Chronic Nitrofurantoin-Induced Lung Injury: A Clinical Review and Case Commentary
Introduction
Nitrofurantoin is a commonly prescribed antimicrobial agent primarily used for the treatment and prevention of urinary tract infections (UTIs). Despite its long-standing reputation for efficacy and safety, nitrofurantoin has been associated with a spectrum of pulmonary adverse effects, particularly when used chronically. This article explores the cause, etiology, pathophysiology, epidemiology, clinical presentation, imaging features, treatment, and prognosis of chronic nitrofurantoin-induced lung injury (CNI-LI), supported by a case study of a 93-year-old female patient.
Etiology and Cause
Nitrofurantoin exerts its antibacterial effects by inhibiting bacterial carbohydrate metabolism and interfering with cell wall synthesis. However, when administered chronically, the drug may provoke an immune-mediated or direct cytotoxic response, leading to lung injury. Risk factors include advanced age, prolonged therapy, female sex, and renal insufficiency.
Pathophysiology
The exact mechanism underlying nitrofurantoin-induced lung injury is not fully understood. Proposed mechanisms include:
Hypersensitivity reaction involving eosinophilic infiltration.
Direct toxicity to alveolar epithelial and endothelial cells.
Oxidative stress from reactive intermediates. Chronic injury is often associated with interstitial lung disease patterns, including organizing pneumonia and nonspecific interstitial pneumonia.
Epidemiology
Pulmonary reactions occur in approximately 1 in 5,000 courses of nitrofurantoin, with chronic reactions being less common than acute ones. Most patients are older adults—often postmenopausal women—receiving long-term prophylaxis for recurrent UTIs.
Case Summary
A 93-year-old woman presented with four weeks of dyspnea and dry cough. She had been on daily nitrofurantoin for recurrent UTIs for the past six months. Oxygen saturation was 83% on room air. Pulmonary examination revealed fine inspiratory crackles at the lung apices. Laboratory tests showed neutrophilic leukocytosis without eosinophilia or liver enzyme elevation. Sputum culture and respiratory viral panel were negative.
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| Figure 1: Chest X-ray showing patchy alveolar opacities in the upper lobes. |
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| Figure 2: CT chest revealing bilateral upper lobe-predominant ground-glass opacities and mild bronchiectasis. |
The diagnosis of chronic nitrofurantoin-induced lung injury was made based on radiologic findings and clinical history of prolonged drug exposure. Treatment involved cessation of nitrofurantoin and initiation of prednisone taper.
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| Figure 3. Follow-up chest P-A at two months |
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| Figure 4: Follow-up CT chest at two months demonstrating near-complete resolution of ground-glass opacities and stable bronchiectasis. |
Clinical Presentation
Patients typically present with subacute onset of:
Dyspnea on exertion
Non-productive cough
Hypoxemia
Malaise or low-grade fever (less common)
Physical examination may reveal bilateral fine crackles without peripheral edema or jugular venous distension.
Imaging Features
Imaging findings vary but are crucial for diagnosis:
Chest Radiograph: Upper lobe-predominant patchy alveolar opacities (Figure 1)
Chest CT: Ground-glass and reticular opacities, often with bronchiectasis (Figure 2)
Chronic changes may improve or stabilize with drug cessation (Figures 3 & 4)
Management and Treatment
Immediate cessation of nitrofurantoin is the cornerstone of therapy.
Glucocorticoids (e.g., prednisone) are often used, particularly in severe or non-resolving cases, with tapering over weeks to months.
Supportive care includes supplemental oxygen and monitoring.
Prognosis
Most patients show clinical and radiologic improvement within weeks to months of drug discontinuation.
Residual bronchiectasis or fibrotic changes may persist.
Early recognition and withdrawal of the offending agent are key to preventing permanent damage.
Quiz Questions
Q1. What is the most critical first step in managing chronic nitrofurantoin-induced lung injury?
a) Antibiotics
b) Intravenous loop diuretics
c) Glucocorticoids
d) Cessation of nitrofurantoin
e) Scheduled nebulized bronchodilators
Answer: d) Cessation of nitrofurantoin
Explanation: Discontinuing the offending agent halts further lung injury and allows healing to begin.
Q2. Which radiographic finding is most consistent with chronic nitrofurantoin-induced lung injury?
a) Pleural effusion
b) Lower lobe consolidation
c) Upper lobe ground-glass opacities
d) Cavitary lesions
e) Pneumothorax
Answer: c) Upper lobe ground-glass opacities
Explanation: This pattern, especially in a patient on long-term nitrofurantoin, supports the diagnosis.
Q3. What is the typical timeframe for radiographic improvement after discontinuation of nitrofurantoin and corticosteroid therapy?
a) 24 hours
b) 1 week
c) 1 month
d) 2 months
e) 6 months
Answer: d) 2 months
Explanation: As in the case study, significant radiologic improvement was observed after 2 months.
References
[1] S. Holmberg and B. B. Boman, "Pulmonary reactions to nitrofurantoin," Chest, vol. 79, no. 3, pp. 344–349, 1981.
[2] D. S. Martin and L. E. Douglas, "Chronic pulmonary reactions to nitrofurantoin," JAMA, vol. 244, no. 25, pp. 2723–2725, 1980.
[3] G. J. George et al., "Imaging findings in nitrofurantoin-induced lung injury," Radiographics, vol. 23, no. 2, pp. 513–520, 2003.
[4] P. M. Pavia and H. L. Neff, "Nitrofurantoin toxicity: a rare cause of chronic interstitial pneumonitis," Am J Med, vol. 72, no. 1, pp. 165–172, 1982.
[5] A. Patel and R. C. Sime, "Drug-induced interstitial lung disease: nitrofurantoin and beyond," BMJ Case Rep, 2017.
[6] A. M. Hanson et al., "Reversible lung disease associated with nitrofurantoin," Clin Respir J, vol. 6, pp. 36–41, 2012.
[7] U. S. Food and Drug Administration, "Nitrofurantoin drug label," [Online]. Available: https://www.fda.gov.
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