiology and Clinical Manifestations

The prime initiator of gram-negative septic shock is endotoxin, a lipopolysaccharide component of the bacterial cell wall. Lipopolysaccharide-stimulated monocytes release cytokines such as tumor necrosis factor and interleukin-1. Profound tissue hypoxia is a cardinal feature. Two distinct phases of septic shock are usually noted: (a) the initial hyperdynamic state or warm shock is characterized by increased cardiac output, decreased peripheral vascular resistance, low central venous pressure, and warm extremities; eventually cardiac decompensation will result in (b) the hypodynamic state or cold shock, which is characterized by decreased cardiac output, increased peripheral vascular resistance, and cool extremities. Fever, leukocytosis, and a profound metabolic acidosis are usual.

Diagnosis

Septic shock presents initially as altered mental status, hyperventilation, and respiratory alkalosis. It can easily be confused with other conditions, and a high index of suspicion must be maintained. Differential diagnosis includes atelectasis, pulmonary embolus, pneumonia, acute hemorrhage, and myocardial infarction. Workup should begin with history, physical examination, urinalysis, CBC, and electrolytes. Patients should be pan-cultured, including blood, urine, sputum, and wounds, before starting antibiotic therapy. Arterial blood gases and serum lactate dehydrogenase levels should be carefully followed. Chest radiograph is mandatory, and plain films of the abdomen and CT scan, IVU, or renal ultrasound may help identify the source of infection.

Management Guidelines

The most important aspect of management is to eliminate the source of infection.

• Drain abscess; relieve obstructive uropathy; and, if necessary, debride wounds.

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• Start appropriate antibiotic therapy immediately, without waiting for culture results.

• Place a central line for access and monitoring the central venous pressure.

• Do not hesitate to float a Swan-Ganz catheter if the hemodynamic condition is in question.

• Use normal saline for fluid resuscitation.

• Avoid overcorrection of metabolic acidosis because this will rapidly resolve after restoring adequate perfusion.

• Use dopamine if pressor agents are needed to support the circulation. Mix 400 mg dopamine in 250 mL D5W, start infusion at 2 g/kg per minute (5 mL/hour for a 70-kg adult), and titrate to blood pressure.

• Digitalization may be useful for patients in obvious cardiac failure.

• Large doses of corticosteroids may be helpful.

• Intubation with mechanical ventilation and positive end-expiratory pressure are important for patients developing respiratory failure and shock lung.

• Monitor patient's progression with arterial blood gases and serum lactate.