What is the treatment for a patient with a urinary tract infection (UTI) resistant to Macrobid (nitrofurantoin)?

Treatment for UTI Resistant to Nitrofurantoin

For a UTI that has failed nitrofurantoin therapy, obtain a urine culture with antimicrobial susceptibility testing and initiate trimethoprim-sulfamethoxazole (TMP-SMX) 160/800 mg twice daily for 7 days as the preferred alternative, provided local E. coli resistance rates are below 20%. 1

Immediate Assessment and Culture

• Perform urine culture with antimicrobial susceptibility testing before initiating alternative therapy, as the infecting organism is presumed not susceptible to nitrofurantoin 1
• Do not delay treatment while awaiting culture results if the patient is symptomatic 1

First-Line Alternative Antibiotics After Nitrofurantoin Failure

Trimethoprim-Sulfamethoxazole (Preferred)

• TMP-SMX 160/800 mg twice daily for 3 days (women) or 7 days (men) is the recommended first-line alternative, but only if local resistance rates are <20% 1, 2
• TMP-SMX is FDA-approved for UTI treatment caused by E. coli, Klebsiella species, Enterobacter species, Morganella morganii, Proteus mirabilis, and Proteus vulgaris 2
• However, resistance rates to TMP-SMX now exceed 20% in many communities, particularly in patients recently exposed to antibiotics or at risk for ESBL-producing organisms 3, 4
• In recurrent UTI populations, E. coli shows 46.6% resistance to TMP-SMX, making it less reliable empirically 5

Fosfomycin (Alternative First-Line)

• Fosfomycin trometamol 3 g single dose is particularly useful for uncomplicated cystitis in women after nitrofurantoin failure 1
• E. coli demonstrates 95.5% susceptibility to fosfomycin, making it an excellent choice when TMP-SMX resistance is suspected 5
• This agent has slightly inferior efficacy compared to standard short-course regimens but remains a valuable option 3

Oral Cephalosporins (Second-Line)

• Cefadroxil 500 mg twice daily for 3 days or other oral cephalosporins (cephalexin, cefixime) can be considered if first-line alternatives fail 1
• Use only if local E. coli resistance is <20% 1
• Cefuroxime shows 82.3% susceptibility against E. coli in recurrent UTI populations 5

Fluoroquinolones: Reserve for Specific Situations

• Fluoroquinolones (ciprofloxacin, levofloxacin) should be reserved as alternative agents, not first-line, due to significant collateral damage to normal flora and promotion of resistance 3
• Ciprofloxacin is FDA-approved for complicated UTIs and acute pyelonephritis 6
• Use fluoroquinolones only when first-line agents cannot be used due to allergy, intolerance, or documented resistance 3
• E. coli shows 39.9% resistance to fluoroquinolones in recurrent UTI populations, limiting their empiric utility 5
• The FDA has issued warnings about serious safety issues affecting tendons, muscles, joints, nerves, and the central nervous system 3

Treatment Duration

• For uncomplicated cystitis after nitrofurantoin failure, treat for 3-7 days depending on the antibiotic chosen 1
• For complicated UTIs or UTIs in men, a 7-day course is generally recommended 1
• Treatment should not exceed what is necessary to minimize adverse effects and resistance development 3

Special Considerations for Resistant Organisms

Extended-Spectrum Beta-Lactamase (ESBL) Producers

• If ESBL-producing organisms are suspected (prior exposure to antibiotics, healthcare-associated infection), oral options include fosfomycin or amoxicillin-clavulanate for E. coli 4
• Parenteral options include carbapenems, piperacillin-tazobactam (for ESBL E. coli only), or ceftazidime-avibactam 4

Carbapenem-Resistant Enterobacteriaceae (CRE)

• For suspected CRE causing simple cystitis, consider single-dose aminoglycoside 1
• For complicated UTI with CRE, use ceftazidime-avibactam, meropenem-vaborbactam, or imipenem-cilastatin-relebactam 1, 4

Vancomycin-Resistant Enterococcus (VRE)

• For VRE causing uncomplicated UTIs, nitrofurantoin 100 mg every 6 hours remains effective despite the initial failure, suggesting the resistance may have been to standard dosing 3

Follow-Up and Monitoring

• Routine post-treatment urinalysis or urine cultures are not indicated for asymptomatic patients 1
• If symptoms persist despite appropriate second-line therapy, consider resistant pathogens, structural or functional abnormalities of the urinary tract, or alternative diagnoses 1
• For women whose symptoms do not resolve by the end of treatment or recur within 2 weeks, repeat urine culture with susceptibility testing 1

Critical Pitfalls to Avoid

• Do not use amoxicillin or ampicillin empirically due to poor efficacy and high prevalence of antimicrobial resistance 3
• Do not use nitrofurantoin for pyelonephritis or upper tract infections, as it does not achieve adequate tissue concentrations 3
• Avoid fluoroquinolones as first-line therapy unless local resistance patterns and patient-specific factors strongly support their use 3
• Do not treat asymptomatic bacteriuria discovered incidentally 3, 1