Is the subcutaneous route an alternative for administering ertapenem to older patients? PHACINERTA study

Background: Antibiotic administration by subcutaneous (SC) injection is common practice in French geriatric wards as an alternative to the intravenous (IV) route, but few pharmacokinetic/pharmacodynamic data are available. Ertapenem is useful for the treatment of infections with ESBL-producing enterobacteria. Objectives: To report and compare ertapenem pharmacokinetic data between IV and SC routes in older persons. Methods: Patients >65years of age receiving ertapenem (1g once daily) for at least 48h (IV or SC, steady-state) were prospectively enrolled. Total ertapenem concentrations [residual (C-0), IV peak (C-0.5) and SC peak (C-2.5)] were determined by UV HPLC. Individual-predicted AUC(0-24) values were calculated and population pharmacokinetic analyses were performed. Using the final model, a Monte Carlo simulation involving 10000 patients evaluated the influence of SC or IV administration on the PTA. Tolerance to ertapenem and recovery were also monitored. ClinicalTrials.gov identifier: NCT02505386. Results: Ten (mean +/- SD age = 87 +/- 7years) and 16 (age = 88 +/- 5 years) patients were included in the IV and SC groups, respectively. The mean C-0 and C-2.5 values were not significantly different between the IV and SC groups (C-0 = 12 +/- 5.9 versus 12 +/- 7.4mg/L, P = 0.97; C-2.5 = 97 +/- 42 versus 67 +/- 41 mg/L, P = 0.99). The mean C-0.5 was higher in the IV group compared with the SC group (C-0.5 = 184 +/- 90 versus 51 +/- 66 mg/L, P = 0.001). The mean individual AUCs (1126.92 +/- 334.99 mg.h/L for IV versus 1005.3 +/- 266.0 mg.h/L for SC, P = 0.38) and PTAs were not significantly different between groups. No severe antibiotic-related adverse effects were noted. Conclusions: SC administration of ertapenem is an alternative to IV administration in older patients.