The term “simple acute cystitis” refers to an acute infection confined to the bladder in a nonpregnant individual. Such infections lack features that suggest the infection extends beyond the bladder, such as fever (>99.9°F/37.7°C), other signs or symptoms of systemic illness (including chills, rigors, and marked fatigue or malaise beyond baseline), flank pain, and CVA tenderness. This definition is distinct from traditional categorizations of UTI and is more focused on the clinical presentation and severity of illness.
Escherichia coli is the most frequent microbial cause of simple acute cystitis, with occasional infections caused by other species of Enterobacteriaceae, such as Klebsiellapneumoniae and Proteus mirabilis, and other bacteria, such as Staphylococcus saprophyticus. The microbial spectrum of simple acute cystitis in patients with recent antimicrobial or other health care exposures may be broader and include other gram-negative bacilli (e.g., Pseudomonas), enterococci, and staphylococci. Increasing rates of resistance in uropathogens have been reported globally.
Simple acute cystitis occurs in a small number of men between 15 and 50 years of age. Symptomatic UTI is much less common in men than women due to longer urethral length, drier periurethral environment (with less frequent colonization around the urethra), and antibacterial substances in prostatic fluid.
Risk factors for UTI with resistant organisms include recent antimicrobial use, health care exposures, and travel to parts of the world where MDR organisms are prevalent.
The classic clinical manifestations of simple acute cystitis in both sexes consist of dysuria, urinary frequency, urinary urgency, and suprapubic pain. Symptoms of simple acute cystitis can be difficult to assess in older or debilitated women, who have several nonspecific urinary symptoms (such as chronic dysuria or urinary incontinence) that could mimic symptoms of simple acute cystitis.
For women with classic symptoms of cystitis, no additional testing is warranted to make the diagnosis. For women with atypical urinary symptoms, the diagnosis is supported by pyuria and bacteriuria on urinalysis and culture.
The diagnosis of simple acute cystitis can be made in a man who presents with typical urinary symptoms, pyuria, and bacteriuria on urine culture without fever or other systemic symptoms, pelvic or perineal pain, CVA tenderness, and other features suggestive of pyelonephritis or acute prostatitis.
Laboratory diagnostic tools for cystitis consist of urinalysis (either by microscopy or by dipstick) and urine culture with susceptibility data. A urine culture should be performed for all men and women with symptoms suggestive of simple acute cystitis.
The selection of an antimicrobial regimen for simple acute cystitis depends on the likelihood of infection with an MDR gram-negative isolate. Before initiation of therapy, urine culture and susceptibility testing are warranted for patients with risk factors for antimicrobial resistance or more serious infection (e.g., those with underlying urologic abnormalities, immunocompromising conditions, and poorly controlled diabetes mellitus).
For patients who do not have risk factors for an MDR gram-negative infection, the first-line antimicrobial agents include:
- Nitrofurantoin monohydrate/macrocrystals (Macrobid®, 100 mg twice daily for five days)
- TMP-SMX (one double-strength tablet [160/800 mg] twice daily for three days)
- Fosfomycin (3 grams of powder mixed in water as a single dose) OR
- Pivmecillinam (400 mg twice daily for five to seven days)
If all of these medications are appropriate options based on patient circumstances, local resistance rates, and prior urinary isolates, nitrofurantoin or TMP-SMX is suggested first rather than fosfomycin or pivmecillinam.
Oral beta-lactams are appropriate alternative options for those who cannot use any of the first-line antimicrobials. If beta-lactams cannot be used, a fluoroquinolone is reasonable. These, however, should be reserved for more serious infections than simple acute cystitis, if possible, because of concerns for adverse effects.
For patients who have risk factors for an MDR gram-negative infection or have a history of an isolate with documented resistance to these agents in the past three months, oral options include:
- Nitrofurantoin monohydrate/macrocrystals (Macrobid®, 100 mg orally twice daily for five days)
- Fosfomycin (3 grams of powder mixed in water as a single dose) OR
- Pivmecillinam (400 mg orally three times daily for three to five days)
If all of these are appropriate options based on patient circumstances, local resistance rates, and prior urinary isolates, nitrofurantoin is preferred. Culture and susceptibility results should be used to guide directed therapy.
Antimicrobial therapy should be deferred until a regimen can be selected based on culture and susceptibility testing results if none of the above options are appropriate because of resistance or other concerns. Studies among women without comorbidities have suggested that deferring antimicrobial therapy until these results are available is a safe strategy for simple acute cystitis. However, suppose there is concern about deferring antimicrobial therapy (e.g., because of bothersome symptoms or risk factors for more serious infection). In that case, options include using one of the oral regimens for simple acute cystitis that was not chosen because of the possibility of resistance or using an initial dose of a parenteral agent, as used in complicated acute UTI.
Patients who have simple acute cystitis in the setting of underlying functional or anatomic urinary tract abnormalities (such as an indwelling catheter, urethral stent, neurogenic bladder, history of nephrolithiasis) may warrant more frequent intermittent catheterization, changing out an indwelling catheter, or urologic/urogynecologic consultation. Additionally, a longer duration of antimicrobial therapy is appropriate since shorter durations have not been well studied in such patients (Fekete, 2021).
Patients who have persistent symptoms after 48 to 72 hours of empiric antimicrobial therapy or have recurrent symptoms within a few weeks of treatment should have urine submitted for culture and susceptibility testing. If symptoms persist during appropriate antimicrobial therapy, radiographic imaging to evaluate for anatomic abnormalities is appropriate.
Men with recurrent simple acute cystitis should undergo evaluation for prostatitis. Urologic evaluation is probably unnecessary in healthy young men with no obvious complicating factors who have a single episode of simple acute cystitis that responds promptly to antimicrobial treatment.
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 man with symptoms of simple acute cystitis, suggest bacterial prostatitis.
Chronic prostatitis should be considered in all men with simple acute cystitis, particularly in those men who have recurrent infections. Urethritis must be considered in sexually active men, and diagnostic tests for Neisseria gonorrhoeae and Chlamydia trachomatis are warranted.
Empiric antimicrobial therapy in men with simple acute cystitis includes:
- Nitrofurantoin monohydrate/macrocrystals (Macrobid®)
- TMP-SMX OR
Beta-lactams are an alternative. However, if there are severe simple acute cystitis symptoms or concern about early involvement of the prostate, a fluoroquinolone is preferred.
Once susceptibility testing results are available, subsequent therapy should be tailored as appropriate. The duration depends on the agent used (fluoroquinolones are given for five days, fosfomycin is given as a single dose, and other agents are given for seven days).