What is the recommended first‑line oral antibiotic regimen for an uncomplicated urinary tract infection in a pregnant woman, including gestational age considerations and contraindications?

Treatment of Urinary Tract Infections in Pregnancy

First-Line Antibiotic Recommendations

Nitrofurantoin is the preferred first-line oral antibiotic for uncomplicated UTI in pregnant women, with fosfomycin as an acceptable alternative. 1

Specific Regimens by Trimester

First Trimester:

• Nitrofurantoin 100 mg twice daily for 7 days is the recommended first-line agent 1
• Fosfomycin trometamol 3 g single dose is an acceptable alternative 1
• Avoid trimethoprim and trimethoprim-sulfamethoxazole due to potential teratogenic effects (neural tube defects) 1
• Nitrofurantoin remains appropriate in the first trimester when no other suitable alternatives are available, despite mixed evidence on birth defects 2, 3

Second and Third Trimesters:

• Nitrofurantoin 100 mg twice daily for 7 days remains first-line 1
• Cephalexin 500 mg four times daily for 7-14 days is the preferred alternative, particularly in the third trimester 1
• Avoid trimethoprim-sulfamethoxazole in the last trimester (risk of kernicterus) 1
• Avoid nitrofurantoin near term (theoretical risk of hemolytic anemia in newborns with G6PD deficiency) 1

Alternative Agents

Cephalosporins (when nitrofurantoin is contraindicated):

• Cephalexin, cefpodoxime, or cefuroxime for 7-14 days 1
• Excellent safety profile throughout pregnancy 1
• Achieve adequate blood and urinary concentrations 1

Fosfomycin:

• Single 3 g dose for uncomplicated lower UTI 1
• Equivalent efficacy to nitrofurantoin with no significant difference in clinical or microbiological cure rates 4
• Limited data for third trimester use compared to cephalosporins 1

Critical Diagnostic Requirements

Always obtain urine culture before initiating treatment to guide antibiotic selection and confirm diagnosis 1

Key diagnostic pitfalls to avoid:

• Dipstick testing has only 50% sensitivity for detecting bacteriuria in pregnancy 1
• Do not rely on negative dipstick to rule out UTI—symptoms warrant culture and empiric treatment regardless 1
• Pyuria screening alone misses approximately 50% of bacteriuria cases 1

Treatment Duration and Follow-Up

Standard treatment course:

• 7 days for symptomatic UTI (not the 3-5 day courses used in non-pregnant women) 1
• 7-14 days for asymptomatic bacteriuria 1
• Longer courses are necessary in pregnancy despite insufficient evidence comparing shorter regimens 1

Mandatory follow-up:

• Repeat urine culture 1-2 weeks after completing treatment to confirm cure 1
• If symptoms persist or recur within 2 weeks, obtain repeat culture with susceptibility testing and assume resistance to the original agent 1
• Retreat with a 7-day course of an alternative antibiotic 1

Special Clinical Scenarios

Asymptomatic Bacteriuria

Pregnancy is the one clinical scenario where asymptomatic bacteriuria must always be treated due to 20-30 fold increased risk of pyelonephritis (from 1-4% with treatment to 20-35% without) 1

Screening protocol:

• Screen all pregnant women at 12-16 weeks gestation (or first prenatal visit if later) with urine culture 1
• Treat with same regimens as symptomatic UTI 1
• Do not perform repeated surveillance testing after initial screen-and-treat, as this fosters antimicrobial resistance 1

Pyelonephritis

Initial parenteral therapy is required for hospitalized patients:

• Ceftriaxone 1-2 g daily OR cefepime 1-2 g twice daily 1
• Transition to oral cephalosporin after clinical improvement 1
• Complete 7-14 day total course 1
• Never use nitrofurantoin for pyelonephritis—it does not achieve therapeutic blood concentrations 1

Group B Streptococcus (GBS) Bacteriuria

Any concentration of GBS in urine during pregnancy requires:

• Treatment at time of diagnosis 1
• Intrapartum GBS prophylaxis during labor 1
• No need for vaginal-rectal screening at 35-37 weeks—GBS bacteriuria automatically qualifies for intrapartum prophylaxis 1

Antibiotics to Avoid Throughout Pregnancy

Fluoroquinolones (ciprofloxacin, levofloxacin):

• Contraindicated throughout all trimesters due to potential adverse effects on fetal cartilage development 1
• Multiple guidelines explicitly recommend against use 1

Trimethoprim-sulfamethoxazole:

• Avoid in first trimester (teratogenic risk—neural tube defects) 1
• Contraindicated in last trimester (kernicterus risk) 1

Critical Clinical Context

Untreated UTI in pregnancy carries severe consequences:

• 20-30 fold increased risk of pyelonephritis 1
• Increased risk of premature delivery and low birth weight infants 1
• Implementation of screening programs decreased pyelonephritis rates from 1.8-2.1% to 0.5-0.6% 1

Treatment urgency:

• Delaying treatment increases risk of pyelonephritis and adverse pregnancy outcomes 1
• Initiate empiric therapy immediately after obtaining culture—do not wait for results 1

Common Pitfalls and How to Avoid Them

1. Using short-course therapy: Pregnant women require 7-day courses, not the 3-day regimens used in non-pregnant women 1

2. Prescribing nitrofurantoin for pyelonephritis: This agent does not achieve therapeutic blood levels and is only appropriate for lower UTI 1

3. Relying on dipstick alone: Always obtain formal urine culture in pregnancy 1

4. Failing to treat asymptomatic bacteriuria: This is the one population where treatment is mandatory 1

5. Using fluoroquinolones: These remain contraindicated despite their efficacy in non-pregnant patients 1