Urinary Tract Infection (UTI) and Cystitis (Bladder Infection) in Females Treatment & Management

Appropriate antibiotic treatment leads to significantly higher symptomatic and bacteriologic cure rates and better prevention of reinfection in women with uncomplicated cystitis. ^[29]  Its negative consequences include promotion of the development of antibiotic resistance in uropathogens and commensal bacteria as well as adverse effects on the gut and vaginal flora. ^[30]

Consequently, evolving practice seeks to achieve good symptom control for uncomplicated acute cystitis while reducing antibiotic use. For example, European practice increasingly includes the option of offering a 48-hour delayed antibiotic prescription to be used at the patient's discretion. ^[31]

The first-choice agents for treatment of uncomplicated acute cystitis in women include nitrofurantoin monohydrate/macrocrystals, trimethoprim-sulfamethoxazole (TMP-SMX), or fosfomycin. Beta-lactam antibiotics may be used when other recommended agents cannot be used. ^{[2, 3]} Fosfomycin and nitrofurantoin monohydrate/macrocrystals should be avoided in patients with possible early pyelonephritis. ^[2] Fluoroquinolones typically are reserved for complicated cystitis.

Empiric antibiotic selection should be based on local resistance patterns. In addition, clinicians may wish to limit use of TMP-SMX in order to reduce the emergence of resistant organisms.

Resistance to TMP-SMX has been associated with concomitant resistance to other antibiotics. Because of the importance of maintaining the effectiveness of TMP-SMX for treatment of serious infections, German national guidelines no longer recommend this agent as first-line empiric treatment for uncomplicated cystitis. ^[3]

Patients who have been hospitalized in urology units tend to have uropathogenic E coli infections with higher antimicrobial resistance, especially ESBL isolates. ^[32]

On average, women with cystitis who receive effective antibiotic treatment experience severe symptoms for somewhat longer than 3 days. ^[14] Complete resolution of symptoms may require approximately 6 days. Features associated with a more prolonged course include a history of somatization, previous cystitis, urinary frequency, and more severe symptoms at baseline. ^[14] Patients who respond to antibiotics do not require follow-up urine cultures.

Without treatment, 25% to 42% of uncomplicated acute cystitis cases in women will resolve spontaneously. ^[29] Even without effective treatment, the likelihood that uncomplicated acute cystitis will progress to pyelonephritis is only around 2%. ^[33]

German investigators reported that symptomatic treatment with ibuprofen (400 mg 3 times daily) did not prove to be inferior to antibiotic treatment with ciprofloxacin. ^[34] This randomized, controlled pilot trial in 79 women with uncomplicated acute cystitis found no significant difference in symptom resolution between the 2 groups. A notable but statistically insignificant difference was that 33.3% of patients in the ibuprofen group and 18% in the ciprofloxacin group required secondary antibiotic treatment.

Unfortunately, there is a low level of adherence to IDSA guidelines by primary care physicians in terms of antibiotic selection and therapy duration for treatment of uncomplicated acute cystitis. Appropriate antibiotics were administered in most (97.6%) cases of uncomplicated UTI, but the recommended treatment duration was followed in only 71.9% of cases. ^{[35, 36]}

Patient disposition

With few exceptions, the vast majority of women with urinary tract infection (UTI) present on an ambulatory basis and can be treated as outpatients. Exceptions include immunocompromised or elderly patients who have a UTI manifesting as a sepsis syndrome with circulatory insufficiency. In this situation, mental status changes (eg, confusion) or profound weakness may prompt paramedical transport to the hospital. Patients with hypotension, tachycardia, and delayed capillary refill require intravenous (IV) fluid resuscitation in the field.

Hospital admission may be indicated for some patients with complicated UTI. Complicating factors include the following:

• Structural abnormalities (eg, calculi, tract anomalies, indwelling catheter, obstruction)

• Metabolic disease (eg, diabetes, renal insufficiency)

• Impaired host defenses (eg, HIV, current chemotherapy, underlying active cancer)

Adequate fluid resuscitation restores effective circulating volume and generous urinary volumes. Antipyretic pain medications may be administered, as appropriate.

Uncomplicated cystitis occurs in patients who have a normal, unobstructed genitourinary tract; who have no history of recent instrumentation; and whose symptoms are confined to the lower urinary tract. Uncomplicated cystitis is most common in young, sexually active women. Patients usually present with dysuria, urinary frequency, urinary urgency, and/or suprapubic pain. Treatment regimens for uncomplicated cystitis in nonpregnant women are provided in Table 1, below.

Table 1. Treatment Regimens for Uncomplicated Cystitis in Nonpregnant Women ^[2] (Open Table in a new window)

Complicated cystitis is associated with an underlying condition that increases the risk for therapeutic failure. Some underlying conditions include diabetes, symptoms for 7 days or longer before seeking care, renal failure, functional or anatomic abnormality of the urinary tract, renal transplantation, an indwelling catheter stent, or immunosuppression. Treatment regimens for complicated cystitis in nonpregnant women are provided in Table 2, below.

Table 2. Treatment Regimens for Complicated Cystitis in Nonpregnant Women ^[17] (Open Table in a new window)

Oral therapy with an antibiotic effective against gram-negative aerobic coliform bacteria, such as E coli, is the principal treatment intervention in patients with lower urinary tract infections.

For women with acute bacterial cystitis who are otherwise healthy and not pregnant, 3 days of therapy with most antimicrobial agents generally is more effective than single-dose therapy and as effective as the same drug administered for a longer duration. Exceptions are nitrofurantoin monohydrate/macrocrystals and beta-lactams as a group. Cystitis in older women or infection caused by Staphylococcus saprophyticus is less responsive to 3 days of therapy; therefore, 7 days of therapy is suggested.

IDSA guidelines recommend TMP-SMX (160 mg/800 mg [1 double-strength tablet] orally given twice daily for 3 days) as an appropriate choice for treatment of acute uncomplicated cystitis if local resistance rates of uropathogens do not exceed 20% or if the infecting strain is known to be susceptible. TMP-SMX should not be used empirically if the patient has received this agent for treatment of UTI during the previous 3 months. ^[2]

Nitrofurantoin monohydrate/macrocrystals has the advantage of taking resistance pressure off the much-used quinolone class. In a 2009 analysis by Olson et al, 29.6% of 176 urinary isolates with E coli studied were resistant to TMP-SMX; none was resistant to nitrofurantoin macrocrystals. Resistance to ciprofloxacin was 1.8% in first-time UTIs, versus 11.8% in recurrent UTIs. The authors recommended considering nitrofurantoin as a first-line agent for uncomplicated lower UTIs. ^[37]

Similarly, a decision and cost analysis by McKinnell et al found that nitrofurantoin minimized cost when the prevalence of fluoroquinolone resistance exceeded 12% or the prevalence of TMP-SMX resistance exceeded 17%. ^[38] On the basis of efficacy, cost, and low impact on promoting antimicrobial resistance, these researchers recommended that clinicians consider nitrofurantoin as a reasonable alternative to TMP-SMX and fluoroquinolones for first-line therapy for uncomplicated UTIs.

Fosfomycin (a single dose of 3 g with 3-4 oz of water) also is an appropriate choice for therapy, where available, because of minimal resistance and propensity for collateral damage. Fosfomycin is approved by the US Food and Drug Administration (FDA) for single-dose treatment in adult women with uncomplicated UTI caused by Escherichia coli or Enterococcus faecalis.

It has been reported that the efficacy of single-dose fosfomycin is inferior to that of standard short-course regimens. ^[2] However, a recent meta-analysis of 27 trials found no difference in efficacy between fosfomycin and other antibiotics for treatment of cystitis and found that fosfomycin was associated with significantly fewer adverse reactions in pregnant women. ^[39]

Fluoroquinolones (eg, ofloxacin, ciprofloxacin, levofloxacin) are highly effective in UTIs, but these agents have a propensity for causing collateral damage and should be reserved for important uses other than acute uncomplicated cystitis. ^[2] IDSA guidelines recommend that fluoroquinolones be used as second-line agents for acute uncomplicated cystitis and as first-line oral therapy for complicated cystitis.

According to the IDSA guidelines, beta-lactam agents (eg, amoxicillin-clavulanate, cefdinir, cefaclor, cefpodoxime-proxetil) in 3–7-day regimens are appropriate second-line choices when other recommended agents cannot be used. The IDSA advises against using amoxicillin or ampicillin for empiric treatment, because these agents have relatively poor efficacy and high rates of resistance. ^[2]

Patients with intense dysuria may obtain symptomatic relief from a bladder analgesic, such as phenazopyridine, to be used for 1-2 days. Avoid long-term use, as this agent may mask symptoms of therapeutic failure or recurrence. Many authors advise stressing the intake of plenty of fluids to promote a dilute urine flow.

In catheterized patients, removal of the catheter is essential for clearance of funguria. If the catheter is still needed, replace it (preferably a day later).

Treatment options vary from topical treatment to systemic therapy. A regimen of amphotericin-B bladder washes for 7 days provides a prompt but nonsustained response. It does not treat systemic mycoses and is inconvenient to administer. Amphotericin B, 0.3 mg/kg IV for 1 dose, is an option that provides a more sustained and systemic response.

Fluconazole 200 mg orally, followed on subsequent days by 100 mg orally once a day for 4-7 days, is a simpler option. This drug is effective against azole-responsive Candida organisms. Generally, azole resistance is observed only in C krusei and C glabrata. Fluconazole provides a good long-term effect but takes a few days to clear the urine.

As mentioned above, Candida auris has become a rapidly growing nosocomial probllem. It is highly contagious and most patients are asymptomatic. The primary route of infection is by contaminated equipment. It can live on all surfaces of the institution (equipment, skin, water) for long periods of time. ^{[19, 40]}

Once a urethral catheter is in place, the daily incidence of bacteriuria is 3% to 10%. Antibiotics should be reserved for patients with clear signs and symptoms of UTI. In these patients, suprapubic aspiration of the bladder is the criterion standard for diagnosing a UTI, although it is not performed often in clinical practice.

Oral fluoroquinolones are the drugs of choice for empiric treatment of acute UTIs. However, these drugs have a propensity for collateral damage and should be reserved for important uses other than acute cystitis.

For more information on this topic, see the Medscape Reference article Urinary Tract Infections in Patients with Spinal Cord Injury.

The physiologic changes associated with pregnancy increase the risk for serious infectious complications from symptomatic and asymptomatic urinary tract infections, even in healthy pregnant women. Consequently, treatment is indicated for pregnant women with asymptomatic bacteriuria, as well as for those with symptomatic UTIs; antibiotic selection may differ, and regimens typically are more prolonged.

For more information, see the Medscape Reference topic Urinary Tract Infections in Pregnancy.

Treatment of UTIs in renal transplant patients is preferably with a fluoroquinolone. TMP-SMX poses the risk of inducing renal failure in the transplanted kidney and consequently should be avoided unless the patient’s creatinine clearance is normal.

Asymptomatic bacteriuria should be treated for 10 days. Parenteral antibiotics should be used for severe infections. The duration of antibiotics for severe infections is 4-6 weeks.

Although asymptomatic bacteriuria is highly contagious, in most patient populations it has not been shown to be harmful. Furthermore, although persons with bacteriuria are at increased risk for symptomatic urinary tract infections, treatment of asymptomatic bacteriuria does not decrease the frequency of symptomatic infections or improve other outcomes. Consequently, screening for or treatment of asymptomatic bacteriuria is not appropriate and should be discouraged. ^[41]

Asymptomatic bacteriuria in women should be treated only in pregnant patients, in patients undergoing a urologic procedure that may produce mucosal bleeding, and in the significantly immunosuppressed (eg, renal transplantation patients). It should not be treated in diabetic persons, elderly individuals, and patients with indwelling catheters. Diabetic women have a high rate of asymptomatic bacteriuria with nonpathogenic strains, which can persist for long periods without progressing to infection. ^[42]

For a full discussion of this topic, see the Medscape Reference article Asymptomatic Bacteriuria. 

Hydration to accentuate unidirectional clearance of bacteriuria is recommended, especially if an obstruction was relieved recently. Drinking cranberry juice (10 oz/day) or taking cranberry tablets may offer some benefit in reducing recurrent UTI and does not appear to be harmful. ^{[43, 44]}

Cranberries contain type A proanthocyanidins. This compound and its urinary metabolites interfere with the adhesiveness of uropathogenic bacteria to the bladder epithelium. ^[45] Their effect is not as significant as antibiotics, but they do not induce bacterial resistance. Because of their variable intestinal absorption, it is difficult to design a valid study comparing them head-to-head with antimicrobials. ^[43]

Urologic consultation is essential in patients with UTIs complicated by obstruction, renal cysts, perinephric abscess, renal carbuncle, or unknown renal masses. Other consultations depend on the patient's underlying state of health and may include an obstetrician, gynecologist, endocrinologist, nephrologist, neurologist, or neurosurgeon. In patients who present to the emergency department, consultation with the patient's primary care provider is suggested.

In the patient with a complicated UTI, coverage for unusual or multiple antibiotic–resistant organisms (eg, Pseudomonas aeruginosa) must be considered. An infectious disease consultation may be helpful in selecting the appropriate antimicrobial agent. Infectious disease input is essential for immunocompromised patients and those infected with unusual or resistant pathogens. A pharmacokinetics consultation is suggested when using aminoglycosides.

The team approach is absolutely required in dealing with C auris infections.

Prophylactic measures are indicated for patients with any of the following:

• Recurrent UTIs

• Spinal cord injury

• Urinary catheters

• Renal transplants

A study of 140 women with recurrent UTIs showed that increased fluid intake reduces the risk for repeat infections. The study participants were otherwise healthy premenopausal women who had experienced three or more UTIs in the preceding year and who self-reported low fluid intake (< 1.5 liters/day). The intervention group was instructed to increase their water intake by an additional 1.5 liters per day, whereas the control group was instructed to continue with their usual intake. At 1 year, the intervention group had experienced 48% fewer UTIs than the control group. The only fluid involved in the study was water, although other fluids would probably provide similar results, and the benefits would probably also apply to postmenopausal women. In addition, the intervention group used 47% fewer courses of antibiotics than the control group (1.8 vs 3.5; P< 0.0001). ^[46]

Sexually active women may attempt voiding immediately after intercourse to lessen the risk for coitus-related introduction of bacteria into the bladder. Some authors recommend large urinary flow volumes as a measure that will reduce the risk for UTI.

Prophylactic regimens for women with frequent recurrent UTIs include postcoital or continuous antibiotics. Women with fewer than 3 UTIs per year may benefit from self-initiated antibiotic therapy. For more information, see the Medscape Reference topic Prevention of Urinary Tract Infections.

In a 12-month randomized study of 28 women with recurrent bacterial cystitis, treatment with intravesical hyaluronic acid and chondroitin sulfate significantly reduced cystitis recurrence and improved urinary symptoms, quality of life, and cystometric capacity, as compared with antibiotic prophylaxis. Intravesical treatment was given once weekly for 4 weeks, then once every 2 weeks twice more. Antibiotic prophylaxis consisted of sulfamethoxazole and trimethoprim once weekly for 6 weeks. ^[47]