An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of such infections. They may either kill or inhibit the growth of bacteria. A limited number of antibiotics also possess antiprotozoal activity. Antibiotics are not effective against viruses such as the common cold or influenza; drugs which inhibit growth of viruses are termed antiviral drugs or antivirals rather than antibiotics. They are also not effective against fungi; drugs which inhibit growth of fungi are called antifungal drugs.
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.
Enterococcus is a large genus of lactic acid bacteria of the phylum Bacillota. Enterococci are gram-positive cocci that often occur in pairs (diplococci) or short chains, and are difficult to distinguish from streptococci on physical characteristics alone. Two species are common commensal organisms in the intestines of humans: E. faecalis (90–95%) and E. faecium (5–10%). Rare clusters of infections occur with other species, including E. casseliflavus, E. gallinarum, and E. raffinosus.
Klebsiella pneumoniae is a Gram-negative, non-motile, encapsulated, lactose-fermenting, facultative anaerobic, rod-shaped bacterium. It appears as a mucoid lactose fermenter on MacConkey agar.
The cephalosporins are a class of β-lactam antibiotics originally derived from the fungus Acremonium, which was previously known as Cephalosporium.
Colistin, also known as polymyxin E, is an antibiotic medication used as a last-resort treatment for multidrug-resistant Gram-negative infections including pneumonia. These may involve bacteria such as Pseudomonas aeruginosa, Klebsiella pneumoniae, or Acinetobacter. It comes in two forms: colistimethate sodium can be injected into a vein, injected into a muscle, or inhaled, and colistin sulfate is mainly applied to the skin or taken by mouth. Colistimethate sodium is a prodrug; it is produced by the reaction of colistin with formaldehyde and sodium bisulfite, which leads to the addition of a sulfomethyl group to the primary amines of colistin. Colistimethate sodium is less toxic than colistin when administered parenterally. In aqueous solutions it undergoes hydrolysis to form a complex mixture of partially sulfomethylated derivatives, as well as colistin. Resistance to colistin began to appear as of 2015.
Cephems are a sub-group of β-lactam antibiotics including cephalosporins and cephamycins. It is one of the most common 4-membered ring heterocycle. Produced by actinomycetes, cephamycins were found to display antibacterial activity against a wide range of bacteria, including those resistant to penicillin and cephalosporins. The antimicrobial properties of Cephem include the attachment to certain penicillin-binding proteins that are involved in the production of cell walls of bacteria.
Carbapenems are a class of very effective antibiotic agents most commonly used for the 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.
Imipenem is an intravenous β-lactam antibiotic discovered by Merck scientists Burton Christensen, William Leanza, and Kenneth Wildonger in the mid-1970s. Carbapenems are highly resistant to the β-lactamase enzymes produced by many multiple drug-resistant Gram-negative bacteria, thus playing a key role in the treatment of infections not readily treated with other antibiotics.
Acinetobacter baumannii is a typically short, almost round, rod-shaped (coccobacillus) Gram-negative bacterium. It is named after the bacteriologist Paul Baumann. It can be an opportunistic pathogen in humans, affecting people with compromised immune systems, and is becoming increasingly important as a hospital-derived (nosocomial) infection. While other species of the genus Acinetobacter are often found in soil samples, it is almost exclusively isolated from hospital environments. Although occasionally it has been found in environmental soil and water samples, its natural habitat is still not known.
Cefoxitin is a second-generation cephamycin antibiotic developed by Merck & Co., Inc. from Cephamycin C in the year following its discovery, 1972. It was synthesized in order to create an antibiotic with a broader spectrum. It is often grouped with the second-generation cephalosporins. Cefoxitin requires a prescription and as of 2010 is sold under the brand name Mefoxin by Bioniche Pharma, LLC. The generic version of cefoxitin is known as cefoxitin sodium.
Thienamycin is one of the most potent naturally produced antibiotics known thus far, discovered in Streptomyces cattleya in 1976. Thienamycin has excellent activity against both Gram-positive and Gram-negative bacteria and is resistant to bacterial β-lactamase enzymes. Thienamycin is a zwitterion at pH 7.
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.
A penem is a type of β-lactam with an unsaturated five-member heterocycle containing a sulfur atom fused to the β-lactam ring. Penems do not occur naturally; all are synthetic. Related to penems are carbapenems, which have a carbon atom in place of the sulfur atom.
Multidrug resistant Gram-negative bacteria are a type of Gram-negative bacteria with resistance to multiple antibiotics. They can cause bacteria infections that pose a serious and rapidly emerging threat for hospitalized patients and especially patients in intensive care units. Infections caused by MDR strains are correlated with increased morbidity, mortality, and prolonged hospitalization. Thus, not only do these bacteria pose a threat to global public health, but also create a significant burden to healthcare systems.
Carbapenem-resistant Enterobacteriaceae (CRE) or carbapenemase-producing Enterobacteriaceae (CPE) are Gram-negative bacteria that are resistant to the carbapenem class of antibiotics, considered the drugs of last resort for such infections. They are resistant because they produce an enzyme called a carbapenemase that disables the drug molecule. The resistance can vary from moderate to severe. Enterobacteriaceae are common commensals and infectious agents. Experts fear CRE as the new "superbug". The bacteria can kill up to half of patients who get bloodstream infections. Tom Frieden, former head of the Centers for Disease Control and Prevention has referred to CRE as "nightmare bacteria". Examples of enzymes found in certain types of CRE are KPC and NDM. KPC and NDM are enzymes that break down carbapenems and make them ineffective. Both of these enzymes, as well as the enzyme VIM have also been reported in Pseudomonas.
Tebipenem is a broad-spectrum orally-administered antibiotic, from the carbapenem subgroup of β-lactam antibiotics. It was developed as a replacement drug to combat bacteria that had acquired antibiotic resistance to commonly used antibiotics. Tebipenem is formulated as the ester tebipenem pivoxil due to the better absorption and improved bioavailability of this form. It has performed well in clinical trials for ear infection and looks likely to be further developed in future. It is only marketed in Japan. Tebipenem is the first carbapenem whose prodrug form, the pivalyl ester, is orally available.
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.
Karen Bush is an American biochemist. She is a Professor of Practice in Biology at Indiana University and the interim director of the Biotechnology program. Bush conducts research focusing on bacterial resistance mechanisms to beta-lactam antibiotics.
Kerry L. LaPlante is an American pharmacist, academic and researcher. She is a Professor of Pharmacy and the Chair of the Department of Pharmacy Practice at the University of Rhode Island, an Adjunct Professor of Medicine at Brown University, an Infectious Diseases Pharmacotherapy Specialist, and the Director of the Rhode Island Infectious Diseases Fellowship and Research Programs at the Veterans Affairs Medical Center in Providence, Rhode Island.
