What are the recommended treatments for uncomplicated urinary tract infections (UTIs) caused by gram-negative bacilli?

From the Guidelines

For uncomplicated urinary tract infections (UTIs) caused by gram-negative bacilli, the recommended first-line treatment is a short course of oral antibiotics, with nitrofurantoin (100mg twice daily for 5 days), trimethoprim-sulfamethoxazole (160/800mg twice daily for 3 days), or fosfomycin (3g single dose) being the preferred options, as stated in the 2021 guidelines from the American College of Physicians 1.

Treatment Options

• Nitrofurantoin (100mg twice daily for 5 days) is a suitable choice due to its minimal resistance and efficacy comparable to trimethoprim-sulfamethoxazole 1.
• Trimethoprim-sulfamethoxazole (160/800mg twice daily for 3 days) is also an appropriate option, given its efficacy and low resistance rates, but its use should be guided by local resistance patterns 1.
• Fosfomycin (3g single dose) is another recommended option, offering the convenience of a single dose, although it may have inferior efficacy compared to standard short-course regimens 1.

Alternative Treatments

• Fluoroquinolones, such as ciprofloxacin or levofloxacin, are highly efficacious but should be reserved for cases where first-line agents cannot be used due to resistance concerns, given their propensity for adverse effects and collateral damage 1.
• Beta-lactams, including amoxicillin-clavulanate, may be used as alternative treatments but are considered less effective than other options and should be used with caution 1.

Considerations

• Treatment selection should consider local resistance patterns, patient allergies, and comorbidities to ensure the most effective and safe treatment outcome 1.
• Adequate hydration is important during treatment to help flush bacteria from the urinary tract, supporting the body's natural defense mechanisms.
• These antibiotics work by targeting various aspects of bacterial metabolism or replication, highlighting the importance of choosing the right antibiotic based on the causative organism and local resistance patterns.

From the FDA Drug Label

1. 12 Uncomplicated Urinary Tract Infections Levofloxacin tablets are indicated for the treatment of uncomplicated urinary tract infections (mild to moderate) due to Escherichia coli, Klebsiella pneumoniae, or Staphylococcus saprophyticus. Urinary Tract Infections For the treatment of urinary tract infections due to susceptible strains of the following organisms: Escherichia coli, Klebsiella species, Enterobacter species, Morganella morganii, Proteus mirabilis and Proteus vulgaris

The recommended treatments for uncomplicated urinary tract infections (UTIs) caused by gram-negative bacilli are:

• Levofloxacin: indicated for the treatment of uncomplicated UTIs due to Escherichia coli or Klebsiella pneumoniae 2
• Trimethoprim-sulfamethoxazole: indicated for the treatment of urinary tract infections due to susceptible strains of Escherichia coli, Klebsiella species, Enterobacter species, Morganella morganii, Proteus mirabilis, and Proteus vulgaris 3

From the Research

Treatment Options for Uncomplicated UTIs Caused by Gram-Negative Bacilli

• The recommended first-line empiric antibiotic therapy for acute uncomplicated bacterial cystitis in otherwise healthy adult nonpregnant females is a 5-day course of nitrofurantoin, a 3-g single dose of fosfomycin tromethamine, or a 5-day course of pivmecillinam 4, 5.
• Second-line options include oral cephalosporins such as cephalexin or cefixime, fluoroquinolones, and β-lactams, such as amoxicillin-clavulanate 4.
• Fluoroquinolones, such as ciprofloxacin, have been used successfully to treat a wide range of community- and hospital-acquired infections, and the rates of fluoroquinolone resistance have remained low 6.

Treatment Options for Complicated UTIs Caused by Gram-Negative Bacilli

• Current treatment options for UTIs due to AmpC- β-lactamase-producing Enterobacteriales include nitrofurantoin, fosfomycin, pivmecillinam, fluoroquinolones, cefepime, piperacillin-tazobactam, and carbapenems 4, 5.
• Treatment options for UTIs due to ESBLs-producing Enterobacteriaceae include nitrofurantoin, fosfomycin, pivmecillinam, amoxicillin-clavulanate, finafloxacin, and sitafloxacin 4.
• Parenteral treatment options for UTIs due to ESBLs-producing Enterobacteriales include piperacillin-tazobactam, carbapenems, ceftazidime-avibactam, ceftolozane-tazobactam, aminoglycosides, and fosfomycin 4.

Considerations for Antimicrobial Resistance

• The emergence and dissemination of antimicrobial resistance can be reduced with the use of agents that have favourable pharmacokinetic/pharmacodynamic profiles and convenient dose administration regimens that facilitate patient adherence and, therefore, pathogen eradication 6.
• The use of fluoroquinolones for empiric treatment of UTIs should be restricted due to increased rates of resistance 4, 5.
• Aminoglycosides, colistin, and tigecycline are considered alternatives in the setting of MDR Gram-negative infections in patients with limited therapeutic options 4, 5.