Nitrofurantoin-Induced Pulmonary Toxicity: Mechanisms, Diagnosis, and Management
Abstract
1. Introduction
2. Mechanism of Toxicity
2.1. Nitrofurantoin Metabolism and Pathways Involved in Lung Tissue Damage
2.2. Potential Immunologic and Oxidative Stress Mechanisms
2.3. Predisposing Factors
2.4. Types of Nitrofurantoin-Induced Pulmonary Toxicity
3. Clinical Presentation and Diagnosis
3.1. Symptoms and Clinical Signs Associated with Nitrofurantoin-Induced Pulmonary Toxicity
3.2. Diagnostic Approach to Nitrofurantoin-Induced Pulmonary Toxicity
3.3. Comparison of Nitrofurantoin-Induced Pulmonary Toxicity to Other Pulmonary Conditions
4. Management and Treatment of Nitrofurantoin-Induced Pulmonary Toxicity
5. Preventive Strategies and Risk Minimization for Nitrofurantoin-Induced Pulmonary Toxicity
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Feature | Acute Nitrofurantoin-Induced Pulmonary Toxicity | Chronic Nitrofurantoin-Induced Pulmonary Toxicity |
---|---|---|
Onset | Within hours to weeks of use | After ≥6 months of use |
Symptoms | Fever, cough, dyspnea, eosinophilia | Progressive cough, dyspnea; usually no fever |
Mechanism | Immune-mediated (Type III hypersensitivity), ROS-related injury | Direct toxicity via ROS; possibly dose-dependent |
Imaging (CT) | Ground-glass opacities may be normal | Ground-glass opacities, honeycombing, fibrosis features |
Histopathology | Interstitial inflammation, eosinophils, vasculitis | Chronic interstitial pneumonitis, vascular sclerosis |
Response to Stopping Drug | Rapid symptom improvement (24–72 h); slower radiographic resolution | Gradual improvement over weeks to months |
Prognosis | Excellent with prompt recognition | Variable; often delayed diagnosis |
Treatment | Stop nitrofurantoin ± steroids | Stop nitrofurantoin ± steroids |
Feature | Nitrofurantoin-Induced Pulmonary Toxicity | Hypersensitivity Pneumonitis | Idiopathic Pulmonary Fibrosis |
---|---|---|---|
Cause | Nitrofurantoin exposure | Inhaled organic or chemical antigens | Idiopathic |
Symptoms | Dry cough, dyspnea | Cough, dyspnea, fever, chills | Dry cough, dyspnea, fatigue, nail clubbing |
Imaging Findings | Ground-glass opacities, occasional fibrosis | Ground-glass opacities, centrilobular nodules, mosaic attenuation | Fibrosis, honeycombing, enlarged mediastinal lymph nodes |
Histopathology | Inflammation and fibrosis (chronic cases) | Inflammation, fibrosis, granulomas | Fibrosis with usual interstitial pneumonia pattern |
Diagnostic Tools | Clinical history, imaging response to drug cessation | Serum IgG for antigen exposure, biopsy showing granulomas | Clinical and radiologic findings, lung biopsy |
Prognosis | Typically reversible upon drug cessation | Variable; can improve if antigen exposure is removed | Progressive, poor prognosis |
Treatment Response | Rapid improvement (acute cases within 24 h, chronic within 3 months) | Improvement if antigen exposure is removed, but can be chronic | Poor response to treatment, progressive decline |
Strategy | Description |
---|---|
Risk Assessment | Identify high-risk populations, including elderly patients and those with renal impairment. |
Renal Function Monitoring | Assess eGFR before prescribing; avoid use in patients with eGFR < 30 mL/min to prevent drug accumulation and toxicity. |
Baseline and Periodic Monitoring | Evaluate renal, hepatic, and pulmonary function regularly, especially in long-term users, to detect early signs of toxicity. |
Alternative Treatments for Recurrent UTIs | Consider alternative antibiotics (e.g., trimethoprim-sulfamethoxazole, fosfomycin, or cephalexin) based on resistance patterns and patient needs. |
Non-Antibiotic Preventive Measures | Utilize probiotics, increased hydration, dietary modifications, cranberry supplements, and D-mannose to reduce UTI recurrence. |
Education and Awareness | Train healthcare providers on risk factors, prescribing guidelines, and monitoring protocols to ensure safe use. |
Shared Decision-Making | Involve patients in treatment decisions, discussing risks, benefits, and alternative options to promote informed choices. |
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Kaye, A.D.; Shah, S.S.; LaHaye, L.; Hennagin, J.A.; Ardoin, A.K.; Dubuisson, A.; Ahmadzadeh, S.; Shekoohi, S. Nitrofurantoin-Induced Pulmonary Toxicity: Mechanisms, Diagnosis, and Management. Toxics 2025, 13, 382. https://doi.org/10.3390/toxics13050382
Kaye AD, Shah SS, LaHaye L, Hennagin JA, Ardoin AK, Dubuisson A, Ahmadzadeh S, Shekoohi S. Nitrofurantoin-Induced Pulmonary Toxicity: Mechanisms, Diagnosis, and Management. Toxics. 2025; 13(5):382. https://doi.org/10.3390/toxics13050382
Chicago/Turabian StyleKaye, Alan D., Shivam S. Shah, Leon LaHaye, John A. Hennagin, Anna K. Ardoin, Alexandra Dubuisson, Shahab Ahmadzadeh, and Sahar Shekoohi. 2025. "Nitrofurantoin-Induced Pulmonary Toxicity: Mechanisms, Diagnosis, and Management" Toxics 13, no. 5: 382. https://doi.org/10.3390/toxics13050382
APA StyleKaye, A. D., Shah, S. S., LaHaye, L., Hennagin, J. A., Ardoin, A. K., Dubuisson, A., Ahmadzadeh, S., & Shekoohi, S. (2025). Nitrofurantoin-Induced Pulmonary Toxicity: Mechanisms, Diagnosis, and Management. Toxics, 13(5), 382. https://doi.org/10.3390/toxics13050382