The carbapenems are beta-lactam antibiotics with a broad spectrum of activity against gram-negative, gram-positive, and anaerobic organisms.1-3 They work by inhibiting bacterial cell wall synthesis by binding to penicillin binding proteins.1-3 Carbapenems should generally be reserved when narrow spectrum antibiotics cannot be utilized due to documented or suspected resistance.4 They are often utilized as the drug of choice for ESBL-producing aerobic gram-negative bacilli when susceptible and indicated.1-3 Of note, the carbapenems do not provide coverage against Methicillin Resistant Staphylococcus Aureus.1-3
As a class, all carbapenems can cause seizures, especially in those with CNS disorders, and can reduce serum concentrations of valproic acid or divalproex sodium.1-3 Concomitant use is not recommended and alternative antibiotic therapy and/or supplemental anticonvulsant therapy should be considered.1-3 Probenecid can also increase the serum concentrations of the carbapenems and is therefore not recommended.1-3 Patients should also be monitored for Clostridioides difficile diarrhea.1-3 Additionally, the carbapenems should be avoided in patients with history of serious anaphylactic beta-lactam hypersensitivity reactions.1-3
The first carbapenem antibiotic, imipenem-cilastatin, was approved in 1985 as a combination of a carbapenem (imipenem) and a renal dehydropeptidase inhibitor (cilastatin).2 Cilastatin blocks enzymatic degradation of imipenem by renal dehydropeptidase, thus preventing renal metabolism of imipenem.2 It is usually dosed every 6 hours and requires renal dose adjustment.2 In addition to valproic acid and divalproex, concomitant use of imipenem-cilastatin with ganciclovir is not recommended due to increased risk of generalized seizures.2 The combination of imipenem/cilastatin/relebactam was approved in 2019 and added relebactam as a beta-lactamase inhibitor.5 Relebactam has been shown to inhibit Ambler class A enzymes (including ESBLs and KPC) and class C enzymes (AmpC).5 Imipenem/cilastatin/relebactam is approved for the treatment of hospital acquired bacterial pneumonia and ventilator associated pneumonia, complicated urinary tract infections and complicated intra-abdominal infections for drug resistant organisms.5
Meropenem was FDA approved in 1996 and is often used for the treatment of complicated skin and skin structure infections, complicated intra-abdominal infections and adds coverage against bacterial meningitis.3 It is frequently dosed every 8 hours, however requires renal dose adjustment.3 Rhabdomyolysis has also been reported with meropenem and the agent should be discontinued if signs and symptoms occur.3 Meropenem-vaborbactam was approved in 2017 and adds a beta-lactamase inhibitor for the treatment of complicated urinary tract infections cause by susceptible bacteria.6 The addition of vaborbactam protects meropenem from degradation from certain beta-lactamases, such as KPC.6 Notably, meropenem and vaborbactam can reduce the effectiveness of hormonal contraceptives and effective non-hormonal forms of contraception are recommended during treatment.6
What You Need to Know
Carbapenems are broad-spectrum beta-lactam antibiotics reserved for resistant infections (notably ESBL-producing gram-negative bacteria), but they carry class-wide risks like seizures and drug interactions with valproic acid and probenecid, and should only be used when narrower options aren't viable.
Each carbapenem has distinct features—ertapenem offers convenient once-daily dosing but lacks Pseudomonas coverage, while newer combinations like imipenem-cilastatin-relebactam and meropenem-vaborbactam add beta-lactamase inhibitors for multidrug-resistant organisms—and the 2026 IDSA guidance now recommends specific agents based on patient severity and infection type.
The June 2026 FDA approval of tebipenem pivoxil, the first oral carbapenem in the US, offers a new option for complicated UTIs caused by resistant organisms, potentially reducing hospital stays tied to IV therapy, though it should currently be reserved for cases with no other treatment alternatives.
Approved in 2001, ertapenem is a once daily intravenous carbapenem often used for broad spectrum coverage of complicated intra-abdominal, skin and skin structure, community acquired pneumonia, complicated urinary tract infections, surgical site infection prophylaxis, and acute pelvic infections.1 Ertapenem offers convenient once daily intravenous dosing and requires renal dose adjustments, however unlike the other carbapenems, it does not provide coverage against Pseudomonas aeruginosa.1 Ertapenem can also be mixed with lidocaine and administered intramuscularly when indicated.1 Co-administration with probenecid can interfere with the tubular secretion of ertapenem, resulting in increases in concentration, which is not recommended.1 Ertapenem also does not provide activity against Enterococcus faecalis.1
The Infectious Disease Society of America (IDSA) published 2026 Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections.7 The guidance suggests intravenous carbapenems (ertapenem, meropenem and imipenem-cilastatin) as the drugs of choice for several multi drug resistant infections, including complicated urinary tract infections and other infections outside of the urinary tract caused by ESBL-Enterobacterales, where toxicities, resistance or intolerance preclude the use of trimethoprim-sulfamethoxazole or fluoroquinolones.7 Imipenem or meropenem are preferred for patients who are critically ill or have hypoalbuminemia.7 Newer beta-lactam-beta-lactamase inhibitors, including meropenem-vaborbactam and imipenem-cilastatin-relebactam, should be reserved for infections caused by MDROs, including those exhibiting carbapenem resistance.7 Additional information and further guidance on this guideline update will be provided in a separate article.
On June 17, 2026, the United States Food and Drug Administration approved tebipenem pivoxil, the first oral carbapenem in the United States approved for complicated urinary tract infections (cUTI) in adults, including pyelonephritis, caused by susceptible microorganisms where limited to no alternative treatment options are available, including Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae species complex, Klebsiella oxytoca, and Enterococcus faecalis.8,9 This recent approval of tebipenem pivoxil has the potential to provide an oral option for complicated urinary tract infections due to susceptible organisms where intravenous carbapenems may have been the only other treatment option, particularly ESBL producing Enterobacterales.4,8,9 Tebipenem pivoxil has shown activity against ESBL producing Enterobacterales, including isolates that are resistant to fluoroquinolones and/or trimethoprim-sulfamethoxazole.8 Approval of tebipenem pivoxil was based on the results of the PIVOT-PO trial.8-10 This trial was a randomized, double-blind, non-inferiority phase 3 trial, which compared the safety and efficacy of tebipenem pivoxil to imipenem-cilastatin in adult patients hospitalized with cUTI or acute pyelonephritis.8-10 The results showed oral tebipenem pivoxil was noninferior to imipenem-cilastatin and demonstrated comparable efficacy in individuals with ESBL producing Enterobacterales.8-10 Approval of an oral carbapenem adds to the unmet need of oral treatment options for difficult to treat multi-drug resistant organisms where carbapenems would be a preferred treatment option.
The typical dose of tebipenem pivoxil is 600mg every 6 hours for 7-10 days and requires renal dose adjustment when eGFR falls below 60 mL/min.8 In addition to the contradictions seen with all other carbapenems, tebipenem is contraindicated in patients with carnitine deficiency or inborn errors of metabolism that may result in carnitine deficiency.8 Additionally, it should also not be co-administered with valproic acid, probenecid or other pivalate-generating medications.8 Utilizing an oral carbapenem and avoiding intravenous agents could potentially decrease hospital stays, thus reducing hospital costs and risks of home intravenous antibiotic therapy.4 Until more data are available and guidelines are updated, oral tebipenem pivoxil should be reserved for individuals with complicated urinary tract infections with no other treatment options and documented susceptibility.8
References
INVANZ [Prescribing Information]. Rahway, NJ. Merck & Co., Inc. February 2026.
PRIMAXIN [Prescribing Information]. Rahway, NJ. Merck & Co., Inc. May 2022.
MERREM [Prescribing Information]. New York, NY. Pfizer Inc. December 2024.
Sayood S, Neuner E, Dumm R, Gandra S. The oral penems and carbapenems. Clin Microbiol Rev. 2025; 38(4): e00042-24. https://doi.org/10.1128/cmr.00042-24
RECARBRIO [Prescribing Information]. Rahway, NJ. Merck & Co., Inc. December 2025.
VABOMERE [Prescribing Information]. Parsippany, NJ. Melinta Therapeutics, LLC. February 2026.
Tamma PD, Bonomo RA, Heil EL. Infectious Disease Society of America 2026 Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections. Accessed July 31, 2026. https://www.idsociety.org/practice-guideline/amr-guidance/
UTEBZI [Prescribing Information]. Durham, NC. GlaxoSmithKline. June 2026.
United States Food and Drug Administration. FDA approves first oral carbapenem therapy for complicated urinary tract infections. Accessed July 28, 2026. Updated June 17, 2026. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-oral-carbapenem-therapy-complicated-urinary-tract-infections
National Library of Medicine. A Study of Oral Tebipenem Pivoxil Hydrobromide (TBP-PI-HBr) Compared to Intravenous Imipenem-cilastatin in Participants with Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP) (PIVOT-PO). ClinicalTrials.gov. Accessed July 30, 2026. Updated March 10, 2026.https://clinicaltrials.gov/study/NCT06059846
