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Nitrofurantoin improves clinical resolution, bacteriologic success in women with UTI

Elaine Soliven
14 May 2018

The use of nitrofurantoin may improve clinical resolution and bacteriologic success rates in women with uncomplicated lower urinary tract infection (UTI) compared with fosfomycin, according to a recent study.

“Five-day nitrofurantoin may be a better alternative to single-dose fosfomycin [as the first-line therapy] for treating uncomplicated UTI in women,” said the researchers.

This open-label, multicentre clinical trial involved 513 non-pregnant women (median age 44 years) who had at least one symptom of lower UTI (eg, dysuria, frequency, urgency, or suprapubic tenderness) and a positive urine dipstick test result (to detect the presence of nitrites or leukocyte esterase). Participants were randomized to receive oral nitrofurantoin (100 mg thrice a day for 5 days; n=255) or fosfomycin (single dose of 3 g; n=258). Urine cultures were collected at every hospital visit, and patients were assessed every 14 and 28 days after therapy completion. [JAMA 2018;319:1781-1789]

Compared with women who received fosfomycin, women treated with nitrofurantoin experienced a significantly higher rate of clinical resolution (defined as complete resolution of signs and symptoms of UTI without prior failure) at 14 days (75 percent vs 66 percent; p=0.03) and 28 days (70 percent vs 58 percent; p=0.004) after therapy completion.

A higher rate of bacteriologic success (defined as eradication of the infecting strain with no recurrence of bacteriuria) was also noted in women who received nitrofurantoin vs fosfomycin at 14 days (82 percent vs 73 percent; p=0.04) and 28 days (74 percent vs 63 percent; p=0.04) after therapy completion.

Of the 377 women who had a positive urine culture at baseline (≥103 colony-forming units/mL or detection of at least one bacterium), Escherichia coli (E. coli) was the most predominant bacterium (61 percent), followed by Klebsiella spp (7 percent), Enterococcus spp (7 percent), and Proteus spp (5 percent).

In a post hoc analysis, women with E. coli infections treated with nitrofurantoin achieved a significant improvement in the rates of clinical resolution (78 percent vs 50 percent; p<0.001) and bacteriologic success (72 percent vs 58 percent; p=0.03) compared with those treated with fosfomycin.

In addition, there was a nonsignificant trend towards a lower incidence of pyelonephritis with nitrofurantoin compared with fosfomycin (0.4 percent vs 2 percent; p=0.22).

“Given increasing antimicrobial resistance … the use of nitrofurantoin and fosfomycin has increased since guidelines began recommending them as first-line therapy for [uncomplicated] lower UTI,” the researchers noted.

“Although patients taking nitrofurantoin experienced superior clinical and microbiologic outcomes, the drug’s overall response rate in this trial was [still] lower than anticipated given earlier reported success rates of up to 90 percent … The open[-label] design may have introduced some level of measurement bias given a subjective primary endpoint,” the researchers said.

“[I]n this trial of acute uncomplicated [lower UTI] with drug-susceptible uropathogens, the jury has deliberated. The verdict is in … The preponderance of evidence described by [the researchers] suggests that nitrofurantoin may have better clinical effectiveness than fosfomycin for the treatment of acute uncomplicated [UTI] among middle-aged women. [Moreover,] in regions of the world where nitrofurantoin susceptibility is preserved, particularly for E. coli, nitrofurantoin can be the agent of choice,” wrote Drs Rupak Datta and Manisha Juthani-Mehta, from the Department of Internal Medicine at Yale School of Medicine in New Haven, Connecticut, US, in an editorial, highlighting the need for future trials assessing various treatments of multidrug-resistant uropathogens. [JAMA 2018;319:1771-1772]
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Tristan Manalac, 09 Oct 2018
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