An uncomplicated urinary tract infection (UTI) is a bacterial infection of the bladder and associated structures. Patients with uncomplicated UTIs have no structural abnormality of the urinary tract and no comorbidities such as diabetes, an immunocompromised state, recent urologic surgery, or pregnancy.Antimicrobial resistance is increasing worldwide, resulting in infections that are more difficult to treat and associated with higher mortality, morbidity and cost ^1-3Uncomplicated urinary tract infections are among the most frequently occurring infections in the United States, resulting in an estimated 8 million office visits and 1 million hospital admissions each year^4,5,6. Between 40% and 50% of women have reported having at least one urinary tract infection in their lives⁷.

Risk factors for urinary tract infections in women include frequent sexual intercourse, lack of urination after intercourse, use of a diaphragm, use of a spermicide, and a history of recurrent urinary tract infections^8,9. Although the long-term adverse effects associated with uncomplicated urinary tract infections appear to be minimal, if left untreated, urinary tract infections can interfere with daily living. One large national survey of urinary isolates from 2015 found resistance rates in As many as 80% of uncomplicated urinary tract infections are caused by Escherichia coli, followed by Staphylococcus saprophyticus in as many as 5% to 15% of cases. Enterococci, Klebsiella species and Proteus mirabilis account for a small percentage of overall infections¹⁰.Limited Australian data are available for antimicrobial resistance rates in community-onset urinary tract infections^11,12.Because most uncomplicated urinary tract infections are treated empirically,Consequently, empiric therapy is more likely to fail.

This has resulted in increasing numbers of patients with uncomplicated urinary tract infections requiring hospitalisation for intravenous antibiotics because there are no oral treatment options .So,it is important for clinicians to recognize resistance patterns of uropathogens in the community to ensure that the most appropriate antimicrobial agent is chosen. Recent reports have demonstrated that the emergence of resistant uropathogens has had a tremendous effect on empiric therapy^{10,13,14,15,16}. The most dramatic increase in resistance in the past few years has been to trimethoprim-sulfamethoxazole.

A recent study that evaluated outpatient women aged 18 to 50 years in the Seattle area who had acute cystitis demonstrated that the prevalence of E coli resistance to trimethoprim and trimethoprim-sulfamethoxazole rose from 9% to 18% in 1992 and 1996, respectively. This study also showed that the resistance of E coli to β-lactams such as ampicillin and first-generation cephalosporins was 34% and 28%, respectively¹³. To further delineate resistance in geographic regions, a national survey was conducted to analyze antimicrobial susceptibilities of urine isolates from female outpatients in 1998. The highest percentage of resistance to E coli (22%) was seen in the western United States (California, Oregon, and Washington), in contrast to the Northeast where resistance was lowest (10%)¹⁵. recently older ‘forgotten’ drugs are being re-explored for the treatment of cystitis^17-20. Nitrofurantoin and fosfomycin are old antibiotics. They share some important properties including high concentrations in the urinary tract, a minimal impact on gastrointestinal flora and a low propensity for resistance. Nitrofurantoin is available as Macrodantin (every 6 hours) and Macrobid (twice daily), with minimal side effects like malaise and rare pulmonary fibrosis. It’s contraindicated with creatinine clearance <50 mL/min due to inadequate urinary concentrations.Fosfomycin  is a single-dose treatment for uncomplicated UTIs, inhibiting bacterial wall synthesis. It has a broad spectrum but doesn’t cover S. saprophyticus and may cause diarrhoea, nausea, and esophageal discomfort.

AIM

The primary aim of this study is to evaluate the efficacy and safety of nitrofurantoin and fosfomycin in the treatment of uncomplicated urinary tract infections (UTIs). Specifically, the study seeks to:

This study was a prospective observational study conducted from Nov 23 to April 24 at the Gynaecology department, Sai samarth hospital and research centre, khargone, MP. It is done by dividing participants into two equal groups of 50. Group A receives nitrofurantoin, while Group B is treated with fosfomycin.  Inclusion criteria, such as having a urinary tract infection, and exclude those with contraindications or severe comorbidities.

Administer nitrofurantoin according to standard dosing guidelines, such as 100 mg orally twice daily for 7 days, and fosfomycin as a single 3-gram dose. Monitor primary outcomes including clinical cure rates, symptom reduction, and microbiological eradication. Assess safety by recording adverse events and side effects. Collect baseline data on participants’ demographics and clinical characteristics, and perform follow-up evaluations at set intervals (e.g., 1 week, 1 month).

Table1: symptoms of UTI

Nitrofurantoin (Group A) shows higher instances of burning, increased urinary frequency, and pus in both age groups compared to Fosfomycin (Group B), which, however, exhibits more frequent sonographic findings of cystitis, especially in the older age group.

Table 2: Previous history of UTI

Nitrofurantoin (Group A) has a total of 15 cases with a history of UTI across both age groups, while Fosfomycin (Group B) had a total of 23 cases, with higher incidence in the older age group.

Table 3:Side effects of drugs

Nitrofurantoin (Group A) shows a total of 8 cases of nausea and 17 cases of diarrhea, while Fosfomycin (Group B) shows 3 cases of nausea and 29 cases of diarrhea, with no reported body aches or intolerances for either group.

Table 4: Recurrence of symptoms F/U after 7 days

Nitrofurantoin (Group A) has a total of 13 cases, with 12 in the 46-60 age group, while Fosfomycin (Group B) has a total of 3 cases, with 2 in the 20-45 age group and 1 in the 46-60 age group.

Table 5:Re-infection in UTI

Nitrofurantoin (Group A) has a total of 10 cases of re-infection, with 8 in the 46-60 age group, while Fosfomycin (Group B) has a total of 3 cases, with 2 in the 20-45 age group and 1 in the 46-60 age group.

Table 6: Treatment failure in UTI

Nitrofurantoin (Group A) shows a total of 5 cases of treatment failure, with 3 in the 46-60 age group, while Fosfomycin (Group B) has no cases of treatment failure.

In our study, we compared the efficacy and side effects of Nitrofurantoin and Fosfomycin for treating urinary tract infections (UTIs) by analysing several parameters including symptoms, side effects, and treatment outcomes.

In our study Nitrofurantoin (Group A) and Fosfomycin (Group B) demonstrated varied results in symptom relief. For the symptom of burning, Nitrofurantoin had 43 cases compared to 49 in the Fosfomycin group. This indicates that Fosfomycin might have a slight advantage in alleviating this discomfort. Increased frequency of urination was reported in 12 cases for Nitrofurantoin and 14 cases for Fosfomycin, showing a slightly higher frequency in the Fosfomycin group. Lower abdominal pain was more prevalent in the Fosfomycin group (28 cases) compared to Nitrofurantoin (19 cases). Sonography showing cystitis was observed in 2 cases for both Nitrofurantoin and Fosfomycin, indicating that neither drug had a significant impact on this diagnostic outcome.Anita K, et al (2019)²¹  the common complaint of the patients was reported by 60% of the patients in both the study groups. The next common complaint was burning micturition, which was observed in 40% in the Fosfomycin group and 51.4% in the Nitrofurantoin group. Pain in the abdomen was the next most common complaint in both the treatment groups. It was reported by 37.1% in the Fosfomycin group and 28.6% in the Nitrofurantoin group. Less common complaints were urgency, fever and dysuria.Huttner and colleagues²² did not report specific clinical complaints of their patients, but the median number of symptoms was 3, ranging from 2 to 4. We have defined clinical improvement as cure (complete resolution of symptoms and signs of UTI without prior failure), failure (need for additional or change in antibiotic treatment due to a UTI or discontinuation due to lack of efficacy or persistence of symptoms). Stein defined clinical response as cure (elimination of all prê therapy symptoms), improvement (most but not all symptoms improved or absent), or failure (not improved from the initial assessment) . In both the treatment groups in their study, 87% of the patients had symptoms for less than 48 hours.

In our study Both groups had similar rates of previous history of UTIs, with Nitrofurantoin (15 cases) and Fosfomycin (23 cases). This suggests that prior history did not significantly influence the treatment outcomes in this study.

In our study Regarding side effects, Nitrofurantoin showed a higher incidence of nausea (8 cases) compared to Fosfomycin (3 cases). Diarrhoea was more frequent in the Fosfomycin group (29 cases) than in the Nitrofurantoin group (17 cases), indicating that Fosfomycin might be more likely to cause gastrointestinal discomfort. Neither drug showed a significant incidence of body ache or intolerance.Anita K, et al, (2019)²¹ seven patients from the Fosfomycin group (20%) reported side effects, while only four patients in the Nitrofurantoin group (12%) reported any side effects. In the Fosfomycin group, one reported gastritis and nausea, and six patients reported loose stools. In the Nitrofurantoin group, one patient reported gastritis and three reported nausea. Whereas, in the randomised trial by Huttner²², 21 of 248 (8%) and 16 of 247 (6%) in the nitrofurantoin and fosfomycin groups, respectively, reported at least one adverse event. Stein and colleagues²³ found that the most common adverse effects related to fosfomycin treatment were diarrhoea (2.4%), vaginitis (1.8%), and nausea (0.8%) . Common side effects associated with nitrofurantoin treatment were nausea (1.6%), vaginitis (1.6%), dizziness (0.8%), and diarrhoea (0.8%). GI adverse events were reported in 3.9% of fosfomycin recipients among women with an uncomplicated lower UTI. Moreover, in a large noncomparative study in 387 women and men with uncomplicated UTIs who received single-dose fosfomycin, adverse events were reported in 4.9 % of patients, with diarrhoea, nausea and vomiting occurring in 3.1, 1.3 and 0.5 % of patients, respectively.

In this study Re-infection rates were slightly higher with Nitrofurantoin (10 cases) compared to Fosfomycin (3 cases), which might suggest a higher likelihood of re-infection with Nitrofurantoin. Shafrir, Asher et al (2023)²⁴ compared the failure rates of fosfomycin and nitrofurantoin for uncomplicated urinary tract infections. We used Meuhedet Health Services' large database to collect data on all female patients, older than 18 years, who were prescribed either antibiotic during 2013–2018. Treatment failure was a composite endpoint of hospitalisation, emergency-room visit, IV antibiotic treatment, or prescription of a different antibiotic, within seven days of the initial prescription. Reinfection was considered when one of these endpoints appeared 8–30 days following the initial prescription. We found 33,759 eligible patients. Treatment failure was more common in the fosfomycin group than the nitrofurantoin group (8.16% vs. 6.87%, p-value &lt; 0.0001). However, reinfection rates were higher among patients who received nitrofurantoin (9.21% vs. 7.76%, p-value &lt; 0.001). Among patients younger than 40 years, patients treated with nitrofurantoin had more reinfections (8.68% vs. 7.47%, p value = 0.024). Treatment failure rates were mildly higher in patients treated with fosfomycin, despite having less reinfections. We suggest that this effect is related to a shorter duration of treatment (one vs. five days) and encourage clinicians to be more patient before declaring fosfomycin failure and prescribing another antibiotic.

In our study Treatment failure was minimal for both drugs, with Nitrofurantoin showing 5 cases of treatment failure and Fosfomycin none.Shafrir, Asher et al (2023)²⁴ Treatment failure was more common among those who were treated with fosfomycin than among those who were treated with nitrofurantoin (8.16% vs. 6.87%, p value < 0.0001). However, reinfection rates were higher among patients who received nitrofurantoin (9.21% vs. 7.76%, p-value < 0.001)

Nitrofurantoin is suitable for uncomplicated lower urinary tract infections. Bacterial resistance is uncommon.Fosfomycin is a safe and effective antibacterial drug for urinary tract infections, but its use should be limited to delay the development of resistance. It will prove to be a useful treatment option for community-based treatment of patients with resistant organisms.

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