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

Abstract

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 >65 years of age receiving ertapenem (1 g once daily) for at least 48 h (IV or SC, steady-state) were prospectively enrolled. Total ertapenem concentrations [residual (C0), IV peak (C0.5) and SC peak (C2.5)] were determined by UV HPLC. Individual-predicted AUC0–24 values were calculated and population pharmacokinetic analyses were performed. Using the final model, a Monte Carlo simulation involving 10 000 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±7 years) and 16 (age=88±5 years) patients were included in the IV and SC groups, respectively. The mean C0 and C2.5 values were not significantly different between the IV and SC groups (C0=12±5.9 versus 12±7.4 mg/L, P=0.97; C2.5=97±42 versus 67±41 mg/L, P=0.99). The mean C0.5 was higher in the IV group compared with the SC group (C0.5=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.

Outpatient Subcutaneous Antimicrobial Therapy (OSCAT) as a Measure to Improve the Quality and Efficiency of Healthcare Delivery for Patients With Serious Bacterial Infections

“…Five studies collected PK data on SC ertapenem with patients (∼60 patients) hospitalized in intensive care unit (35), ID (26,27), or geriatrics (36), they confirmed a decreased Cmax and increased time to achieve it. After a 1 g dose of ertapenem, the bioavailability was 99 ± 18% after SC administration compared with IV (35).…”

“…After a 1 g dose of ertapenem, the bioavailability was 99 ± 18% after SC administration compared with IV (35). In a population PK analysis and PK/PD simulation based on the pharmacokinetics of IV and SC ertapenem in patients with BJI in a geriatric population, SC administration resulted in slightly higher or comparable time above the MIC compared with IV (27,36).…”

Effectiveness of Subcutaneous Administration of Antibiotics to Control Infections in Elder Palliative Patients: A Systematic Review

“…The mean days of treatment were 21 days, [30][31][32][33][34][35][36] considering that the study by Pouderoux et al 35 was an outlier, as they had a particularly longer follow-up period of 433 days. The application is described to be within the hospital, 20,32,36 homes, nursing homes, acute geriatric units, rehabilitation centers, and long-term care facilities. 30,31,34,35 The preparation of the administered solution was specified in some of the studies as well as the equipment used and the time of application.…”

“…14,18 The subcutaneous (SC) route is a promising alternative to antibiotic therapy. [19][20][21] However, its use does not have solid theoretical support as highlighted by several systematic reviews. [22][23][24][25] There is a paucity of data about the capacity to achieve the needed antibiotic concentration at the site of infection through the subcutaneous route.…”

Pharmacokinetic/Pharmacodynamic Dosage Individualization of Suppressive Beta-Lactam Therapy Administered by Subcutaneous Route in Patients With Prosthetic Joint Infection

“…Three beta-lactams were used as suppressive therapy by SC route: ertapenem, ceftriaxone, and ceftazidime. Subcutaneous administration of those three drugs is still off-label in France but is supported by several clinical reports and studies (6,7,(9)(10)(11). The decision of suppressive antibiotic therapy was taken by a multidisciplinary team including infectious disease physicians, surgeons, and microbiologists.…”