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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.
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.
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.
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.
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.
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".
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.
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.
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.
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.
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 in 2015 for treating complicated urinary tract (cUTI) and complicated intra-abdominal infections (cIAI) caused by antibiotic-resistant pathogens, including those caused by multidrug resistant Gram-negative bacterial pathogens.
Ceftolozane/tazobactam, sold under the brand name Zerbaxa, (Merck) 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.
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.
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.
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.
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.
Imipenem/cilastatin/relebactam, sold under the brand name Recarbrio(Merck), 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
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- 1 2 3 4 "Vaborem EPAR". European Medicines Agency. 24 September 2018. Retrieved 6 November 2019.
- 1 2 3 4 5 6 7 8 "Vabomere (combination) Monograph for Professionals". Drugs.com. Retrieved 6 November 2019.
- ↑ "Meropenem / vaborbactam (Vabomere) Use During Pregnancy". Drugs.com. Retrieved 6 November 2019.
- ↑ 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.
- 1 2 3 "FDA approves new antibacterial drug" (Press release). U.S. Food and Drug Administration (FDA). 29 August 2017.
This article incorporates text from this source, which is in the public domain . - ↑ 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.
{{cite journal}}: CS1 maint: overridden setting (link) - ↑ Hanretty AM, Kaur I, Evangelista AT, Moore WS, Enache A, Chopra A, et al. (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.
