Treatment of Klebsiella pneumoniae Urinary Tract Infections
For non-carbapenem-resistant Klebsiella pneumoniae UTIs, aminoglycosides (particularly gentamicin) are the first-line treatment, with a single-dose regimen sufficient for simple cystitis and 7-10 days for complicated infections. 1, 2 For carbapenem-resistant strains, ceftazidime-avibactam or meropenem-vaborbactam should be used as first-line therapy. 3, 1
Treatment Algorithm Based on Resistance Pattern
Non-Resistant Klebsiella pneumoniae
First-line options:
- Aminoglycosides (gentamicin): Single-dose for simple cystitis, as urinary concentrations reach 25-100 times plasma levels 1
- Levofloxacin: 750 mg daily for 5 days (complicated UTI) or 250 mg daily for 3 days (uncomplicated UTI) 4
- Nitrofurantoin: 100 mg every 6 hours for uncomplicated lower UTI 5
Second-line options:
ESBL-Producing Klebsiella pneumoniae
Oral options for uncomplicated UTI:
- Fosfomycin: 3 g single dose 3, 5
- Nitrofurantoin: 100 mg every 6 hours 5
- High-dose amoxicillin-clavulanate: 2875 mg amoxicillin/125 mg clavulanic acid twice daily, down-titrated every 7-14 days 6
Parenteral options for complicated UTI:
- Piperacillin-tazobactam (for ESBL E. coli only, not K. pneumoniae) 5
- Carbapenems (ertapenem, meropenem) 5
- Ceftazidime-avibactam 5
- Aminoglycosides with therapeutic drug monitoring 1
Carbapenem-Resistant Klebsiella pneumoniae (CRKP)
First-line parenteral therapy:
Alternative parenteral options:
- Imipenem-cilastatin-relebactam: 1.25 g IV every 6 hours 3, 1
- Plazomicin: 15 mg/kg IV every 12 hours 3
- Cefiderocol 5
Oral options for uncomplicated CRKP cystitis:
- Single-dose aminoglycoside (with caution and susceptibility confirmation) 3, 1
- Fosfomycin: 3 g single dose 3
Critical Implementation Considerations
Therapeutic Drug Monitoring
- Mandatory for aminoglycosides, polymyxins, and carbapenems in all patients, especially those with renal dysfunction 3, 1
- Optimizes dosing, improves efficacy, and reduces nephrotoxicity 1
Renal Function Monitoring
- Monitor creatinine and estimated GFR regularly during treatment 1
- Avoid nephrotoxic combinations: Do not combine aminoglycosides with polymyxins or other nephrotoxic agents 3
- Adjust doses based on creatinine clearance for all renally-eliminated antibiotics 1
Treatment Duration
- Simple cystitis: Single-dose aminoglycoside or 3-day course 1
- Uncomplicated UTI: 7-10 days 1
- Complicated UTI/pyelonephritis: 10-14 days 1
- CRKP infections: Minimum 10-14 days, guided by clinical response 3
Special Populations
Chronic Kidney Disease Patients
- Aminoglycosides remain first-line but require aggressive therapeutic drug monitoring 1
- Single-dose regimens preferred for simple cystitis to minimize nephrotoxicity 1
- Avoid nitrofurantoin in CKD stage 3 or higher 1
Transplant Recipients
- Avoid nephrotoxic agents when possible (colistin, aminoglycosides at prolonged courses) 7
- Consider chloramphenicol as salvage therapy for XDR strains when other options are nephrotoxic 7
- High-dose amoxicillin-clavulanate effective for recurrent ESBL-producing K. pneumoniae UTIs 6
Common Pitfalls to Avoid
Do not use fluoroquinolones or trimethoprim-sulfamethoxazole empirically without susceptibility testing due to high resistance rates in many communities 5
Do not use ceftriaxone or other third-generation cephalosporins for ESBL-producing strains, even if in vitro susceptibility suggests activity 5
Do not delay switching to targeted therapy once susceptibility results are available—carbapenem overuse drives resistance 3
Verify carbapenem MIC before using polymyxin-carbapenem combinations—only effective if meropenem MIC ≤8 mg/L for CRE 3