Nitrofurantoin

Conditions
1. Uncomplicated Urinary Tract Infection
  1. For lower tract infections only (Bladder Infections)
  2. Does NOT cover Acute Pyelonephritis
2. Urinary Tract Infection Prophylaxis
Activity
1. Covers many urinary pathogens
2. Does NOT cover Pseudomonas, Klebsiella, Proteus Serratia or Acinetobacter

Urine pH >8
1. Associated with Nitrofurantoin resistance >40% (associated with protease species)
2. See efficacy below
G6PD Deficiency
Prolonged use longer than 6 months
Prolonged use >14 days in age over 65 years
1. Relative contraindication if normal Renal Function >60 ml/min
Creatinine Clearance <30-40 ml/min
1. Short-term use <14 days appears safe at GFR >30 ml/min
Pregnancy after 36 weeks (or last 4 weeks of pregnancy)
1. Risk of Hemolytic Anemia and Neonatal Jaundice
References
1. (2018) Presc Lett 25(8)
2. Oplinger (2013) Ann Pharmacother 47(1):106-11 [PubMed]

Take immediately after food to increase absorption (decreases gastrointestinal upset)
Uncomplicated Urinary Tract Infection
1. Nitrofurantoin
  1. Take 50 to 100 mg orally four times daily for 7 days (or 3 days after urine sterile)
2. Macrobid (age >12 years old)
  1. Take 100 mg orally twice daily for 5 days
3. Course: 5 days (instead of 7) is sufficient for uncomplicated UTI in non-pregnant women
  1. Gupta (2007) Arch Intern Med 167(20):2207-12 [PubMed]
Urinary Tract Infection Prophylaxis (avoid use >6 months)
1. Nitrofurantoin: Take 50 to 100 mg orally at bedtime

Avoid in age <1 month old (Risk of Hemolytic Anemia and Neonatal Jaundice)
Take immediately after food to increase absorption (decreases gastrointestinal upset)
Uncomplicated Urinary Tract Infection
1. Nitrofurantoin
  1. Give 5-7 mg/kg/day divided four times daily orally for 7 days (or 3 days after urine sterile)
  2. Maximum: 100 mg/dose
2. Macrobid (age >12 years old): 100 mg orally twice daily for 7 days
Urinary Tract Infection Prophylaxis
1. Give 1 mg/kg/day divided orally once to twice daily

Common
1. Nausea and Vomiting
  1. Decreased with longer acting preparation (Macrobid)
2. Urine Color change
  1. Urine may appear brown
Serious
1. Pulmonary fibrosis (with chronic Nitrofurantoin use)
2. Acute Nitrofurantoin Pulmonary Toxicity
  1. Avoid in eGFR <30 to 40 ml/min
  2. Avoid longterm use in eGFR <60 ml/min
3. Neuropathy
4. Hepatotoxicity
  1. Monitor Liver Function Tests with longterm use

Very high efficacy in lower Urinary Tract Infections (resistance to typical coliforms is <2%)
However Nitrofurantoin resistance rises to >40% when Urine pH >8
1. High Urine pH is often associated with protease species infections
2. High Urine pH also decreases renal reabsorption of Nitrofurantoin
3. Nordt and Rech (2024) Toxicology Sessions: UTI Nitrofurantoin + Urine pH Summary, EM:Rap, 7/29/2024

Lactation
1. Considered safe in Lactation after first month of life (unless maternal G6PD Deficiency)
Pregnancy
1. Considered safe in first 2 trimesters
2. Avoid after 36 weeks or last 4 weeks of pregnancy
  1. Risk of Hemolytic Anemia and Neonatal Jaundice