Acute simple cystitis in adult and adolescent males

INTRODUCTION — Urinary tract infections (UTIs) include cystitis (infection of the bladder/lower urinary tract) and pyelonephritis (infection of the kidney/upper urinary tract).

This topic will review the approach to males with typical symptoms of acute cystitis when there is no concern that the infection has extended beyond the bladder. We consider this to be acute simple cystitis. When there is concern that the infection has possibly extended beyond the bladder (eg, when there is flank pain or other features suggestive of pyelonephritis, pelvic or perineal pain, fever, and/or other signs of systemic illness, including sepsis) we consider this to be a complicated UTI. This approach to categorizing UTI (table 1) differs from other conventions, as discussed in detail below.

Our approach to complicated UTI is discussed elsewhere. (See "Acute complicated urinary tract infection (including pyelonephritis) in adults and adolescents".)

In males, cystitis can occur in the setting of prostatitis; this is discussed elsewhere. (See "Acute bacterial prostatitis" and "Chronic bacterial prostatitis".)

Acute simple cystitis in females and UTIs in special populations are discussed elsewhere:

●(See "Acute simple cystitis in adult and adolescent females".)

●(See "Urinary tract infections and asymptomatic bacteriuria in pregnancy".)

●(See "Catheter-associated urinary tract infection in adults".)

●(See "Urinary tract infection in kidney transplant recipients".)

●(See "Recurrent simple cystitis in women".)

Asymptomatic bacteriuria is also discussed in detail elsewhere. (See "Asymptomatic bacteriuria in adults".)

UTI in children is also discussed separately.

TERMINOLOGY — We use the term acute simple cystitis to refer to an acute urinary tract infection (UTI) that is presumed to be confined to the bladder (table 1). Such infections lack signs or symptoms that suggest an infection extending beyond the bladder, which include:

•Fever (>99.9°F/37.7°C) – This temperature threshold is not well defined and should be individualized, taking into account baseline temperature, other potential contributors to an elevated temperature, and the risk of poor outcomes should empiric antimicrobial therapy be inappropriate.

•Other signs or symptoms of systemic illness (including chills or rigors, significant fatigue or malaise beyond baseline).

•Flank pain.

•Costovertebral angle tenderness.

•Pelvic or perineal pain, which can suggest accompanying prostatitis. (See "Acute bacterial prostatitis" and "Chronic bacterial prostatitis".)

If any of these signs or symptoms are present in the setting of pyuria and bacteriuria, we consider the patient to have acute complicated UTI or prostatitis and manage the patient differently. By this definition, pyelonephritis is a complicated UTI, regardless of patient characteristics. (See "Acute complicated urinary tract infection (including pyelonephritis) in adults and adolescents".)

According to this terminology, males can have acute simple cystitis depending on their presentation and do not by default have complicated UTI.

We also do not automatically consider patients with underlying urologic abnormalities (such as nephrolithiasis, strictures, stents, or urinary diversions), immunocompromising conditions (such as neutropenia or advanced HIV infection), or poorly controlled diabetes mellitus to have a complicated UTI if they have no concerning symptoms for upper tract or systemic infection. However, such patients can be at higher risk for more serious infection and have not traditionally been included in studies evaluating the antibiotic regimens we typically use for acute simple cystitis. Thus, we follow such patients more closely and/or have a low threshold to manage them as complicated UTI (eg, if they have subtle signs or symptoms that could be suggestive of more extensive infection). Many patients with significant urologic abnormalities come to clinical attention for UTI because of signs or symptoms consistent with complicated UTI as defined here (rather than features of simple cystitis alone).

Other populations, such as renal transplant recipients, have unique management considerations and thus are not included in the above categorization. These populations are discussed elsewhere. (See "Urinary tract infection in kidney transplant recipients".)

These definitions of acute simple cystitis and complicated UTI are different from other categorizations, which themselves are somewhat variable. Specifically, cystitis or pyelonephritis in a nonpregnant, premenopausal woman without underlying urologic abnormalities has traditionally been termed acute uncomplicated UTI [1], and complicated UTI has been defined, for the purposes of treatment trials, as cystitis or pyelonephritis in a patient with underlying urologic abnormalities. Individuals who do not fit into either category have often been treated as having a complicated UTI by default. Thus, is has been conventional to consider all UTIs in males as complicated, since the majority occur in infants or in older adults in association with urologic abnormalities, such as bladder outlet obstruction (eg, due to prostatic hyperplasia) or instrumentation. In addition, it is not always possible to rule out prostate infection. However, we favor an approach to treatment based on the extent of infection and severity of illness. Since complicated UTI, as defined here, is a more serious infection than simple cystitis, the efficacy of an antimicrobial agent is of greater importance, and certain agents used for simple cystitis should not be used for complicated UTI because they do not achieve adequate levels in tissue, which may be important for cure. Risk for infection with drug-resistant organisms is a consideration in antibiotic selection for both simple cystitis and acute complicated UTI.

EPIDEMIOLOGY — Acute simple cystitis occurs in a very small proportion of males between 15 and 50 years of age. The incidence is approximately five to eight urinary tract infections (UTIs) per year per 10,000 young to middle-aged males [2,3].

Symptomatic UTI is much less common in males than in females. This is due to longer urethral length, drier periurethral environment (with less frequent colonization around the urethra), and antibacterial substances in prostatic fluid.

Risk factors associated with acute simple cystitis in males include insertive anal intercourse and lack of circumcision [4].

CLINICAL MANIFESTATIONS — Clinical manifestations of cystitis consist of dysuria, urinary frequency, urgency, and/or suprapubic pain.

Prostatitis should be considered in males presenting with cystitis symptoms that are recurrent or are accompanied by pelvic or perineal pain or fever. (See "Acute bacterial prostatitis" and "Chronic bacterial prostatitis".)

Fever, chills, rigors, and other signs of systemic illness are not compatible with a diagnosis of acute simple cystitis and raise the possibility of pyelonephritis, prostatitis, or other complication of UTI. (See "Acute complicated urinary tract infection (including pyelonephritis) in adults and adolescents" and "Acute bacterial prostatitis".)

DIAGNOSTIC APPROACH

Initial evaluation — Urinary tract infection (UTI) should be suspected in males who have dysuria, urinary frequency or urgency, and/or suprapubic pain. Males should be asked about fevers, chills, and other systemic symptoms, as well as flank, pelvic, or perineal pain. If symptoms are suggestive of extension of infection outside of the bladder, physical examination should include assessment for fever, costovertebral angle tenderness, abdominal examination, and, if pelvic or perineal pain are present, a cautious digital rectal examination to evaluate for a tender prostate.

Laboratory diagnostic tools consist of urinalysis (either by microscopy or by dipstick) and urine culture with susceptibility data. A urine Gram stain may be helpful in guiding the choice of empiric therapy pending culture results. A urine culture should be performed in all males with symptoms suggestive of cystitis.

The possibility of a urethritis should be considered in males who are sexually active. (See 'Differential diagnosis' below.)

Urine collection — Details on optimal urine collection when UTI is suspected are presented elsewhere. (See "Sampling and evaluation of voided urine in the diagnosis of urinary tract infection in adults", section on 'Urine sampling'.)

Briefly, a midstream urine (collection of urine after the initial stream has been passed) is preferred for UTI evaluation. This contrasts with a first-catch urine (collection of the initial stream of urine), which is preferred for evaluation of urethritis. Thus, different urine specimens should be used when evaluating for both UTI and urethritis. (See "Urethritis in adult males", section on 'First-catch urine'.)

Urinalysis — Urinalysis for evaluation of pyuria is a valuable laboratory diagnostic test for UTI. Pyuria is present in almost all males with acute cystitis; its absence strongly suggests an alternative diagnosis [5,6].

The most accurate method for assessing pyuria is to examine an unspun, voided midstream urine specimen with a hemocytometer; an abnormal result is ≥10 leukocytes/microL [5]. White blood cell casts in the urine are diagnostic of upper tract infection, which would indicate a complicated UTI.

Interpretation of urinalysis results is further discussed separately. (See "Sampling and evaluation of voided urine in the diagnosis of urinary tract infection in adults", section on 'Dipsticks' and "Sampling and evaluation of voided urine in the diagnosis of urinary tract infection in adults", section on 'Microscopy for pyuria'.)

Urine culture — A midstream urine culture is recommended to confirm the diagnosis of UTI in males, using colony count criteria of ≥10³ colony-forming units/mL of a predominant species [7]. In females in whom coliform bacteria (eg, Escherichia coli) are isolated, lower colony counts are likely to represent infecting organisms [8,9]. It is unknown if the same is true for males.

The spectrum of isolates causing simple cystitis in males is not well defined but is likely similar to that in females. E. coli (75 to 95 percent) is the predominant bacteria, with occasional other species of Enterobacteriaceae, such as Klebsiella pneumoniae and Proteus mirabilis [10,11]. (See "Acute simple cystitis in adult and adolescent females", section on 'Microbiology'.)

Diagnosis — The diagnosis of acute simple cystitis can be made in a man who presents with typical urinary symptoms (urgency, frequency, dysuria), pyuria (on microscopy or dipstick), and bacteriuria (on urine culture) in the absence of fever or other systemic symptoms, pelvic or perineal pain, costovertebral angle tenderness, or other features suggestive of pyelonephritis or prostatitis (table 1).

Any of these features suggest an alternative diagnosis, potentially acute bacterial prostatitis or acute complicated UTI. (See "Acute bacterial prostatitis" and "Acute complicated urinary tract infection (including pyelonephritis) in adults and adolescents".)

We also have a lower threshold to consider patients with risk factors for more serious infection as having acute complicated UTI, for example, if they have subtle signs or symptoms of possible upper tract or systemic infection. Such risk factors include urologic abnormalities (eg, nephrolithiasis, strictures, stents, or urinary diversions), immunocompromising conditions (eg, neutropenia or advanced HIV infection), or poorly controlled diabetes mellitus.

Additional evaluation — Dedicated urologic evaluation is probably not necessary in young healthy males with no obvious complicating factors who have rare, sporadic episodes (eg, years apart) of simple cystitis that respond promptly to antimicrobial treatment [12,13]. Males with recurrent cystitis should be evaluated for predisposing features or causative factors (such as prostatic hypertrophy or other urinary tract obstruction). In particular, recurrent infection with the same strain of bacteria should prompt evaluation for chronic prostatitis. (See "Chronic bacterial prostatitis", section on 'Diagnosis' and "Clinical manifestations and diagnosis of urinary tract obstruction (UTO) and hydronephrosis".)

DIFFERENTIAL DIAGNOSIS — Dysuria, urinary frequency and urgency, and pyuria can also be seen with acute bacterial prostatitis (table 2). The presence of fever, chills, malaise, myalgias, pelvic or perineal pain, or obstructive symptoms such as dribbling and hesitancy (due to acute urinary retention) in a man with symptoms of cystitis suggests acute bacterial prostatitis. Pain radiating to the tip of the penis has also been described in patients with acute prostatitis, but the sensitivity and specificity of this symptom has not been validated. Any of these signs and symptoms should prompt performance of gentle digital rectal examination, and the finding of an edematous and tender prostate helps to confirm this alternate diagnosis. (See "Acute bacterial prostatitis", section on 'Diagnosis' and "Acute bacterial prostatitis", section on 'Differential diagnosis'.)

Underlying chronic prostatitis should be considered in males with cystitis, particularly in those males who have recurrent UTIs caused by the same strain of bacteria. (See "Chronic bacterial prostatitis".)

Urethritis must be considered in sexually active males; evaluation and diagnosis of urethritis are discussed in detail elsewhere. (See "Urethritis in adult males", section on 'Diagnosis'.)

TREATMENT — Cystitis in males is uncommon, and there are no comparative antimicrobial treatment trials from which to draw evidence-based recommendations. Our approach to management is based on indirect evidence from trials in females and more limited data in males. (See "Acute simple cystitis in adult and adolescent females", section on 'Management'.)

Antimicrobial selection — Although cystitis in males is generally classified in the literature as a complicated urinary tract infection (UTI), it is reasonable to consider a healthy man without a neurogenic bladder who has mild to moderate dysuria, urinary frequency and/or urgency, with no symptoms or signs of infection outside the bladder, as having simple cystitis. For empiric antimicrobial treatment of such males, we use one of the first-line regimens recommended for females:

●Nitrofurantoin monohydrate/macrocrystals (Macrobid, 100 mg orally twice daily)

●Trimethoprim-sulfamethoxazole (TMP-SMX, one double-strength tablet [160 mg TMP/800 mg SMX] orally twice daily)

●Fosfomycin (3 grams of powder mixed in water as a single dose)

The choice among them should be individualized based on patient circumstances (allergy, tolerability, expected adherence), local community resistance prevalence, availability, and cost. If the patient has taken one of the agents in the preceding three months, a different one should be selected. Based on data on UTI in females, empiric TMP-SMX should be avoided if the regional prevalence of resistance is known to exceed 20 percent [14,15]. Nitrofurantoin or fosfomycin are particularly useful if multidrug resistance is documented or suspected (table 3). As in females, beta-lactams can be used cautiously if other options are not appropriate because of allergy/intolerance or concerns about resistance. (See "Acute simple cystitis in adult and adolescent females", section on 'Alternative antimicrobial options'.)

Nitrofurantoin, fosfomycin, and beta-lactams do not achieve reliable tissue concentrations in the prostate and may not adequately treat subclinical prostatitis. Thus, for males who have more severe cystitis symptoms or concern about early involvement of the prostate, we use trimethoprim-sulfamethoxazole (one double-strength tab orally twice daily) or a fluoroquinolone (ciprofloxacin 500 mg orally twice daily or 1000 mg extended release once daily, or levofloxacin 750 mg orally once daily) for empiric therapy since they achieve more reliable tissue concentrations than other antimicrobial agents [2,4]. Because of concerns about the adverse effects of fluoroquinolones, they should only be used if there is concern about subclinical prostatitis or more severe illness [16]. If a fluoroquinolone is used, patients should be advised about the uncommon but potentially serious musculoskeletal and neurologic adverse effects. If there is concern for risk of resistance to fluoroquinolones in such patients (eg, because of prior urinary isolates or high local prevalence of resistance), our approach to empiric therapy is similar to that for complicated UTI, which is discussed in detail elsewhere. (See "Acute complicated urinary tract infection (including pyelonephritis) in adults and adolescents", section on 'Outpatients'.)

Once susceptibility testing results are available, subsequent therapy should be tailored as appropriate.

Duration of therapy — There are few studies that have evaluated the optimal duration of antimicrobial therapy in males with cystitis. Fluoroquinolones can be given for five days, and other agents can be given for seven days. Fosfomycin is given as a single dose, but there is no experience with the use of this regimen in males with simple cystitis.

In males with simple cystitis who have no signs or symptoms suggestive of pyelonephritis or prostatitis (eg, fever, flank pain, pelvic pain, prostatic tenderness on digital rectal exam if this part of the examination is performed), a seven-day or shorter course of an antimicrobial to which the infecting strain is susceptible is likely to be sufficient. This approach is supported by findings of a double-blind trial of 272 males who were starting ciprofloxacin or trimethoprim-sulfamethoxazole for symptoms of a UTI (mainly dysuria, frequency, and urgency) and were randomly assigned to receive seven days of the chosen antibiotic followed by seven days of placebo or receive 14 days of the antibiotic [17]. There was no detected difference in the rate of clinical cure 14 days following completion of the active antibiotic (93 versus 90 percent) or in the rate of recurrent symptoms within 28 days (10 versus 13 percent) with 7 versus 14 days of therapy. This trial confirmed findings of retrospective studies, which also suggested similar outcomes in clinical cure and recurrence risk with short (seven days or less) versus long (more than seven days) antimicrobial courses for males with UTI [18]. In one database study of 573 males attending outpatient clinics, treatment for more than seven days was actually associated with a higher risk of recurrence when males with urologic abnormalities, immunocompromising conditions, prostatitis, pyelonephritis, nephrolithiasis, and benign prostatic hyperplasia were excluded from the analysis (odds ratio 2.62) [19]. Longer courses of antibiotics may also be associated with a higher risk of adverse events (eg, Clostridioides difficile infection) [18].

When fluoroquinolones specifically are used, a course as short as five days is likely effective. In a trial of patients with complicated UTI, five days of levofloxacin was equivalent to 10 days of ciprofloxacin [20].

FOLLOW-UP — Follow-up urine cultures are not needed in males with acute simple cystitis whose symptoms resolve on antimicrobials. For patients who had hematuria on initial presentation, a urinalysis should be repeated several weeks following antimicrobial therapy to evaluate for persistent hematuria. (See "Etiology and evaluation of hematuria in adults", section on 'Overall approach to the evaluation'.)

Patients who have worsening or persistent symptoms after 48 to 72 hours of appropriate antimicrobial therapy or have recurrent symptoms within a few weeks of treatment should have additional evaluation for other potential conditions that may be causing those symptoms and for factors that might be compromising clinical response. This includes repeat urine culture And, potentially, empiric treatment with another antimicrobial agent.

Males with persistent or recurrent symptoms following a course of antimicrobial therapy for cystitis also warrant evaluation for the possibility of underlying prostatitis. (See "Chronic bacterial prostatitis", section on 'Diagnosis'.)

Subsequent treatment should be tailored to the susceptibility profile of the causative organism isolated. If symptoms persist in the setting of appropriate antimicrobial therapy, urological evaluation or radiographic imaging (generally with computed tomography) is appropriate to evaluate for anatomic abnormalities that would interfere with response to antimicrobial treatment.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Urinary tract infections in adults".)

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Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

●Beyond the Basics topics (see "Patient education: Urinary tract infections in adolescents and adults (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Terminology – We use the term “acute simple cystitis” to refer to an acute urinary tract infection (UTI) that is confined to the bladder in a nonpregnant individual (table 1). Features suggesting that the infection extends beyond the bladder are absent. These include fever (>99.9°F/37.7°C) or other features of systemic infection, pelvic or perineal pain, flank pain, and costovertebral angle tenderness. (See 'Terminology' above.)

●Incidence – Acute simple cystitis occurs in a small number of males between 15 and 50 years of age. Symptomatic UTI is much less common in males than in females. This is due to longer urethral length, drier periurethral environment (with less frequent colonization around the urethra), and antibacterial substances in prostatic fluid. (See 'Epidemiology' above.)

●Clinical suspicion and evaluation – The classic clinical manifestations of cystitis consist of dysuria, urinary frequency, urinary urgency, and suprapubic pain. In males with such symptoms, we check a urinalysis (either by microscopy or by dipstick) and urine culture with susceptibility testing. (See 'Clinical manifestations' above and 'Initial evaluation' above.)

●Diagnosis – The diagnosis of acute simple cystitis can be made in a male who presents with typical urinary symptoms, pyuria, and bacteriuria on urine culture in the absence of fever or other systemic symptoms, pelvic or perineal pain, costovertebral angle tenderness, and other features suggestive of pyelonephritis or acute prostatitis. The absence of pyuria or bacteriuria suggests an alternate diagnosis (table 2). (See 'Diagnosis' above.)

●Differential diagnosis and additional evaluation – Fever, chills, or malaise suggest a complicated UTI (including pyelonephritis) or bacterial prostatitis. In particular, pelvic or perineal pain, pain radiating to the tip of the penis, or obstructive symptoms such as dribbling and hesitancy (due to acute urinary retention) in a male with symptoms of cystitis suggest bacterial prostatitis. Chronic prostatitis should be considered in all males with cystitis, particularly in those with recurrent infections. Urethritis must be considered in sexually active males, and diagnostic tests for Neisseria gonorrhoeae and Chlamydia trachomatis are warranted. (See 'Differential diagnosis' above and "Acute complicated urinary tract infection (including pyelonephritis) in adults and adolescents" and "Acute bacterial prostatitis" and "Chronic bacterial prostatitis" and "Urethritis in adult males".)

Urologic evaluation is probably not necessary in young healthy males with no obvious complicating factors who have rare, sporadic episodes of cystitis that respond promptly to antimicrobial treatment. (See 'Additional evaluation' above.)

●Antibiotic therapy – For empiric antimicrobial therapy of males with acute simple cystitis, we suggest nitrofurantoin monohydrate/macrocrystals, trimethoprim-sulfamethoxazole (TMP-SMX), or fosfomycin (table 4) (Grade 2C). Beta-lactams are an alternative. However, if there are severe cystitis symptoms or uncertainty about prostate involvement (eg, equivocal prostatic tenderness), we prefer trimethoprim-sulfamethoxazole or a fluoroquinolone. Once susceptibility testing results are available, subsequent therapy should be tailored as appropriate. (See 'Treatment' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Thomas M Hooton, MD, who contributed to earlier versions of this topic review.