Empiric antimicrobial selection for women with acute simple cystitis

DS: double-strength; ESBL: extended-spectrum beta-lactamase; MDR: multidrug-resistant; TMP-SMX: trimethoprim-sulfamethoxazole; UTI: urinary tract infection.

* Among debilitated patients, many generalized signs or symptoms, such as falls, changes in functional status, and changes in mental status, are frequently attributed to UTI, although growing evidence indicates that these are not reliable predictors of bacteriuria or cystitis. We do not routinely test urine in elderly or debilitated patients with nonspecific changes in mental or functional status in the absence of focal urinary tract symptoms and fever, and instead hydrate, carefully observe, and assess other potential contributing factors.

¶ We 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).

Δ The temperature threshold used to determine whether to treat a patient as simple cystitis versus complicated UTI is not well defined and should take into account baseline temperature, other potential contributors to an elevated temperature, and the risk of poor outcomes should empiric antibiotic therapy be inappropriate.

◊ An MDR isolate is nonsusceptible to at least one agent in three or more antimicrobial classes; this includes ESBL-producing isolates.

§ Even in the absence of risk factors for resistance, we also check culture and susceptibility testing on patients with risk factors for more serious infection to ensure adequacy of the empirically chosen regimen. Such patients include those with underlying urologic abnormalities, immunocompromising conditions, and poorly controlled diabetes.

¥ Reasons to avoid these options include an allergy or intolerance to the agent, an unmodifiable drug interaction, or history of a resistant urinary isolate within the past three months.

‡ Nitrofurantoin should be avoided if the creatinine clearance is <30 mL/minute.

† TMP-SMX and trimethoprim should be avoided if the known community prevalence among Enterobacteriaceae is >20%, but efficacy is high for susceptible organisms.

** Deferring antimicrobial therapy until a regimen can be selected based on results of culture and susceptibility testing may be a reasonable alternative for otherwise healthy patients with mild or ambivalent symptoms. Studies have suggested that deferring antibiotic therapy until culture and susceptibility tests are available is a safe strategy for otherwise healthy women who have mild simple cystitis without evidence of infection extending beyond the bladder. Analgesics can be used for symptomatic therapy.

¶¶ If all of these are appropriate options based on patient circumstances and prior urinary isolates, we favor nitrofurantoin over fosfomycin. Although they appear to have generally comparable efficacy, overuse of fosfomycin may result in increasing resistance. Thus, we favor reserving use of fosfomycin for documented MDR infections or when nitrofurantoin cannot be used. Pivmecillinam is not as effective but is commonly used in Europe because of a low risk of selecting for resistance.

ΔΔ If all of these are appropriate options based on patient circumstances and prior urinary isolates, we favor nitrofurantoin or TMP-SMX over fosfomycin. Although they appear to have generally comparable efficacy, fosfomycin retains activity against many MDR isolates, and overuse of it may result in increasing resistance. Thus, we favor reserving it for suspected MDR infections or when other first-line agents cannot be used. Pivmecillinam is not as effective but is commonly used in Europe because of a low risk of selecting for resistance.

◊◊ Trimethoprim is an option for individuals who have a sulfonamide (but not trimethoprim) allergy.

§§ Although cefdinir does not achieve high urinary concentrations, it may be sufficient to treat cystitis with susceptible organisms. Cephalexin is not as well studied as the other beta-lactam options listed.

¥¥ When possible, fluoroquinolones should be reserved for more serious infections than acute uncomplicated cystitis. If used, patients should be advised about the uncommon but potentially serious musculoskeletal and neurologic adverse effects associated with fluoroquinolones.