What is the recommended treatment for a patient with a urinary tract infection (UTI) positive for Klebsiella and Escherichia coli (E. coli)?

Treatment of Polymicrobial UTI with Klebsiella and E. coli

For a UTI positive for both Klebsiella and E. coli, initiate empirical treatment with intravenous ceftriaxone (1-2g IV daily) or amoxicillin-clavulanate plus an aminoglycoside, then tailor therapy based on culture susceptibilities for 7-14 days. 1

Initial Empirical Therapy

The presence of both organisms indicates a polymicrobial infection requiring broad-spectrum coverage. Start with IV third-generation cephalosporin (ceftriaxone) as first-line empirical therapy while awaiting susceptibility results. 1 Alternative regimens include amoxicillin plus aminoglycoside (gentamicin 7.5 mg/kg/day divided every 8 hours or tobramycin 5 mg/kg/day divided every 8 hours) or a second-generation cephalosporin plus aminoglycoside. 2, 1

Critical First Steps

• Obtain urine culture and susceptibility testing immediately before starting antibiotics—this is mandatory for any complicated UTI to guide de-escalation. 1
• Both E. coli and Klebsiella are common uropathogens, with E. coli causing approximately 75% of UTIs and Klebsiella representing a significant proportion of complicated cases. 2
• The polymicrobial nature suggests this may be a complicated UTI, particularly if the patient has risk factors such as diabetes, immunosuppression, structural abnormalities, indwelling catheters, or recurrent infections. 2

Antibiotic Selection Based on Susceptibilities

Once susceptibility results return, tailor therapy to the narrowest effective agent:

• Levofloxacin (750 mg daily for 5-10 days) is FDA-approved for complicated UTIs caused by E. coli and Klebsiella pneumoniae. 3 However, avoid fluoroquinolones if the patient has recent fluoroquinolone exposure (within 6 months) or recurrent UTI history due to high resistance rates. 1

• Amoxicillin-clavulanate can be effective if susceptibilities confirm sensitivity—standard dosing is 20-40 mg/kg/day in 3 doses for oral therapy. 2 For ESBL-producing strains, high-dose amoxicillin-clavulanate (2875 mg amoxicillin + 125 mg clavulanic acid twice daily) has shown success in breaking resistance. 4

• Avoid ampicillin, trimethoprim-sulfamethoxazole, and first-generation cephalosporins as empiric choices—resistance rates for E. coli and Klebsiella to these agents are extremely high (up to 75% for ampicillin). 5, 6

Treatment Duration

• Treat for 7-14 days depending on clinical response and patient sex. 1
• Males require 14 days when prostatitis cannot be excluded. 1
• Patients who are clinically stable and able to tolerate oral intake can transition from IV to oral therapy after 24-48 hours of clinical improvement. 2

Special Considerations for Resistance

ESBL-Producing Organisms

If susceptibilities reveal ESBL-producing E. coli or Klebsiella:

• Carbapenems (meropenem, ertapenem) are the traditional first-line agents for ESBL infections. 4, 7
• High-dose amoxicillin-clavulanate (2875/125 mg twice daily with dose titration) represents an alternative to carbapenems in select cases. 4
• Aminoglycosides (amikacin) show the least resistance and can be effective for ESBL UTIs. 5, 7
• Nitrofurantoin maintains good activity against E. coli but shows variable resistance with Klebsiella. 5

Multidrug-Resistant Patterns

• Tigecycline and colistin are last-resort options for extensively drug-resistant Klebsiella, though colistin carries nephrotoxicity risk. 7
• Doxycycline may be effective for susceptible MDR strains based on local susceptibility patterns. 8
• Fosfomycin can be considered for resistant organisms, though clinical response may be limited. 7

Common Pitfalls to Avoid

• Do not delay culture collection—starting antibiotics before obtaining cultures is acceptable, but the specimen must be collected first. 1
• Do not treat asymptomatic bacteriuria if discovered incidentally. 1
• Do not use nitrofurantoin for febrile UTIs or suspected pyelonephritis—it does not achieve therapeutic blood concentrations. 2
• Do not assume susceptibility based on previous cultures—resistance patterns change, particularly with recurrent infections. 6
• Recognize risk factors for ESBL infection: diabetes, recurrent UTI, previous antibiotic use, and prior hospitalization all increase ESBL likelihood. 6

Monitoring and Follow-Up

• Expect clinical improvement within 24-48 hours of appropriate therapy. 2
• If symptoms persist beyond 48-72 hours, consider imaging to evaluate for complications (abscess, obstruction, stones) or bacterial persistence. 2
• Rapid recurrence (within 2 weeks) suggests bacterial persistence requiring imaging workup for structural abnormalities. 2