Hypothesis / aims of study
Urinary tract infections are common bacterial infections among pregnant women as it has been reported that about half of women will catch at least one of the UTIs during their life time and also about 25% of them will experience recurrence (1). Uncomplicated lower urinary tract infection and asymptomatic bacteriuria are reported to be the main common types of UTIs in women in which the UTI is often pointed to acute cystitis characterized by symptoms such as dysuria, hematuria, and/or suprapubic pain which requires a course of antibiotic therapy (2). Current guidelines recommend an early use of antibiotics as main treatments of UTIs , despite the frequent use of antibiotic usually leads to bacterial resistance, which exacerbates the resistant pathogens either multidrug-resistant or extensive drug resistant , which causes more complicated UTIs(3). Fosfomycin is usually given as a single dose of 3 g weekly which can result in good tolerance. Moreover, the common side effects that has been reported from taking fosfomycin in other clinical trials were mainly affecting the GIT such as diarrhea, nausea, or vaginitis. Many research on randomized controlled trials showed that fosfomycin single dose had similar efficacy to 3-7 days of other antibiotic regimens such as cephalosporin, cotrimoxazole, or nitrofurantoin in uncomplicated UTI (4-6).
Objective: To compare the efficacy and safety of fosfomycin compared to nitrofurantoin and cephalosporin in pregnant women presented with lower urinary tract infection
Study design, materials and methods
This was a prospective, double blinded, and randomized controlled trial conducted at the Department of Obstetrics and Gynecology from August 2019 till August 2020. One hundred and twenty pregnant women between 12 and 36 gestational age were enrolled in our study according to the following inclusion criteria: Patients with uncomplicated lower UTIs either asymptomatic or cystitis, while the exclusion criteria were: a) History to allergy to fosfomycin; b) Irritable bowel syndrome; c) Diabetes or immune-compromised patients; d) History of congenital anatomic urinary anomalies.
Our sample size was calculated using Epi info 0.7 programs with two-sided confidence level of 95% with power of study with 80%; the Z score for 95% CI equaled 1.96 and 0.84 for the power of the study. The estimated sample size were 122 patients, but we were able to obtain only 120 patients. Patients were randomly allocated into three groups, where the randomization process was generated using a random number table. And the allocation system was done using opaque closed envelopes by 1:1:1 ratio in which each envelope contained one assignment for each patient.
Group I (n= 40 cases): received a single dose of 3 g fosfomycin orally weekly.
Group II (n= 40 cases): received 100 mg nitrofurantoin three times daily orally for 7 days.
Group III (n=40 cases): received 500 mg cephalosporin three times daily for 7 days.
The fosfomycin patients’ group were advised to take the fosfomycin dose by dissolving it into half cup of water, then take it before bedtime. Also, they were advised to empty their bladder before taking the fosfomycin
dose, while other groups were given the prescribed dose in capsule form. Not any of the participant nor the authors were aware of the allocation system as well as which intervention patients have taken.
All included patients were subjected at the beginning of the study to:
A) Detailed clinical history including age, parity, gestational age, any presenting symptoms, menstrual history such as first day of last menstrual period (LMP) and expected date of delivery (EDD).
B) Full clinical examination including general examination such as measurement of blood pressure, pule, temperature, and presence of edema, and abdominal examination such as fundal level, organomegaly, and renal angle tenderness.
C) Investigation including ultrasound for pregnancy and urinary track assessment, and laboratory tests as complete urine analysis and urine culture test. After 7 days of the trial, a questionnaire for relief of symptoms, compliance, or any complications was taking from all patients.
The designed questionnaire set by authors’ collaboration was made of two major sections: first section comprised the demographics data about patients, and the second section considered the efficacy of the treatment along with any reported side effect of the drug taken.
Results
In our study, there was no statistical significance difference between the studied groups as regard to their age. In our study, there was no statistical significance difference between the studied groups as regard to their demographic data (age, gravidity, parity previous type of delivery) however the incidence of urinary tract infection increases with progression of gestational age and due to compression of uterus on ureter specially the right side. In our study, there was no statistical significance difference between the studied groups as regard to their urine analysis results. In our study, there was no statistical significance difference between the studied groups as regard to their culture results. After one week of first course of therapy, another urine analysis and culture were done and we revealed that 95% of cases have taken single-dose of three g Fosfomycin were cured. The second group who has taken seven days course of Nitrofurantoin, only 92%. The third group who has taken seven days course of Cephalosporine, only 90% were cured. In our study, we revealed that single-dose of three g Fosfomycin was more effective than 7 days course of Nitrofurantoin and seven days course of Cephalosporine treatment. In our study, the compliance of the drugs was better in Fosfomycin group 95% versus 92%.
Interpretation of results
The repeated courses of different antibiotics aligned with repeated lower urinary tract infections resulted in highly bacterial resistant to most of antibiotics used which requires shifting to treat the UTIs in pregnant women as early as possible so we can increase the health as well as the decrease in progressive UTIs during pregnancy. (7,8)
Our study showed cure rate (97.1%) in fosfomycin group, which was better than other 2 groups, however Ceran et al. (9) reported comparable results when compared fosfomycin with ciprofloxacin along with disappearance of side effects in about 80% of the cases.