Intermittent Meropenem therapy as effective as continuous therapy in sepsis patients: JAMA

Continuous meropenem medication did not enhance the composite outcome of death and the development of pandrug-resistant or substantially drug-resistant bacteria at day 28 in critically sick sepsis patients as compared to intermittent delivery, says an article published in the Journal of American Medical Association.

An extremely popular beta-lactam antibiotic is meropenem. When administered as a continuous infusion to maintain drug levels above the minimum inhibitory concentration, meropenem demonstrates its highest pharmacodynamic effectiveness. Continuous meropenem dosing may lead to better clinical results than intermittent administration. Giacomo Monti and his team conducted this study to see if continuous meropenem administration in critically ill sepsis patients reduces a composite of mortality and the emergence of pandrug-resistant or extensively drug-resistant bacteria in comparison to intermittent administration.

This was a randomized, double-blind clinical trial that enrolled patients in 31 intensive care units at 26 hospitals in 4 nations (Croatia, Kazakhstan, Italy, and Russia) who were critically sick and had sepsis or septic shock and had been administered meropenem by their treating doctors. Between June 5, 2018, and August 9, 2022, patients were enrolled; the last 90-day follow-up was finished in November 2022. Meropenem, an antibiotic, was randomly administered to patients in equal doses either continuously (n = 303) or intermittently (n = 304). On day 28, a composite of all-cause mortality and the appearance of microorganisms that were extensively or widely drug-resistant was the main result.

The key findings of this study were:

All 607 patients underwent the 90-day mortality follow-up and were counted in the measurement of the 28-day main outcome.

Septic shock was present in 369 individuals, or 61% of the total.

The median length of meropenem treatment was 11 days (IQR, 6-17 days), while the median time from hospital admission to randomization was 9 days.

There was just one crossover occurrence noted.

In the continuous administration group, 142 patients (47%) and in the intermittent administration group, 149 patients (49%) experienced the main result.

None of the four secondary results reached statistical significance.

There were no documented seizures or allergic reactions associated with the trial medication.

Both the continuous treatment group and the intermittent administration group had death rates of 42% at 90 days.

Reference:

Monti, G., Bradić, N., Marzaroli, M., Konkayev, A., Fominskiy, E., Kotani, Y., Likhvantsev, V. V., Momesso, E., Nogtev, P., Lobreglio, R., Redkin, I., Toffoletto, F., Scandroglio, A. M., Gallicchio, F., … Ballestra, M. (2023). Continuous vs Intermittent Meropenem Administration in Critically Ill Patients With Sepsis. In JAMA. American Medical Association (AMA). https://doi.org/10.1001/jama.2023.10598