Is tobramycin (an aminoglycoside antibiotic) safe for use during pregnancy?

Tobramycin Use During Pregnancy

Tobramycin should be avoided during pregnancy if possible, especially during the first trimester, due to potential risks of eighth cranial nerve damage and nephrotoxicity to the fetus. 1

Pregnancy Category and Risk Classification

Tobramycin is classified as:

• FDA Pregnancy Category D
• TGA (Therapeutic Goods Administration) Category D 1

This classification indicates that there is evidence of human fetal risk, but the potential benefits may outweigh the risks in certain situations.

Risks Associated with Systemic Tobramycin Use During Pregnancy

First Trimester

• AVOID if possible - Highest risk period for teratogenic effects 1
• Risk of fetal malformations is greatest during organogenesis

Second and Third Trimester

• Associated with eighth cranial nerve damage (ototoxicity) in the fetus
• Streptomycin (another aminoglycoside) has documented cases of eighth cranial nerve damage 1
• Unconfirmed theoretical risk of nephrotoxicity to the fetus 1

Pharmacokinetic Considerations During Pregnancy

• Decreased clearance (by 21-27.6%) of tobramycin after 28 weeks gestation 2, 3
• Increased half-life and mean residence time in the third trimester 3
• Evidence suggests accumulation of tobramycin in the fetus 2, 3

Recommendations for Use During Pregnancy

1. Use only as second- or third-line treatment when other antibiotics have failed to control severe infections 1
2. If tobramycin must be used:
   • Prefer once-daily dosing regimen to limit potential nephrotoxicity and ototoxicity 2, 3
   • Monitor drug levels carefully
   • Consider switching to inhaled route where possible 1

Topical Ophthalmic Tobramycin During Pregnancy

For topical eye drops:

• Inhaled/topical tobramycin has minimal systemic absorption and is considered to have minimal risk 1
• The European Respiratory Journal classifies inhaled tobramycin as "Compatible" during pregnancy 1
• Limited information exists specifically about ophthalmic preparations during pregnancy 4

Breastfeeding Considerations

• Tobramycin is present in breast milk in small amounts 1
• After IV dose, avoid breastfeeding for 2 hours following injection when tobramycin concentration is maximal 1
• Low oral bioavailability overall, but unknown in premature infants and neonates in first weeks of life 1
• If treatment is prolonged, renal function should be monitored in the neonate and an auditory test performed 1

Clinical Decision Algorithm

1. First question: Is there an effective alternative antibiotic with better safety profile?

   • If yes → Use alternative (e.g., penicillins, cephalosporins)
   • If no → Proceed to step 2

2. Second question: Is the infection severe enough to warrant potential fetal risk?

   • If no → Avoid tobramycin
   • If yes → Proceed to step 3

3. Administration route:

   • Topical/inhaled route preferred when possible (minimal systemic absorption)
   • If systemic administration required, use once-daily dosing and monitor levels carefully

Important Caveats and Pitfalls

• Do not assume that topical ophthalmic preparations are completely safe - some systemic absorption can occur
• Do not use tobramycin as first-line therapy during pregnancy when safer alternatives exist
• Monitor renal function and hearing in neonates if mother received tobramycin during pregnancy
• The risk-benefit ratio must be carefully evaluated in each case, with maternal infection severity weighed against potential fetal risks