Meropenem/vaborbactam

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Meropenem/vaborbactam
Combination of
Meropenem Beta-lactam antibiotic
Vaborbactam Beta-lactamase inhibitor
Clinical data
Trade names Vabomere, Vaborem, others
AHFS/Drugs.com Monograph
License data
Routes of
administration
Intravenous
ATC code
Legal status
Legal status
Identifiers
CAS Number
KEGG

Meropenem/vaborbactam, sold under the brand name Vabomere among others, is a combination medication used to treat complicated urinary tract infections, complicated abdominal infections, and hospital-acquired pneumonia. [1] [2] [3] It contains meropenem, a beta-lactam antibiotic, and vaborbactam, a beta-lactamase inhibitor. [3] It is given by injection into a vein. [3]

Contents

Common side effects include headache, inflammation at the site of injection, nausea, diarrhea, liver inflammation, and low blood potassium. [3] Severe side effects may include anaphylaxis, seizures, and Clostridioides difficile-associated diarrhea. [3] It is unclear if use during pregnancy is safe. [4] Meropenem works by blocking the construction of the bacterial cell wall while vaborbactam blocks the breakdown of meropenem by some beta-lactamases. [3]

The combination was approved for medical use in the United States in 2017, and in the European Union in 2018. [3] [2] It is on the World Health Organization's List of Essential Medicines. [5]

Medical uses

It is used to treat complicated urinary tract infections, complicated abdominal infections, and hospital-acquired pneumonia. [3] [2]

Side effects

The most common adverse reactions were headache, infusion site reactions and diarrhea. Serious risks include allergic reactions and seizures and Meropenem/vaborbactam should not be used in people with severe allergic reactions to penicillins. [6]

Antimicrobial activity

Meropenem/vaborbactam retains antimicrobial activity against class A and class C β-lactamase-producing Enterobacterales, especially those producing ESBL, KPC, and AmpC determinants. Meropenem/vaborbactam is also active against strains of Enterobacterales producing other types of class A serine carbapenemases (e.g. SME and NMC-A enzymes). Resistance to meropenem/vaborbactam in KPC-producing Enterobacterales is currently very rare and mostly due to porin inactivation. Interestingly, meropenem/vaborbactam retains activity also against strains producing KPC mutants that confer resistance to ceftazidime/avibactam (e.g., KPC-8, KPC-31). The activity of meropenem/vaborbactam against P. aeruginosa and A. baumannii was found to be similar to that of meropenem alone. In fact, in these species, meropenem resistance is largely mediated by mechanisms that are not antagonized by vaborbactam (e.g., outer-membrane impermeability, upregulation of efflux systems, and production of class B or class D β-lactamases). No antimicrobial activity has been reported for MBL-producing Gram-negatives and OXA-48-producing Enterobacterales. [7]

History

In a study of 545 adults with complicated urinary tract infections, 98 percent of adults treated with meropenem/vaborbactam compared with about 94 percent of adults treated with piperacillin/tazobactam were cured defined as improvement in symptoms and a negative urine culture. About seven days after completing treatment, roughly 77 percent of adults treated with Vabomere compared with about 73 percent of those treated with piperacillin/tazobactam had resolved symptoms and a negative urine culture. [6]

In August 2017, the US Food and Drug Administration approved the combination to treat complicated urinary tract infections and pyelonephritis. [6]

Research

Successful bacteremia clearance in a child has been reported using a meropenem-vaborbactam dose of 40 mg/kg every 6 hours given over 3 hours. It attained 100% of meropenem serum concentrations above the minimum inhibitory concentration for at least 40% of the dosing interval. [8]

Related Research Articles

<span class="mw-page-title-main">Beta-lactamase</span> Class of enzymes

Beta-lactamases (β-lactamases) are enzymes produced by bacteria that provide multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams and carbapenems (ertapenem), although carbapenems are relatively resistant to beta-lactamase. Beta-lactamase provides antibiotic resistance by breaking the antibiotics' structure. These antibiotics all have a common element in their molecular structure: a four-atom ring known as a beta-lactam (β-lactam) ring. Through hydrolysis, the enzyme lactamase breaks the β-lactam ring open, deactivating the molecule's antibacterial properties.

<span class="mw-page-title-main">Aztreonam</span> Chemical compound

Aztreonam, sold under the brand name Azactam among others, is an antibiotic used primarily to treat infections caused by gram-negative bacteria such as Pseudomonas aeruginosa. This may include bone infections, endometritis, intra abdominal infections, pneumonia, urinary tract infections, and sepsis. It is given by intravenous or intramuscular injection or by inhalation.

<span class="mw-page-title-main">Amoxicillin/clavulanic acid</span> Combination antibiotic medication

Amoxicillin/clavulanic acid, also known as co-amoxiclav or amox-clav, sold under the brand name Augmentin, among others, is an antibiotic medication used for the treatment of a number of bacterial infections. It is a combination consisting of amoxicillin, a β-lactam antibiotic, and potassium clavulanate, a β-lactamase inhibitor. It is specifically used for otitis media, streptococcal pharyngitis, pneumonia, cellulitis, urinary tract infections, and animal bites. It is taken by mouth or by injection into a vein.

<span class="mw-page-title-main">Meropenem</span> Broad-spectrum antibiotic

Meropenem, sold under the brand name Merrem among others, is an intravenous carbapenem antibiotic used to treat a variety of bacterial infections. Some of these include meningitis, intra-abdominal infection, pneumonia, sepsis, and anthrax.

<span class="mw-page-title-main">Tazobactam</span> Chemical compound

Tazobactam is a pharmaceutical drug that inhibits the action of bacterial β-lactamases, especially those belonging to the SHV-1 and TEM groups. It is commonly used as its sodium salt, tazobactam sodium.

<span class="mw-page-title-main">Piperacillin</span> Antibiotic medication

Piperacillin is a broad-spectrum β-lactam antibiotic of the ureidopenicillin class. The chemical structure of piperacillin and other ureidopenicillins incorporates a polar side chain that enhances penetration into Gram-negative bacteria and reduces susceptibility to cleavage by Gram-negative beta lactamase enzymes. These properties confer activity against the important hospital pathogen Pseudomonas aeruginosa. Thus piperacillin is sometimes referred to as an "anti-pseudomonal penicillin".

<span class="mw-page-title-main">Piperacillin/tazobactam</span> Combination antibiotic medication

Piperacillin/tazobactam, sold under the brand name Tazocin among others, is a combination medication containing the antibiotic piperacillin and the β-lactamase inhibitor tazobactam. The combination has activity against many Gram-positive and Gram-negative bacteria including Pseudomonas aeruginosa. It is used to treat pelvic inflammatory disease, intra-abdominal infection, pneumonia, cellulitis, and sepsis. It is given by injection into a vein.

<span class="mw-page-title-main">Carbapenem</span> Class of highly effective antibiotic agents

Carbapenems are a class of very effective antibiotic agents most commonly used for treatment of severe bacterial infections. This class of antibiotics is usually reserved for known or suspected multidrug-resistant (MDR) bacterial infections. Similar to penicillins and cephalosporins, carbapenems are members of the beta-lactam antibiotics drug class, which kill bacteria by binding to penicillin-binding proteins, thus inhibiting bacterial cell wall synthesis. However, these agents individually exhibit a broader spectrum of activity compared to most cephalosporins and penicillins. Furthermore, carbapenems are typically unaffected by emerging antibiotic resistance, even to other beta-lactams.

<span class="mw-page-title-main">Cefotaxime</span> Chemical compound

Cefotaxime is an antibiotic used to treat several bacterial infections in humans, other animals, and plant tissue culture. Specifically in humans it is used to treat joint infections, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, sepsis, gonorrhea, and cellulitis. It is given either by injection into a vein or muscle.

Ampicillin/sulbactam is a fixed-dose combination medication of the common penicillin-derived antibiotic ampicillin and sulbactam, an inhibitor of bacterial beta-lactamase. Two different forms of the drug exist. The first, developed in 1987 and marketed in the United States under the brand name Unasyn, generic only outside the United States, is an intravenous antibiotic. The second, an oral form called sultamicillin, is marketed under the brand name Ampictam outside the United States, and generic only in the United States. Ampicillin/sulbactam is used to treat infections caused by bacteria resistant to beta-lactam antibiotics. Sulbactam blocks the enzyme which breaks down ampicillin and thereby allows ampicillin to attack and kill the bacteria.

β-Lactamase inhibitor Drugs that inhibit β-Lactamase enzymes

Beta-lactamases are a family of enzymes involved in bacterial resistance to beta-lactam antibiotics. In bacterial resistance to beta-lactam antibiotics, the bacteria have beta-lactamase which degrade the beta-lactam rings, rendering the antibiotic ineffective. However, with beta-lactamase inhibitors, these enzymes on the bacteria are inhibited, thus allowing the antibiotic to take effect. Strategies for combating this form of resistance have included the development of new beta-lactam antibiotics that are more resistant to cleavage and the development of the class of enzyme inhibitors called beta-lactamase inhibitors. Although β-lactamase inhibitors have little antibiotic activity of their own, they prevent bacterial degradation of beta-lactam antibiotics and thus extend the range of bacteria the drugs are effective against.

<span class="mw-page-title-main">Avibactam</span> Chemical compound

Avibactam is a non-β-lactam β-lactamase inhibitor developed by Actavis jointly with AstraZeneca. A new drug application for avibactam in combination with ceftazidime was approved by the FDA on February 25, 2015, for treating complicated urinary tract (cUTI) and complicated intra-abdominal infections (cIAI) caused by antibiotic resistant-pathogens, including those caused by multi-drug resistant Gram-negative bacterial pathogens.

<span class="mw-page-title-main">Ceftolozane/tazobactam</span> Antibiotic

Ceftolozane/tazobactam, sold under the brand name Zerbaxa, is a fixed-dose combination antibiotic medication used for the treatment of complicated urinary tract infections and complicated intra-abdominal infections in adults. Ceftolozane is a cephalosporin antibiotic, developed for the treatment of infections with gram-negative bacteria that are resistant to conventional antibiotics. It was studied for urinary tract infections, intra-abdominal infections and ventilator-associated bacterial pneumonia.

<span class="mw-page-title-main">Ceftazidime/avibactam</span> Combination antibiotic medication

Ceftazidime/avibactam, sold under the brand name Avycaz among others, is a fixed-dose combination medication composed of ceftazidime, a cephalosporin antibiotic, and avibactam, a β-lactamase inhibitor. It is used to treat complicated intra-abdominal infections, urinary tract infections, and pneumonia. It is only recommended when other options are not appropriate. It is given by infusion into a vein.

<span class="mw-page-title-main">Vaborbactam</span> Chemical compound

Vaborbactam (INN) is a non-β-lactam β-lactamase inhibitor discovered by Rempex Pharmaceuticals, a subsidiary of The Medicines Company. While not effective as an antibiotic by itself, it restores potency to existing antibiotics by inhibiting the β-lactamase enzymes that would otherwise degrade them. When combined with an appropriate antibiotic it can be used for the treatment of gram-negative bacterial infections.

<span class="mw-page-title-main">Cefiderocol</span> Antibiotic

Cefiderocol, sold under the brand name Fetroja among others, is an antibiotic used to treat complicated urinary tract infections when no other options are available. It is indicated for the treatment of multi-drug-resistant Gram-negative bacteria including Pseudomonas aeruginosa. It is given by injection into a vein.

<span class="mw-page-title-main">Relebactam</span> Chemical compound

Relebactam is a chemical compound used in combination with antibiotics to improve their efficacy. As a beta-lactamase inhibitor, it blocks the ability of bacteria to break down a beta-lactam antibiotic. In the United States, relebactam is approved for use in the combination imipenem/cilastatin/relebactam (Recarbrio).

Imipenem/cilastatin/relebactam, sold under the brand name Recarbrio, is a fixed-dose combination medication used as an antibiotic. In 2019, it was approved for use in the United States for the treatment of complicated urinary tract and complicated intra-abdominal infections. It is administered via intravenous injection.

Aztreonam/avibactam, sold under the brand name Emblaveo, is a combination of aztreonam, a β-lactam antibiotic, and avibactam, a β-Lactamase inhibitor, developed by AbbVie and Pfizer for aerobic Gram-negative infections. Drug resistance to the combination has been reported.

Cefepime/enmetazobactam, sold under the brand name Exblifep, is a medication used for the treatment of urinary tract infections. It is a fixed dose combination containing cefepime, a cephalosporin antibacterial, and enmetazobactam, a beta-lactamase inhibitor.

References

  1. 1 2 "Vabomere- meropenem-vaborbactam injection, powder, for solution". DailyMed. 19 October 2023. Retrieved 26 July 2024.
  2. 1 2 3 4 "Vaborem EPAR". European Medicines Agency. 24 September 2018. Retrieved 6 November 2019.
  3. 1 2 3 4 5 6 7 8 "Vabomere (combination) Monograph for Professionals". Drugs.com. Retrieved 6 November 2019.
  4. "Meropenem / vaborbactam (Vabomere) Use During Pregnancy". Drugs.com. Retrieved 6 November 2019.
  5. World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl: 10665/325771 . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  6. 1 2 3 "FDA approves new antibacterial drug" (Press release). U.S. Food and Drug Administration (FDA). 29 August 2017.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  7. Principe L, Lupia T, Andriani L, Campanile F, Carcione D, Corcione S, et al. (April 2022). "Microbiological, Clinical, and PK/PD Features of the New Anti-Gram-Negative Antibiotics: β-Lactam/β-Lactamase Inhibitors in Combination and Cefiderocol-An All-Inclusive Guide for Clinicians". Pharmaceuticals. 15 (4): 463. doi: 10.3390/ph15040463 . PMC   9028825 . PMID   35455461.
  8. Hanretty AM, Kaur I, Evangelista AT, Moore WS, Enache A, Chopra A, Cies JJ (December 2018). "Pharmacokinetics of the Meropenem Component of Meropenem-Vaborbactam in the Treatment of KPC-Producing Klebsiella pneumoniae Bloodstream Infection in a Pediatric Patient". Pharmacotherapy. 38 (12): e87–e91. doi:10.1002/phar.2187. PMID   30300440. S2CID   52948188.