What is the recommended treatment for a patient with a Klebsiella pneumoniae urinary tract infection (UTI)?

Treatment for Klebsiella pneumoniae UTI

For non-resistant Klebsiella pneumoniae UTI, use oral fluoroquinolones (levofloxacin 750 mg daily for 5 days or ciprofloxacin 500-750 mg twice daily for 7 days) as first-line therapy if local resistance is <10%, or oral cephalosporins (cefpodoxime 200 mg twice daily for 10 days) if fluoroquinolone resistance is higher. 1

Uncomplicated Klebsiella UTI (Cystitis)

First-line options:

• Nitrofurantoin if the organism is susceptible 2
• Fluoroquinolones (levofloxacin 750 mg daily for 5 days or ciprofloxacin 500-750 mg twice daily for 7 days) if local resistance is <10% 1, 3
• Cefpodoxime 200 mg twice daily for 10 days when fluoroquinolone resistance is elevated 1
• Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 14 days only if local resistance is <20% and the patient has not used this antibiotic in the previous 3-6 months 1

Treatment duration: 3-5 days for uncomplicated cystitis 2

Critical caveat: Avoid fluoroquinolones as empiric therapy if local resistance rates are >10% or if the patient has used fluoroquinolones in the last 6 months 2

Uncomplicated Pyelonephritis

Recommended approach:

• Initial parenteral therapy with ceftriaxone 1-2 g once daily, followed by oral step-down based on susceptibility results 1, 2
• Treatment duration: 7 days for uncomplicated pyelonephritis 1, 2
• Levofloxacin is FDA-approved for acute pyelonephritis caused by Klebsiella pneumoniae, including cases with concurrent bacteremia 3

Complicated Klebsiella UTI

Empiric parenteral options for non-resistant strains:

• Ceftriaxone 1-2 g once daily 1
• Amoxicillin plus an aminoglycoside 2
• Second-generation cephalosporin plus an aminoglycoside 2

Treatment duration: 7-14 days (14 days for men when prostatitis cannot be excluded) 1

Essential step: Obtain urine culture and susceptibility testing before finalizing therapy 1

ESBL-Producing Klebsiella pneumoniae UTI

For severe infections:

• Carbapenems are recommended as the primary treatment 2
• Beta-lactam/beta-lactamase inhibitors (BLBLI) provide moderate-certainty evidence for non-inferiority to carbapenems in pyelonephritis caused by third-generation cephalosporin-resistant Enterobacterales 4

For non-severe infections:

• Aminoglycosides or intravenous fosfomycin may be considered 2

Oral options for ESBL-producing Klebsiella UTI:

• Pivmecillinam, fosfomycin, finafloxacin, and sitafloxacin are treatment options 5
• High-dose amoxicillin-clavulanic acid (2875 mg amoxicillin twice daily with 125 mg clavulanic acid twice daily) has shown success in breaking resistance in select cases, particularly in outpatient settings with recurrent UTIs 6

Parenteral options for ESBL-producing Klebsiella:

• Carbapenems (including meropenem-vaborbactam, imipenem-cilastatin-relebactam) 5
• Ceftazidime-avibactam 5
• Ceftolozane-tazobactam 5
• Aminoglycosides (including plazomicin) 5
• Cefiderocol, fosfomycin, sitafloxacin, and finafloxacin 5

Carbapenem-Resistant Klebsiella pneumoniae (CRE) UTI

For simple cystitis due to CRE:

• Single-dose aminoglycoside (amikacin or gentamicin) is recommended as first-line therapy 1
• Aminoglycosides are superior to tigecycline for cUTI caused by CRE (moderate certainty of evidence) 4

For complicated UTI due to CRE:

• Ceftazidime-avibactam 2.5 g IV every 8 hours is a preferred newer agent 4, 1
• Meropenem-vaborbactam is recommended as a treatment option for CRE-UTI 4
• Imipenem-cilastatin-relebactam is recommended as a treatment option for CRE-UTI 4
• Plazomicin is recommended as a treatment option for CRE-UTI 4

For severe CRE infections:

• Meropenem-vaborbactam or ceftazidime-avibactam if active in vitro (conditional recommendation, moderate and low certainty of evidence, respectively) 4

For non-severe CRE infections:

• Consider using an old antibiotic (chosen from among those active in vitro on an individual basis and according to the source of infection) under antibiotic stewardship principles 4

Additional CRE treatment options:

• Colistin, fosfomycin, aztreonam and ceftazidime-avibactam, aztreonam and amoxicillin-clavulanate, cefiderocol, and tigecycline 5

Critical warning: Tigecycline should NOT be used for bloodstream infections due to suboptimal outcomes 1. Aminoglycosides are preferred over tigecycline for cUTI caused by CRE 4

Special Considerations

Aminoglycoside advantages:

• Aminoglycosides achieve urinary concentrations exceeding peak plasma levels by 25- to 100-fold, making them highly effective for UTIs 4
• Single-dose aminoglycoside therapy is effective for lower urinary tract infections with microbiologic cure rates of 87-100% 4
• Aminoglycosides have shown better clinical outcomes compared with tigecycline-containing regimens for CRE UTI 4

Important caveats:

• Avoid third-generation cephalosporins for empiric treatment of Klebsiella UTI due to high resistance rates 1
• Infectious disease consultation is highly recommended for multidrug-resistant organism infections 1
• Automated susceptibility testing may not be reliable for multidrug-resistant organisms; Etest minimum inhibitory concentrations should be considered for critical cases 1, 7
• Assess clinical response within 48-72 hours of initiating therapy; if no improvement, reassess diagnosis and consider alternative antimicrobial therapy based on culture results 2

Antimicrobial stewardship:

• De-escalate to narrower-spectrum antibiotics when possible based on susceptibility results 2
• Use new antimicrobials wisely for treatment of UTIs caused by MDR-organisms to avoid resistance development 5