What Type of Medication is Macrobid (Nitrofurantoin)?
Macrobid (nitrofurantoin) is a broad-spectrum bactericidal antibiotic specifically designed for treating urinary tract infections, with activity concentrated in the urinary tract rather than systemic tissues. 1
Drug Classification and Mechanism
Nitrofurantoin belongs to the nitrofuran class of antibiotics and has been in clinical use for over 70 years since FDA approval in the 1950s. 2, 3
It functions as a bactericidal agent (kills bacteria rather than just inhibiting growth) by interfering with bacterial cell wall synthesis, protein production, and DNA replication in both Gram-positive and Gram-negative organisms. 4
The WHO classifies nitrofurantoin as an "Access" antibiotic in the AWaRe framework, meaning it has lower resistance potential and should be prioritized to preserve broader-spectrum agents. 5
Pharmacokinetic Properties
Nitrofurantoin achieves high urinary concentrations while maintaining only low blood drug levels, making it uniquely suited for urinary tract infections but ineffective for systemic infections. 1, 6
The drug has a short elimination half-life and is rapidly excreted primarily through urine and bile, with minimal tissue binding or prolonged plasma protein attachment. 6
It is well absorbed orally when given in appropriate formulations, with first-order kinetics best described by a one-compartment open model. 6
Spectrum of Activity
Nitrofurantoin demonstrates effectiveness against common uropathogens including E. coli, Klebsiella species, Enterobacter species, Enterococcus species (including vancomycin-resistant enterococci), and Staphylococcus aureus. 2, 4
It maintains activity against many multidrug-resistant organisms, which has led to its resurgence as first-line therapy for uncomplicated lower UTIs. 4, 7
The drug has shown remarkably low rates of R-factor resistance development compared to newer antimicrobials, making it valuable in the era of increasing antimicrobial resistance. 3
Clinical Indications
First-line agent for acute uncomplicated cystitis (lower urinary tract infections) in premenopausal, nonpregnant women without urological abnormalities, typically dosed as 100 mg twice daily for 5 days. 2
Used for recurrent UTI prophylaxis and treatment of asymptomatic bacteriuria in pregnancy. 3
Appropriate for nosocomial UTI prophylaxis related to urinary tract instrumentation. 3
Critical Limitations and Contraindications
Should NOT be used for pyelonephritis (upper urinary tract infections) or when early pyelonephritis is suspected, as it does not achieve adequate tissue concentrations outside the urinary tract. 2
Contraindicated in patients with creatinine clearance under 60 mL/minute or clinically significant elevated serum creatinine, as renal impairment enhances the risk of severe adverse effects. 1
Avoid in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency due to risk of hemolytic anemia, which affects 10% of Black patients and small percentages of Mediterranean and Near-Eastern populations. 1
Serious Adverse Effects Requiring Monitoring
Pulmonary reactions (acute, subacute, or chronic) including diffuse interstitial pneumonitis or pulmonary fibrosis can develop, particularly with therapy exceeding 6 months; these have been cited as contributing causes of death. 1
Hepatotoxicity including hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis occur rarely but can be fatal; patients require periodic monitoring of liver function tests. 1
Peripheral neuropathy which may become severe or irreversible has been reported, with fatalities documented; risk is enhanced by renal impairment, anemia, diabetes, electrolyte imbalance, and vitamin B deficiency. 1
Clostridium difficile-associated diarrhea can occur with nitrofurantoin use, as with nearly all antibacterial agents. 1