Population pharmacokinetic and pharmacodynamic analysis of amikacin and gentamicin in hospitalised neonates: a comparative simulation study from two tertiary hospitals in Ghana

In the fragile first days of life, a newborn's body is a landscape of rapid and profound change. Organs that functioned in the womb must suddenly adapt to the outside world, and the kidneys, which filter waste from the blood, are still learning their trade. For infants born prematurely or with low birth weight, this learning curve is steep, and their ability to process medicines is unpredictable. In hospitals across the developing world, where resources are scarce and the threat of infection is high, doctors rely on a small group of powerful antibiotics called aminoglycosides to fight deadly bacterial sepsis. These drugs are effective because they kill bacteria quickly, but they walk a razor-thin line between healing and harm. If the dose is too low, the bacteria survive and multiply; if the dose is too high, the drug can damage the baby's kidneys or hearing. The challenge is that every baby is different, and without the ability to constantly test drug levels in the blood, doctors must guess the right amount based on weight and age alone.

This uncertainty is particularly acute in Ghana, where a common and dangerous bacterium called Klebsiella pneumoniae has become increasingly resistant to the standard antibiotic gentamicin. In many neonatal intensive care units, this resistance has reached such high levels that the first-line treatment often fails before it even begins. Yet, doctors still use these drugs because they are affordable and widely available. The question facing clinicians is not just which drug to choose, but how to dose it safely when the bacteria they are fighting have changed, and when the babies they are treating are physiologically unique. A new study from two major hospitals in Ghana sought to answer this by using computer simulations to map out exactly how these drugs behave in the bodies of local newborns, aiming to find a dosing strategy that kills the infection without hurting the patient.

The researchers focused on two specific antibiotics: gentamicin and amikacin. They gathered data from 122 newborns admitted to the neonatal units of the 37 Military Hospital in Accra and the University Hospital at KNUST in Ho. These infants were between zero and twenty-eight days old, with birth weights ranging from very low to normal. Of these, 78 received gentamicin and 44 received amikacin. Because the hospitals did not have the equipment to measure drug levels in every baby's blood, the team used a sophisticated computer modeling approach. They took the known physical characteristics of the babies—such as their weight, how far along their pregnancy was when they were born, and how many days they had been alive—and fed this information into a mathematical model that simulates how the body processes drugs. They then ran thousands of virtual scenarios to see how different dosing schedules would play out for a population of newborns like those in their study.

The simulations revealed that the way these drugs move through a baby's body is dictated almost entirely by two factors: the size of the baby and the maturity of their kidneys. As a baby grows and their kidneys develop, they clear the drug from their system faster. This means that a fixed dose based simply on weight is often too much for a tiny, premature infant and too little for a larger, more mature one. The study found that for the drug gentamicin, a dose of 4 milligrams per kilogram of body weight given once every twenty-four hours offered the best balance. This regimen was highly effective at reaching the levels needed to kill bacteria that are still susceptible to the drug, while keeping the risk of toxic buildup in the blood low. However, the simulations also showed that increasing the dose or giving it more frequently caused a sharp rise in the risk of kidney damage, as higher doses led to progressively higher trough concentrations that narrowed the therapeutic margin.

For amikacin, the story was different. The simulations indicated that this drug performs better against the specific strains of bacteria that have developed resistance to gentamicin. When the researchers tested a regimen of 7.5 milligrams per kilogram given twice a day, they found it could achieve the necessary drug levels to fight bacteria with higher resistance levels, while still maintaining a very low risk of toxicity. This was a crucial finding because it suggested that amikacin could be a safe and effective alternative when the bacteria are known or suspected to be resistant to gentamicin. The study highlighted that simply giving higher doses of gentamicin to overcome resistance would lead to unacceptably high levels of toxicity in the blood, making the switch to amikacin a more viable strategy for resistant cases.

The researchers also looked at how these drugs behave in the smallest and most vulnerable infants, those born with very low birth weight. The data showed that these tiny babies clear the drugs much more slowly than their larger peers. If they are given the same standard dose as a heavier baby, the drug stays in their system too long, creating a high risk of harm. The study suggests that for these infants, the timing of the dose is just as important as the amount. Extending the time between doses allows the baby's immature kidneys enough time to clear the drug before the next one is given. This insight challenges the common practice of using rigid, one-size-fits-all charts for dosing and points toward a more nuanced approach where the schedule is adjusted based on the baby's size and age.

Ultimately, the study provides a clear, evidence-based guide for doctors working in resource-limited settings where advanced testing is not available. It confirms that while gentamicin remains a viable option for treating infections caused by susceptible bacteria, its use must be carefully managed to avoid toxicity. More importantly, it establishes that amikacin is a superior choice when resistance is suspected, provided it is given at the specific dose and frequency identified in the simulations. By moving away from guesswork and toward a strategy that accounts for the unique physiology of each newborn, these findings offer a practical path to saving lives. The work does not claim to have solved the problem of antibiotic resistance, but it does provide a concrete, locally tested framework for using the tools at hand more effectively, ensuring that the medicine meant to heal does not inadvertently cause harm.