Stability and antibacterial activity of cefepime during continuous infusion

Abstract

The stability of cefepime during simulated continuous infusion was determined with a motorized portable infusion pump worn over a period of 24 to 36 h. Susceptibility testing on cefepime solutions over time indicates that the degradation products do not exhibit antibacterial activity. Cefepime stability at 24 h following continuous infusion was 94.3% +/- 1.0%, which supports the use of continuous infusion.

FIG. 1.

Left panel, stability of cefepime solution under refrigerated and freezer storage conditions. Each set of paired columns represents one storage condition (shaded bar) and stability after storage and use as a 24-h simulated CI (unshaded bar). Ninety percent stability is indicated by the dashed line. Right panel, variability in temperature throughout the 24-h CI period.

FIG. 2.

(A) Degradation of cefepime at 37°C. Observed degradation curve (solid line) and the measured pH during the cefepime degradation (dashed line). When the pH increases as a result of cefepime breakdown, cefepime degradation deviates from predicted first-order kinetics. Inset shows the Arrhenius plot of the degradation of cefepime (k) at four different temperatures ranging from 1°C to 55°C. Temperatures on the x axis are measured in kelvins. A log linear relationship exists between the degradation of cefepime and temperature (r² > 0.99), with a slope of −4.16 × 10³ and intercept of 11.4. The activation energy was calculated to be 81.4 kJ mol⁻¹ K⁻¹. (B) Antibacterial activity during cefepime degradation. The apparent MIC increases proportionally with the percentage of cefepime remaining (first-order polynomial, r² > 0.73; second-order polynomial, r² > 0.90), which indicates that the degradation products do not exhibit significant antibacterial activity.