Urinary Tract Infection (UTI) in Males

Complications

Complications of acute bacterial prostatitis include bacteremia, septic shock, prostatic abscess, epididymitis, seminal vesiculitis, and pyelonephritis. Suspect a prostate abscess if fever does not resolve within 48 hours; if confirmed, add anaerobic coverage, and arrange for drainage.

Gonococcal and nongonococcal urethritis may progress to prostatitis, epididymitis, or orchitis, especially in younger patients. Urethral strictures (secondary to inflammation within the urinary tract) may form in up to 5% of patients; this must be kept in mind when evaluating patients with residual obstructive symptoms after treatment.

Other complications from UTI include fistula formation, recurrent infection, bacteremia, hydronephrosis and pyonephrosis, and gram-negative sepsis. Pyonephrosis refers to infected hydronephrosis associated with suppurative destruction of the kidney parenchyma, which results in nearly total loss of renal function.

Complication risk factors appear to be prolonged use of aminoglycosides (>2wk), high serum trough levels (>2), advanced age, baseline renal insufficiency, concomitant conditions (eg, diabetes mellitus), and concomitant nephrotoxic drugs (eg, amphotericin B). (See Presentation and Workup.)

Patient education

For patient education information, see Prevention of Urinary Tract Infection (UTI), Prostatitis, Acute Bacterial Prostatitis, Epididymitis, Acute Epididymitis, Orchitis, and Bladder Cancer.

The usual route of inoculation in males is with gram-negative aerobic bacilli from the gut, with Escherichia coli being the most common offending organism. Recent hospitalization, urinary catheter, and fluoroquinolone use in the past 6 months are independent risk factors for fluoroquinolone resistance in community-onset febrile E coli UTI. Fluoroquinolone resistance may be a marker of broader resistance, including extended-spectrum beta-lactamase (ESBL) positivity.[5]  

Older males with prostatic hypertrophy have incomplete bladder emptying, predisposing them to UTI on the basis of urinary stasis. However, in males aged 3 months to 50 years, the incidence of UTI is low; therefore, the possibility of an anatomic abnormality must be entertained in this age group.

Entry of microorganisms into the prostate gland almost always occurs via the urethra; with intraprostatic reflux of urine, bacteria migrate from the urethra or bladder through the prostatic ducts. Other possibilities include entry via the hematogenous route, via the lymphatics from the rectum, and during prostate surgery. However, many patients have no known precipitating event.

Prostatic fluid contains various antibacterial substances, including zinc and antibodies, which are lacking in some patients with chronic bacterial prostatitis. Interestingly, acute prostatitis usually does not result in chronic prostatitis, and chronic bacterial prostatitis usually is not antedated by acute prostatitis. Of men referred for prostatitis, less than 10% have either acute or chronic bacterial prostatitis.

Acute and chronic prostatitis

In the 1800s, prostatitis was thought to be secondary to excessive alcohol consumption or physical or sexual activity. It often was associated with gonorrhea and could be fatal or lead to abscess formation. By the 1920s, most cases were attributed to microorganisms, and antibiotics combined with prostate massage were standard therapy after World War II. Although the role of bacteria was questioned in the 1950s, it was reemphasized in 1968 when Meares and Stamey described their "4-glass test."[6]

Acute prostatitis is caused by an acute infection of the entire prostate gland, resulting in fever and localized pain. Microscopically, neutrophilic infiltrates, diffuse edema, and microabscesses may be seen, which may coalesce into larger collections.

Chronic prostatitis may be caused by inflammatory or noninflammatory diseases. This condition may arise via dysfunctional voiding, intraprostatic reflux, chronic exposure to microorganisms, autoimmune mechanisms, irritative urinary metabolites, and as a variant of neuropathic pain. Chronic bacterial prostatitis often produces few or no symptoms related to the prostate, but it probably is the most common cause of relapsing UTI in men.

Chronic prostatitis has been subdivided by the National Institutes of Health (NIH) into the following categories:

• Category II: Chronic bacterial prostatitis
• Category III: Chronic abacterial prostatitis. Category IIIA is chronic, inflammatory abacterial prostatitis, and category IIIB is chronic, noninflammatory abacterial prostatitis, also known as  chronic pelvic pain or prostatodynia.
• Category IV: Asymptomatic, inflammatory prostatitis

Chronic bacterial prostatitis is the most common cause of relapsing UTI in men, with E coli as the main causative organism (80%), but other gram-negative bacteria and enterococci also may be observed. Rare cases may be caused by yeasts (eg, Candida, Blastomyces, Histoplasma, Cryptococcus) and mycobacteria. Whether Staphylococcus epidermidis, S aureus, and diphtheroids are pathogenically significant is doubtful, and the evidence supporting a causative role for Chlamydia and Ureaplasma is not convincing.[7]

Epididymitis

Epididymitis is a clinical syndrome caused by infection or inflammation of the epididymis. This condition is the most common cause of acute scrotum in adult male populations. Long-term complications include abscesses, infarction, recurrence, chronic pain, and infertility.

The pathophysiology of epididymitis is divided; Chlamydia trachomatis and Neisseria gonorrhoeae are the most common pathogens in patients younger than 35 years, whereas Enterobacteriaceae and gram-positive cocci are frequent pathogens in older patients. In either case, infection results from retrograde ascent of infected urine from the prostatic urethra into the vas deferens and, finally, into the epididymis.

Orchitis

Because of the widespread use of mumps vaccination, orchitis no longer is a common infection in the United States. Orchitis is one of the few genitourinary infections to result from a viral pathogen.

Mumps orchitis occurs in 18% of postpubertal boys infected with the mumps virus. Other viruses that can cause the disease include coxsackie B, mononucleosis, and varicella. Unlike most genitourinary infections, viral particles are spread to the testicle by the hematogenous route. Granulomatous orchitis is rare and results from hematogenous dissemination of tuberculosis, fungi, and actinomycosis.

Pyelonephritis

Pyelonephritis is an infection of the renal parenchyma. Infection usually occurs in a retrograde, ascending fashion from the bladder, but it may occur hematogenously. The ureteral orifice becomes edematous and loses its 1-way valve function during infection. Retrograde flow of bacteria into the upper urinary tracts and into the renal parenchyma results in clinical symptoms.

Bacteremia, particularly with virulent organisms such as S aureus, can result in pyelonephritis with focal renal abscesses. Bacterial adherence allows for mucosal colonization and subsequent infection by an ascending route. Whereas type 1 pili are produced by most uropathogenic strains of E coli, P-pili, which bind to the uroepithelial glycosaminoglycan layer, are found in most strains of E coli that cause pyelonephritis. Genotypic factors may affect uroepithelial susceptibility to these adherence molecules. Endotoxin from gram-negative organisms can retard ureteral peristalsis.

E coli is responsible for approximately 25% of cases in males, with Proteus and Providencia causing many remaining infections; Klebsiella, Pseudomonas, Serratia, and enterococci are less frequent.

Bacterial cystitis

Bacterial cystitis without concomitant infection in other portions of the genitourinary tract is believed to be a rare event in males. The abrupt onset of irritative voiding symptoms (eg, frequency, urgency, nocturia, dysuria) and suprapubic pain are clinically diagnostic.

Most cases of bacterial cystitis occur by an ascending mechanism. Bacterial cystitis in the male is uncommon in the absence of anatomic abnormality, defect in bladder emptying mechanism, or urethral catheterization (eg, poor bladder emptying from prostatic obstruction or dysfunctional voiding). Elevated postvoid residuals allow bacteria to multiply to critical levels. High voiding pressures and poor bladder compliance diminish the natural uroepithelial resistance to infection.

Urethritis

Urethritis has been described for thousands of years. The term gonorrhea (gonus meaning seed, rhoia meaning flow) was coined by Galen. The urethral nonsquamous epithelium can be penetrated by N gonorrhoeae, resulting in periurethral microabscesses. Necrotic debris is sloughed into the urethra lumen, producing a milky penile discharge.

Gonococcal urethritis remains the most reported communicable bacterial disease in the United States.

Urinary catheter–associated UTIs

Up to 25% of hospitalized patients have urinary catheters inserted; of these individuals, 10-27% develop UTIs. In fact, UTI accounts for approximately 40% of all nosocomial infections; 15% of these infections occur in clusters and often involve highly resistant organisms.

The single most important risk factor for nosocomial bacteriuria and UTI is the presence of an indwelling urethral catheter; 80% of nosocomial UTIs are associated with the use of urethral catheters. Once the urethral catheter is in place, the daily incidence of bacteriuria is 3-10%. Because most patients who become bacteriuric do so by 30 days, that is a convenient dividing line between short- and long-term catheterization.

Epididymitis

Chlamydia trachomatis and N gonorrhoeae are the most common pathogens in patients younger than 35 years with UTI, whereas Enterobacteriaceae and gram-positive cocci are frequent pathogens in older patients.

Orchitis

Orchitis is one of the few genitourinary infections resulting from viral pathogens, such as the mumps, coxsackie B, Epstein-Barr (EBV), and varicella (VZV) viruses. Granulomatous orchitis is rare and results from hematogenous dissemination of tuberculosis, fungi, and actinomycosis. Brucella has been associated with orchitis; clinically, these patients resemble those with tuberculosis. Colorado tick fever also has been associated with epididymo-orchitis.

Secondary orchitis is a more common condition; it is a late complication of untreated epididymitis.

Pyelonephritis and cystitis

Bacteria responsible for pyelonephritis and cystitis in males include E coli, Klebsiella, Enterobacter, Proteus, Pseudomonas, Serratia, Enterococcus, and Staphylococcus species.

Urethritis

N gonorrhoeae is the most common cause of urethritis in males; nongonococcal causes of urethritis include C trachomatis (in up to 50% of cases), Ureaplasma urealyticum, Trichomonas vaginalis, and herpes simplex virus (HSV). The role of Mycoplasma in urethritis is controversial.

Catheter-associated bacteriuria

Short-term catheters are placed for a mean duration of 2-4 days. The usual indications are for acute illnesses, output measurement, perioperative routine, and acute retention. Approximately 15% of patients develop bacteriuria, usually with a single organism (E coli). Catheter-associated bacteriuria usually resolves after the catheter is removed; however, one third of patients may have symptoms, and bacteremia is the most serious complication. Approximately 10-30% of patients develop a fever, and the risk for postoperative wound infection associated with bacteriuria is increased.

Long-term catheters are placed for chronic medical or neurologic problems, including chronic urinary retention and incontinence. Essentially all patients develop bacteriuria, which is polymicrobial in up to 95% of cases. New pathogens often emerge, whereas many persist because of adherence properties (fimbrial adhesion in Providencia and E coli) or their effect on the local environment (Proteus and Morganella).

Catheter obstruction in long-term catheterization may occur, via an interaction between bacteria, the glycocalyx, protein, and crystals; Proteus mirabilis is a potent producer of urease, which alkalinizes the urine, precipitating struvite and apatite.

Young men rarely develop UTIs, and the prevalence of bacteriuria is 0.1% or less. There is an early peak incidence during the first 3 months of life; in neonates, UTIs occur more frequently in boys than in girls (with a male-to-female ratio of 1.5:1), and they often are part of the syndrome of gram-negative sepsis. The cumulative incidence of symptomatic UTI (including pyelonephritis) in boys during the first 10 years of life has been reported at 1.1-1.6%.

The incidence of true UTI in adult males younger than 50 years is low (approximately 5-8 per year per 10,000). In this population, the symptoms of dysuria or urinary frequency usually are due to sexually transmitted disease (STD)–related infections of the urethra (eg, gonococcal and nongonococcal urethritis) and prostate.[8]

In men, the most frequent chief complaint related to urinary tract infection (UTI) is dysuria. In fact, complaints of dysuria, urinary frequency, and urgency are approximately 75% predictive for UTI, whereas the acute onset of hesitancy, urinary dribbling, and slow stream are only approximately 33% predictive for it. Other aspects to inquire about include the following:

• Previous UTI(s)
• Nocturia, gross hematuria, any changes in the color and/or consistency of the urine
• Prostatic enlargement
• Urinary tract abnormalities - personally and within their families
• Comorbid conditions - eg, diabetes
• Human immunodeficiency virus (HIV) status
• Immunosuppressive treatments for other conditions - eg, prednisone
• Any previous surgeries or instrumentation involving the urinary tract

In a younger man, the presence of UTI often is associated with anatomic abnormality. In the absence of this history, a detailed sexual history may implicate activities such as sex with a new partner, sex with multiple partners, or other risk-taking behavior associated with sexually transmitted disease (STD)-related urethritis, prostatitis, or epididymitis that may lead to UTI.

Certain patients are at increased risk for urosepsis and complications, such as the very sick and the immunosuppressed, as well as those with a history of genitourinary surgery, a neurogenic bladder, papillary necrosis (sickle cell disease, diabetes, or analgesic abuse), and a history of ureteral stricture or tumor with obstruction.

Males who present with genitourinary complaints warrant a thorough general physical examination, with particular attention to the vital signs, kidneys, bladder, prostate, and external genitalia.

Auscultation over the upper abdominal quadrants and the costovertebral angles may reveal the bruits of renal artery stenosis, an aneurysm, or an arteriovenous malformation. The costovertebral angles should be percussed for tenderness. Palpation of the suprapubic area should be performed; a bladder that contains 500mL or more of fluid often is palpable as a suprapubic mass.

The external genitalia should be examined carefully. The penis should be examined for the presence of ulcers or lesions, and special attention should be paid to the urethral meatus for the presence of erythema or discharge. The testes and epididymis must be examined and palpated for tenderness and swelling.

A rectal examination with a 360° sweep of the interior of the rectum followed by careful palpation of the prostate can be performed. However, in patients with suspected acute bacterial prostatitis, palpation can be painful and may lead to bacteremia. Some authorities note that it is of little benefit in diagnosing acute prostatitis and state that prostatic massage should not be conducted in the setting of UTI or urethritis.

Physical findings of UTI may include the following:

• Fever
• Tachycardia
• Flank pain/costovertebral angle tenderness
• Abdominal tenderness in the suprapubic area
• Scrotal hematoma, hydrocele, masses, or tenderness
• Meatal discharge
• Prostatic tenderness
• Inguinal adenopathy

These syndromes tend to occur in young and middle-aged men. Symptoms may include pain (in the perineum, lower abdomen, testicles, or penis or with ejaculation), bladder irritation, and, sometimes, blood in the semen.

Acute prostatitis

Acute prostatitis typically presents with spiking fever, chills, malaise, myalgia, dysuria, pelvic or perineal pain, and cloudy urine. Obstructive symptoms can result from swelling of the acutely inflamed prostate, and these range from dribbling and hesitancy to anuria. A less common presentation is with a vague, flulike illness.

Careful examination of the prostate is not contraindicated in acute bacterial prostatitis, but prostatic massage is contraindicated. Upon examination, the prostate is warm, swollen, soft ("boggy"), and extremely tender. The patient may have a fever and appear acutely uncomfortable; hypotension may be noted.

A rectal examination with a 360° sweep of the interior of the rectum followed by careful palpation of the prostate can be performed. However, in patients with suspected acute bacterial prostatitis, palpation can be painful and may lead to bacteremia. Some authorities note that it is of little benefit in diagnosing acute prostatitis and state that prostatic massage should not be conducted in the setting of UTI or urethritis.

Chronic prostatitis

Patients with chronic prostatitis, by definition, have had symptoms for at least 3 months. Although this condition is not life threatening, the patient's quality of life has been compared with someone with unstable angina or active Crohn disease. Interestingly, many with chronic bacterial prostatitis are asymptomatic.

Chronic bacterial prostatitis and nonbacterial prostatitis have similar presentations, including dysuria, frequency, urgency, perineal discomfort, and a low-grade temperature. The only way to differentiate between these 2 entities is through culture of prostatic secretions.

Prostatodynia, a noninflammatory disorder, also has a symptom complex similar to that of chronic prostatitis, except that the patient does not give a history of recurrent UTIs.

In chronic bacterial prostatitis, the physical findings are variable. A low-grade fever may be present, and the rectal examination may be unremarkable or may reveal severe anal sphincter spasm. The prostate may be mildly or extremely tender.

Examination of urine voided after prostate massage is more helpful diagnostically than quantitating the amount of pain experienced during the digital examination. The Meares-Stamey 4-glass test with prostatic massage is a classic diagnostic test for chronic prostatitis. Prostatic massage should not be conducted in the setting of UTI or urethritis.

In early epididymitis, the epididymis is tender and indurated, but the testis itself is nontender and soft. In hours to days, inflammation progresses to the adjacent testicle and patients may complain of scrotal pain and swelling, as well as urinary frequency, urgency, or dysuria. Identifying the lateral sulcus between the testicle and epididymis then becomes increasingly difficult, and discerning testis from epididymis may be impossible.

Dysuria, frequency, urgency, and suprapubic pain usually are present in patients with cystitis. Fever and flank pain may be present, but not usually. Note that symptoms cannot reproducibly differentiate cystitis (lower UTI) from pyelonephritis (upper UTI).

The most common presentation of orchitis is in a patient in the later stages of epididymitis. In this situation, inflammation has spread to the adjacent testicle and results in a tender, warm, and swollen hemi-scrotal mass. Patients have the characteristic history and urinary findings of epididymitis.

Of patients with orchitis resulting from tuberculosis, 70% have other genitourinary or pulmonary symptoms of this disease.

Viral orchitis is notable for the other symptoms of the particular virus involved. Orchitis occurs in approximately 18% of postpubertal boys infected with the mumps virus; symptoms usually begin within 1 week of parotitis. Up to 30% of cases are bilateral, and sterility develops in up to 10% of cases.

Patients with pyelonephritis appear ill; have fever, chills, and flank pain; and may have hypotension. Although fever is very suggestive of pyelonephritis, it also has been demonstrated in some males with simple cystitis. Note that 30-50% of pyelonephritis cases may be silent, without clinical symptoms.

In the older male, prostate enlargement along with delayed presentation are the primary causes of pyelonephritis. Other historical risk factors include nephrolithiasis, neurogenic bladder, prostatitis, or symptom duration greater than 5 days.

Classic findings with pyelonephritis include fever, chills, and flank pain/costovertebral angle tenderness that follow the symptoms of UTI; these findings are combined with pyuria and bacteriuria. Occasionally, the urinalysis and urine culture findings are negative, such as when an obstruction of the upper urinary tract is present due to stone disease.

The differential diagnoses include appendicitis, diverticulitis, pancreatitis, and lower-lobe pneumonia.

The incubation period of gonococcal urethritis is 2-6 days. Occasionally, 2 weeks may elapse before symptoms such as dysuria; thick, milky discharge; and pruritus occur.

The incubation period of nongonococcal urethritis (NGU) is 2-6 weeks. The symptoms are less severe, and the discharge may be clearer than with gonococcal urethritis. Patients are likely to have a higher level of education (ie, 90% of urethritis cases in college health services is NGU) and fewer sexual contacts.

Because patients with urethritis have a thick, milky discharge, the underpants may be impressively stained. Typically, patients with gonorrhea have a thicker, more copious discharge, but significant overlap with chlamydial urethritis is not uncommon.

Gram stain is the key to an immediate diagnosis, although patients frequently have co-infections.

Clinical and microbiologic criteria for the diagnosis of UTI are not well established in catheterized hospitalized patients. Symptoms in these individuals may be atypical or may be attributed to other disease processes, and no reliable colony count cutoff defines significant bacteriuria.

Low-level (100-1000 colony-forming units [CFU] per mL) colonization can progress to high-level (>100,000 CFU/mL) bacteriuria within 3 days in 96% of catheterized patients who are cultured on subsequent days (and not treated with antimicrobials). Thus, most experts agree that growth of more than 100 CFU/mL of a predominant pathogen represents catheter-associated UTI (CAUTI).

The workup of urinary tract infections (UTIs) is dependent on the suspected diagnosis. Urinalysis, Gram staining, and urine culture should always be obtained. The threshold for establishing true UTI includes documenting 2-5 or more white blood cells (WBCs) or 15 bacteria per high-power field (HPF) in a centrifuged urine sediment.

As with females, a positive nitrite test is poorly sensitive but highly specific for UTI. False positives are uncommon.

Low-grade proteinuria commonly occurs in UTIs. More than 2g of protein per 24 hours suggests glomerular disease.

The older, toxic-appearing patient frequently is diabetic or is immunocompromised. They may be at risk for emphysematous pyelonephritis. Radiographic studies (eg, kidney, ureters, bladder [KUB] should be conducted to exclude this diagnosis that cannot be missed.

Urine specimens may be obtained by suprapubic aspiration, catheterization, or midstream clean catch. Most males can perform a midstream clean catch reasonably well, with a reliability approaching that of suprapubic aspiration. Uncircumcised men must retract the prepuce and cleanse the glans before obtaining a specimen. If the patient is unable to cooperate, a catheterized specimen or suprapubic aspiration is necessary.

Bacteriuria without pyuria suggests contamination or colonization. Pyuria without bacteriuria suggests nongonococcal urethritis (NGU), genitourinary tuberculosis, stone disease, or malignancy.

If a Gram stain of an uncentrifuged clean-catch midstream urine sample reveals the presence of 1 bacterium per oil-immersion field, this represents 10,000 bacteria/mL of urine. A specimen (5mL) that has been centrifuged for 5 minutes at 2000 revolutions per minute (rpm) and examined under high power after Gram staining allows for the identification of bacteria in lower numbers. In general, Gram staining has a sensitivity of 90% and a specificity of 88%.

Urine culture remains the gold standard for the diagnosis of UTI. Collected urine should be immediately sent for culture; if not, it should be refrigerated at 4°C. Two culture techniques (dip slide, agar) are used widely and are accurate.

The exact number of bacteria in a urine culture that is needed to define UTI in a man is a bit controversial; generally, positive results are seen if there are more than 1000 colony-forming units (CFU)/mL of urine, much lower than the threshold for women.[9] However, most authors would accept a value of more than 10,000 CFU/mL. Some advocate the treatment of any pathogens growing in a patient with symptoms of UTI.

Imaging and urologic intervention should be considered in the following patients:

• Patients with a history of kidney stones, especially struvite stones, are candidates for urosepsis.
• Patients with diabetes are susceptible to emphysematous pyelonephritis, and they may require immediate nephrectomy; persons with diabetes also may develop obstruction from necrotic renal papillae that are sloughed into the collecting system and obstruct the ureter.
• Patients with polycystic kidneys are prone to abscess formation.
• Patients with tuberculosis are prone to developing ureteral strictures, fungus balls, and stones.

Imaging in the emergency department typically is not necessary unless concomitant obstructive uropathy is suspected, as this is an emergent condition that requires prompt intervention. Modalities for this include ultrasonography, contrasted computed tomography (CT) scanning, or helical CT scanning of the urinary system (currently preferred by most experts).

Plain film imaging

Plain films may localize stone densities, but identification within the urinary tract cannot be confirmed. Uric acid and some struvite stones are radiolucent. Plain films provide no information about the renal parenchyma or function.

Ultrasonography

Measurement of the postvoid residual by bladder scan or ultrasonography should be performed on every patient admitted to the hospital for UTI. Its use may minimize the need for Foley catheter insertion.

Renal ultrasonography is a noninvasive study that requires no contrast and provides useful information about the renal parenchyma. This imaging modality can be performed at the bedside in a hemodynamically unstable patient, and it can help to detect hydronephrosis, pyonephrosis, and perirenal abscess. However, the quality of the study depends on the skill of the examiner; the study may be of little benefit in patients who are obese. Ureteral dilatation secondary to UTIs may mimic obstruction.

Transrectal ultrasonography is the study of choice to demonstrate a prostate abscess[10] ; a CT or magnetic resonance imaging (MRI) scan also may be useful. Virtually all men older than 60 years have some prostatic calculi (see the CT scan below); however, no correlation exists between chronic prostatitis and the presence or absence of prostatic calculi.

Prostatic calcifications in a male with a urinary tract infection.

Scrotal ultrasonography with Doppler interrogation and radionuclide scans can be helpful in equivocal cases to differentiate the causes of acute scrotum, including epididymitis, torsion of the spermatic chord, and torsion of a testicular appendage. Torsion of the spermatic cord must be assumed until proven otherwise, because necrosis can develop in less than 3 hours. Consultation with a urologist is mandatory in all but the most clear-cut cases of torsion because the standard is to try to intervene in less than 3 hours.

CT scanning

Noncontrast helical CT scanning is the preferred diagnostic test for obstructive nephrolithiasis. CT scanning with contrast is the imaging study of choice, offering excellent information about the renal parenchyma and the collecting system. It is also a functional study when the excretory phase is included, which demonstrates the site and degree of obstruction very well.

In acute bacterial prostatitis, inflammation is observed in part or all of the gland. This is characterized by marked infiltration with neutrophils and diffuse edema. Microabscesses may be present, and these may coalesce into larger collections.

The histology of chronic bacterial prostatitis is that of focal, nonacute inflammation; however, this finding is not diagnostic, because it may be observed in men without bacterial infection. Because chronic bacterial prostatitis may be a focal disease, needle biopsies may be unreliable. Occasionally, biopsies reveal a granulomatous prostatitis of unknown cause.

The most accurate method to measure pyuria is counting leukocytes in unspun fresh urine using a hemocytometer chamber; more than 10 WBCs/mL is considered abnormal. Examination for pyuria is a sensitive (80-95%), but nonspecific (50-76%), method of diagnosing UTI. WBC counts determined from a wet mount of centrifuged urine are not reliable measures of pyuria. An uncontaminated specimen is suggested by a lack of squamous epithelial cells.

White cell casts in urine specimens may be observed in conditions other than infection, and they may not be observed in all cases of pyelonephritis. If the patient has evidence of acute infection and white cell casts are present, the infection likely represents pyelonephritis. A spun sample (5mL at 2000rpm for 5min) is best used for evaluation of cellular casts.

The presence of leukocyte esterase on a dipstick test is a rapid screening for pyuria; it is 57-96% sensitive and 94-98% specific for identifying pyuria.

The nitrite test is a rapid screening test for bacteriuria; false-negative test results are seen in low-grade bacteriuria, but false-positive results are rare. A positive nitrite test has 27% sensitivity and 94% specificity for UTI when the cutoff is 100,000 CFU/mL.

In acute bacterial prostatitis, most patients have pyuria and bacteriuria, allowing the infecting organism to be isolated by midstream urine collection. Blood cultures, a complete blood count (CBC), and a basic metabolic panel should be obtained.

In chronic bacterial prostatitis, bacteria and leukocytes may or may not be observed in prostate-specific secretions (ie, expressed prostatic secretions [EPS] or a third midstream bladder specimen [VB3] postprostatic massage). More than 15 leukocytes/HPF is abnormal.

4-Glass test

Although the 4-glass test is considered the standard for the diagnosis of chronic prostatitis, it is used infrequently.

The 4-glass test was described by Meares and Stamey in 1968 to accurately localize bacteria (ie, urethra vs prostate).[6] One should obtain simultaneous cultures of: (1) urethral urine,(ie, first voided bladder specimen [VB1]); (2) midstream urine (ie, second midstream bladder specimen [VB2]); (3) EPS; and (4) VB3.

The tests should be performed when the patient does not have significant bacteriuria, and the specimens must be quantitatively cultured immediately after collection.

If bacteriuria is present, antibiotics should be given for 2-3 days to sterilize the urine; these agents are not effective against chronic bacterial prostatitis. If the number of bacteria in EPS ejaculate or VB3 exceeds that in VB1 or VB2 by at least 10-fold, the infection is prostatic in origin.

Note: The above approaches are seldom utilized outside of a specialty clinic.

Premassage/postmassage test

A simpler procedure for the diagnosis of chronic prostatitis was suggested by Nickel.[11] In the premassage and postmassage test, urine is obtained before and after prostate massage. These specimens are sent for culture and sediment microscopy. If bacteria and leukocytosis in the postmassage specimen exceed those in the premassage specimen, category II prostatitis is suggested. Leukocytosis alone indicates category IIIA, whereas no bacteria or leukocytosis indicates category IIIB.

Postvoid residual urine volume measurement

Measurement of the postvoid residual urine volume may be helpful in the older patient for whom prostatism is suspected. Although this measurement traditionally is performed via catheterization, some institutions are using ultrasonography for this measurement.[12] If the postvoid residual urine volume is significantly elevated, a urinary catheter must be placed and urologic consultation obtained.

Urodynamic studies

Chronic prostatitis may result in an element of bladder neck obstruction, which may be demonstrated by urodynamic studies and may be corrected with transurethral surgery.[4]

In epididymitis, a microscopic examination of the urethral secretions is helpful only in cases with very mild symptoms, when torsion is not a consideration. Leukocytes and bacteria on a Gram stain would suggest epididymitis (unless the patient previously had a vasectomy).

Torsion of the spermatic cord and torsion of a testicular appendage would be the main differential diagnosis considerations. Spermatic cord torsion normally is diagnosed using ultrasonography, which is very sensitive and specific, or with surgical exploration. The latter does not alter the outcome of epididymitis if the testicle is inadvertently explored to pursue torsion.

Of patients with orchitis resulting from tuberculosis, 70% have other genitourinary or pulmonary symptoms of this disease. Testing urine for acid-fast bacilli (AFB), testing using purified-protein derivative (PPD), and performing chest radiography are helpful.

Testicular cancer is the most common malignancy in males aged 15-35 years. Although it usually presents as a painless intraparenchymal mass, 10% of cases present after minor trauma. For this reason, any patient felt to have a lesion within the parenchyma of the testicle should be referred for immediate urologic evaluation.

Microscopic hematuria is found in approximately 50% of cystitis cases; when microscopic hematuria is found without symptoms or pyuria, it should prompt a search for malignancy. Other conditions that should be considered include calculi, vasculitis, renal tuberculosis, and glomerulonephritis. In a developing country, hematuria is suggestive of schistosomiasis, which can be associated with salmonellosis and squamous cell malignancies of the bladder.

In younger men, differentiation of UTI from urethritis may necessitate a urethral smear and culture or urinary antigen testing for chlamydia and N gonorrhoeae.

For urethritis, a urethral swab obtained 1 hour after the last micturition is 95% sensitive and 99% specific for gonorrhea. Inflammatory cells without intracellular gram-negative diplococci suggest nongonococcal urethritis (NGU).

A small swab should be carefully inserted approximately 1 inch into the male urethra and rotated about its axis 5 times. The swab then should be withdrawn and immediately streaked onto either chocolate agar or Thayer-Martin/New York City media. The same swab then should be rolled onto a slide, which should then be heat-fixed and stained (ie, Gram stain). Importantly, roll the specimen on only a very limited part of the slide; this will make the microscopic search easier. The same swab then may be sent for chlamydia testing, although many public health facilities do not have the funds to test males for this disease.

Chocolate agar is heated blood agar; the heating causes the red blood cells (RBCs) to lyse, releasing their intracellular contents, thereby enhancing the recovery of fastidious organisms such as N gonorrhea. This media is perfectly suited for culturing the male urethra, which is normally sterile. Thayer-Martin and New York City agars have antibiotics (including vancomycin) incorporated into them, thereby limiting the growth of competing bacteria that may overgrow the gonococcus.

These media are perfect for culturing the female cervix, the pharynx, or the anus. They also can be used for the male urethra, although the vancomycin may inhibit the growth of the gonococcus, creating a false-negative culture result. All Neisserial growths must be confirmed as gonorrhea with a quadFERM test (a 2h carbohydrate degradation method for detecting Neisseria species); gonorrhea will only change the color in the glucose well.

Male UTIs should be recognized as complications of ongoing upper tract infection. The initial treatment regimen is based on the local sensitivity patterns of the organisms that are to be focused upon. The primary value of the initial culture is to allow adjustment of the treatment plan if antibiotic sensitivity testing demonstrates a resistant organism.

In the elderly, pyelonephritis carries a 3% mortality rate. This dictates that the initial empiric therapy will be based on the likelihood of resistant organisms in the community.

The decision to treat young men who are sexually active for UTI versus sexually transmitted disease (STD) – related urethritis rests primarily on epidemiologic grounds (eg, recent new sexual partner, multiple sexual partners).

Consultation with a urologist is essential for the treatment of UTIs in adult males with the following:

• Suspected underlying anatomic abnormality - however, this consultation can be completed on an outpatient basis, unless obstructive uropathy is present
• Acute scrotal infection - consultation is needed in all but the most clear-cut cases.
• All forms of prostatitis - in acute bacterial prostatitis, suprapubic drainage may be required if acute urinary retention occurs

The following are suggested consultations:

• Infectious disease specialist - when unusual or resistant microorganisms have already been isolated; and / or one or more of the community's uropathogens demonstrate high rates of resistance (>15%)
• Infections of the immunosuppressed
• Pharmacokinetics specialist especially when using aminoglycosides or other drugs that pose a significant risk to the given patient.

Pain specialists may be needed to control discomfort in patients with nonbacterial prostatitis. Chronic abacterial prostatitis shares the following with other chronic pain syndromes: (1) pain as a primary complaint; (2) discord between symptoms and findings; and (3) history of multiple unsuccessful treatments. Providers of alternative healing (eg, hypnotherapists) and a psychiatrist or psychologist also may be needed.

Patients who are free of significant underlying conditions such as significant renal dysfunction, and whose vital signs demonstrate the ability to comply with oral therapy, are candidates for outpatient therapy. In a responsible adult, check in with them to see how everything is going. Formal medical follow-up should be arranged for 48-72 hours.

If the patient appears toxic, has obstructive uropathy, has stones, is unable to tolerate fluids by mouth, has significant comorbid disease, or otherwise is unable to care for himself at home, inpatient admission is recommended. For example, consider admission for UTI for elderly patients and patients who have diabetes, who are immunocompromised, or who show signs of dehydration, hyperpyrexia, or rigors.

Initial inpatient treatment includes intravenous (IV) antimicrobial therapy with a third-generation cephalosporin, such as ceftriaxone; a fluoroquinolone, such as ciprofloxacin; or an aminoglycoside. Antipyretics, analgesics, and adequate IV fluids to restore appropriate circulatory volume and promote adequate urinary flow are also important.

Pharmacotherapy 

In patients with risk factors associated with an unfavorable prognosis, such as old age, debility, renal calculi, recent hospitalization or instrumentation, diabetes, sickle cell anemia, underlying carcinoma, or intercurrent cancer chemotherapy, the antimicrobial coverage should be broadened and an antipseudomonal agent should be added.

Adult males with UTI should receive a 10- to 14-day course of antibiotics. Outpatient regimens include a fluoroquinolone, trimethoprim-sulfamethoxazole (TMP-SMZ), minocycline, or nitrofurantoin (should not be given if glomerular filtration rate < 50). Treat the symptom of dysuria with phenazopyridine.[13, 14, 15, 16]

Unfortunately, the prevalence of uropathogens resistant to TMP-SMZ, nitrofurantoin, and first-generation cephalosporins has continued to rise. There are data that suggest overall resistance to TMP-SMZ is approximately 25% (range, 10-45%), based on the area of the country, and resistance to nitrofurantoin is slightly higher. Fluoroquinolone resistance is an increasing problem. Despite these concerns, fluoroquinolones remain the preferred initial drug therapy for many providers.[17]

Aminoglycoside-related complications

As previously stated, prolonged use of aminoglycosides (>2wk) is a complication risk factor, including for cranial nerve (CN) VIII damage (hearing loss and vestibular dysfunction). Fortunately, most aminoglycoside use in treating serious UTIs is limited to less than 1 week.

Unfortunately, monitoring for CN VIII dysfunction is less than optimal; by the time it is detectable (even subclinically, by weekly audiograms and/or electronystagmograms), the damage has been done and is irreversible. This is because of differences in half-lives between sera and because of the endolymph and perilymph that bathe the inner ear. However, monitoring allows the damage to be minimized. Remember that the auditory and vestibular systems function independently; therefore, consideration should be given to monitoring each.

Animal models suggest that doses of aminoglycosides given at night or to a patient who has been fasting or is dehydrated may be more ototoxic. The possibly protective roles of calcium and calcium channel blockers await further study.

Dietary considerations

Keeping the patient well hydrated is important, especially if an obstruction was recently relieved.

Drinking cranberry juice offers little benefit. Although it appears to inhibit E coli from adhering to human uroepithelium, the amounts of bacteriostatic hippuric acid that are present are unlikely to be clinically effective.

For complicated UTIs associated with struvite calculi, foods and vitamin supplements rich in phosphorus and magnesium are advised. Remember that divalent cations (eg, magnesium) can chelate oral fluoroquinolones, preventing their absorption from the gut.

Activity considerations

Bedrest and avoiding certain activities (eg, bike riding) may be beneficial in patients with prostatitis. For patients with category IIIB (chronic, noninflammatory, abacterial) prostatitis, bedrest for 2 weeks has been advocated. Sitting on ring cushions can be a simple way to minimize symptoms.

In urethritis, sexual activity may be resumed when both partners have completed treatment; barrier methods are encouraged. No one knows for certain when sexual activity may be resumed for the other topics discussed in this article.

To eradicate prostatitis, therapeutic drug levels must be achieved within the prostatic acini. Other challenges include prostatic calculi (a nidus for infection), inspissated secretions and microabscesses, and biofilms produced by offending organisms. Bladder outlet obstruction promotes stasis (and thus infection).

Antimicrobial agents

Nitrofurantoin, sulfonamides, vancomycin, penicillins, and cephalosporins do not penetrate well into the prostate.

Antibiotics that penetrate well into the acid milieu of the prostate are nonpolar and lipid-soluble and have a high measure of acid strength, a small molecular radius, and low serum protein binding. Drugs that best fit these criteria are the fluoroquinolones, doxycycline, minocycline (particularly effective against methicillin-resistant Staphylococcus aureus [MRSA]), trimethoprim (available in the United States only as trimethoprim-sulfamethoxazole [TMP-SMZ]), rifampin, and erythromycin. Of this group, the fluoroquinolones appear to achieve the best tissue levels. Erythromycin maybe used as a second-line agent when culture results are available.

The combination antimicrobial TMP-SMZ generally should be avoided. Only the TMP penetrates the prostate, and its sulfa component may be nephrotoxic. Generally, if TMP is not available because of formulary reasons, resort to quinolone or tetracycline.

Rifampin should never be used alone. It needs to be given with at least 1 other antibiotic to which the pathogen is sensitive, since resistance to rifampin develops quite quickly. Basically, rifampin should be given only under special circumstances.

Quinolones

Quinolones can be divided into first, second, third, and fourth generations. First-generation drugs (nalidixic acid) are not effective for prostatic infections. Third- and fourth-generation fluoroquinolones provide increased streptococcal and anaerobic coverage, which is not needed to treat prostatic infections.

The second-generation quinolones widely used to treat prostatic infection include ciprofloxacin, ofloxacin, norfloxacin, and levofloxacin. These drugs all are bactericidal against gram-negative bacilli; however, because of increased resistance, they are no longer recommended by the US Centers for Disease Control and Prevention (CDC) for N gonorrhoeae infections.[18]

Levofloxacin is most effective against susceptible strains of Enterococcus faecalis and has the advantage of once-daily dosing. Although all the second-generation drugs are used to treat prostatitis, only ofloxacin has been approved by the US Food and Drug Administration (FDA) for this indication.

Antibiotic concentrations

Regarding antibiotic concentrations in the prostate, interpreting the literature is difficult because many different terms are used (eg, "mean concentration in prostatic tissue," "mean concentration in prostatic fluid, prostatic tissue/serum ratio, prostatic fluid/serum ratio," and "stromal/epithelial ratio"). Furthermore, these specimens are often obtained in patients with benign prostatic hypertrophy or carcinoma (ie, not prostatitis).

One also must note the host being tested; TMP-SMZ penetrates the dog prostate far better than it does the human prostate, probably because of differences in semen pH. Although some antibiotics appear to be more suitable by certain criteria, clinical efficacy probably is the bottom line.

Nonantimicrobial agents

Many nonantimicrobial agents are available for prostatitis. Narcotics, nonsteroidal anti-inflammatory drugs (NSAIDs), and tricyclic antidepressants (TCAs; eg, amitriptyline) may be needed for pain relief. Hormonal manipulation with a 5-alpha-reductase inhibitor (finasteride) may decrease glandular inflammation; lycopene, prominent in tomato sauces, also may diminish glandular swelling.

Diazepam and baclofen may decrease sphincter or perineal muscle spasm. Alpha blockers may minimize ductal reflux and dysfunctional voiding.

Because of tadalafil’s possible effect in BPH, it may be useful in preventing recurrent UTIs.[19]

Nonpharmaceutical therapy

Nonpharmaceutical approaches also may be used for prostatitis. An example of "what's old is new" is prostate massage. For decades prior to the antibiotic era, prostate massage was the primary therapy for prostatitis. In difficult cases, repetitive prostate massage may be of benefit because of its potential for improving antibiotic penetration and improving drainage of clogged ducts.

The primary management of prostatitis is medical therapy. In certain circumstances, however, surgical intervention may be required.

Acute bacterial prostatitis

The intensely inflamed prostate allows antimicrobials to easily pass from the plasma. Hospitalized patients with acute bacterial prostatitis can receive various antimicrobials; parenteral ampicillin and gentamicin often are used. In most cases, the fever resolves in 2 days.

Once improved, appropriate oral agents include TMP-SMZ or a fluoroquinolone (preferred). Therapy should be continued for a minimum of 4 weeks to prevent chronic bacterial prostatitis from developing. Analgesics and stool softeners may be helpful.

If the patient with acute prostatitis has significant urinary obstruction, a Foley catheter can be gently inserted. If this is too uncomfortable, a suprapubic cystotomy may be required. The catheter can usually be removed 1-2 days later.

Chronic bacterial prostatitis

Although chronic bacterial prostatitis is very difficult to cure medically, an attempt should be made to cure this condition with antimicrobial therapy.[20, 21, 22, 23] Long-term results with TMP-SMZ (15-60% cure rate) probably reflect the inability of sulfa drugs to penetrate the noninflamed prostate; the usual regimen is 1 double-strength TMP-SMZ dose twice a day for 3 months.

The combination of TMP with rifampin may be useful but needs further study in chronic bacterial prostatitis. Some evidence suggests that 30 days of a fluoroquinolone may be superior to TMP-SMZ.

Coverage for Chlamydia and Ureaplasma should be considered for patients with category IIIA prostatitis (ie, leukocytosis without demonstrable bacteria).

If therapy fails, appropriate management of chronic bacterial prostatitis is to either treat acute exacerbations or to try chronic suppressive therapy (using half-normal doses).

Antimicrobials are not needed for asymptomatic patients who have evidence of inflammation on biopsy specimens or in secretions (category IV prostatitis); however, antimicrobials should be considered for men who are infertile who have bacteria or inflammation in their semen.

Surgery

Surgery is indicated only for a few specific conditions, including bladder neck obstruction, prostatic calculi (seen in the image below), and recurrent infection with the same bacteria.[4]

Prostatic calcifications in a male with a urinary tract infection.

Transurethral incision of the bladder neck benefits some patients with bladder neck obstruction; however, transurethral balloon dilatation of the prostate is not helpful. A partial transurethral prostatectomy (TURP) removes only part of the infected gland and, therefore, benefits only one third of patients.

Radical or total prostatectomy usually is not required or beneficial; complications include incontinence and impotence. Patients for whom a radical TURP or total prostatectomy should be considered are those with either prostatic calculi or those in whom the same bacteria have been consistently isolated from prostatic specimens. A prostate biopsy may confirm that the bacteria are actually originating from the prostate. These are rarely cured by antimicrobials alone; drainage is best achieved by an ultrasonographically guided needle.

Other surgical interventions may be needed to remove or address other complications, such as bladder calculi (seen in the image below).

Bladder calculi in a male with a urinary tract infection.

For epididymitis, antibiotic treatment for patients younger than 35 years should target Chlamydia and gonococci. Ceftriaxone (intramuscular [IM] 250mg) followed by doxycycline (oral [PO] 100mg twice daily [bid] for 7-10 days) usually is effective.

Epididymitis therapy for older men should address enteric gram-negative rods. TMP-SMZ (double-strength, 1 dose PO bid) or a fluoroquinolone can be used; a 30-day course covers concomitant prostatic infection.

When risk factors for urosepsis are present, such as fever or urinary retention, the patient should be hospitalized, and IV antibiotics should be started.

Of cases of acute scrotum, 90% are caused by epididymitis, torsion of the spermatic chord, and torsion of a testicular appendage.

Torsion of the spermatic cord must be assumed until proven otherwise, because unresolved torsion of the cord is likely to result in irreversible necrosis in less than 12 hours. Consultation with a urologist is mandatory in all but the most clear-cut cases for operative salvage of the torsed testicle.

The surgical intervention is detorsion and orchidopexy, with orchidopexy of the contralateral side (because this side is predisposed to torsion at a later date).

Most patients with pyelonephritis should undergo imaging studies to rule out other lesions, and IV antibiotic treatment should be initiated empirically with an aminoglycoside and ampicillin. Third- and fourth-generation cephalosporins, a carbapenem, or aztreonam also provides broad gram-negative rod coverage.

Fluid resuscitation is important if the blood pressure is unstable or if the patient is very old.

IV antibiotics are usually continued until the patient is afebrile for 24 hours, and then oral therapy is prescribed to complete at least 14 days of treatment; 30 days of treatment are typically necessary, because most cases are due to chronic prostatitis.

Urologic consultation should be considered for patients whose condition does not respond rapidly to antibiotics. In 1 study, fever persisted for 3 days in 13% of hospitalized patients with pyelonephritis, but none had complications; prolonged fever was associated with high baseline creatinine levels, younger age, and a high peripheral white blood cell (WBC) count.

Emphysematous pyelonephritis

Patients with diabetes are prone to develop emphysematous pyelonephritis, which is characterized by gas formation in the urinary tract. It often requires immediate nephrectomy for survival.

Orchitis

For viral orchitis, supportive therapy with scrotal support, cold compresses, and bedrest is all that is needed. The use of estrogens, gammaglobulin, and steroids has been advocated by some, but these have not been shown to decrease the risk for sterility or shorten the duration of symptoms. Symptoms usually resolve spontaneously in 7-10 days.

In cases of mumps orchitis, the patient and their family should be advised that sterility develops in up to 10% of affected individuals. Because no treatment is available for this entity, it is important that the measles-mumps-rubella (MMR) vaccine be administered in childhood and repeated in late adolescence.

Cystitis

For the few men with uncomplicated cystitis, TMP-SMZ can be used in areas where resistant E coli number less than 20%; alternatively, a fluoroquinolone can be used. The length of treatment should be 7-10 days.

Urethritis

For urethritis, ceftriaxone (125mg IM as a single dose) treats penicillinase-producing N gonorrhoeae. Treatment for nongonococcal urethritis (NGU) should also be given (doxycycline 100mg PO bid for 7 days).

Sexual partners should be treated, and patient counseling regarding safe sex is paramount; cases need to be reported to public health departments.

Preprocedure prophylaxis, condom use, and appropriate use of urinary catheters can reduce the risk of infections and complications.[24]

Unfortunately, instillation of antimicrobial agents into the bladder (unidirectional flow from the bladder to the bag is best), placing antimicrobials in the urine-drainage bag (which breaks the closed-drainage system), use of methenamine, and rigorous meatal cleansing are of little benefit. A guideline from the Infectious Diseases Society of America (IDSA) advises against the routine addition of antimicrobials or antiseptics to the drainage bag of patients who are catheterized in an effort to reduce the risk for catheter-associated bacteriuria or catheter-associated UTI (CAUTI).[25]

Preoperative prophylaxis

Preoperative antibiotics can reduce complications. Procedures of concern include open, transurethral, or laser prostatectomy; transrectal prostate biopsy; cystoscopy in patients with preoperative bacteriuria or a preoperative indwelling catheter; and renal transplantation. Before antibiotic coverage, the rate of septicemia from a transrectal biopsy was 5-10%; currently, the rate is less than 0.1%. Fluoroquinolones are the prophylactic drugs of choice for urologic procedures.

Post-transurethral prostatectomy (TURP) bacteriuria rates are approximately 10% in patients who receive systemic antibiotics, compared with approximately 35% in those who do not. Single-dose therapy is as effective as longer treatment courses.

Unfortunately, neither cefuroxime nor ciprofloxacin has been shown to reduce the rate of bacteriuria (approximately 20%) after lithotripsy.

The American Heart Association recommends antimicrobial prophylaxis to prevent bacterial endocarditis in patients with moderate- to high-risk cardiac conditions. High-risk conditions include the presence of prosthetic valves, the previous occurrence of bacterial endocarditis, complex cyanotic congenital heart diseases, and the presence of surgically constructed systemic pulmonic shunts. Moderate-risk conditions include most other congenital heart diseases, hypertrophic cardiac myopathy, and mitral prolapse with regurgitation.

For patients with moderate- or high-risk cardiac conditions, urologic procedures that warrant prophylaxis include prostate surgery, cystoscopy, and urethral dilatation; prophylaxis is not recommended for inserting a Foley catheter in a patient with uninfected urine.

Antibiotic regimens

Regimens for high-risk patients include ampicillin (or vancomycin) plus gentamicin. Ampicillin is given as 2000mg IM or IV within 30 minutes of starting the procedure; 6 hours later, 1000mg of ampicillin (or amoxicillin PO) is given once. Gentamicin is dosed at 1.5 mg/kg IV or IM (not to exceed 120mg) and is given only once, with the first dose of ampicillin. For patients allergic to ampicillin, 1000mg of vancomycin is given IV over 1-2 hours only once; it should be completed within 30 minutes of starting the procedure.

For kidney transplant recipients, TMP/SMZ (1 dose PO daily) beginning 2-4 days after surgery and continuing for 4-8 months was found to reduce the incidence rate of UTIs from 38% to 8% (especially after the catheter was removed), cut febrile hospital days and bacterial infections (during and after hospitalization) in half, and reduce graft rejection.

Regimens for moderate-risk patients include amoxicillin or vancomycin. Amoxicillin is given only once, in a 2000mg dose administered orally 1 hour before the procedure. For patients allergic to amoxicillin, 1000mg of vancomycin is given intravenously over 1-2 hours only once; it should be completed within 30 minutes of starting the procedure.

Prevention of STD-related infections

Condoms are useful in preventing sexually transmitted diseases (STD) such as urethritis; latex condoms help to prevent the transmission of the human immunodeficiency virus (HIV). Remember that these patients are at risk for more than 1 infection (gonorrhea, chlamydia, syphilis, hepatitis B, herpes, Trichomonas, HIV). The risk of acquiring HIV from an infected sexual partner is approximately 0.3% on average; the risk is 30-50% for herpes and gonorrhea. If abstaining is not an option, condoms are the best protection.

Prevention of CAUTIs

According to the IDSA 2009 guideline for the diagnosis, prevention, and treatment of CAUTI in adults, if an indwelling catheter has been in place for more than 2 weeks at the onset of CAUTI and remains indicated, the catheter should be replaced to promote continued resolution of symptoms and to reduce the risk of subsequent catheter-associated infection.[25]

The guideline also states that an indwelling catheter may be considered at the patient’s request in exceptional cases and when other approaches to management of incontinence have proven ineffective.[25]

According to the IDSA guideline, strategies to reduce the use of catheterization have been proven effective and may have more impact on the incidence of CAUTI and asymptomatic bacteriuria than other approaches addressed in the guidelines.[25]

The CDC 2009 guideline for the prevention of CAUTI states that catheter use and duration should be minimized in all patients, especially those at higher risk for CAUTI (women, elderly persons, patients with impaired immunity).[26] The CDC guideline recommends the following preventive measures[26] :

• Catheters should be used only for appropriate indications
• Catheters should be kept in place only for as long as needed
• Indwelling catheters in operative patients should be removed as soon as possible postoperatively
• Use of urinary catheters for treatment of incontinence should be avoided in patients and nursing home residents

Appropriate indications for indwelling urethral catheters include the relief of bladder outlet obstruction, treatment of urinary incontinence in a patient with an open sacral wound, and monitoring of urine output; they are also indicated for use during prolonged surgical procedures.

The CDC guideline recommends that clinicians avoid the routine use of systemic antimicrobials to prevent CAUTI in patients requiring either short- or long-term catheterization.[26]

Polymicrobial bladder infections are not uncommon in catheterized patients, and nonpathogenic organisms can be significant in catheterized patients. According to the CDC guideline, in acute care hospital settings, aseptic technique and sterile equipment for catheter insertion must be used to minimize the risk for CAUTI.[26]

At least 7 steps can be taken to prevent CAUTIs. However, although these steps can postpone a UTI for weeks, they will not be totally successful in patients with long-term catheterization.

Step 1

Catheterization should be avoided when not required (catheters have been found to be unnecessary in 41-58% of patient days) and should be terminated as soon as possible.

Step 2

Suprapubic catheters are associated with a lower risk for UTI. For men who require long-term catheterization, local genitourinary complications (meatal erosion, prostatitis, epididymitis) may be reduced, and patients may be more satisfied, but mechanical complications are increased. Contraindications include bleeding disorders, previous lower abdominal surgery or irradiation, and morbid obesity.

Step 3

Condom catheters are also associated with a lower risk of bacteriuria than are indwelling catheters, as long as the catheter is not manipulated frequently. However, these are difficult to use in uncircumcised men.

Step 4

Most patients using intermittent catheterization become bacteriuric within a few weeks. The incidence rate is 1-3% per insertion.

Step 5

Aseptic indwelling catheter insertion, a properly maintained closed-drainage system (with ports in the distal catheter for needle aspiration of urine[25] ), and unobstructed urine flow are essential. Catheters with hydrophilic coatings reduce or delay the onset of bacteriuria and are more comfortable for the patient. Only properly trained individuals who are skilled in the correct technique of aseptic catheter insertion and maintenance should take on this task.[26]

Step 6

Urinary catheters coated with silver also reduce the risk for CAUTI. Silver alloy seems to be more effective than silver oxide, and using these more expensive catheters in patients who are at highest risk is reasonable.[27]

Step 7

Because many CAUTIs occur in clusters, good handwashing before and after catheter care is essential.

See Urinary Catheterization in Men and Urinary Catheterization in Women for procedural information on catheterization.

If a patient fails to respond to antibiotics, an abscess should be considered. Upper- and lower-tract studies (eg, helical CT scanning, ultrasonography, cystoscopy) are important to consider in older patients at risk for anatomic abnormalities.

Follow-up urine cultures are warranted in males with UTIs; however, follow-up urethral cultures are not routinely warranted unless the man is symptomatic, in which case the symptoms are likely to be the result of exogenous reinfection.

Consider admission for UTI for elderly patients and patients who have diabetes, who are immunocompromised, or who show signs of toxicity such as dehydration, hyperpyrexia, rigors, or inability to tolerate oral fluids or medications. Also admit if the patient is unable to care for themself.

Fluoroquinolone resistance has dramatically risen throughout the world. The major approach to dealing with this has been to restrict their use, often by limiting the duration of therapy. This can result in suppressing the infectious process that may flare up months later with the same pathogen. By that time, the organism may have become totally or partially resistant.

In addition, the required rate of adherence is impossible to achieve with the growing numbers of health care providers (eg, Nurse Practitioners) who have prescriptive powers.

The monitoring process of antibiotic therapy remains very basic. It is based on signs and symptoms such as clinical appearance, body temperature, and urine/ blood cultures along with the occasional measurement of CRP or sedimentation rate. These often do not have the capability to detect the ongoing inflammatory response of the patient to the sequestered pathogens. Failure to do so may transform the acute process into a chronic one. Testing for other inflammatory products will certainly increase the yield. Since such are not routinely tested for, the challenge is to survey these markers and then develop devices for screening.[28]  

It is only fairly recently that the important role that the intestinal microbiome plays in recurrent UTIs has become known. The term microbiome refers to a community of microbes that live in a defined part of the body such as the GI tract or oral cavity. The term also refers to the essential role in maintaining human health. The normal flora of the gut eradicate pathogens that have infected the gut but also other parts of the body.

At times, the invader is able to migrate from the mucosa into the wall of gut where it may remain dormant. So protected from the host's immune system, it may develop mutations(dysbiosis) that allow it to escape and reinfect the urinary tract. This recurrence defines the Gut-Bladder Axis,[29] and this is why antimicrobial resistance is ever growing to the point of possibly ending the antibiotic era.

Fortunately, substances such as D- mannose exist that do prevent bacteria from adhering and invading the gut uroepithelial cells. As with antibiotics, their effectiveness is target dependent.[30]

.  

.   

The goals of pharmacotherapy are to eradicate the infection in order to reduce mortality and morbidity, and to prevent complications. The empiric choice should be based on the overall medical condition of the individual. Because of the progressive increase in the resistance of uropathogens, the local sensitivity profile has become the most important factor in this process (see below[31, 32] ). Anesi et al reported 54% of Enterobacteriaceae UTIs with varying degrees of resistance to extended-spectrum cephalosporins recurred within a median time of 69 days.[33]  

Due to the high prevalence of antimicrobial resistance among N gonorrhoeae, it is important to carefully review relevant clinical history of the patient and precisely determine the etiology of urinary symptoms in males. If gonorrhea is suspected, a fluoroquinolone antibiotic should not be prescribed because of widespread resistance by N gonorrhoeae. Dual therapy with ceftriaxone IM/IV plus azithromycin PO is recommended by the CDC sexually transmitted diseases treatment guidelines.[34]

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Below are listed commonly employed antibiotics

Ciprofloxacin (Cipro)

Ciprofloxacin is a fluoroquinolone with activity against pseudomonads, streptococci, methicillin-resistant S aureus (MRSA), S epidermidis, and most gram-negative organisms, but it has no activity against anaerobes. This agent inhibits bacterial deoxyribonucleic acid (DNA) synthesis and growth. Ciprofloxacin is indicated for urinary tract infections (UTIs) and chronic bacterial prostatitis.

Levofloxacin (Levaquin)

Levofloxacin is a fluoroquinolone with better gram-positive activity but less activity against Pseudomonas aeruginosa than ciprofloxacin. This agent is an active L-isomer of ofloxacin. Ciprofloxacin is indicated for complicated and uncomplicated urinary tract infections. It is also used for the treatment of chronic bacterial prostatitis.

Trimethoprim-sulfamethoxazole (Bactrim, Bactrim DS, Septra, Septra DS)

Trimethoprim-sulfamethoxazole (TMP-SMZ) is a combination antimicrobial agent designed to take advantage of synergy between TMP and sulfonamides. The antibacterial activity of TMP-SMZ includes common urinary tract pathogens, except Pseudomonas aeruginosa.

SMZ inhibits dihydropteroate synthetase, preventing incorporation of para-aminobenzoic acid (PABA) into dihydrofolate and subsequent synthesis of tetrahydrofolate. This agent has broad bacteriostatic activity against aerobic gram-positive and gram-negative organisms, with little activity against anaerobes; unfortunately, SMZ does not penetrate well into the kidney.

Ampicillin (Omnipen, Polycillin, Principen)

Ampicillin is an aminopenicillin beta lactam that impairs cell wall synthesis in actively dividing bacteria by binding to and inhibiting penicillin-binding proteins in the cell wall. This agent has enhanced activity against anaerobes and gram-negative aerobes and is generally used in combination with an aminoglycoside for empiric or directed activity against E faecalis urinary tract infections (UTIs).

Amoxicillin (Moxatag, Trimox)

Amoxicillin is a penicillin antibiotic that interferes with the synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria.

Gentamicin (Garamycin, Gentacidin)

Gentamicin is a bactericidal aminoglycoside antibiotic that inhibits bacterial protein synthesis by binding to the ribosome. This agent has activity against a variety of aerobic gram-negative bacteria, as well as E faecalis and staphylococcal species, and it is used with or without ampicillin to treat acute prostatitis in the hospitalized patient when Enterococcus is a concern. Gentamicin is the only aminoglycoside with appreciable activity against gram-positive organisms.

The dosing regimens for gentamicin are numerous. Adjust the dose based on creatinine clearance (CrCl) and changes in the volume of distribution. Ideal body weight (IBW) should be used for calculations (the drug is not fat soluble).

Trough serum levels should be monitored to ensure adequate clearance and reduce toxicity (< 2 mcg/mL). Peak levels should also be monitored after 4-5 half-lives when it is dosed more often than once daily (qd).

Once-daily dosing should only be used when treating gram-negative infections, as this takes advantage of its concentration-dependent killing and its postantibiotic effect. However, gentamicin exhibits neither of these properties against gram-positive infections. (For synergy against gram-positive organisms, use 1 mg/kg q8h).

Tobramycin (TOBI)

Tobramycin is an aminoglycoside used for gram-negative bacterial coverage, with better pseudomonal coverage than gentamicin. This agent is commonly used in combination with agents against gram-positive organisms and those that cover anaerobes.

Consider using tobramycin when penicillins or other less-toxic drugs are contraindicated, when bacterial susceptibility tests and clinical judgment indicate its use, and in mixed infections caused by susceptible strains of staphylococci and gram-negative organisms. Its dosing regimens are numerous and are adjusted based on the CrCl and changes in the volume of distribution.

Ceftriaxone (Rocephin)

Ceftriaxone is a third-generation cephalosporin that has a broad gram-negative spectrum, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms. By binding to 1 or more penicillin-binding proteins, this agent arrests bacterial cell wall synthesis and inhibits bacterial growth.

Vancomycin (Firvanq, Vancocin)

Vancomycin is a potent antibiotic directed against gram-positive organisms and active against Enterococcus species. It is indicated for patients who cannot receive or have failed to respond to penicillins and cephalosporins or who have infections with resistant staphylococci. It is used in conjunction with gentamicin for prophylaxis in penicillin-allergic patients undergoing gastrointestinal or genitourinary procedures.

Ceftazidime (Fortaz, Tazicef)

Ceftazidime is a third generation cephalosporin and a bactericidal agent that exerts its effect by inhibiting the enzymes responsible for cell wall synthesis. Caution should be used with this agent, as nephrotoxicity has been reported following concomitant administration of cephalosporins with aminoglycoside antibiotics or potent diuretics such as furosemide.

In addition, chloramphenicol has been demonstrated to be antagonistic to beta-lactam antibiotics, including ceftazidime, based on in vitro studies and time kill curves with enteric gram-negative bacilli. Because of the possibility of antagonism in vivo, particularly when bactericidal activity is desired, avoid this drug combination.

Doxycycline (Vibramycin, Vibra-Tabs)

Doxycycline is a broad-spectrum, bacteriostatic antibiotic in the tetracycline class. It inhibits protein synthesis and, thus, bacterial growth by binding to the 30S and, possibly, the 50S ribosomal subunits of susceptible bacteria. It may block dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Ertapenem (Invanz)

Ertapenem has bactericidal activity from inhibition of cell wall synthesis, which is mediated through ertapenem binding to penicillin-binding proteins. This agent is stable against hydrolysis by a variety of beta lactamases, including penicillinases, cephalosporinases, and extended-spectrum beta lactamases. Ertapenem is hydrolyzed by metallo–beta lactamases.

Aztreonam (Azactam, Cayston)

Aztreonam is a monobactam that inhibits cell wall synthesis during bacterial growth. It is active against gram-negative bacilli but has very limited gram-positive activity and is not useful against anaerobes. It lacks cross sensitivity with beta-lactam antibiotics, and it may be used in patients allergic to penicillins or cephalosporins.

Nitrofurantoin (Macrodantin, Furadantin)

Nitrofurantoin is a bactericidal antibiotic indicated for acute cystitis and UTIs caused by E coli, enterococci, S aureus, and strains of Klebsiella and Enterobacter species.

Rifampin (Rifadin)

Rifampin is an antituberculosis agent that inhibits RNA synthesis in bacteria by binding to the beta subunit of DNA-dependent RNA polymerase, which, in turn, blocks RNA transcription.

Class Summary

Urinary analgesics, such as phenazopyridine, can help to treat the symptoms of dysuria.

Phenazopyridine

Phenazopyridine is compatible with antibacterial therapy and can help to relieve pain and discomfort before antibacterial therapy controls infection. It is used for symptomatic relief of pain, burning, urgency, frequency, and other discomfort arising from irritation of the lower urinary tract mucosa caused by infection, trauma, surgery, endoscopic procedures, or passage of sounds or catheters. The analgesic action may reduce or eliminate the need for systemic analgesics or narcotics.

Linezolid

Fosfomycin

Minocycline

Cefepime

Ceftazidime/avibactam