Long term nitrofurantoin induced interstitial lung disease: a case series and literature review

Main Article Content

Samiha Naureen
Simon Hart
Nadia Jawad
Nuala Kennan
Shoaib Faruqi

Keywords

Nitrofurantoin, Interstitial Lung Disease, Radiology

Abstract

Background and aim: In the UK, prophylactic use of nitrofurantoin is recommended in women who have 3 or more UTI per year. Reported cases of nitrofurantoin-induced pulmonary toxicity are limited and the exact mechanism of chronic nitrofurantoin induced lung reaction is unclear. In England, the national trend for prescribing Nitrofurantoin has gone up significantly in the last 10 years. We reviewed 10 cases of nitrofurantoin-induced pulmonary fibrosis diagnosed in last 8 years at our ILD Service. We aimed to reviewe patient demographics, time to presentation, lung function and imaging characteristics. Methods: We reviewed our ILD database from the year 2012 to 2020. 10 patients were identified diagnosed as Nitrofurantoin Induced Interstitial Lung Disease. All the cases were reviewed in MDT comprising Radiologists and clinicians with interest for ILD. We documented age, sex, initial renal function, eosinophil count, spirometry and radiology findings. In this case series, we focus on various CT findings and reversibility of radiological abnormality following cessation of Nitrofurantoin. Results: The mean age of our patient cohort is 80 years and all were female. The mean time to presentation from prescription was 17 months. Pre-treatment mean eGFR was 76ml/min/1.73m2.7 out of 10 patients had CT findings of ground glass opacity and traction bronchiectasis. 4 patients were treated with prednisolone. The patients in this series improved symptomatically with or without treatment with steroid following cessation of nitrofurantoin therapy, but irreversible changes in the chest imaging may contribute to long term morbidity. Conclusions: Cautious counselling should be undertaken prior to nitrofurantoin prescription regardless of renal function.


 

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References

1. Skeoch S, Weatherley N, Swift A et al. Drug-Induced Interstitial Lung Disease: A Systematic Review. J Clin Med 2018 Oct 15;7(10):356. doi: 10.3390/jcm7100356.
2. Price JR, Guran LA, Gregory WT, McDonagh MS. Nitrofurantoin vs other prophylactic agents in reducing recurrent urinary tract infections in adult women: a systematic review and meta- analysis. Am J Obstet Gynecol 2016;215(5):548-60.
3. Hammond A, Stuijfzand B, Avison MB, Hay AD. Antimicrobial resistance associations with national primary care antibiotic stewardship policy: Primary care-based, multilevel analytic study. PLoS One. 2020 May 14;15(5):e0232903. doi: 10.1371/journal.pone.0232903. PMID: 32407346; PMCID: PMC7224529
4. Boyd MR. Metabolic activation and lung toxicity: a basis for cell-selective pulmonary damage by foreign chemicals. Environ Health Perspect 1984;55:47-51. doi:10.1289/ehp.845547.
5. Marshall ADL, Dempsey OJ. Is nitrofurantoin lung on the increase? BMJ 2013;346: f3897. doi: 10.1136/bmj.f3897.
6. Urinary Tract Infection (Recurrent): Antimicrobial prescribing. NICE guidelines, May 2018. https://www.nice.org.uk/guidance/ng112/documents/draft-guideline
7. Nitrofurantoin now contraindicated in most patients with an estimated glomerular filtration rate (eGFR) of less than 45 ml/min/1.73m2. GOV.UK, 12 February 2015.https://www.gov.uk/drug-safety-update/nitrofurantoin-now-contraindicated-in-most-patients-with-an-estimated-glomerular-filtration-rate-egfr-of-less-than-45-ml-min-1-73m2.
8. Tatley, M. Pulmonary Reactions with Nitrofurantoin. MEDSAFE- New Zealand Medicines and Medical Devices Safely Authority Prescriber Update 2002;23(2): 24-25. https://medsafe.govt.nz/profs/puarticles/nitrofurant.
9. Boyd MR. Metabolic activation and lung toxicity: a basis for cell-selective pulmonary damage by foreign chemicals. Environ Health Perspect 1984;55:47-51. doi:10.1289/ehp.845547.
10. Vahid B, Wilderore B. Nitrofurantoin pulmonary toxicity: a brief review. The Internet Journal of Pulmonary Medicine 2005 ;Volume 6 Number 2.
11. Chin AJ, Rashid S, Gharibeh TR, Kibbe PS, Wynbrandt JH. Interstitial lung disease secondary to long-term nitrofurantoin use. Am J Case Rep. 2020;21:e920386. Published 2020 Apr 2. doi:10.12659/AJCR.920386