What are the antibiotics of choice for treating Gram-negative bacterial infections indicated by urinalysis?

Antibiotic Selection for Gram-Negative UTIs

For uncomplicated cystitis caused by Gram-negative bacteria, nitrofurantoin is the preferred first-line agent, while for pyelonephritis or complicated UTIs, ceftriaxone (if IV therapy needed) or fluoroquinolones (if local resistance <10%) represent the most appropriate empirical choices. 1

First-Line Treatment for Uncomplicated Cystitis

Nitrofurantoin is the drug of choice for uncomplicated lower UTIs caused by Gram-negative organisms 1:

• Dosing: 5-day course (various formulations available) 2
• Rationale: Robust efficacy evidence while sparing more systemically active agents for other infections 1
• Coverage: Excellent activity against E. coli and most common Gram-negative uropathogens 2

Alternative First-Line Options

When nitrofurantoin cannot be used, consider 2:

• Fosfomycin trometamol: 3g single oral dose 2
• Pivmecillinam: 400mg three times daily for 3-5 days 2
• TMP/SMX: 160/800mg twice daily for 3 days (only if local resistance <20%) 1, 2

Agents to Avoid

Do not use amoxicillin or ampicillin for empirical treatment due to very high worldwide resistance rates and poor efficacy against Gram-negative uropathogens 2.

Treatment for Pyelonephritis and Complicated UTIs

Oral Therapy Options

For patients who can take oral medications 1:

• TMP/SMX or first-generation cephalosporins are reasonable first-line agents, but selection must be guided by local resistance patterns 1
• Fluoroquinolones (if local resistance <10%):
  • Levofloxacin 750mg once daily for 5-7 days 3, 4
  • Ciprofloxacin 500-750mg twice daily for 7 days 3
  • Levofloxacin offers superior convenience with once-daily dosing and shorter duration (5 vs 7 days) 3

Intravenous Therapy

Ceftriaxone is the recommended empirical IV choice for patients requiring hospitalization, due to low resistance rates and clinical effectiveness 1:

• Use unless risk factors for multidrug resistance are present 1
• Dosing: Standard IV dosing per institutional protocols 1

For severe complicated UTIs with Gram-negative pathogens 4, 5:

• Levofloxacin 750mg IV once daily 4
• Ciprofloxacin 400mg IV twice daily 3
• Consider increasing ciprofloxacin to 750mg twice daily for Pseudomonas aeruginosa 5

Antipseudomonal Coverage

Reserve agents with antipseudomonal activity (e.g., ciprofloxacin, levofloxacin at higher doses, carbapenems) only for patients with risk factors for nosocomial pathogens 1:

• Recent hospitalization
• Recent antibiotic exposure
• Indwelling catheters
• Known colonization with resistant organisms

Treatment Duration

Uncomplicated Cystitis 1

• Nitrofurantoin: 5 days
• Fluoroquinolones: 3 days
• TMP/SMX: 3 days
• Fosfomycin: Single dose

Pyelonephritis 1

• β-lactams: 7 days
• Fluoroquinolones: 5-7 days (5 days for levofloxacin/ofloxacin; 7 days for ciprofloxacin)

Gram-Negative Bacteremia from Urinary Source 1

• 7 days total (clear recommendation based on contemporary evidence)

Critical Decision Algorithm

1. Determine infection severity:

   • Uncomplicated cystitis → Nitrofurantoin first-line 1, 2
   • Pyelonephritis/complicated UTI → Proceed to step 2

2. Assess need for IV therapy:

   • IV required → Ceftriaxone (unless MDR risk factors) 1
   • Oral acceptable → Proceed to step 3

3. Check local resistance patterns:

   • Fluoroquinolone resistance <10% → Levofloxacin 750mg daily × 5 days 3
   • Fluoroquinolone resistance ≥10% → TMP/SMX or cephalosporin (if local resistance acceptable) 1

4. Assess for Pseudomonas risk factors:

   • Present → Use antipseudomonal agent (ciprofloxacin, levofloxacin, or carbapenem) 1
   • Absent → Standard coverage adequate 1

Common Pitfalls to Avoid

• Never use fluoroquinolones as first-line for uncomplicated cystitis when nitrofurantoin, fosfomycin, or pivmecillinam are available—reserve them to prevent resistance 3, 2
• Do not empirically use antipseudomonal agents without specific risk factors, as this promotes resistance 1
• Avoid β-lactams (including amoxicillin-clavulanate) when alternatives exist, as they have inferior efficacy and more adverse effects for UTIs 2
• Always obtain urine culture before treatment in pyelonephritis, complicated UTIs, or when symptoms don't resolve 2
• Adjust therapy based on culture results when available—local resistance patterns should always guide final antibiotic selection 1, 2