Urinary Tract Infection - Uncomplicated Xử trí

Patient preference should always be considered when determining the management of urinary tract infections. The choice of antibiotics for empirical therapy should be based on spectrum and susceptibility patterns of uropathogens; efficacy; tolerability; adverse effects, including ecological effects; availability; and cost.

Treatment is not required for asymptomatic bacteriuria in postmenopausal women and should be managed the same as for premenopausal women. Treatment of asymptomatic bacteriuria should be reserved for situations in which clear patient benefit has been demonstrated to minimize the risk of promoting antimicrobial resistance and eliminating a potentially protective colonizing strain. In postmenopausal women, treatment of acute cystitis and pyelonephritis is the same with premenopausal women.

Acute Uncomplicated Cystitis

Management with nonsteroidal anti-inflammatory drugs (NSAIDs) or phytotherapy may reduce antibiotic use, with studies showing an overall 63% reduction in antibiotic therapy.  Short courses of antimicrobial therapy (eg penicillins [Pivmecillinam], cephalosporins, Fosfomycin, Nitrofurantoin, Trimethoprim, or sulphonamides [not to be given in the last trimester]) may be considered for the treatment of cystitis in pregnancy.

First-line Agents

First-line agents should have minimal resistance and tendency for ecological adverse effects (ie minimal effect on normal fecal flora). Fosfomycin and Nitrofurantoin should not be used if pyelonephritis is suspected.

Fosfomycin (single dose)

Fosfomycin is a phosphonic acid derivative that has activity against both Gram-negative and Gram-positive bacteria. This has an inferior microbiological efficacy rate but a comparable clinical efficacy rate as compared with standard short-course regimens. In vitro studies have shown activity against Vancomycin-resistant enterococci, Methicillin-resistant S aureus (MRSA) and extended-spectrum beta-lactamase (ESBL)-producing Gram-negative rods.

Nitrofurantoin (for 5 days)

Antibacterial activity is limited to the urinary tract and is suitable only for the treatment or prophylaxis of uncomplicated urinary tract infection (UTI). This has low resistance rates with an 88-93% clinical cure rate and an 81-92% bacterial cure rate based on studies. Clinical and microbiological cure rates are similar to that of Co-trimoxazole. This is not to be given during the end of pregnancy.

Pivmecillinam (for 3-5 days)

Pivmecillinam is an extended-Gram-negative spectrum penicillin that is used only for the treatment of urinary tract infections. This is an agent of choice in some European countries due to low rates of resistance.

Alternative Agents

Co-trimoxazole (for 3 days)

Co-trimoxazole remains to be effective in treating patients with acute uncomplicated cystitis and may be considered in areas where the resistance rate to E coli is <20%. This has early clinical and microbiological cure rates of 90-100%. Use of Co-trimoxazole is associated with increased resistance but generally does not have a tendency for ecological adverse effects. This is not to be given in the last trimester of pregnancy.

Trimethoprim (for 5 days)

Trimethoprim may be considered in areas where the resistance rate to E coli is <20%. This is not to be given in the first trimester of pregnancy.

Cephalosporins and Aminopenicillins with Beta-lactamase Inhibitors

Cephalosporins and aminopenicillins with beta-lactamase inhibitors are recommended only in patients with acute uncomplicated cystitis when other recommended agents cannot be used. These have inferior efficacy in managing acute uncomplicated cystitis, probably due to the persistence of the vaginal reservoir for infection. These antimicrobials also cause collateral ecological damage. Broad-spectrum cephalosporins have been shown to be associated with extended-spectrum beta-lactamase (ESBL) resistance among Gram-negative bacteria.

Aminopenicillins (eg Amoxicillin, Ampicillin)

Aminopenicillins (eg Amoxicillin, Ampicillin) alone are no longer recommended to be used for empirical treatment due to increased worldwide drug resistance to E coli, increased selection for ESBL-producing bacteria, and negative ecological effects. Aminopenicillins in combination with a beta-lactamase inhibitor (eg Ampicillin/sulbactam, Amoxicillin/clavulanic acid) and oral cephalosporins are not recommended for empirical therapy due to adverse effects but may be considered in select patients. Broad-spectrum cephalosporins have been shown to be associated with ESBL resistance among Gram-negative bacteria.

Fluoroquinolones (for 3 days)

Fluoroquinolones should only be used in cases where other agents cannot be used due to the possibility of promoting resistance among uropathogens and other organisms that can cause more serious infections at other sites. Increased usage was shown to increase rates of methicillin-resistant Staphylococcus aureus (MRSA). Overall clinical and microbiological efficacy rates are consistently high and remain effective for the treatment of acute uncomplicated cystitis, but it has an increased resistance rate, and its use is strictly regulated due to side effects. Single-dose therapy is available but with possibly lower efficacy rates than longer regimens.

Acute Uncomplicated Pyelonephritis

Selection of antimicrobial agent for empirical therapy will depend on local sensitivity patterns of uropathogens, whether or not the patient is hospitalized, and the relative costs of therapy. In cases where local resistance patterns are not known, empirical therapy should include an initial intravenous (IV) dose of a long-acting parenteral antimicrobial agent and start with a broader-spectrum agent, then narrow the therapy when laboratory results are available. Oral therapy should always be considered in patients with mild to moderate symptoms. Parenteral therapy should be used in patients who are too ill to take oral antibiotics and then switched to oral therapy once tolerated. Patients with signs of urosepsis should be given empiric antimicrobial therapy with coverage for ESBL-producing organisms.

Patients should be treated for a total of 7-14 days. Therapy for >14 days has not shown any benefit and is not recommended except in relapse cases caused by the same pathogen. In pregnant women with pyelonephritis, outpatient management with appropriate parenteral antimicrobials may be considered for mild cases if close follow-up is feasible, whereas severe cases generally require hospitalization and supportive care.

Fluoroquinolones (for 5-7 days)

Fluoroquinolones are recommended as a first-line oral therapeutic option in areas with a <10% resistance rate to E coli. These may also be given IV as initial treatment for patients requiring hospitalization.

Cephalosporins 







Third-generation oral cephalosporins may be used as an alternative agent in patients with mild to moderate pyelonephritis. Studies have demonstrated similar clinical efficacy to Ciprofloxacin. Parenteral cephalosporins may be given in hospitalized patients in areas with ESBL-producing E coli resistance rates of <10%. An initial parenteral dose of Ceftriaxone is recommended in areas with a >10% fluoroquinolone resistance rate and when Co-trimoxazole, Cefpodoxime, Ceftibuten or other oral beta-lactam agents were used empirically. This has shown to significantly improve the microbiological eradication rate and moderately improve the clinical cure rates in patients with resistance to Co-trimoxazole. The combination of Ceftriaxone and Co-trimoxazole was shown to result in improved clinical and bacterial cure rates. Ertapenem is an alternative agent for patients with allergies or expected resistance to Ceftriaxone. Aminoglycosides are given to patients who cannot use either agent. Ceftolozane/tazobactam and Ceftazidime/avibactam can also be used as empirical parenteral therapies in pyelonephritis.

Aminoglycosides

Aminoglycosides may be considered in areas with fluoroquinolone-resistant and ESBL-producing E coli (>10%). An initial parenteral 24-hour dose of aminoglycoside is recommended in areas with a >10% fluoroquinolone resistance rate or when oral beta-lactam agents are used empirically.

Carbapenems

Carbapenems may be considered in areas with >10% rates of fluoroquinolone-resistant and ESBL-producing E coli or in patients with early culture findings of multidrug-resistant organisms. Doripenem may be considered in Ceftazidime-non-susceptible pathogens.

Aminopenicillin with Beta-lactamase Inhibitor

Aminopenicillin with a beta-lactamase inhibitor cannot be given as empirical therapy for acute uncomplicated pyelonephritis but can be used after susceptibility testing has shown growth of a susceptible Gram-positive organism. This may be given to hospitalized patients with infections with known susceptible Gram-positive pathogens.

Co-trimoxazole (for 14 days)

Co-trimoxazole cannot be given as empirical therapy due to increasing E coli resistance rates but can be used after sensitivity has been confirmed through susceptibility testing. This may be used as an alternative agent in patients with fluoroquinolone hypersensitivity or known resistance.

Other Agents

New antimicrobial agents that may be used for the inpatient treatment of pyelonephritis with early culture results indicating multidrug-resistant microbes include Cefiderocol, Plazomicin, Imipenem/cilastatin and Meropenem/vaborbactam, which should be based on local resistance patterns and optimized on the basis of drug susceptibility results. Meropenem/vaborbactam may be considered in carbapenem-resistant Enterobacterales.

Pharmacological Therapy for Recurrent Urinary Tract Infection

Antibiotic Treatment

Acute self-treatment using a short-course regimen may be an option in women with clearly documented recurrent infections and compliant with medical instructions who are not suitable for or unwilling to take long-term daily prophylaxis. Treatment is modified once culture results are available. Depending on local resistance patterns, first-line agents usually include Nitrofurantoin, Fosfomycin and Co-trimoxazole which are given in the shortest possible duration (ie <7 days). Antibiotic resistance may be treated with a short course of culture-guided parenteral antibiotics. Treatment of asymptomatic bacteriuria in otherwise healthy patients with recurrent UTI is not recommended.

Prophylaxis

Prevention of recurrent cystitis involves counseling on risk-factor avoidance, use of non-antimicrobial measures, and antimicrobial prophylaxis. This should be given after eradication of urinary tract infection has been confirmed through a negative culture obtained 1-2 weeks after treatment. The choice of antibiotic should depend on severity and frequency of previous symptoms, complication risk, previous urine culture and susceptibility results, history of antibiotic use and risk for resistance, and the patient's medication preference. Treatment duration is variable (eg 3-6 months to 1 year) and must include periodic monitoring and assessment.

Continuous low-dose or postcoital antimicrobial prophylaxis may help prevent recurrent UTI when non-antimicrobial interventions have failed. Antibiotics given include Nitrofurantoin, Trimethoprim, or Fosfomycin; Cefalexin or Cefaclor may be given during pregnancy. Consider postcoital prophylaxis in pregnant women with a history of frequent urinary tract infections prior to pregnancy.

Co-trimoxazole and Norfloxacin as prophylactic agents were shown to reduce the recovery rate of aerobic Gram-negative uropathogens. Nitrofurantoin intermittently sterilizes the urine and possibly inhibits bacterial attachment, causing a lower recurrence rate. Methenamine hippurate is recommended as an alternative option to prophylactic antibiotics to reduce recurrent cystitis episodes in patients without renal tract abnormalities.

Other Treatments

Vaginal Estrogen replacement may be advised to postmenopausal women with no contraindications who experience recurrent UTI if behavioral and personal hygiene measures alone are ineffective. This has been shown to cause the reappearance of vaginal lactobacilli, which lowers vaginal pH, preventing the overgrowth and colonization of Enterobacteriaceae in the vagina. Immunomodulatory agents have limited evidence for short-term prevention of recurrent cystitis in adult women; among available options, OM-89 and MV140 are the most studied, with MV140 showing the most promising results. Other promising non-antimicrobial alternatives include probiotics (eg Lactobacillus spp), D-mannose and endovesical Hyaluronic acid/chondroitin sulfate instillation, though further evidence is needed before these are recommended. 

Acute Uncomplicated Cystitis

Advise women with acute cystitis about antibiotic-sparing treatment and prevention options and ensure they are fully informed about the supporting level of evidence for each approach. A combination of xyloglucan, hibiscus, and propolis is effective in relieving acute cystitis symptoms and preventing recurrence. Randomized controlled trial (RCT) evidence suggests that Centaurii herba, Levistici radix, and Rosmarini folium, as well as L-methionine combined with Hibiscus sabdariffa and Boswellia serrata, may relieve acute cystitis symptoms compared to Fosfomycin trometamol. Evidence regarding the effectiveness of D-mannose in reducing the frequency of cystitis episodes is inconsistent. Consider non-antibiotic therapy as an alternative to antibiotics in non-geriatric patients, using shared decision-making.

Recurrent Urinary Tract Infection (UTI)

Behavioral modifications such as increasing fluid intake, postcoital urination (within 15 minutes after sexual intercourse), avoiding occlusive underwear, and wiping from back to front after defecation or douching may help reduce the risk of recurrent UTI. Additional fluid intake of 1.5 L in premenopausal women with recurrent UTI who were low-volume drinkers (<1.5 L a day) reduced the number of cystitis episodes and antibiotic usage over a 12-month period.

Centaurii herba, Levistici radix, and Rosmarini folium are effective in preventing recurrence and reducing antibiotic use. Cranberry products may be helpful for symptom relief in acute cystitis and to prevent recurrence, but evidence on benefits is inconclusive. Acupuncture may be an alternative option in preventing recurrent UTI in women who are unresponsive to or intolerant of antibiotic prophylaxis. Consider specialist referral to facilitate identification and/or treatment of a possible anatomical or functional cause of recurrent UTI.