Diagnosing and treating acute uncomplicated acute cystitis and pyelonephritis
Females 18 years of age and older
Patients with urinary tract infection (UTI) commonly present to Urgent Care (UC) and there is the potential for over-diagnosis and inappropriate treatment. Understanding the elements of accurate diagnosis and appropriate treatment will lead to the best patient outcomes.
UTIs may be categorized as uncomplicated or complicated. Uncomplicated UTIs involve nonpregnant females without fever or other systemic symptoms (chills, significant fatigue or malaise), recent urological procedures, indwelling devices, underlying urologic abnormalities, or immunosuppression, and are much more common than complicated UTIs, which comprise all other patients and scenarios. This document discusses the diagnosis and treatment of acute uncomplicated cystitis and pyelonephritis only.
The differential diagnosis of uncomplicated acute cystitis includes pyelonephritis, sexually transmitted infections, vaginitis, ureteral and bladder calculi, and noninfectious cystitis and urethritis. History, physical examination, pelvic examination and associated testing, urinalysis, and urine culture may be needed to distinguish between these.
The most recent evidence-based treatment guidelines for uncomplicated cystitis were published in 2011 by the Infectious Diseases Society of America (IDSA)1.
Evidence based guideline with strength of evidence
The IDSA treatment guidelines published in 2011 are the most recent evidence-based guidelines and are being updated. At the time of publication, the strength of antibiotic treatment recommendations was Grade A and B, according to the IDSA Handbook on Clinical Practice Guideline Development, referred to in the guideline itself, which indicates good (Level A) or moderate (Level B) strength. The quality of evidence was related predominately to randomized controlled trials (Quality level I) but also respected authority opinion (Quality level III) in some cases.
The time since publication may create some uncertainty in terms of current relevance, but while awaiting an authoritative update, there are no alternatives available. The goals of the guideline were to provide a reasonable empiric approach to the selection of antibiotics to maximize the chance of cure while reducing the harms associated with inappropriate antibiotic prescription.
History and Physical Examination2
The accurate diagnosis of UTI has been shown to correlate with the absence of symptoms of vaginal irritation or discharge and the presence of specific urinary symptoms (dysuria, urinary frequency, urinary urgency, suprapubic pain and hematuria). These are sufficiently predictive that tele-diagnosis based on history alone is reasonable in certain situations. For example, the presence of dysuria and frequency in a patient without vaginal discharge yields a very high likelihood ratio (LR) of 24.6 for decision-making. In comparison, when vaginal discharge or irritation is present in a patient with either dysuria or frequency (but not both), the LR is 0.7.
The presence of flank pain and fever also increases the probability of UTI, but supports a more complicated infection possibly being present. Low abdominal discomfort can indicate UTI but also broadens the differential diagnosis, and so the absence of significant abdominal tenderness should be sought.
“Self-diagnosis” of UTI by a patient based on current symptoms being similar to prior UTI is also an accurate indicator for diagnosis, though an UTI very closely following another should increase suspicion of resistance to prior antimicrobial therapy or a more complicated infection or alternative diagnosis being present.
Urinalysis and Urine Culture2,3
Urinalysis may be used to increase or decrease the probability of a UTI after historical and exam features establish a pretest probability. The presence of leukocyte esterase or nitrites on urine dipstick or white blood cells on microscopic exam increases the likelihood of UTI and a normal urinalysis decreases the likelihood.
The diagnostic value added by urinalysis is highest when results are concordant with the history and much lower when they are not. For example, when the pretest likelihood of UTI is high based on history and exam, a normal urinalysis cannot rule out UTI. And even such a “positive” urinalysis is less likely to support the diagnosis of UTI when urinary symptoms are not present. Moreover, when evaluating patients with nonspecific symptoms such as fever or altered mental status but without urinary tract symptoms, diagnoses other than UTI should be considered, regardless of urinalysis results.
Though often considered the gold standard for UTI diagnosis, the sensitivity and specificity of urine culture for diagnosing UTI is not perfect and many factors (specimen collection and transport methods, lab handling) can affect results. Patients with UTI can have negative or inconclusive (single organism below a defined threshold, e.g., 100k colony-forming unit/cc or the presence of multiple organisms) results and those without UTI may have positive cultures (asymptomatic bacteriuria). Concordance with history, exam and urinalysis adds the most diagnostic value.
Urine culture and sensitivity results can guide treatment and are strongly recommended for patients with complicated UTI, patients with risk factors for complication and patients with high risk for antibiotic resistance (history of multidrug resistance urine culture and recent within the past three months hospitalization and use of fluoroquinolones, trimethoprim/sulfamethoxazole and broad-spectrum beta-lactam). They do inform knowledge of local antimicrobial resistance but are not typically needed for uncomplicated UTI. The evaluation of patients with uncomplicated but recurrent or repeated UTI symptoms may benefit from urine culture.
Antibiotic treatment for UTI1
In any case where culture and sensitivity results are available, choice of therapy can be based on those results and the antibiotic preference order explained below.
For uncomplicated UTI, unless contraindicated, empiric treatment (in the absence of urine culture and sensitivity results) should be limited to one of the following:
● Nitrofurantoin monohydrate/macrocrystals 100 mg PO BID x 5 days
● Trimethoprim-sulfamethoxazole 160/800 mg (one double strength tablet) PO BID x 3 days (avoid if typical uropathogen resistance prevalence is known to be > 20%, or if used for UTI within the previous 3 months)
● Fosfomycin trometamol 3 g PO single dose
● Pivmecillinam 400 gm PO BID x 5 days (not available in the US)
● Beta-lactam agents such as amoxicillin-clavulanate, cefdinir, cefaclor, and cefpodoxime in 3-7 day courses can be considered if none of the above can be used. Cephalexin may be considered as well, but may be less effective, according to the guidelines.
● Fluroquinolones (ofloxacin, ciprofloxacin, levofloxacin) may be effective in 3 day regimens but due to higher side effects are considered alternatives if none of the above can be used.
● Amoxicillin or ampicillin should not be used due to higher resistance levels.
For pyelonephritis treatable as an outpatient (stable, nonpregnant, nontoxic patient, who is able to take PO medications), urine culture and sensitivity should be performed prior to treatment. Empiric treatment options while awaiting culture and sensitivity results include:
If typical uropathogen resistance prevalence is known to be < 10% to the agent listed
● Ciprofloxacin 500 mg PO BID x 7 days with or without ciprofloxacin 400 mg IV at time of initial visit
● Levofloxacin 750 mg PO daily or Ciprofloxacin ER 1000 mg daily x 7 days
If typical uropathogen resistance prevalence could be > 10% to the agent listed
● Ciprofloxacin 500 mg PO BID, Levofloxacin 750 mg PO daily or Ciprofloxacin ER 1000 mg daily WITH ceftriaxone 1 g (IV or IM) or a consolidated 24-hour dose of an aminoglycoside at time of initial visit
● Trimethoprim-sulfamethoxazole 160/800 mg (one double strength tablet) PO BID for 14 days WITH ceftriaxone 1 g (IV or IM) or a consolidated 24-hour dose of an aminoglycoside at time of initial visit
● If none of the above can be used, Beta-lactam agents such as amoxicillin-clavulanate, cefdinir, cefaclor, and cefpodoxime x 10-14 days can be considered WITH ceftriaxone 1 g (IV or IM) or a consolidated 24-hour dose of an aminoglycoside at time of initial visit
● Though effective for acute cystitis, renal penetration of nitrofurantoin, fosfomycin and pivmecillinam is poor, and these are not options for the treatment of pyelonephritis.
● The diagnosis of UTI starts with a patient’s symptoms. Complaints of urinary frequency, discomfort, and symptoms similar to prior UTI are highly sensitive and specific. The presence of vaginal symptoms (e.g., discharge or irritation) favors a vaginal etiology rather than UTI.
● Urinalysis is not necessary when the history strongly supports the diagnosis. It is more helpful when there is indeterminate probability after history and exam. A positive urinalysis may not indicate UTI requiring treatment when there are no specific urinary symptoms or exam findings.
● Use of antibiotics in accordance with the IDSA guidelines1 as above provides a reasonable empiric approach which maximizes the chance of cure while reducing the harms associated with inappropriate antibiotic prescription.
● The guidelines emphasize specific narrow spectrum antibiotics and shorter time courses, so avoid prescribing broader-spectrum antibiotics or longer time courses than recommended.
● Clinicians should be aware that the antibiotic choices for cystitis differ from pyelonephritis due to renal penetration of medication.
● Knowledge of local antibiotic resistance is important in modifying any planned empiric regimen.
● The main value of urine culture is in determining whether empiric antibiotic treatment needs to be changed for patients with complicated or recurrent UTI, and culture should be obtained in these situations. Urine culture is not needed for cases of nonrecurrent, uncomplicated cystitis.
● Diagnostically, a negative culture does not rule out a UTI and a positive culture does not diagnose a UTI. Urine culture adds the most value to UTI diagnosis when it matches the pretest probability based on history, exam and urinalysis.
1. Gupta et al. International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women: A 2010 Update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011;52(5):e103-20. DOI: 10.1093/cid/ciq257
2. Bent S, et al. Does this woman have an acute uncomplicated urinary tract infection? JAMA. 2002;287:2701-10. DOI: 10.1001/jama.287.20.2701
3. Werneburg GT, et al. Diagnostic stewardship for urinary tract infection: A snapshot of the expert guidance. Cleve Clin J Med. 2022;89(10):581-7. DOI: 10.3949/ccjm.89a.22008
Joseph Toscano, MD and Cesar Mora Jaramillo, MD FAAFP FCUCM