Clinical strategies to ensure efficacy and safety

Drug choice is always important as we need to consider the safety of the foetus, not just its efficacy for the pregnant woman. Gentamicin can be a lifesaving treatment for both the mother and the foetus.

Use in pregnancy

Aminoglycosides are used for a range of life-threatening infections during pregnancy, such as chorioamnionitis, pyelonephritis, and even pelvic inflammatory diseases and pelvic abscesses. However, due to the risk of kidney and hearing damage in the mother and foetus, aminoglycosides are only used in pregnancy when there are no reasonable alternatives.

Although data are limited, aminoglycosides do not appear to cause congenital malformations, reduce birth weight, or result in premature births. Gentamicin is generally the aminoglycoside of choice in pregnancy as there is more published literature to support its use, both in terms of the infections it is used to treat and its safety profile in pregnancy.

Considerations when using aminoglycosides in pregnant women, regardless of regimen

• Rationale: Only use when necessary or when alternative antibiotics are not suitable. As well as suitability in pregnancy, some patients may be allergic to first-choice antibiotics.
• Regimen: Use once-daily dosing for the shortest possible duration. Adverse effects are related to prolonged periods of aminoglycoside exposure.
• Calculating renal function: This can be difficult to estimate due to changes that occur in pregnancy. 24-hour urine creatinine monitoring is most accurate, but many clinicians use the Cockcroft-Gault equation but based on pre-pregnancy (booking) weight.
• Calculating dose: This should be based on the pre-pregnancy (booking) weight, not the actual weight of the mother at the time of prescribing.
• Monitoring for mother: Monitoring of aminoglycoside levels and toxicity should be done as normal, based on the regimen prescribed. However, some clinicians increase the frequency of renal function monitoring in pregnant women. If surgery is required, the neuromuscular blocking properties of aminoglycosides, in addition to those of anaesthetics, must be kept in mind.
• Monitoring for the foetus: The foetus will be exposed to the aminoglycoside via the mother, so hearing and kidney function should be tested after birth. However, current research does not suggest such exposure does result in harm.

Dosing recommendations

As you learned in Week 2, traditionally, we have administered low doses of aminoglycosides two to three times a day, yet research showed that many patients needed higher doses to get effective therapy. We also know from previous sections of this course that higher blood concentrations of aminoglycoside (which have a concentration-dependent action) lead to improved clinical outcomes for patients and enhance the efficacy of the antibiotic, although raises concerns of toxicity.

The Royal College of Obstetricians and Gynecologists (RCOG), now recommends aminoglycosides, and gentamicin in particular, to be given once daily in pregnant women, as it is believed to be more effective and safer.

The graph below (adapted from Ward and Theiler, 2009) demonstrates how a traditional multiple-dose-per-day regimen of gentamicin does not obtain the high-peaks desired for optimal bacterial killing, but does increase the length of time spent above the threshold for gentamicin toxicity (about 2 mg/L).

Similar data has been reported in other studies, leading some clinicians to use once-daily gentamicin during pregnancy and in the post-partum period. Doses of 5 mg/kg once daily of gentamicin have been shown to be effective and safe for both the mother and foetus. Alongside this, the costs and environmental impact of administering and monitoring once-daily gentamicin dosing are lower than multiple dosing regimens.

However, due to the small size of these studies and remaining concerns over the effects of aminoglycosides on the foetus, many clinicians still prefer to use the conventional regimen of multiple daily dosing.