Is Macrobid (nitrofurantoin) effective against gram-negative rods?

Macrobid Coverage of Gram-Negative Rods

Macrobid (nitrofurantoin) is effective against most lactose-fermenting gram-negative rods that cause urinary tract infections, including E. coli and Klebsiella species, but it does NOT cover non-fermenting gram-negative rods like Pseudomonas aeruginosa. 1

Spectrum of Activity

Gram-Negative Rods Covered by Nitrofurantoin

Nitrofurantoin demonstrates excellent activity against common lactose-fermenting gram-negative uropathogens:

• E. coli - the most common cause of UTIs, with maintained susceptibility despite widespread resistance to other agents 1, 2
• Klebsiella species - including many ESBL-producing strains 2, 3
• Enterobacter species - effective coverage for urinary isolates 2
• Other Enterobacteriaceae - most lactose-fermenting strains remain susceptible 4

Critical Limitations: Gram-Negative Rods NOT Covered

Nitrofurantoin has poor activity against:

• Pseudomonas aeruginosa - intrinsically resistant due to reduced permeability of the outer cell envelope 5
• Acinetobacter species - shows reduced permeability to macrolides and nitrofurans 5
• Proteus species - generally resistant
• Serratia species - generally resistant

Clinical Context Matters

When Nitrofurantoin is Appropriate for Gram-Negative Rods

Nitrofurantoin should be used ONLY for lower urinary tract infections (uncomplicated cystitis):

• First-line agent for uncomplicated cystitis at 100mg twice daily for 5 days when caused by susceptible gram-negative rods 6
• Effective against multidrug-resistant organisms including ESBL-producers and carbapenemase-producers in the urinary tract 6, 3
• Maintains stable susceptibility patterns unlike fluoroquinolones which face increasing resistance 1

When Nitrofurantoin Should NOT Be Used

Critical pitfalls to avoid:

• Never use for pyelonephritis (upper UTI) - inadequate tissue penetration 6
• Never use for complicated UTIs - insufficient systemic levels 6
• Never use for bacteremia from gram-negative rods - does not achieve adequate blood levels 6
• Never use for non-urinary infections - concentrates only in urine 1

Resistance Considerations

Nitrofurantoin has unique resistance characteristics:

• Minimal resistance development even after decades of use, likely due to multiple mechanisms of action 4
• Remains effective against ESBL-producers: 65% of ESBL-producing E. coli and 51% of carbapenem-resistant strains retain susceptibility 3
• Resistance requires multiple mutations in the nfsA gene, making it less likely to develop 3

Practical Algorithm for Use

When treating suspected gram-negative rod UTI:

1. Identify infection site: Lower UTI (cystitis) vs. upper UTI (pyelonephritis) vs. complicated UTI
2. If uncomplicated cystitis: Nitrofurantoin is first-line for lactose-fermenting gram-negative rods 1, 6
3. If pyelonephritis or complicated UTI: Choose fluoroquinolones, TMP-SMX (if susceptible), or other systemic agents - NOT nitrofurantoin 6
4. If Pseudomonas suspected: (macerated wounds, chronic catheter, nosocomial) - nitrofurantoin will NOT work; use antipseudomonal agents 5

The key distinction is that nitrofurantoin covers the common gram-negative rods that cause simple bladder infections, but fails against non-fermenters and cannot treat systemic or upper tract infections due to inadequate tissue penetration.