A 2023 clinical consensus by the American College of Obstetricians and Gynecologists (ACOG) Committee explored the management of urinary tract infections (UTIs) in pregnant individuals. The panel stated that choice of antibiotic therapy depends not only on culture results but also on susceptibility patterns and safety profiles, and includes nitrofurantoin, β-lactams, sulfonamides, and fosfomycin. Fosfomycin is dosed at 3 grams orally once as part of its treatment regimen. [1]
The typical treatment duration for asymptomatic bacteriuria (ASB) is generally 5–7 days, which reflects the standard duration chosen in most studies. Fosfomycin is an exception and has demonstrated good efficacy as a single-dose treatment for ASB and symptomatic acute cystitis, making it a viable option for 1-day treatment. While 3-day treatment courses are recommended and commonly used for acute cystitis in nonpregnant women, there is a lack of studies evaluating a 3-day course for ASB. [1]
Additionally, there is a lack of substantial evidence supporting a 3-day treatment regimen for acute cystitis during pregnancy. Nevertheless, studies evaluating single-dose fosfomycin against longer antibiotic courses for UTIs suggest that the single-dose approach offers similar clinical outcomes and could enhance patient compliance. Furthermore, preliminary research has not shown any increased risk of adverse pregnancy outcomes related to fosfomycin, indicating its potential as a safe treatment option. However, caution is advised when considering nitrofurantoin and fosfomycin if there is uncertainty in differentiating cystitis from pyelonephritis, due to their limited efficacy in achieving therapeutic tissue concentrations in the kidney. [1]
The 2019 update of the Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria by the Infectious Diseases Society of America (IDSA) highlighted that fosfomycin, administered as a single dose, is effective in eliminating bacterial presence in the urine. However, its clinical use during pregnancy has been limitedly evaluated, raising concerns about its safety and efficacy in this population. Critical outcomes like the development of pyelonephritis and the risk of preterm labor have not been extensively studied in pregnant women receiving this treatment. [2]
A 2020 systematic review and meta-analysis investigated the efficacy and safety of single-dose fosfomycin tromethamine compared to other antibiotics in women with lower uncomplicated urinary tract infections (uUTI) and pregnant women with either uUTI or ASB. This analysis incorporated data from 21 studies that included 3,103 patients in total. Nine of these studies specifically focused on clinical resolution in 2,122 women, while microbiological resolution was analyzed across all identified studies. The included studies varied in design, with some employing double-blind and single-blind methodologies, and others were open-label randomized controlled trials. The findings revealed no significant difference in clinical resolution between fosfomycin tromethamine and comparator antibiotics (odds ratio [OR] 0.89; 95% confidence interval [CI] 0.71–1.10) among non-pregnant and pregnant women. Moreover, the resolution of microbiological infections was statistically similar between the treatment groups, regardless of pregnancy status (OR 1.11; 95% CI 0.92–1.34). In terms of safety, the meta-analysis did not identify any significant differences in adverse event profiles between single-dose fosfomycin tromethamine and other antibiotics, with the most common side effects being mild and predominantly gastrointestinal in nature. The study concluded that fosfomycin tromethamine is an effective and safe treatment option for women with lower uUTI and pregnant women with uUTI or ASB, offering comparable efficacy to multiple-dose regimens of other antibiotics. These findings suggest that single-dose fosfomycin tromethamine may have the added benefit of increased patient compliance due to its convenient dosing, without compromising safety or effectiveness. Subgroup analyses based on the type of comparator antibiotics supported the overall findings, indicating the robustness of fosfomycin tromethamine as a treatment option across a range of antibiotic comparators. [3]
Another 2022 systematic review and meta-analysis examined the efficacy of single-dose antibiotic therapy for UTIs during pregnancy. The review analyzed data from nine randomized controlled trials, which collectively involved 1,063 pregnant women. All studies utilized urine culture as the standard for confirming microbiologic cure. The meta-analysis found no statistically significant difference between single-dose and extended antibiotic therapy, suggesting comparable efficacy in achieving microbiologic cure. Notably, the single-dose treatments primarily involved fosfomycin, with some studies also exploring the use of amoxicillin and co-trimoxazole. Although limited data were available, most studies reported no significant difference in recurrence rates between the treatment groups. The occurrence of adverse effects and complications were not equally reviewed across the studies however it was noted that the most reported adverse effects were gastrointestinal issues and it was generally low and similar between the single-dose and extended therapy groups. Despite the inclusion of older studies with varied methodologies, the meta-analysis demonstrated that single-dose antibiotic regimens, especially those using fosfomycin, were as effective and as safe as longer regimens, potentially offering a similar microbiologic cure rate with the added advantage of increased patient compliance.[4]
A comprehensive 2025 systematic review and meta-analysis also assessed the efficacy and safety of single-dose fosfomycin in treating uncomplicated UTIs in women. The analysis included data from 22 randomized controlled trials encompassing both nonpregnant women and pregnant women with UTIs and ASB. The results indicated that single-dose fosfomycin demonstrated clinical and microbiological efficacy comparable to other antibiotics, such as nitrofurantoin, quinolones, β-lactams, and sulfonamides, with no significant differences in adverse events across the trials. Notably, the analysis found no substantial publication bias, with consistent outcomes suggesting the implementation of a single 3 g dose of fosfomycin as an effective and safe therapeutic option on women.. This approach may enhance compliance and potentially minimize antibiotic resistance, underscoring fosfomycin's value as a viable alternative for managing uncomplicated UTIs in women. [5]
Additionally, a 2013 review evaluated the use of fosfomycin trometamol as a single-dose oral treatment for acute lower urinary UTIs and asymptomatic bacteriuria in pregnant women. This study examined the pharmacokinetic and pharmacodynamic properties of fosfomycin trometamol, highlighting its efficacy against common uropathogens such as Escherichia coli, including strains that produce extended-spectrum beta-lactamase (ESBL), Proteus mirabilis, Klebsiella pneumoniae, and Staphylococcus saprophyticus. The review noted that resistance rates for these pathogens have remained relatively stable over time. It was emphasized that the drug achieves high concentrations in the urine following a single 3 g oral dose, contributing to its effectiveness in treating uncomplicated lower UTIs. The paper detailed several clinical trials where single-dose fosfomycin trometamol demonstrated comparable clinical and bacteriological efficacy to multi-day regimens of other first-line antibiotics such as ciprofloxacin, norfloxacin, cotrimoxazole, and nitrofurantoin in women with uncomplicated UTIs. Additionally, it showed similar effectiveness to 5- and 7-day courses of cefuroxime axetil and amoxicillin/clavulanic acid in pregnant women. The review also highlighted the drug's well-tolerated profile, with gastrointestinal adverse events like diarrhea and nausea being the most common. The findings underscored fosfomycin trometamol as an important option for first-line empirical treatment of uncomplicated lower UTIs, offering benefits such as reduced costs, improved compliance, and less potential for developing bacterial resistance. [6]
An abstract describes a 2011 randomized controlled trial that evaluated the efficacy of single-dose fosfomycin trometamol compared to 5-day courses of amoxicillin clavulanate and cefuroxime axetil for treating lower urinary tract infections (UTIs) during pregnancy. This prospective study enrolled 90 pregnant women out of 324 who presented with symptoms of UTIs between September 2007 and May 2008. Participants were randomized into three equal groups to receive either a single dose of fosfomycin trometamol or a 5-day regimen of the other antibiotics. The analysis ultimately included follow-up data from a total of 84 patients, with 28 receiving fosfomycin trometamol, 27 on amoxicillin clavulanate, and 29 on cefuroxime axetil. The trial found no significant differences among the treatment groups in terms of demographics, clinical success, microbiological cure rates, or adverse effects. However, fosfomycin trometamol demonstrated significantly higher drug compliance compared to the other regimens (P<0.05). These results suggest that fosfomycin trometamol offers a comparable efficacy to traditional treatments but with improved patient compliance, highlighting its potential as a preferred option for managing UTIs in pregnant women due to its simpler administration and adherence advantages. [7]