meropenem
Regulatory sources consulted
Approved indications
- Serious infections caused by susceptible organisms, including pneumonia, complicated urinary or intra-abdominal infections, puerperal infections, skin infections, meningitis, and febrile neutropenia.
Contraindications
Absolute
- Hypersensitivity to meropenem 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 83988
- Major warning · Clostridioides difficile-associated diarrhea and colitis may occur during or after treatment; assess significant diarrhea. — CIMA/AEMPS, ficha técnica 83988
- 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 83988
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 83988
- 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 83988
- HighOral anticoagulants
Mechanism: It may increase anticoagulant effect.
Recommendation: Monitor INR during and after treatment.
CIMA/AEMPS, ficha técnica 83988
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)
There is a need for additional therapeutic options for serious infections caused by Gram-negative pathogens. In the phase 3, descriptive REVISIT study, we investigated the safety and efficacy of aztreonam-avibactam in the treatment of complicated intra-abdominal infections or hospital-acquired pneumonia or ventilator-associated pneumonia (HAP-VAP) caused, or suspected to be caused, by Gram-negative bacteria. This prospective, multinational, open-label, central assessor-masked study enrolled adults who were hospitalised with a complicated intra-abdominal infection or HAP-VAP. Patients were randomly allocated via block randomisation using interactive response technology stratified by infection type in a 2:1 ratio to aztreonam-avibactam (with metronidazole for complicated intra-abdominal infection) or meropenem with or without colistin for 5-14 days for complicated intra-abdominal infection or 7-14 days for HAP-VAP. The primary endpoint was clinical cure at the test-of-cure visit (within 3 days before or after day 28) in the intention-to-treat (ITT) population. Secondary endpoints included 28-day mortality in the ITT population and safety in patients in the ITT population who received study drug (safety analysis set). No formal hypothesis testing was planned. The study was registered with ClinicalTrials.gov (NCT03329092) and EudraCT (2017-002742-68) and is complete. Between April 5, 2018, and Feb 23, 2023, we screened 461 patients. 422 patients were enrolled and randomly allocated (282 in the aztreonam-avibactam group and 140 in the meropenem group, forming the ITT analysis set), of whom ten patients (seven in the aztreonam-avibactam group and three in the meropenem group) were randomly allocated but did not receive study treatment. 271 (64%) of 422 patients had at least one Gram-negative pathogen from an adequate specimen identified at baseline. The most frequent baseline pathogens were Enterobacterales (252 [93%] of 271). Overall, 19 (24%) of 80 isolates tested for c
Whether β-lactam antibiotics administered by continuous compared with intermittent infusion reduces the risk of death in patients with sepsis is uncertain. To evaluate whether continuous vs intermittent infusion of a β-lactam antibiotic (piperacillin-tazobactam or meropenem) results in decreased all-cause mortality at 90 days in critically ill patients with sepsis. An international, open-label, randomized clinical trial conducted in 104 intensive care units (ICUs) in Australia, Belgium, France, Malaysia, New Zealand, Sweden, and the United Kingdom. Recruitment occurred from March 26, 2018, to January 11, 2023, with follow-up completed on April 12, 2023. Participants were critically ill adults (≥18 years) treated with piperacillin-tazobactam or meropenem for sepsis. Eligible patients were randomized to receive an equivalent 24-hour dose of a β-lactam antibiotic by either continuous (n = 3498) or intermittent (n = 3533) infusion for a clinician-determined duration of treatment or until ICU discharge, whichever occurred first. The primary outcome was all-cause mortality within 90 days after randomization. Secondary outcomes were clinical cure up to 14 days after randomization; new acquisition, colonization, or infection with a multiresistant organism or Clostridioides difficile infection up to 14 days after randomization; ICU mortality; and in-hospital mortality. Among 7202 randomized participants, 7031 (mean [SD] age, 59 [16] years; 2423 women [35%]) met consent requirements for inclusion in the primary analysis (97.6%). Within 90 days, 864 of 3474 patients (24.9%) assigned to receive continuous infusion had died compared with 939 of 3507 (26.8%) assigned intermittent infusion (absolute difference, -1.9% [95% CI, -4.9% to 1.1%]; odds ratio, 0.91 [95% CI, 0.81 to 1.01]; P = .08). Clinical cure was higher in the continuous vs intermittent infusion group (1930/3467 [55.7%] and 1744/3491 [50.0%], respectively; absolute difference, 5.7% [95% CI, 2.4% to 9.1%]). Other secon
Klebsiella pneumoniae carbapenemase (KPC) variants, which refer to the substitution, insertion, or deletion of amino acid sequence compared to wild blaKPC type, have reduced utility of ceftazidime-avibactam (CZA), a pioneer antimicrobial agent in treating carbapenem-resistant Enterobacterales infections. So far, more than 150 blaKPC variants have been reported worldwide, and most of the new variants were discovered in the past 3 years, which calls for public alarm. The KPC variant protein enhances the affinity to ceftazidime and weakens the affinity to avibactam by changing the KPC structure, thereby mediating bacterial resistance to CZA. At present, there are still no guidelines or expert consensus to make recommendations for the diagnosis and treatment of infections caused by KPC variants. In addition, meropenem-vaborbactam, imipenem-relebactam, and other new β-lactam-β-lactamase inhibitor combinations have little discussion on KPC variants. This review aims to discuss the clinical characteristics, risk factors, epidemiological characteristics, antimicrobial susceptibility profiles, methods for detecting blaKPC variants, treatment options, and future perspectives of blaKPC variants worldwide to alert this new great public health threat.
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. Doripenem is no longer marketed in the US. No information is available on the clinical use of doripe