Urinary%20tract%20infection%20-%20uncomplicated Treatment

• Choice of antibiotic for empirical therapy should be based on spectrum and susceptibility patterns of uropathogens, efficacy, tolerability, adverse effects including ecological effects, availability, and cost
• No specific antibiotic regimen is recommended for pregnant women since all antibiotics studied were shown to be effective; short courses of antimicrobial therapy (eg penicillins, cephalosporins, Fosfomycin, Nitrofurantoin, Trimethoprim, sulphonamides) may be considered
• Treatment is not required for asymptomatic bacteriuria in postmenopausal women and management should be as for premenopausal women
• In postmenopausal women, treatment of acute cystitis and pyelonephritis is the same to that in premenopausal women; however, short-term treatment in cystitis is not well-established

Acute Uncomplicated Pyelonephritis

Choice of Empiric Therapy 

• Selection of antimicrobial agent 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 initial intravenous (IV) dose of a long-acting parenteral antimicrobial agent and starting with a broader-spectrum agent and then narrowing the therapy when laboratory results are available
  • Patients with signs of urosepsis should be given empiric antimicrobial therapy with coverage for extended spectrum β-lactamase (ESBL)-producing organisms  
  • 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, then switch to oral therapy once tolerated
• Patient 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

Acute Uncomplicated Cystitis

First-line Options 

• Appropriate agents should have minimal resistance and tendency for ecological adverse effects (eg minimal effect on normal fecal flora)
  • Fosfomycin and Nitrofurantoin should not be used if early pyelonephritis is suspected
• Fosfomycin (single dose)
  • A phosphonic acid derivative that has activity against both Gram-negative and Gram-positive bacteria
  • Has inferior microbiological efficacy rate but with comparable clinical efficacy rate as compared with standard short-course regimens
  • In vitro studies have shown activity against Vancomycin-resistant enterococci (VRE), Methicillin-resistant S aureus (MRSA), and ESBL-producing Gram-negative rods
• Nitrofurantoin (for 5-7 days)
  • Antibacterial activity is limited to the urinary tract and is suitable only for the treatment or prophylaxis of uncomplicated UTIs
  • Has low resistance rates and with 88-93% clinical cure rate and 81-92% bacterial cure rate based on studies
    • With similar clinical and microbiological cure rates as with Co-trimoxazole
  • Not to be given during the end of pregnancy
• Pivmecillinam (for 3-7 days)
  • An extended Gram-negative spectrum penicillin that is used only for the treatment of UTI
  • Has a low risk of selection for resistance and because of its low resistance rates, it is an agent of choice in some European countries
  • Randomized trials showed clinical efficacy is less than the other recommended agents

Alternative Agents  

• Co-trimoxazole (for 3 days)
  • Remains to be effective in treating patients with acute uncomplicated cystitis and may be considered in areas where resistance rate to E coli is <20%
    • Has early clinical and microbiological cure rates of 90-100%
  • Use is associated with increased resistance but generally does not have a tendency for ecological adverse effects
  • Not to be given in the last trimester of pregnancy
• Trimethoprim (for 5 days)
  • May be considered in areas where resistance rate to E coli is <20%
  • Not to be given in the first trimester of pregnancy 
• Cephalosporins and aminopenicillins with β-lactamase inhibitors
  • Recommended only in patients with uncomplicated cystitis when other recommended agents cannot be used
  • Have inferior efficacy in managing acute cystitis which is probably due to persistence of the vaginal reservoir for infection; these antimicrobials also cause ecological collateral damage
  • Broad-spectrum cephalosporins have been shown to be associated with ESBL resistance among Gram-negative bacteria
• Aminopenicillins (eg Amoxicillin, Ampicillin) alone are no longer recommended to be used for empirical treatment due to increased worldwide drug resistance to E coli and 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
• Fluoroquinolones (for 3 days)
  • 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 MRSA
  • Overall clinical and microbiological efficacy rates are consistently high and remain very effective for the treatment of acute cystitis however has increased resistance rate
  • Single-dose therapy is available but with possibly lower efficacy rates than with longer regimens

Acute Uncomplicated Pyelonephritis

Fluoroquinolones (for 5-7 days) 

• Recommended as 1st-line oral therapeutic option in areas with <10% resistance rate to E coli, parenteral in severe cases

Cephalosporins 

• 3rd generation oral cephalosporins may be used as an alternative agent in patients with mild-moderate pyelonephritis
  • Studies have demonstrated similar clinical efficacy as with Ciprofloxacin
  • An initial parenteral dose of Ceftriaxone is recommended when Cefpodoxime, Ceftibuten or Co-trimoxazole was used empirically
• 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 >10% fluoroquinolone-resistance rate or when Co-trimoxazole or oral β-lactam agents were used empirically
    • Shown to significantly improve the microbiological eradication rate and moderately improve the clinical cure rates in patients with resistance to Co-trimoxazole
    • 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 allergy or expected resistance to Ceftriaxone, and aminoglycosides are given to patients who cannot use either agents
• Ceftolozane/tazobactam and Ceftazidime/avibactam can also be used as empirical parenteral therapies in uncomplicated pyelonephritis 

Aminoglycoside

• 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 >10% fluoroquinolone resistance rate or when oral β-lactam agents were used empirically

Carbapenem

• 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-nonsusceptible pathogens

Aminopenicillin with β-lactamase Inhibitor

• Cannot be given as empirical therapy for acute pyelonephritis but can be used after susceptibility testing has shown growth of susceptible Gram-positive organism
• May be given in hospitalized patients in infections with known susceptible Gram-positive pathogens

Co-trimoxazole (for 14 days) 

• 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

Other Agents

• New antimicrobial agents that may be used for the inpatient treatment of uncomplicated 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 optimised on the basis of drug susceptibility results
  • Meropenem/vaborbactam may be considered in carbapenem-resistant Enterobacteriaceae

Recurrent UTI

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 the long-term daily prophylaxis    
  • Treatment is modified once culture results are available 
• Depending on local resistance patterns, 1st-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 patients with recurrent UTI is not recommended

Prophylaxis

• Should be given after eradication of UTI has been confirmed through a negative culture obtained 1-2 weeks after treatment
  • Choice of antibiotic should depend on severity and frequency of previous symptoms, complications risk, previous urine culture and susceptibility results, history of antibiotic use and risk for resistance and 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 antibiotic and post-coital prophylaxis are given when non-antimicrobial interventions have been unsuccessful 
  • Antibiotics given include Co-trimoxazole, Nitrofurantoin, Trimethoprim, Fosfomycin, or a quinolone (Norfloxacin or Ciprofloxacin); Cefalexin or Cefaclor may be given
  • Consider post-coital prophylaxis in pregnant women with a history of frequent UTIs 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 lower recurrence rate
• Methenamine may be considered as an alternative option to prophylactic antibiotics

Other Treatments

• Vaginal Estrogen replacement may be advised to peri and postmenopausal women with no contraindications who experience recurrent UTI
  • Has been shown to cause reappearance of vaginal lactobacilli which lowers vaginal pH preventing the overgrowth and colonization of Enterobacteriaceae in the vagina
• Immunoactive prophylaxis (OM-89) can be recommended for women with recurrent UTI 
  • Other promising non-antimicrobial alternatives include probiotics (eg Lactobacillus spp), D-mannose and intravesical hyaluronic acid/chondroitin instillation, though further evidence is needed before these are recommended

• Behavioral modifications such as increasing fluid intake, post-coital urination (within 15 minutes after sexual intercourse), avoiding occlusive underwear or douching, etc, may help reduce the risk of recurrent UTI
• Cranberry products may be helpful; evidence on benefits are inconclusive
• Acupuncture may be an alternative option in preventing recurrent UTI in women who are unresponsive to or intolerant of antibiotic prophylaxis