What antibiotic is safe for a pregnant female with a urinary tract infection (UTI)?

Safe Antibiotics for UTI in Pregnancy

Cephalexin (500 mg four times daily for 7-14 days) is the safest and most appropriate first-line antibiotic for treating UTIs across all trimesters of pregnancy, with nitrofurantoin as an acceptable alternative in the first and second trimesters only. 1, 2

First-Line Treatment by Trimester

First Trimester

• Nitrofurantoin (50-100 mg four times daily OR 100 mg twice daily for 5-7 days) is the preferred agent according to European Urology guidelines 1, 2
• Cephalexin (500 mg four times daily) is equally appropriate and achieves excellent blood and urinary concentrations with an excellent safety profile 1, 2
• Fosfomycin (single 3g dose) is an acceptable alternative for uncomplicated cystitis 1, 2

Second Trimester

• All first-line agents remain appropriate: nitrofurantoin, cephalexin, and fosfomycin 2

Third Trimester

• Cephalexin is the preferred first-line agent (500 mg four times daily for 7-14 days) 1, 2
• Avoid nitrofurantoin near term due to theoretical risk of hemolytic anemia in the newborn 2
• Amoxicillin-clavulanate (20-40 mg/kg per day in 3 doses) is appropriate if the pathogen is susceptible 1, 3

Critical Treatment Duration and Monitoring

• Always obtain urine culture before initiating treatment to guide antibiotic selection 1, 2
• Treat for 7-14 days to ensure complete eradication, despite insufficient evidence for shorter regimens 1, 2
• Repeat urine culture 1-2 weeks after completing treatment to confirm cure 1, 2

Antibiotics to AVOID Throughout Pregnancy

• Fluoroquinolones (ciprofloxacin, levofloxacin) should be avoided throughout all trimesters due to potential adverse effects on fetal cartilage development 2, 4
• Trimethoprim and trimethoprim-sulfamethoxazole should be avoided in the first trimester due to potential teratogenic effects (anencephaly, heart defects, orofacial clefts) 1, 2, 4
• Trimethoprim-sulfamethoxazole should also be avoided in the third trimester 2

Why Treatment Cannot Be Delayed

• Untreated bacteriuria increases pyelonephritis risk 20-30 fold (from 1-4% with treatment to 20-35% without) 1, 2
• Treatment reduces premature delivery and low birth weight infants 1, 2
• Pregnancy is the ONE clinical scenario where even asymptomatic bacteriuria must always be treated 1, 2
• Implementation of screening programs decreased pyelonephritis rates from 1.8-2.1% to 0.5-0.6% 1

Special Considerations for Pyelonephritis

• Do NOT use nitrofurantoin for suspected pyelonephritis as it does not achieve therapeutic bloodstream concentrations 1, 2
• Initial parenteral therapy may be required for severe infections, with transition to oral therapy after clinical improvement 1
• Cephalosporins are the preferred agents for pyelonephritis in pregnancy 1, 2

Group B Streptococcus (GBS) Detection

• GBS bacteriuria in any concentration during pregnancy requires treatment at diagnosis PLUS intrapartum prophylaxis during labor 1, 2

Common Pitfall to Avoid

Despite the 2011 ACOG recommendation cautioning against nitrofurantoin in the first trimester, more recent European Urology guidelines (reflected in the 2025 evidence) actually recommend it as first-line for first trimester UTIs 1, 2. However, cephalexin remains the safest choice across all trimesters if you want a single agent that works throughout pregnancy without trimester-specific restrictions 1, 2.