Unrecognized Interstitial Lung Disease as a Result of Chronic Nitrofurantoin Use

Abstract

Drug-induced interstitial lung disease is a rare condition attributed to several medications, including antimicrobial agents such as amphotericin B, anti-inflammatory agents such as methotrexate, biologic agents such as bevacizumab, and cardiovascular agents and chemotherapeutic agents. We describe the case of a 73-year-old female who developed interstitial lung disease following chronic use of nitrofurantoin for a urinary tract infection (UTI). The patient was taking nitrofurantoin 100 mg capsules twice daily for approximately 3 years. She presented to the hospital with complaints of a persistent dry cough that started 2 years previously. Her chest radiograph revealed bilateral reticular opacities and some atelectasis. Computed tomography of the chest demonstrated development of subpleural reticular opacities with minimal honeycombing. The patient had a severe restrictive defect on her pulmonary function tests, with a significant reduction in her carbon monoxide diffusion capacity. Multiple infectious disease and autoimmune tests were negative. Utilizing the algorithm of Naranjo (score of 9), it was determined that chronic use of nitrofurantoin was the definite cause of the patient’s interstitial lung disease. Nitrofurantoin was discontinued and she was treated with oxygen and started on an oral steroid, both of which were continued permanently once discharged. Upon discharge, the patient was maintained on 5 L of oxygen at rest and 10 L of oxygen when ambulating. Unfortunately, her lung disease ultimately resulted in her demise several months after her diagnosis. This case report illustrates the importance of rapid recognition of drug-induced lung injuries and discontinuation of the offending agent.

Acute lung toxicity by nitrofurantoin

“…Nitrofurantoin is a common antibiotic used for the treatment of uncomplicated UTIs. The risk of an adverse reaction to nitrofurantoin increases with the patient’s age and is higher in women than in men 5 7 8. The first case of acute pulmonary toxicity due to nitrofurantoin was reported by Israel and Diamond in 1962, demonstrating a clear cause-and-effect relationship by intentional rechallenge with the drug 5…”

Nitrofurantoin-Induced Pulmonary Toxicity: Always Review the Medication List

“…Fortunately, severe toxicities are rather rare, occurring in one of 511 patients (0.2%; 95% CI <0.01% to 1.2%) when reviewing seventeen randomized controlled trials [9]. Clinical improvement typically is seen in weeks to months; however, a majority of patients will have some residual lung disease [6,14].…”

“…Physical exam findings are non-specific and can include inspiratory crackles, clubbing, +/- hypoxemia [ 6 ]. Imaging findings in chronic pneumonitis include most commonly a non-dominant pattern of bilateral ground-glass opacities versus less common bilateral asymmetric areas of consolidation with patchy ground-glass opacities versus rare honeycombing [ 6 , 10 , 13 , 14 ]. Of note, pleural effusions are uncommon in chronic pneumonitis as compared to acute hypersensitivity.…”

Drug-Induced Interstitial Lung Disease from a Misdiagnosed Infection

“…2 Nitrofurantoin is commonly used to treat UTIs. [3][4][5] It is usually well tolerated and is the only safe antibiotic in pregnancy. 1 Nitrofurantoin-induced interstitial lung disease (NIILD) is seen in <1% of patients.…”

“…3 With rising bacterial resistance, nitrofurantoin is increasingly used to treat UTIs. [4][5] Although NIILD is rare, nitrofurantoin should only be used in a proven UTI. To minimize the risk of NIILD and bacterial resistance, prophylactic treatment should not exceed 6 months.…”