Urinary tract infections in men

Case presentation 3

A 40-year-old man presented to his physician with a 3-day history of dysuria. The pain was moderately severe but only present during voiding. He had no urethral discharge and he had no pelvic pain. He had not been sexually active for over 1 month prior to his dysuria. On examination, his temperature was 37-4°C and the general physical exam was normal. The rectal examination showed a mildly enlarged but non-tender prostate. Urine analysis showed pyuria and bacteriuria. Urine culture was obtained and he was given ciprofloxacin 750 mg every 12 hours pending culture results. The culture eventually showed 105 colony forming units per milliliter of Escherichia coli susceptible to ciprofloxacin.

Clinical presentation

The presentation in this case is comparable to UTIs that are seen in women. However, in men it is important to consider involvement of the prostate gland as well as the bladder, ureters, and kidneys. The literature on UTI in men is limited and groups together urinary infections, such as cystitis and pyelonephritis, with prostatitis. It is easy to "rule in" prostatitis with a variety of clinical features (prostate tenderness, post-prostate examination urethral discharge) because acute prostatitis is often defined as a

UTI in a man with additional features supporting prostate inflammation.56 However, in men with features of UTI, it can be impossible to rule out some degree of prostatitis at the time of initial diagnosis since there may be only subtle or subclinical features of prostate involvement, which would only be revealed by prostate biopsy or culture of prostatic secretions. Thus the absence of prostate tenderness or post-prostate examination urethral discharge does not exclude the possibility of prostatitis in a man with dysuria and positive urine cultures.56 Because of this overlap, acute prostatitis and UTI can be considered to form a continuum in men. Some older literature refers to this as "recurrent UTI in men" or chronic prostatitis because of the incomplete response to the short courses of antibiotics used at the time.57


Prostatitis is a common condition and has protean manifestations. Several classification schemes have been devised to account for the variable characteristics that can be present. A recent NIH consensus classification has been developed to standardize prostatitis variants and permit more meaningful research.58 This system creates four categories:

• acute bacterial prostatitis

• chronic bacterial prostatitis

• chronic prostatitis/pelvic pain syndrome (with inflammatory and non-inflammatory subtypes)

• asymptomatic inflammatory prostatitis.

Although having reproducible definitions for the advancement of clinical research is reasonable, this division is difficult to translate into everyday clinical practice. Acute and bacterial chronic prostatitis share similarities with UTI since all three are infections. However, it is much less clear what the relationship is between infection and the other two forms of prostate disease. The exact distinction between acute and chronic bacterial prostatitis in this working definition is imprecise and does not specify the number of days of symptoms needed to invoke a diagnosis of prostatitis. This difficulty is also reflected in clinical trials of bacterial prostatitis. Of interest, it is widely believed that the chronic bacterial and non-bacterial forms of prostatitis account for about 90% of cases of prostatitis. A large population-based study in Canada showed that nearly 10% of men (aged 20-74) had symptoms consistent with prostatitis other than acute bacterial prostatitis and there was a fairly smooth age distribution throughout the group.59 A similar survey in Minnesota also showed that 9% of men (aged 40-70) had symptoms typical of prostatitis other than acute bacterial prostatitis.60 However, among men with prior prostatitis (including acute bacterial prostatitis), there was a significant increase in the age-related risk of prostatitis (20% at age 40, 38% at age 60, and 50% at age 50), suggesting that the various chronic prostatitis syndromes can have a remitting/relapsing form that tends not to resolve completely irrespective of the intervention.


The diagnosis of UTI in men is made in a similar fashion to that in women. Urine collection is less likely to be compromised by contamination from skin flora. Pyuria and bacteriuria are both highly predictive of significant positive cultures. The lower limit of a positive quantitative culture is 103 colony-forming units per ml.61 The sensitivity and specificity of this cut-off were both 97%, and it was unimportant as to whether a clean-catch mid-stream specimen or an uncleansed first void specimen was used.


The evaluation of the cause of UTI in men differs from that in women since it is believed that there should be some diagnosable anatomic or physiologic factor to account for the UTI in men.62 Recent studies in this area mostly come from referral centers and thus may suffer from referral bias. For example, a Scandinavian study of 83 men with UTI showed that 19 men had some upper tract finding and 35 men had lower tract problems.63 There was a correctable defect in only one man with an upper tract lesion, but 41% of the men had a lower tract abnormality. Only 18% of the men were found to have previously unrecognized, correctable abnormalities with the multiple modalities used to study the lower tract: cysto-urethroscopy, uroflowmetry, digital rectal examination, and measurement of post-void residual by abdominal ultrasound. There is no mention of how many of these men actually underwent a corrective procedure. A study designed to compare intravenous urography (IVU) with ultrasound and plain film showed that half of the men studied had some abnormality (most of which were not correctable).64 The most common problem found was bladder outflow obstruction that was actually diagnosed by urodynamics (which was not part of the formal study protocol but was available for many but not all of the patients). There was no mention of how many men received treatment for any abnormality found. A community-based study from Australia showed that of gay men with UTI (one-third of whom were HIV-positive), clinical management was satisfactory and, of the men who underwent further investigation, only 14% had detectable abnormalities and again there was no report on how many of these men underwent a corrective procedure.65 One thing lacking in all these studies is a sense of the rate of baseline abnormalities in similar populations of men without UTIs. Given the high rate of prostate symptoms recorded in community-based surveys,59,60 UTIs might simply coexist with some of the voiding problems and other prostate complaints seen in so many men. An additional issue that might be contributory is the referral bias of the studies performed by urologists.63,64 If the primary care providers suspected some anatomical or physiological problem in these men, they might have referred them for evaluation more quickly than for men with UTIs who evinced no symptoms.

Treatment strategies for men

The organisms that cause urinary tract infections in men (including acute and chronic prostatitis) are essentially the same as those found in women. The same virulence factors (P fimbriae, adhesins, hemolysins) that make bacteria good uropathogens in women (particularly as a cause of pyelonephritis) also make them uropathogenic in men.66-68 Thus, E. coli, Klebsiella spp., Proteus spp., Enterococcus spp., and various other gram-negative bacteria comprise the vast majority of uropathogens in men.

There are few studies comparing treatment strategies for male urinary tract infection or prostatitis in randomized controlled trials. There are no systematic reviews. Because of the possibility of concurrent prostatitis in men with UTI, the drugs selected for initial therapy are often those that penetrate into the prostate gland. These include TMP and the fluoroquinolones. Whilst other classes of drugs may be effective in the treatment of UTI in men, these drugs are active against most uropathogens. TMP is often given in a fixed combination with SMX. Clinical trials of TMP-SMX for UTI in males have, however, been disappointing. In an effort to compare a short course (10 days) to a long course (12 weeks) for recurrent UTI, the investigators of a multicenter US Veterans Administration study tried to recruit appropriate patients to randomize.69 Of the 306 patients screened, only 38 were randomized and only 30 were available for analysis at the end of the study period. Of the men screened, 17% were excluded because of comorbidity, 28% for paramorbidity, 6% for comedication, 24% for lack of compliance, and 9% for miscellaneous reasons. This left 46 men to study. Four of them did not have meaningful outcome on localization tests (which would likely not be considered very important today, but were required for study entry). Of the 42 remaining men, four could not be randomized. Eight more were dropped from the study for a variety of protocol violations leaving a total of 30. Notably, fewer than half of the men studied were symptomatic from their UTI, and two did not even have pyuria. Of interest, the long course of therapy was superior - 60% success for 12 weeks and only 20% for 10 days (RR 3; 95% CI 1-01-8-95). Recurrent infections were from the same organism in the majority of cases. Another study of 42 men with recurrent UTI showed that a longer course of treatment (6 weeks v 2 weeks) had a lower failure rate at a 6-week post-treatment follow up visit (68% v 32%; RR = 2-2; 95% CI 1-05-4-49).70

In contrast to TMP-SMX, the clinical response to fluoroquinolones in men with UTI is much better. Fluoroquinolones have good prostate penetration in animal models, and agents studied appear comparable in the treatment of male UTI/prostatitis. When norfloxacin was compared with TMP-SMX in 109 men in a randomized controlled trial, the bacterial eradication rate of 93% with norfloxacin compared with 67% with TMP-SMX (P < 0-05).71

Ofloxacin, a drug that has largely been replaced by its /-isomer, levofloxacin, was studied in an unblinded comparison to indanyl carbenicillin (an oral form of the drug that has an FDA indication for UTI/prostatitis) and to TMP-SMX.72 The population included men and women in equal numbers; however, treatment arms were not stratified by gender, an important limitation. Treatment failure with carbenicillin was 25%

compared with no treatment failures with ofloxacin (0%) (P = 0-048). The comparison with TMP-SMX was done in a larger group (173 patients) and the outcomes were similar in both treatment arms, although the trend for clinical cure favored ofloxacin. Only 117 patients were evaluable for clinical cure: 93% of ofloxacin-treated patients were cured as compared with 85% of TMP-SMX-treated patients for an RR of 0-92 (95% CI 0-81-1-04).

In another study, ciprofloxacin was compared with TMP-SMX in men with UTI.73 There was no significant difference in outcomes at late follow up (4-6 weeks), but the early bacterial eradication rate (days 5-9 following antibiotics) favored ciprofloxacin (82% v 52% P = 0-035). The drug doses used in the study were low (ciprofloxacin 250 mg p.o. every 12 hours, and TMP-SMX 160/800 mg p.o. every 12 hours) and the duration was brief (mean of 7 days). An open label study of ciprofloxacin for chronic bacterial prostatitis showed a good outcome with a 4-week course.74 The bacteriologic cure rate was 92% at 3 months after the end of therapy and 70% at 2 years post therapy.

How does this evidence apply to the example of the patient in Case 3 above? The treatment with ciprofloxacin is rational and should be of at least 2 week's duration. Assuming that he makes a good recovery and has no further symptoms, he does not need investigative studies, but incomplete resolution or relapse should occasion a workup. An ultrasound and plain abdominal radiograph can look for structural lesions such as kidney stones or hydronephrosis. A urologic evaluation could find problems with bladder emptying or structural disease of the lower urinary tract (including the prostate gland). While his prognosis is good, he may require a longer course of antibiotics for subsequent UTI.

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