What is the next treatment option for a patient with a urinary tract infection (UTI) who has failed Macrobid (nitrofurantoin)?

From the Guidelines

For a urinary tract infection (UTI) that has failed treatment with nitrofurantoin (Macrobid), the next recommended option is typically trimethoprim-sulfamethoxazole (Bactrim, Septra) at a dose of 160/800 mg (one double-strength tablet) twice daily for 3-5 days, as recommended by the most recent guidelines 1.

Considerations for Treatment

When considering the next step in treatment for a UTI that has failed Macrobid, several factors must be taken into account, including local resistance patterns, patient-specific factors, and the severity of the infection.

• The choice of antibiotic should be guided by the results of a urine culture and susceptibility testing, if available.
• If the patient has kidney involvement or signs of systemic infection, a longer course of 7-14 days may be needed.
• Other alternatives include fosfomycin as a single 3-gram dose or cephalexin 500 mg four times daily for 5-7 days, as outlined in previous guidelines 1.

Importance of Urine Culture

It is essential to obtain a urine culture before starting the new antibiotic to guide therapy based on the specific bacteria causing the infection and its susceptibility pattern.

• Patients should complete the full course of antibiotics even if symptoms improve.
• Drinking plenty of water and following up if symptoms persist or worsen are also crucial components of management.

Treatment Failure

Treatment failure with Macrobid may occur due to bacterial resistance, inadequate drug concentration in the urine, or infection with organisms naturally resistant to nitrofurantoin.

• The European Association of Urology guidelines suggest that ciprofloxacin should only be used if the local resistance rate is <10% 1.
• The Wikiguidelines group consensus statement provides recommendations for the duration of treatment based on the syndrome and antimicrobial class used 1.

From the FDA Drug Label

2 DOSAGE AND ADMINISTRATION

2.1 Important Administration Instructions To minimize the potential for gastrointestinal intolerance, amoxicillin should be taken at the start of a meal. 2. 2 Dosage for Adults and Pediatric Patients Aged 3 Months (12 weeks) and Older Treatment should be continued for a minimum of 48 to 72 hours beyond the time that the patient becomes asymptomatic, or evidence of bacterial eradication has been obtained It is recommended that there be at least 10 days’ treatment for any infection caused by Streptococcus pyogenes to prevent the occurrence of acute rheumatic fever. In some infections, therapy may be required for several weeks. Table 1 Genitourinary Tract Mild/ Moderate 500 mg every 12 hours or 250 mg every 8 hours 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours Severe 875 mg every 12 hours or 500 mg every 8 hours 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours

The next option for a UTI that failed Macrobid could be amoxicillin. The recommended dosage for a genitourinary tract infection is:

• Mild/Moderate: 500 mg every 12 hours or 250 mg every 8 hours for adults, or 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours for pediatric patients.
• Severe: 875 mg every 12 hours or 500 mg every 8 hours for adults, or 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours for pediatric patients. Treatment should be continued for a minimum of 48 to 72 hours beyond the time that the patient becomes asymptomatic, or evidence of bacterial eradication has been obtained 2.

From the Research

UTI Treatment Options After Macrobid Failure

If a patient has failed Macrobid (nitrofurantoin) treatment for a urinary tract infection (UTI), there are several alternative treatment options available.

• The choice of next treatment option depends on various factors, including the severity of the infection, the patient's medical history, and local antimicrobial resistance patterns 3.
• Second-line options for UTI treatment include oral cephalosporins such as cephalexin or cefixime, fluoroquinolones, and β-lactams, such as amoxicillin-clavulanate 3.
• For patients with ESBL-producing E. coli, treatment options include nitrofurantoin, fosfomycin, pivmecillinam, amoxicillin-clavulanate, finafloxacin, and sitafloxacin 3.
• Parenteral treatment options for UTIs due to ESBL-producing Enterobacteriales include piperacillin-tazobactam, carbapenems, ceftazidime-avibactam, and aminoglycosides including plazomicin 3.

Comparison of Antibiotic Efficacy

• A network meta-analysis of randomized controlled trials compared the efficacy of different antibiotics for UTI treatment, including ciprofloxacin, gatifloxacin, and amoxicillin-clavulanate 4.
• The analysis found that ciprofloxacin and gatifloxacin were the most effective treatments, while amoxicillin-clavulanate was the least effective 4.
• A systematic review and meta-analysis compared the efficacy and safety of fosfomycin and nitrofurantoin for the treatment of uncomplicated lower UTI in women, finding no significant differences in clinical and microbiological cure rates 5.

Duration of Nitrofurantoin Treatment

• A retrospective cohort study compared the effectiveness of 5 versus 7 days of nitrofurantoin treatment for UTI in women with diabetes, finding no clinically significant difference in treatment failure within 28 days 6.
• The study suggested that a 5-day treatment course may be considered to reduce cumulative nitrofurantoin exposure in patients with diabetes 6.