ertapenem
Regulatory sources consulted
Approved indications
- Intra-abdominal infections, community-acquired pneumonia, acute gynecologic infections and diabetic foot infections, and colorectal prophylaxis, caused by susceptible organisms.
Contraindications
Absolute
- Hypersensitivity to ertapenem or other carbapenems, or a history of a severe immediate reaction to another beta-lactam.
Clinical warnings
- Major warning · Severe hypersensitivity or anaphylaxis may occur; review beta-lactam allergy history and discontinue if an allergic reaction develops. — CIMA/AEMPS, ficha técnica 02216001
- Major warning · Clostridioides difficile-associated diarrhea and colitis may occur during or after treatment; assess significant diarrhea. — CIMA/AEMPS, ficha técnica 02216001
- Major warning · Accumulation, especially with renal impairment or unadjusted doses, may cause encephalopathy, myoclonus, or seizures; adjust for renal function and monitor neurologic status. — CIMA/AEMPS, ficha técnica 02216001
Drug interactions
- HighValproic acid and valproate
Mechanism: Carbapenems rapidly and markedly lower valproate concentrations, risking loss of seizure control.
Recommendation: Avoid the combination; consider another antibacterial or anticonvulsant. Level monitoring alone may be insufficient.
CIMA/AEMPS, ficha técnica 02216001
- ModerateProbenecid
Mechanism: Probenecid increases exposure by reducing renal elimination.
Recommendation: Avoid the combination when advised by the label or monitor for adverse reactions.
CIMA/AEMPS, ficha técnica 02216001
Adverse events
Common (≥1%)
Nausea, diarrhea, and rash
Rare but serious
Anaphylaxis, C. difficile colitis, and severe cytopenias
Pregnancy and lactation
During pregnancy, use only when clinically indicated. Assess breastfeeding according to milk exposure and the infant’s condition described in the product information.
Recent literature (PubMed)
SUMMARYThe carbapenems remain some of the most effective options available for treating patients with serious infections due to Gram-negative bacteria. Carbapenemases are enzymes that hydrolyze carbapenems and are the primary method driving carbapenem resistance globally. Detection of carbapenemases is required for patient management, the rapid implementation of infection prevention and control (IP&C) protocols, and for epidemiologic purposes. Therefore, clinical and public health microbiology laboratories must be able to detect and report carbapenemases among predominant Gram-negative organisms from both cultured isolates and direct from clinical specimens for treatment and surveillance purposes. There is not a "one size fits all" laboratory approach for the detection of bacteria with carbapenemases, and institutions need to determine what fits best with the goals of their antimicrobial stewardship and IP&C programs. Luckily, there are several options and approaches available for clinical laboratories to choose methods that best suits their individual needs. A laboratory approach to detect carbapenemases among bacterial isolates consists of two steps, namely a screening process (e.g., not susceptible to ertapenem, meropenem, and/or imipenem), followed by a confirmation test (i.e., phenotypic, genotypic or proteomic methods) for the presence of a carbapenemase. Direct from specimen testing for the most common carbapenemases generally involves detection via rapid, molecular approaches. The aim of this article is to provide brief overviews on Gram-negative bacteria carbapenem-resistant definitions, types of carbapenemases, global epidemiology, and then describe in detail the laboratory methods for the detection of carbapenemases among Gram-negative bacteria. We will specifically focus on the Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii complex. Limited information indicates that ertapenem produces low levels in milk that are not expected to ca
Antibiotic therapy is effective and safe for uncomplicated acute appendicitis in adults, but randomized clinical trial results exceeding 5 years are missing. To determine the 10-year appendicitis recurrence and appendectomy rate in patients with uncomplicated appendicitis treated with antibiotics. Ten-year observational follow-up of patients in the Appendicitis Acuta (APPAC) multicenter randomized clinical trial comparing appendectomy with antibiotics at 6 Finnish hospitals from November 2009 to June 2012, where 530 patients (aged 18-60 years) with uncomplicated acute appendicitis diagnosed by computed tomography were randomly assigned to appendectomy (n = 273) or antibiotics (n = 257). Last follow-up was April 29, 2024. This current analysis focused on assessing the 10-year appendicitis recurrence rate among patients assigned to antibiotics. Open appendectomy vs antibiotics with intravenous ertapenem sodium (1 g/d) for 3 days followed by 7 days of oral levofloxacin (500 mg once daily) and metronidazole (500 mg 3 times/d). Prespecified 10-year secondary end points included late (after 1 year) appendectomy and appendicitis recurrence rate after antibiotics and complications. Post hoc outcomes included the detection of possible appendiceal tumors among patients in the antibiotic group undergoing appendectomy or with an intact appendix using magnetic resonance imaging. Additional post hoc outcomes were quality of life and patient satisfaction. At 10-year follow-up, 253/257 patients (98.4%) randomized to receive antibiotics (median age, 33 years; 102 [40.3%] female) were assessed for appendicitis recurrence, with a true appendicitis recurrence rate (appendicitis at histopathology) of 37.8% (95% CI, 31.6%-44.1% [87/230]) and a cumulative appendectomy rate of 44.3% (95% CI, 38.2%-50.4% [112/253]). Overall, the 10-year cumulative complication rate in the group randomized to appendectomy was 27.4% (95% CI, 21.6%-33.3% [62/226]) and 8.5% (95% CI, 4.8%-12.1% [19/224]) in the
Subcutaneous (SC) administration of antibiotics represents an attractive alternative to the intravenous (IV) route. We performed a systematic electronic search of PubMed and the Cochrane Library for all articles published prior to April 2022, using the key terms and MeSH terms 'subcutaneous', 'antibiotic' and the international non-proprietary name of antibiotics. A total of 30 studies were selected including data on the efficacy and tolerability of antibiotics, and seven studies that were conducted in healthy subjects, for relevant information regarding the safety and tolerability of antibiotics. Comparative studies have shown that efficacy is similar for the SC and IV routes for ceftriaxone, teicoplanin and ertapenem. The SC use of other antibiotics such as ampicillin, ceftazidime, cefepime, piperacillin/tazobactam, metronidazole and fosfomycin has also been described. These results have largely been corroborated by pharmacokinetic/pharmacodynamic analyses, especially for time-dependent antibiotics. Complications of SC treatment are rarely severe, with no reports of bacteraemia or other invasive infection related to this route of administration. Therapeutic drug monitoring has been proposed to adapt the dose and avoid toxicity. The rationale for using SC administration of ceftriaxone, ertapenem and teicoplanin is strong in patients with non-severe infections. It is already commonly practised in some countries, particularly in France. Other antibiotics could be administered subcutaneously, but further studies are needed to validate their use in clinical practice. Further research is needed to safely generalize and optimize this route of administration whenever possible. This would reduce the risk of catheter-related infections and their complications, together with the length of hospital stay.
There is a need for oral antibiotic agents that are effective against multidrug-resistant gram-negative uropathogens. Tebipenem pivoxil hydrobromide is an orally bioavailable carbapenem with activity against uropathogenic Enterobacterales, including extended-spectrum beta-lactamase-producing and fluoroquinolone-resistant strains. In this phase 3, international, double-blind, double-dummy trial, we evaluated the efficacy and safety of orally administered tebipenem pivoxil hydrobromide as compared with intravenous ertapenem in patients with complicated urinary tract infection or acute pyelonephritis. Patients were randomly assigned, in a 1:1 ratio, to receive oral tebipenem pivoxil hydrobromide (at a dose of 600 mg every 8 hours) or intravenous ertapenem (at a dose of 1 g every 24 hours) for 7 to 10 days (or up to 14 days in patients with bacteremia). The primary efficacy end point was overall response (a composite of clinical cure and favorable microbiologic response) at a test-of-cure visit (on day 19, within a ±2-day window) in the microbiologic intention-to-treat population. The noninferiority margin was 12.5%. A total of 1372 hospitalized adult patients were enrolled; 868 patients (63.3%) were included in the microbiologic intention-to-treat population (50.8% of whom had complicated urinary tract infections and 49.2% of whom had pyelonephritis). An overall response was seen in 264 of 449 patients (58.8%) who received tebipenem pivoxil hydrobromide, as compared with 258 of 419 patients (61.6%) who received ertapenem (weighted difference, -3.3 percentage points; 95% confidence interval [CI], -9.7 to 3.2). Clinical cure at the test-of-cure visit was observed in 93.1% of the patients in the microbiologic intention-to-treat population who received tebipenem pivoxil hydrobromide and 93.6% of patients who received ertapenem (weighted difference, -0.6 percentage point; 95% CI, -4.0 to 2.8); the majority of patients with microbiologic response failures at the test-of-cure