The Clinical Efficacy of Nitrofurantoin for Treating Uncomplicated Urinary Tract Infection in Adults: A Systematic Review of Randomized Control Trials

Abstract

<b><i>Objective:</i></b> To provide an updated systematic review of randomized control trials (RCTs) to investigate the clinical and microbiological efficacy of nitrofurantoin compared to other antibiotics or placebo for treatment of uncomplicated urinary tract infections (uUTI). A secondary aim is to assess whether nitrofurantoin use is associated with increased side effects compared to other treatment regimens. <b><i>Summary:</i></b> The review was performed according to PRISMA guidelines. We searched 4 databases for articles published from database inception to May 6, 2020: (1) PubMed electronic database of the National Library of Medicine, (2) Web of Science, (3) Embase, and (4) Cochrane Library. Nine RCTs were selected for the review. RCTs were a mixture of double-blind, single-blind, and open-label trials. The most common comparators were trimethoprim-sulfamethoxazole and fosfomycin tromethamine. Overall study quality was poor with a high risk of bias. The clinical cure rates in nitrofurantoin ranged from 51 to 94% depending on the length of follow-up, and bacteriological cure rates ranged from 61 to 92%. Overall the evidence suggests that nitrofurantoin is at least comparable with other uUTI treatments in terms of efficacy. Patients taking nitrofurantoin reported fewer side effects than other drugs and the most commonly reported were gastrointestinal and central nervous system symptoms. <b><i>Key Messages:</i></b> Evidence on the clinical and bacteriological efficacy of nitrofurantoin is sparse, with a lack of new data, and hampered by high risk of bias. Although no firm conclusions can be made on the current base of evidence, the studies generally suggest that nitrofurantoin is at least comparable to other common uUTI treatments in terms of clinical and bacteriological cure. More robust research with well-designed double-blinded RCTs is needed.

Outpatient management of urinary tract infections by medical officers in Nairobi, Kenya: lack of benefit from audit and feedback on adherence to treatment guidelines

“…An additional area of emphasis was the choice of antimicrobial agent. Some guidelines list nitrofurantoin as the empiric treatment of choice because of up to 94% and bacteriological cure rates of up to 92%, as well as lower rates of side effects in comparison to other antibiotics [ 33 ]. The importance is even greater in the local setting of much higher resistance rates for cephalosporins and quinolones than for nitrofurantoin.…”

Similarities in Bacterial Uropathogens and Their Antimicrobial Susceptibility Profile in Diabetics and Their Non-Diabetic Caregivers at a National Diabetes Management and Research Centre, Accra-Ghana

“…It is said to be effective against most Gram-positive and Gram-negative organisms. Clinical cure rates in nitrofurantoin have been reported to range from 51 to 94% depending on the length of follow-up, and bacteriological cure rates range from 61 to 92% [ 63 ]. Therefore, it is not surprising that it is among the most effective antibiotics in this study.…”

Interstitial pneumonitis secondary to long-term nitrofurantoin use with improved clinical course secondary to corticosteroids

“…5 Nitrofurantoin is generally a safe drug that can present with non-severe adverse effects, such as headache, nausea, vomiting, and diarrhea. 5,6 In addition, more rare and serious reactions can occur. The most concerning side effects involve pulmonary toxicity that usually occurs with long-term use.…”

“…7,9 Ground glass opacities can be seen on high resolution chest CT. 9 Biopsy specimens demonstrate interstitial inflammation and alveolar exudates. 6 Chronic lung injury occurs with prolonged use and is seen more often in elderly women. 10 In a review of 921 cases by Holmberg and coauthors, the median onset of symptoms was after more than 12 months of use.…”