COMPARISON OF NITROFURANTOIN WITH FOSFOMYCIN in TREATING CYSTITIS IN WOMEN

INTRODUCTION Urinary tract infection (UTI) is a broad term that encompasses a spectrum of infectious syndromes that affect the urinary tract anywhere from the urethra to the kidneys. UTIs are one of the most common infections, and it is reported that 50%-60% of women have at least one UTI in their lifetime.1 It is the second most common reason for antibiotic prescriptions, after respiratory tract infections.2 Acute uncomplicated cystitis is an infection of the bladder and urethra that affects mainly women and girls from 2 years of age and pyelonephritis is an infection of the renal parenchyma. Escherichia coli is the most common causative pathogen of both diseases and accounts for approximately 85% of community-acquired UTIs and 50% of hospital-acquired UTIs.3,4,5 There have been recent reports of an increasing level of antibiotic resistance in pathogens causing uncomplicated UTIs.6,7 The 2017-2018 WHO GLASS (Global Antimicrobial Resistance and Use Surveillance System) report indicates >70% resistance to ceftriaxone and ciprofloxacin in E. coli isolated from UTIs in Pakistan.7,8 A previous study on UTI pathogens in Karachi found that 49% of Gram-positive and 57% of Gram-negative bacteria were resistant to ciprofloxacin.5,9 Despite of this, ciprofloxacin is readily available over the counter in an oral suspension throughout Pakistan and is prescribed widely by physicians.9 This high level of resistance indicates that the use of the antibiotic as a first-line treatment for UTI in Pakistan needs to be reconsidered. It has been shown in studies that there is low resistance rates to fosfomycin and nitrofurantoin.10,11,12,13,14 Given increasing antimicrobial resistance, guidelines for the treatment of uncomplicated lower urinary tract infections (UTIs) were modified in 2010 to recommend nitrofurantoin and fosfomycin as first-line agents; their use has since increased exponentially.3,12,15Worldwide first-line agents for uncomplicated UTIs include nitrofurantoin, sulfamethoxazole/trimethoprim and fosfomycin.16 Nitrofurantoin is bacteriostatic, not bactericidal, and must be used for 5 to 7 days. It is the preferred drug for low-dose long-term prophylaxis in patients with recurrent UTIs.17 Fosfomycin is FDA-approved as a 3gram single-dose therapy for uncomplicated UTIs.18 A single dose will provide therapeutic urinary concentrations for 2 to 4 days and is comparable to 7- to 10-day therapy with other agents.18,19

OBJECTIVE As the use of nitrofurantoin and fosfomycin has increased since guidelines began recommending them as first-line therapy for lower urinary tract infection (UTI). This study will be conducted to compare the clinical and microbiologic efficacy of nitrofurantoin and fosfomycin in women with cystitis.

RATIONALE Fosfomycin and nitrofurantoin are increasingly being prescribed in outpatients for the oral treatment of urinary tract infection (UTI). The newest guidelines for empirical treatment of women with uncomplicated urinary tract infections (UTIs) advise clinicians to choose among three venerable antibiotics: trimethoprim-sulfamethoxazole, nitrofurantoin, and fosfomycin. Although both nitrofurantoin and fosfomycin have shown efficacy against most urinary pathogens, no recent head-to-head comparisons have been reported. So, this study will be conducted to compare effectiveness of both drugs.

OPERATIONAL DEFINITIONS:

1. Cystitis is infection of urinary bladder. Uncomplicated cystitis refers to lower urinary tract infection in women who are otherwise healthy. Complicated cystitis is associated with risk factors (diabetes, renal transplantation, pregnancy, immunocompromised, indwelling catheter, abnormality of urinary tract) that increase the chances of antibiotic failure.20
2. Pyelonephritis is infection of renal parenchyma resulting in fever, pain in lumber region and vomiting.
3. Adverse effects of Nitrofurantoin: Headache, dizziness, nausea, diarrhea, vomiting, loss of appetite, chest pain, numbness in hands and feet, brown urine.20
4. Adverse effects of Fosfomycin: vaginal discharge, abdominal pain, headache, back pain, bodyaches , indigestion, dryness of throat, heavy painful menstruation, skin rash, weakness.20
5. Clinical response was defined as clinical resolution (complete resolution of symptoms and signs of urinary tract infection without prior failure).
6. Clinical failure (need for additional or change in, antibiotic treatment due to a urinary tract infection, or discontinuation due to lack of efficacy).
7. Indeterminate (either persistence of symptoms without objective evidence of infection or any extenuating circumstances precluding a classification of clinical resolution/failure).
8. Microbiologic response was defined as resolution (eradication of the infecting strain with no recurrence of bacteriuria [<103 colony-forming units/mL] during follow-up) or failure (bacteriuria ≥103 colony- forming units/mL with the infecting strain).21