Is nitrofurantoin (Macrobid) an appropriate first‑line oral agent for an uncomplicated lower urinary tract infection caused by Staphylococcus saprophyticus?

Will Macrobid (Nitrofurantoin) Treat Staphylococcus saprophyticus UTI?

Yes, nitrofurantoin (Macrobid) is an excellent first-line choice for uncomplicated lower urinary tract infections caused by Staphylococcus saprophyticus, as this organism retains high susceptibility to nitrofurantoin despite decades of use. 1

Microbiological Activity Against S. saprophyticus

• Nitrofurantoin has maintained robust activity against S. saprophyticus for over 60 years, with resistance rates remaining exceptionally low (<1% worldwide) despite widespread use since the 1950s. 1, 2
• S. saprophyticus is the second most common cause of uncomplicated cystitis in young women (accounting for 5–15% of cases), and nitrofurantoin provides reliable coverage against this pathogen alongside E. coli and Enterococcus species. 1

Recommended Dosing Regimen

• Nitrofurantoin 100 mg orally twice daily for 5 days achieves approximately 93% clinical cure and 88% microbiological eradication for uncomplicated lower UTI. 3, 4
• A 5-day course is superior to 3-day regimens, which show diminished clinical efficacy (61–70% cure rates). 5
• The 7-day regimen offers no additional benefit over 5 days for uncomplicated cystitis. 5

When Nitrofurantoin Should NOT Be Used

• Contraindicated when estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m² because therapeutic urinary concentrations cannot be achieved. 3, 4
• Do not use for suspected pyelonephritis or upper urinary tract involvement (fever >38°C, flank pain, costovertebral angle tenderness), as tissue penetration is insufficient. 3, 4
• Avoid in the last trimester of pregnancy due to theoretical risk of neonatal hemolytic anemia. 4

Advantages Over Alternative Agents

• Nitrofurantoin causes minimal disruption of intestinal flora compared with fluoroquinolones and broad-spectrum cephalosporins, thereby reducing the risk of Clostridioides difficile infection and other collateral antimicrobial damage. 3, 4, 2
• Unlike trimethoprim-sulfamethoxazole (which should only be used when local E. coli resistance is <20%) and fluoroquinolones (which carry serious adverse-effect warnings), nitrofurantoin maintains excellent susceptibility patterns and a favorable safety profile for short-term use. 3, 4

Safety Profile for Short-Term Use

• Adverse events are infrequent (5–16%), mild, reversible, and predominantly gastrointestinal (nausea, diarrhea). 5
• Serious hypersensitivity reactions such as pulmonary fibrosis, hepatotoxicity, and polyneuropathy are associated with long-term or chronic use, not the 5-day regimen recommended for acute uncomplicated cystitis. 1, 5

Clinical Decision Algorithm

1. Confirm uncomplicated lower UTI: dysuria, frequency, urgency without fever, flank pain, pregnancy, catheter use, or immunosuppression. 3
2. Verify normal renal function (eGFR ≥30 mL/min/1.73 m²). 3, 4
3. Prescribe nitrofurantoin 100 mg orally twice daily for 5 days as first-line therapy. 3, 4
4. Obtain urine culture only if symptoms persist after therapy, recur within 2–4 weeks, or if upper-tract involvement is suspected. 3, 4

Common Pitfall to Avoid

• Do not use nitrofurantoin for complicated UTIs, male patients, or when pyelonephritis cannot be excluded, as efficacy data are lacking for these populations and tissue penetration is inadequate. 3, 4, 1