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Year : 2022  |  Volume : 11  |  Issue : 5  |  Page : 18-20

Nitrofurantoin-induced interstitial lung disease

Department of General Medicine, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India

Date of Submission01-Oct-2020
Date of Acceptance25-May-2021
Date of Web Publication30-Aug-2022

Correspondence Address:
Mallikarjuna Shetty
Associate Professor, Department of General Medicine, Nizam's Institute of Medical Sciences, Hyderabad 500 082, Telangana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/JCSR.JCSR_86_20

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We report the case of a 55-year-old woman diagnosed with interstitial lung disease due to long-term nitrofurantoin therapy that was administered for recurrent urinary tract infection. Despite distorted pulmonary parenchymal architecture and patchy fibrosis confirmed by computed tomography of the thorax, the symptoms and radiographic findings disappeared within 3 months after the administration of prednisone. This case shows that nitrofurantoin-induced lung disease may run a benign course and respond favourably to corticosteroids, even when there is radiographic evidence of established lung fibrosis. This case report highlights the need for vigilance of pulmonary toxicity in patients taking long-term nitrofurantoin therapy.

Keywords: Drug toxicity, interstitial lung disease, nitrofurantoin

How to cite this article:
Salman M, Marikanty A, Reddy SK, Shetty M. Nitrofurantoin-induced interstitial lung disease. J Clin Sci Res 2022;11, Suppl S1:18-20

How to cite this URL:
Salman M, Marikanty A, Reddy SK, Shetty M. Nitrofurantoin-induced interstitial lung disease. J Clin Sci Res [serial online] 2022 [cited 2022 Dec 7];11, Suppl S1:18-20. Available from: https://www.jcsr.co.in/text.asp?2022/11/5/18/355078

  Introduction Top

Nitrofurantoin is a frequently used antibiotic for treatment and prophylaxis against urinary tract infections (UTI). It is a relatively safe medication with rare side effects. First described in 1957, pulmonary toxicity with nitrofurantoin has a incidence of 1 in 5000 first administrations for acute severe disease.[1] Chronic pulmonary reactions are 10–20 times less frequent than acute reactions.[2]

Sub-acute/chronic pulmonary reactions of this type usually occur in elderly; onset is insidious and interstitial lung disease (ILD) and fibrosis may develop. High-resolution computed tomography (HRCT) in patients with interstitial pneumonia is characterised by a predominantly reticular pattern, often related to the presence of established pulmonary fibrosis, particularly when associated with distorted parenchymal architecture.[3]

We report the case of a woman on long-term nitrofurantoin therapy who developed ILD with radiographic findings suggestive of pulmonary fibrosis which resolved after drug withdrawal and corticosteroid therapy. Describing this relatively rare adverse reaction to a commonly prescribed antibiotic may remind clinicians to consider drug toxicity in patients who develop new onset of pulmonary symptoms while taking nitrofurantoin.

  Case Report Top

A 55-year-old woman was admitted with progressively worsening dyspnoea, even on minimal exertion, and dry cough, for the past 6 months. She was a diabetic, hypertensive and was treated for acute pyelonephritis 1 year back. She was a non-smoker and had been receiving nitrofurantoin (100 mg/day) intermittently for the past 12 months as prophylaxis for recurrent UTI. She had not been exposed to toxic substances, was not taking any other medications, and denied drug abuse. She had no fever, wheezing, chest pain, joint pains, rash and oedema.

The physical examination revealed tachypnoea and tachycardia, but there was no cyanosis or clubbing. Abundant Velcro like end inspiratory crackles in the lower two-thirds of both lungs and an ejection systolic murmur at base of the heart were audible on auscultation. All other findings of the physical examination were normal.

Arterial blood gas analysis showed arterial oxygen tension (PaO2) of 80 mm Hg on room air. The haematology and biochemical parameters were normal. Anti-nuclear antibodies, rheumatoid factor, anti-neutrophil cytoplasmic antibodies, circulating immune complexes, antitopoisomerase I (anti-Scl-70), anti-Ro and anti-La antibodies were negative. Microbiological studies and Mantoux test were negative.

The chest radiograph was normal. HRCT showed patchy changes of parenchymal fibrosis, bilaterally ground-glass opacities with areas of intralobular septal thickenings, subtle architectural distortion affecting both lungs prominent in the left lower lobe with hazy pleural interface. The sub pleural areas of parenchymal fibrosis were noted affecting segments of lingual [Figure 1]. No pleural effusion or enlarged lymph nodes was observed. The pulmonary function tests, electrocardiography and two-dimensional echocardiography were normal. Bronchoscopy and bronchoalveolar lavage fluid analysis showed no abnormality.
Figure 1: Non-contrast enhanced computed tomography of the chest showing areas of ground-glass haziness with inter-lobular septal thickening noted in the left lower lobe

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Based on the findings, a diagnosis of nitrofuratoin-induced ILD was made, and the drug was withdrawn. Oral prednisolone therapy (1 mg/Kg/day) was started, along with appropriate management of diabetes and hypertension. The patient's respiratory symptoms and parameters improved significantly within a few days starting from the second day. The patient was discharged with tapering doses. At 3 months post-admission, lung sounds were normal and HRCT confirmed complete resolution of the pulmonary infiltrates and fibrosis [Figure 2]. Six months later, she was asymptomatic, all respiratory function tests were normal and no radiographic evidence of recurrence had been detected.
Figure 2: Repeat non-contrast enhanced computed tomography of the chest of the same patient in [Figure 1] showing significant reduction in ground-glass haziness and interlobular septal thickening as compared to previous scan. Mild subpleural fibrosis is noted in the left lower lobe

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  Discussion Top

Nitrofurantoin is a synthetic nitrofuran antimicrobial used for more than 50 years in UTIs. Long-term use is known to cause serious adverse effects including pulmonary and hepatic toxicity, renal failure and peripheral neuropathy.[2] Nitrofurantoin-induced ILD has been reported from a number of countries. In New Zealand, Centre of Adverse Reaction Monitoring Database revealed that 34% of the nitrofurantoin adverse reactions are associated with pulmonary damage.[2] In Australia, Adverse Drug Reactions Advisory Committee reported 46 nitrofurantoin-induced pulmonary reactions from 1995 to 2004; 87% of them were related to chronic nitrofurantoin use with exposure between 8 months and 16 years.[2] Mayo Clinic 2005 from the United States reviewed 18 patients with NIILD 1997–2002.[4]

Nitrofurantoin-induced pulmonary toxicity is categorised either as acute or chronic in presentation. The presentations of acute pulmonary toxicity include fever, chills, cough, dyspnoea, elevated erythrocyte sedimentation rate, eosinophilia and chest pain and diffuse pulmonary infiltrates on chest radiograph. The development of acute toxicity most often occurs within 3–8 days of nitrofurantoin initiation.

Unlike the acute form, chronic nitrofurantoin-induced pulmonary toxicity has a slow, insidious onset, often presenting months to years after treatment is initiated. Middle aged and older women dominate the patient population likely due to the susceptibility to recurrent UTI in this sex and age group.[5] As in this case, patients typically present with gradually increasing shortness of breath and non-productive cough with bilateral, scattered crackles on physical examination and diffuse bilateral interstitial infiltrates on chest radiograph and bilateral patchy ground glass attenuation and fibrosis on chest HRCT. It does not appear that acute toxicity leads to chronic toxicity or that chronic lesions follow an acute reaction to nitrofurantoin. Currently, the mechanism of nitrofurantoin-induced pulmonary toxicity has not fully been elucidated, but chronic toxicity is thought to be related to direct oxidative damage to the lungs whereas acute due to hypersensitivity reaction.[2]

Around 10%–30% of patients show some kind of response to corticosteroids, usually after 2 or 3 months of treatment, although complete remissions are rare. Three cases of radiographic resolution of established, apparently irreversible pulmonary fibrosis in elderly patients who had received nitrofurantoin therapy for 1–3 years have been recently described.[1],[3] One of them had a histologic study to confirm the diagnosis.[1]

Our patient presented radiographic evidence that suggested irreversible pulmonary fibrosis and her clinical symptoms improved rapidly from day 2 and radiographic findings resolved within 3 months, following corticosteroid therapy. To the best of our knowledge, this is the first patient in whom radiological confirmed rapid recovery from severe nitrofurantoin-induced ILD is being reported from our country.

In conclusion, pulmonary toxicity should be suspected and closely monitored in patients on long-term nitrofurantoin therapy, and the drug should be discontinued at the first sign of any abnormalities. HRCT is a useful for detecting fibrotic response and for assessing the reversibility of interstitial lesions following therapy. Clinical improvement tends to be rapid, but complete radiographic resolution may be prolonged. Corticosteroid treatment should be initiated as the earliest because radiographic changes caused by secondary to pulmonary fibrosis can improve or even resolve completely, as in our case.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Viejo MA, Fernández Montes A, Montes JV, Gómez-Román JJ, Ibarbia CG, Hernández JL. Rapid resolution of nitrofurantoin-induced interstitial lung disease. Arch Bronconeumol 2009;45:352-5.  Back to cited text no. 1
Medsafe. Prescriber Update Articles. Pulmonary Reactions with Nitrofurantoin; May 2002. Available from: http://www.medsafe.govt.nz/profs/PUarticles/nitrofurant.htm.  Back to cited text no. 2
Sheehan RE, Wells AU, Milne DG, Hansell DM. Nitrofurantoin-induced lung disease: Two cases demonstrating resolution of apparently irreversible CT abnormalities. J Comput Assist Tomogr 2000;24:259-61.  Back to cited text no. 3
Lin DC, Bhally H. Nitrofurantoin-induced interstitial lung disease. N Z Med J 2007;120:U2753.  Back to cited text no. 4
Holmberg L, Boman G, Böttiger LE, Eriksson B, Spross R, Wessling A. Adverse reactions to nitrofurantoin. Analysis of 921 reports. Am J Med 1980;69:733-8.  Back to cited text no. 5


  [Figure 1], [Figure 2]


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