Lower urinary tract infection

Urine dipstick.

For many women with dysuria, lack of vaginal discharge, and classic acute simple cystitis (not in the setting of rUTI), no additional testing is warranted to make the diagnosis. For those with suggestive, but not clearly diagnostic, features, a urinary dipstick can be helpful to rule out an infection but may have less of a role in confirming an infection. In these settings, the absence of nitrites and leukocyte esterase lowers the probability of UTI. Nitrites are seen in the setting of gram-negative bacteria because these types of bacteria convert nitrates to nitrites. Leukocyte esterase on urinary dipstick corresponds to pyuria, or white blood cells in the urine. False-negative nitrite results could occur in the setting of gram-positive bacteria, but cystitis is uncommon in patients without pyuria. More commonly, false-positive urine dipstick results are seen, especially when voided specimens are used. In women, poor collection techniques and vaginal contamination with voided samples contribute to false-positive findings ( ). Therefore, although urine dipsticks can provide clinical information, ultimately the provider should incorporate clinical judgment and/or additional diagnostic testing when making final decisions regarding treatment.

Microscopic urinalysis.

Microscopic examination of urine can detect the presence of bacteria, leukocytes, and red blood cells. Pyuria is defined as 10 or more leukocytes/mL or 3 or more leukocytes/high-powered field of unspun urine. As earlier, in the absence of pyuria, the diagnosis of UTI should be questioned. Pyuria has been proposed as a way to differentiate between acute UTI and ASB, but recent guidelines recommend that the diagnosis of ASB can be made even in the setting of pyuria. Patients could exhibit pyuria with negative urine culture (i.e., sterile pyuria) if urinalysis is performed after initiating antimicrobial therapy. Neither microscopic hematuria nor bacteriuria on urinalysis is a particularly sensitive finding for UTI. However, microscopic urinalysis is the gold standard for evaluation of hematuria outside of infection (see Chapter 40 ). Beyond this standard indication for testing, it is likely an unnecessary cost.

Urine culture.

Urine culture may not be necessary for acute cystitis, but the primary disadvantage of symptom-based diagnosis is that it may result in overtreatment and inappropriate antibiotic use. This is especially possible in older women, where symptoms of UTI overlap with other noninfectious bladder symptom conditions. Urine culture is considered the reference standard for diagnosis of UTI. Cultures should be submitted for scenarios such as negative urine dipstick test in a symptomatic patient, poor response to initial therapy, and recurrent symptoms less than 1 month after treatment for a previous UTI. As mentioned previously, although a culture result of 10 ⁵ CFU/mL or more in a voided urine sample has historically been considered diagnostic for UTI, some feel that 100 CFU/mL or more should suffice in a patient who has symptoms consistent with UTI, as well as pyuria. If there is a suspicion for pyelonephritis (i.e., fever, costovertebral tenderness/flank pain), then a urine culture and antibiotic susceptibilities should always be obtained.

Antibiotics for simple cystitis.

The Infectious Diseases Society of America (IDSA) published an updated clinical practice guideline on the treatment of women with acute uncomplicated cystitis and pyelonephritis in 2010. They note that the focus of these guidelines is treatment of nonpregnant, premenopausal women with no known urological abnormalities. Postmenopausal women, those without rUTI, and/or those with well-controlled diabetes without urological sequelae can usually be treated with the same recommendations.

The three first-line antibiotics for UTI treatment are nitrofurantoin, trimethoprim-sulfamethoxazole (TMP-SMX), and fosfomycin ( Table 36.2 ). Fluoroquinolones should only be used if there is any suspicion for early pyelonephritis.

Nitrofurantoin is bacteriostatic and therapeutically active only in the lower urinary tract. It is effective against E. coli and many gram-negative species with low levels of resistance. However, it can be ineffective against other uropathogens. TMP-SMX is a broad-spectrum antibiotic that covers gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, and most gram-negative bacteria. In regions where there is greater than 20% local E. coli resistance to TMP-SMX, an alternative treatment should be given. Reported duration of TMP-SMX treatment has ranged from 3 to 14 days, with the 3-day course having similar efficacy to 5- to 10-day regimens. Finally, fosfomycin tromethamine, the stable salt form of fosfomycin, is taken in a single dose that becomes highly concentrated in the urine, resulting in urine levels that persist for 30 to 40 hours. Fosfomycin has activity against both gram-positive and gram-negative bacteria, including S. aureus , Enterococcus , Pseudomonas aeruginosa , and Klebsiella pneumoniae . There are relatively low levels of resistance to fosfomycin, making it a drug of choice in infections with multidrug-resistant organisms, but there is some suggestion that single-dose regimen may have less efficacy than other therapies. When first-line medications are not available or cannot be prescribed because of patient allergies, intolerances, or bacterial resistance, second-line antimicrobials, β-lactams, and fluoroquinolones can be used. Although 3-day fluoroquinolone regimens (i.e., ciprofloxacin and levofloxacin) are efficacious, they are not first-line agents because of increasing resistance, higher expense, and serious adverse events, as described in a 2016 Food and Drug Administration warning.

Antimicrobial-sparing strategies.

Given that acute simple cystitis has a low risk of progression in patients without risk factors for serious infection ( ), antimicrobial-sparing strategies are attractive to consider. Delaying antimicrobial therapy while awaiting urine culture results appears to be a reasonable approach in women without comorbidities, especially if empiric therapy is complicated by resistance or drug intolerance. In a randomized trial of nonpregnant women younger than 75 years of age with acute simple cystitis, symptom duration and severity were similar with immediate antimicrobial therapy compared with four other strategies, including delayed antimicrobial therapy and antimicrobial therapy based on a symptom score, urinalysis findings, or urine culture results ( ). One large, retrospective database analysis of patients 65 years of age or older with lower UTI suggested an association between delaying antimicrobial therapy and subsequent bloodstream infection within 60 days, but this study had significant limitations, including potential misdiagnosis of cystitis ( ).

Substituting antiinflammatory agents for antimicrobial therapy has also been evaluated, but currently is not recommended as the initial approach to management of symptomatic acute simple cystitis. Two trials comparing nonsteroidal antiinflammatory drugs (ibuprofen and diclofenac) to antibiotics (fosfomycin and norfloxacin) showed that between 50% and 75% of women achieved symptom improvement, but there were higher incidences of pyelonephritis or additional therapy in the nonsteroidal antiinflammatory arms ( ; ).