What oral antibiotic options are available for treating a urinary tract infection caused by Carbapenem-Resistant Enterobacteriaceae (CRE), specifically Klebsiella pneumoniae?

From the Guidelines

Oral antibiotic options for treating urinary tract infections caused by Carbapenem-Resistant Enterobacteriaceae (CRE) Klebsiella pneumoniae are limited, but fosfomycin, nitrofurantoin, and trimethoprim-sulfamethoxazole can be considered based on susceptibility testing 1. When considering oral treatment options, it's essential to prioritize antibiotics that have shown efficacy against CRE, particularly in the context of urinary tract infections.

• Fosfomycin is often preferred due to its broad-spectrum activity, including against many strains of CRE, and can be administered at a dose of 3 grams as a single dose or every 48-72 hours for 3 doses 1.
• Nitrofurantoin can be used at 100 mg four times daily for 7 days if the isolate is susceptible and the infection is limited to the lower urinary tract, as indicated by studies suggesting its effectiveness in such cases 1.
• Trimethoprim-sulfamethoxazole at a dose of 160/800 mg twice daily for 7-14 days may be effective if susceptibility is confirmed, although resistance rates can be high in CRE strains 1. It's crucial to obtain antimicrobial susceptibility testing before initiating therapy, as CRE strains often carry multiple resistance mechanisms 1. For complicated or severe infections, oral options may be insufficient, and intravenous antibiotics like colistin, tigecycline, or newer agents such as ceftazidime-avibactam might be necessary, as suggested by guidelines for the treatment of infections caused by multidrug-resistant Gram-negative bacilli 1. Treatment should be guided by urine culture results, patient-specific factors, and local resistance patterns, with close monitoring for clinical improvement and follow-up cultures to ensure infection resolution 1.

From the FDA Drug Label

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

Urinary Tract Infections and Shigellosis in Adults and Pediatric Patients, and Acute Otitis Media in Children Adults: The usual adult dosage in the treatment of urinary tract infections is 4 teaspoonfuls (20 mL) of sulfamethoxazole and trimethoprim oral suspension every 12 hours for 10 to 14 days.

Oral antibiotic options for treating a urinary tract infection caused by Carbapenem-Resistant Enterobacteriaceae (CRE), specifically Klebsiella pneumoniae, include:

• Trimethoprim/Sulfamethoxazole (PO): The drug label indicates that it can be used to treat urinary tract infections due to susceptible strains of Klebsiella species 2.
• Fosfomycin (PO): Although the label does not specifically mention CRE or Klebsiella pneumoniae, it can be used to treat acute cystitis, which is a type of urinary tract infection 3.

However, it is essential to note that the effectiveness of these options against CRE, including Klebsiella pneumoniae, may vary depending on the specific susceptibility patterns of the organism. Culture and susceptibility testing should be performed to guide the selection of appropriate therapy 2.

From the Research

Oral Antibiotic Options for Treating UTIs Caused by CRE

The treatment of urinary tract infections (UTIs) caused by Carbapenem-Resistant Enterobacteriaceae (CRE), such as Klebsiella pneumoniae, is challenging due to limited antibiotic options. However, several oral antibiotics have shown efficacy against these resistant bacteria.

• Fosfomycin: This antibiotic has been shown to be effective against CRE, including Klebsiella pneumoniae, in several studies 4, 5, 6, 7. Fosfomycin has a broad spectrum of activity and is often used as a last-resort treatment for UTIs caused by multidrug-resistant bacteria.
• Nitrofurantoin: Although not as effective as fosfomycin, nitrofurantoin has also been shown to have activity against CRE, including Klebsiella pneumoniae 4, 6. However, its use may be limited by resistance rates and potential side effects.
• Pivmecillinam: This antibiotic has been shown to be effective against ESBL-producing Klebsiella pneumoniae 4, but its efficacy against CRE is less well established.
• Fluoroquinolones: Although often resistant to fluoroquinolones, some CRE isolates may still be susceptible to these antibiotics 4. However, their use should be guided by susceptibility testing due to high resistance rates.
• Amoxicillin-clavulanate: This antibiotic has been shown to be effective against some ESBL-producing Enterobacteriaceae, including Klebsiella pneumoniae 4, but its efficacy against CRE is less well established.

Key Considerations

When using oral antibiotics to treat UTIs caused by CRE, it is essential to consider the following:

• Susceptibility testing: Antibiotic susceptibility testing should be performed to guide treatment decisions and ensure the chosen antibiotic is effective against the specific CRE isolate.
• Resistance rates: Resistance rates to oral antibiotics can be high among CRE isolates, so treatment decisions should be based on local epidemiology and susceptibility patterns.
• Combination therapy: In some cases, combination therapy with multiple antibiotics may be necessary to achieve optimal treatment outcomes 8.
• New antibiotics: Several new antibiotics, such as ceftazidime-avibactam and meropenem-vaborbactam, have shown promise against CRE and may become available for treatment in the future 8.