What antibiotics should be avoided in a pregnant female with Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency suffering from a Urinary Tract Infection (UTI)?

Antibiotics to Avoid in Pregnant Women with G6PD Deficiency and UTI

In pregnant women with G6PD deficiency suffering from a UTI, avoid nitrofurantoin, trimethoprim-sulfamethoxazole (co-trimoxazole), and sulfonamides, as these medications can trigger hemolytic anemia. 1, 2, 3, 4

Primary Medications to Avoid

Nitrofurantoin

• Nitrofurantoin is contraindicated in G6PD deficiency due to its oxidant properties that can cause hemolytic anemia, with 42 cases (13%) of hemolytic episodes reported in G6PD-deficient individuals out of 318 total episodes. 2, 3
• While some evidence suggests lower risk than other oxidant drugs, solid evidence exists to prohibit its use in G6PD-deficient patients. 2, 3
• This is particularly important as nitrofurantoin is otherwise commonly used as first-line therapy for UTIs in pregnancy. 5, 6

Trimethoprim-Sulfamethoxazole (Co-trimoxazole)

• Co-trimoxazole should be avoided in G6PD-deficient pregnant women as sulfonamides are associated with fetal hemolytic anemia and hyperbilirubinemia of the neonate. 1
• The European Respiratory Society guidelines specifically state to avoid co-trimoxazole in babies who are G6PD deficient, jaundiced, or premature during breastfeeding. 1
• A case report documented acute hemolytic crisis triggered by sulphamethoxazole in a pregnant woman with G6PD deficiency. 4
• Sulfonamide use is associated with hyperbilirubinemia and use at delivery is linked to fetal hemolytic anemia. 1

Other Sulfonamides

• All sulfonamide-containing antibiotics should be avoided throughout pregnancy in G6PD-deficient patients, particularly during the first trimester and at delivery. 1, 4

Safe Alternative Antibiotics for UTI Treatment

First-Line Safe Options

• Amoxicillin 500 mg three times daily for 3-7 days is safe and effective for GBS UTI in pregnancy without G6PD concerns. 7
• Cephalexin 500 mg four times daily for 3-7 days is another safe first-line option. 7
• Ampicillin (pivampicillin) remains a safe beta-lactam option with no teratogenic effects or G6PD-related concerns. 5
• Pivmecillinam is efficient against both cystitis and pyelonephritis without G6PD contraindications. 5

Second-Line Safe Options

• Cefazolin and other first-generation cephalosporins are safe alternatives. 1, 7
• Amoxicillin-clavulanate can be used safely, though it should be avoided in women at risk of preterm delivery due to very low risk of necrotizing enterocolitis. 1

Antibiotics Requiring Caution

• Ciprofloxacin and other fluoroquinolones are not contraindicated in G6PD deficiency but should be used cautiously in pregnancy due to concerns about fetal cartilage damage in animal studies, though human data suggest low risk. 1
• If a fluoroquinolone is necessary, ciprofloxacin should be chosen over other options. 1

Special Considerations for Group B Streptococcus

If GBS is Isolated

• Any concentration of GBS in urine during pregnancy requires immediate treatment followed by mandatory intrapartum IV antibiotic prophylaxis during labor. 7, 8
• Penicillin G (5 million units IV initially, then 2.5 million units IV every 4 hours until delivery) is the preferred intrapartum prophylaxis regimen and is safe in G6PD deficiency. 7, 8
• Ampicillin (2 g IV initially, then 1 g IV every 4 hours) is an acceptable alternative for intrapartum prophylaxis. 7, 8

For Penicillin-Allergic Patients with G6PD Deficiency

• Cefazolin (2 g IV initially, then 1 g IV every 8 hours) is the preferred alternative for patients without high-risk allergy symptoms. 7, 8
• Clindamycin (900 mg IV every 8 hours) can be used if the isolate is confirmed susceptible and the patient has high-risk allergy symptoms. 7, 8
• Vancomycin (1 g IV every 12 hours) is recommended if susceptibility is unknown or the isolate is resistant to clindamycin. 7, 8

Critical Clinical Pitfalls

Common Errors to Avoid

• Do not assume that treating the UTI eliminates the need for intrapartum prophylaxis in GBS bacteriuria—this is a dangerous error as recolonization is typical. 8
• Do not use doxycycline as it causes tooth discoloration and bone growth suppression in the fetus, and should be avoided during the second and third trimesters. 1
• Do not prescribe metronidazole as first-line therapy unless no safer alternatives exist, as it is associated with fetal damage in animals. 1

Monitoring Requirements

• Screen for hemolytic anemia if oxidant drugs were inadvertently given by monitoring hemoglobin, reticulocyte count, and bilirubin levels. 4
• Ensure laboratory reports of GBS bacteriuria are communicated to both the anticipated site of delivery and the ordering provider. 8
• Document G6PD deficiency prominently in the medical record to prevent inadvertent prescription of contraindicated medications. 3, 4