What is the treatment for Urinary Tract Infection (UTI) caused by Gram-negative bacilli?

From the Guidelines

For treating a urinary tract infection (UTI) caused by gram-negative bacilli, the recommended treatment duration is 7 days, as supported by recent guidelines 1. When considering the treatment of UTIs caused by gram-negative bacilli, it's essential to note that the choice of antibiotic and duration of treatment can significantly impact patient outcomes in terms of morbidity, mortality, and quality of life.

Key Considerations

• The most recent and highest quality study 1 provides a clear recommendation for the treatment of gram-negative bacteremia from a urinary source, suggesting a 7-day treatment duration.
• This recommendation is based on multiple RCTs that demonstrated noninferiority of 7 days compared with 14 total days of treatment for patient-oriented outcomes such as clinical cure, clinical failure, relapse, and all-cause mortality.
• While specific drugs are not recommended, it is crucial to ensure that the chosen antibiotic and dosage are optimized for the patient and the urinary focus of infection.

Treatment Options

• Fluoroquinolones, such as ciprofloxacin or levofloxacin, are commonly used for treating UTIs caused by gram-negative bacilli.
• Trimethoprim-sulfamethoxazole is another effective option, provided local resistance patterns permit its use.
• For more severe or complicated cases, broader-spectrum antibiotics like ceftriaxone, gentamicin, or piperacillin-tazobactam may be necessary.

Additional Recommendations

• Urine culture and sensitivity testing should guide definitive therapy, allowing for targeted antibiotic selection based on the specific organism and its susceptibility profile.
• Adequate hydration is important during treatment to help flush bacteria from the urinary tract.
• Gram-negative bacilli commonly causing UTIs include Escherichia coli, Klebsiella, Proteus, and Pseudomonas species, with E. coli being the most frequent pathogen. As emphasized by the guidelines 1, the treatment approach should prioritize evidence-based recommendations to optimize patient outcomes.

From the FDA Drug Label

To reduce the development of drug-resistant bacteria and maintain the effectiveness of sulfamethoxazole and trimethoprim tablets and other antibacterial drugs, sulfamethoxazole and trimethoprim tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to empiric selection of therapy 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 treatment for Urinary Tract Infection (UTI) caused by Gram-negative bacilli is trimethoprim-sulfamethoxazole (PO), which is effective against susceptible strains of:

• Escherichia coli
• Klebsiella species
• Enterobacter species
• Morganella morganii
• Proteus mirabilis
• Proteus vulgaris 2

From the Research

Treatment Options for UTI caused by Gram-negative Bacilli

The treatment for Urinary Tract Infections (UTIs) caused by Gram-negative bacilli depends on various factors, including the severity of the infection, the presence of antibiotic resistance, and the patient's overall health.

• First-line empiric antibiotic therapy for acute uncomplicated bacterial cystitis in otherwise healthy adult nonpregnant females includes a 5-day course of nitrofurantoin, a 3-g single dose of fosfomycin tromethamine, or a 5-day course of pivmecillinam 3, 4.
• Second-line options include oral cephalosporins such as cephalexin or cefixime, fluoroquinolones, and β-lactams, such as amoxicillin-clavulanate 3.
• For UTIs caused by AmpC-β-lactamase-producing Enterobacteriales, treatment options include nitrofurantoin, fosfomycin, pivmecillinam, fluoroquinolones, cefepime, piperacillin-tazobactam, and carbapenems 3, 4.
• For UTIs caused by extended-spectrum β-lactamases (ESBLs)-producing Enterobacteriaceae, treatment options include nitrofurantoin, fosfomycin, pivmecillinam, amoxicillin-clavulanate, finafloxacin, and sitafloxacin 3, 4.
• Parenteral treatment options for UTIs due to ESBLs-producing Enterobacteriales include piperacillin-tazobactam, carbapenems, ceftazidime-avibactam, ceftolozane-tazobactam, and aminoglycosides 3, 4.
• Treatment options for UTIs caused by carbapenem-resistant Enterobacteriales (CRE) include ceftazidime-avibactam, meropenem/vaborbactam, imipenem/cilastatin-relebactam, colistin, fosfomycin, aztreonam, and aminoglycosides 3, 4, 5.
• For UTIs caused by multidrug-resistant (MDR)-Pseudomonas spp., treatment options include fluoroquinolones, ceftazidime, cefepime, piperacillin-tazobactam, carbapenems, aminoglycosides, colistin, ceftazidime-avibactam, and ceftolozane-tazobactam 3, 4, 5.

Antibiotic Resistance and Treatment

Antibiotic resistance is a growing concern in the treatment of UTIs caused by Gram-negative bacilli.

• The use of fluoroquinolones for empiric treatment of UTIs should be restricted due to increased rates of resistance 4.
• Aminoglycosides, colistin, and tigecycline are considered alternatives in the setting of MDR Gram-negative infections in patients with limited therapeutic options 4.
• Novel combinations, such as betalactam or carbapenem and betalactamase inhibitor, have been approved for the treatment of complicated UTIs caused by MDR Gram-negatives 5.
• An interdisciplinary approach, including urologists, microbiologists, and infectious disease physicians, is strongly advised to ensure prudent use and to avoid the development of resistance to novel anti-infective substances 5.

Real-World Effectiveness of Antibiotic Stepdown Strategies

Real-world data suggest that oral stepdown therapy with fluoroquinolones or trimethoprim-sulfamethoxazole has similar effectiveness as intravenous β-lactams for the treatment of Gram-negative complicated urinary tract infection with bacteremia 6.

• High-bioavailability β-lactams were associated with a higher risk of recurrence, which was not mitigated by longer treatment durations 6.
• Most high-bioavailability β-lactams were not optimally dosed for bacteremia, highlighting the need for further data to define optimal dosing and duration to mitigate treatment failures 6.