Should levofloxacin be started for a urinary tract infection (UTI) with urine culture (UCx) showing Staphylococcus aureus and Klebsiella, both susceptible to levofloxacin?

Should Levofloxacin Be Started for This Mixed UTI?

No, levofloxacin should not be started as empiric therapy for this mixed-organism urinary tract infection showing both Staphylococcus aureus (50,000-100,000 CFU/mL) and Klebsiella (5,000 CFU/mL), despite in vitro susceptibility to levofloxacin. This clinical scenario requires careful consideration of the infection type, organism significance, and guideline-based antimicrobial stewardship principles.

Key Clinical Considerations

Mixed Culture Interpretation

• The presence of S. aureus at 50,000-100,000 CFU/mL with concurrent Klebsiella at 5,000 CFU/mL suggests a complicated UTI, as S. aureus is an uncommon uropathogen and typically indicates either hematogenous seeding, instrumentation, or structural abnormality 1
• The lower colony count of Klebsiella (5,000 CFU/mL) may represent contamination or colonization rather than true infection, though Klebsiella is a recognized pathogen in complicated UTIs 1

Why Fluoroquinolones Should Be Avoided Here

Fluoroquinolones like levofloxacin should be reserved for important uses other than routine UTI treatment and are not first-line agents 1. The guidelines are explicit about this:

• Fluoroquinolones have significant propensity for collateral damage (disruption of normal flora leading to resistance and secondary infections) 1
• Ciprofloxacin and other fluoroquinolones should only be used for complicated UTI when local resistance rates are <10%, when the entire treatment can be given orally, when the patient doesn't require hospitalization, or when there is anaphylaxis to β-lactam antimicrobials 1
• Fluoroquinolones should not be used for empirical treatment in patients from urology departments or when patients have used fluoroquinolones in the last 6 months 1

Recommended Treatment Approach

For this complicated UTI with systemic symptoms (if present), the preferred empirical regimen is a combination therapy 1:

• Amoxicillin plus an aminoglycoside, OR
• A second-generation cephalosporin plus an aminoglycoside, OR
• An intravenous third-generation cephalosporin 1

If the patient is hemodynamically stable without systemic symptoms, consider:

• A β-lactam agent targeting both organisms based on susceptibilities
• Treatment duration of 7-14 days (14 days for men when prostatitis cannot be excluded) 1

Critical Pitfalls to Avoid

• Do not assume levofloxacin is appropriate simply because both organisms test susceptible in vitro - antimicrobial stewardship principles and guideline recommendations supersede susceptibility testing alone 1
• Do not ignore the unusual nature of S. aureus in urine - this warrants investigation for underlying urological abnormalities, recent instrumentation, or bacteremia 1
• Do not use fluoroquinolones as first-line therapy when guideline-recommended alternatives are available - this contributes to resistance development 1

When Levofloxacin Might Be Considered

Levofloxacin could be appropriate in this specific scenario only if:

• The patient has documented anaphylaxis to β-lactam antibiotics 1
• Local fluoroquinolone resistance rates are confirmed <10% 1, 2
• The patient does not require hospitalization and can complete oral therapy 1
• No fluoroquinolone use in the preceding 6 months 1
• After addressing any underlying urological abnormality 1

If levofloxacin is ultimately chosen, the FDA-approved dosing for complicated UTI is 750 mg once daily for 5 days or 250-500 mg once daily for 10 days 3, though the 5-day regimen at 750 mg is supported by recent evidence 2.