Fatal Nitrofurantoin-Induced Pulmonary Toxicity: A Potentially Preventable Medical Error

The majority of patients affected with nitrofurantoin pulmonary toxicity are elderly women [1]. The proposed mechanism of toxicity is either idiosyncratic oxydant-mediated tissue injury by nitrofurantoin metabolites causing depletion of cellular glutathione (chronic form) or by immunological response induced by nitrofurantoin metabolites acting as heptanes and resulting a hypersensitivity reaction (acute form) [2]. Acute and chronic hepatic toxicity similar in pattern to pulmonary toxicity have been reported. Clinical manifestations of nitrofurantoininduced pulmonary toxicity can be acute, sub-acute and chronic [3]. Acute presentation is the most common form and is characterized by fever, rash, arthralgia, non-productive cough, chest pain, and dyspnea within days to weeks after the exposure. Recurrence of acute toxicity has been described with rechallenge of nitrofurantoin in a patient who did not tolerate it initially [4,5]. Sub-acute presentations have more insidious onset of symptoms, with most cases having received nitrofurantoin for several weeks to months. Chronic presentation and pulmonary fibrosis is typically seen in patients on nitrofurantoin therapy for several months or years with usual presenting symptoms of progressive dyspnea, fatigue and cough. Fulminant pulmonary hemorrhage presenting with hemoptysis and respiratory failure has also been described [6]. Here we report an elderly female with subacute pulmonary symptoms after exposure to nitrofurantioin who succumbed to death from rapidly progressive respiratory failure.