β-lactam antibiotics are a broad class of
antibioticIn common usage, an antibiotic is a substance or compound that kills or inhibits the growth of bacteria...
s that include
penicillinPenicillin is a group of antibiotics derived from Penicillium fungi. Penicillin antibiotics are historically significant because they are the first drugs that were effective against many previously serious diseases such as syphilis and Staphylococcus infections...
derivatives (
penamPenams are a subclass of the broader β-lactam family of antibiotics and related compounds. Penams contain a β-lactam ring fused to a 5-membered ring, where one of the atoms in the ring is a sulfur and the ring is fully saturated. Penicillin is a member of this family of compounds....
s),
cephalosporinThe cephalosporins are a class of β-lactam antibiotics originally derived from Acremonium, which was previously known as "Cephalosporium"....
s (
cephemCephems are a sub-group of beta-lactam antibiotics including cephalosporins and cephamycins....
s), monobactams, and
carbapenemCarbapenems are a class of beta-lactam antibiotics with a broad spectrum of antibacterial activity. They have a structure that renders them highly resistant to beta-lactamases...
s, that is, any antibiotic agent that contains a
β-lactam||-||-||-||-||-||-||}A beta-lactam ring is a lactam with a heteroatomic ring structure, consisting of three carbon atoms and one nitrogen atom...
nucleus in its molecular structure. They are the most widely-used group of antibiotics.
While not true antibiotics, the
β-lactamase inhibitorA beta-lactamase inhibitor is a drug given in conjunction with a beta-lactam antibiotic. Although the inhibitor does not usually have significant antibiotic activity on its own, it inhibits activity of beta-lactamase, a protein that confers resistance of beta-lactam antibiotics to...
s are often included in this group.
β-lactam antibiotics are indicated for the prophylaxis and treatment of
bacteriaThe bacteria are a large group of unicellular microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
l infections caused by susceptible organisms. At first, β-lactam antibiotics were mainly active only against
Gram-positiveGram-positive bacteria are those that are stained dark blue or violet by Gram staining. This is in contrast to Gram-negative bacteria, which cannot retain the crystal violet stain, instead taking up the counterstain and appearing red or pink...
bacteria, yet the recent development of broad-spectrum β-lactam antibiotics active against various
Gram-negativeGram-negative bacteria are those bacteria that do not retain crystal violet dye in the Gram staining protocol. In a Gram stain test, a counterstain is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color...
organisms has increased their usefulness.
β-Lactam antibiotics are bactericidal, and act by inhibiting the synthesis of the
peptidoglycanPeptidoglycan, also known as murein, is a polymer consisting of sugars and amino acids that forms a mesh-like layer outside the plasma membrane of bacteria, forming the cell wall. The sugar component consists of alternating residues of β- linked N-acetylglucosamine and N-acetylmuramic acid residues...
layer of bacterial
cell wallA cell wall is a tough, flexible and sometimes fairly rigid layer that surrounds some types of cells. It is located outside the cell membrane and provides these cells with structural support and protection, and also acts as a filtering mechanism. A major function of the cell wall is to act as a...
s.
β-lactam antibiotics are a broad class of
antibioticIn common usage, an antibiotic is a substance or compound that kills or inhibits the growth of bacteria...
s that include
penicillinPenicillin is a group of antibiotics derived from Penicillium fungi. Penicillin antibiotics are historically significant because they are the first drugs that were effective against many previously serious diseases such as syphilis and Staphylococcus infections...
derivatives (
penamPenams are a subclass of the broader β-lactam family of antibiotics and related compounds. Penams contain a β-lactam ring fused to a 5-membered ring, where one of the atoms in the ring is a sulfur and the ring is fully saturated. Penicillin is a member of this family of compounds....
s),
cephalosporinThe cephalosporins are a class of β-lactam antibiotics originally derived from Acremonium, which was previously known as "Cephalosporium"....
s (
cephemCephems are a sub-group of beta-lactam antibiotics including cephalosporins and cephamycins....
s), monobactams, and
carbapenemCarbapenems are a class of beta-lactam antibiotics with a broad spectrum of antibacterial activity. They have a structure that renders them highly resistant to beta-lactamases...
s, that is, any antibiotic agent that contains a
β-lactam||-||-||-||-||-||-||}A beta-lactam ring is a lactam with a heteroatomic ring structure, consisting of three carbon atoms and one nitrogen atom...
nucleus in its molecular structure. They are the most widely-used group of antibiotics.
While not true antibiotics, the
β-lactamase inhibitorA beta-lactamase inhibitor is a drug given in conjunction with a beta-lactam antibiotic. Although the inhibitor does not usually have significant antibiotic activity on its own, it inhibits activity of beta-lactamase, a protein that confers resistance of beta-lactam antibiotics to...
s are often included in this group.
Clinical use
β-lactam antibiotics are indicated for the prophylaxis and treatment of
bacteriaThe bacteria are a large group of unicellular microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
l infections caused by susceptible organisms. At first, β-lactam antibiotics were mainly active only against
Gram-positiveGram-positive bacteria are those that are stained dark blue or violet by Gram staining. This is in contrast to Gram-negative bacteria, which cannot retain the crystal violet stain, instead taking up the counterstain and appearing red or pink...
bacteria, yet the recent development of broad-spectrum β-lactam antibiotics active against various
Gram-negativeGram-negative bacteria are those bacteria that do not retain crystal violet dye in the Gram staining protocol. In a Gram stain test, a counterstain is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color...
organisms has increased their usefulness.
Mode of action
β-Lactam antibiotics are bactericidal, and act by inhibiting the synthesis of the
peptidoglycanPeptidoglycan, also known as murein, is a polymer consisting of sugars and amino acids that forms a mesh-like layer outside the plasma membrane of bacteria, forming the cell wall. The sugar component consists of alternating residues of β- linked N-acetylglucosamine and N-acetylmuramic acid residues...
layer of bacterial
cell wallA cell wall is a tough, flexible and sometimes fairly rigid layer that surrounds some types of cells. It is located outside the cell membrane and provides these cells with structural support and protection, and also acts as a filtering mechanism. A major function of the cell wall is to act as a...
s. The peptidoglycan layer is important for cell wall structural integrity, especially in
Gram-positiveGram-positive bacteria are those that are stained dark blue or violet by Gram staining. This is in contrast to Gram-negative bacteria, which cannot retain the crystal violet stain, instead taking up the counterstain and appearing red or pink...
organisms. The final transpeptidation step in the synthesis of the peptidoglycan is facilitated by
transpeptidaseA transpeptidase is a bacterial enzyme that cross-links the peptidoglycan chains to form rigid cell walls. This enzyme is also known by several other names including DD-peptidase, DD-transpeptidase, D-alanyl-D-alanine carboxypeptidase and serine-type D-Ala-D-Ala carboxypeptidase.The protein...
s known as penicillin-binding proteins (PBPs).
β-Lactam antibiotics not only block the division of bacteria, including
cyanobacteriaCyanobacteria, also known as blue-green algae, blue-green bacteria or Cyanophyta, is a phylum of bacteria that obtain their energy through photosynthesis. The name "cyanobacteria" comes from the color of the bacteria = blue)...
, but also the division of cyanelles, the
photosyntheticPhotosynthesis is a process that converts carbon dioxide into organic compounds, especially sugars, using the energy from sunlight. Photosynthesis occurs in plants, algae, and many species of Bacteria, but not in Archaea...
organelleIn cell biology, an organelle is a specialized subunit within a cell that has a specific function, and is usually separately enclosed within its own lipid membrane....
s of the
GlaucophyteThe glaucophytes, also known as glaucocystophytes or glaucocystids, are a small group of freshwater microscopic algae. Together with the red algae and Viridiplantae they form the Archaeplastida...
s, and the division of
chloroplastChloroplasts are organelles found in plant cells and other eukaryotic organisms that conduct photosynthesis. Chloroplasts capture light energy to conserve free energy in the form of ATP and reduce NADP to NADPH through a complex set of processes called photosynthesis.The word chloroplast is...
s of
bryophyteBryophytes are all embryophytes that are non-vascular: they have tissues and enclosed reproductive systems, but they lack vascular tissue that circulates liquids. They neither have flowers nor produce seeds, reproducing via spores...
s. In contrast, they have no effect on the
plastidPlastids are major organelles found in the cells of plants and algae. Plastids are the site of manufacture and storage of important chemical compounds used by the cell...
s of the highly developed
vascular plantVascular plants are those plants that have lignified tissues for conducting water, minerals, and photosynthetic products through the plant. Vascular plants include the ferns, clubmosses, flowering plants, conifers and other gymnosperms...
s. This is supporting the
endosymbiotic theoryThe endosymbiotic theory concerns the origins of mitochondria and plastids , which are organelles of eukaryotic cells. According to this theory, these organelles originated as separate prokaryotic organisms that were taken inside the cell as endosymbionts...
and indicates an
evolutionIn biology, evolution is change in the genetic material of a population of organisms from one generation to the next. Though changes produced in any one generation are normally small, differences accumulate with each generation and can, over time, cause substantial changes in the population, a...
of plastid division in land
plantPlants are living organisms belonging to the kingdom Plantae. They include familiar organisms such as trees, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The scientific study of plants, known as botany, has identified about 350,000 extant species of plants, defined as seed plants,...
s .
β-lactam antibiotics are analogues of D-alanyl-D-alanine - the terminal
amino acidAmino acids are molecules containing an amine group, a carboxylic acid group and one of the twenty R-groups. These molecules are particularly important in biochemistry, where this term refers to alpha-amino acids with the general formula H
2NCHRCOOH, where R is an organic substituent...
residues on the precursor NAM/NAG-peptide subunits of the nascent peptidoglycan layer. The structural similarity between β-lactam antibiotics and D-alanyl-D-alanine facilitates their binding to the active site of penicillin-binding proteins (PBPs). The β-lactam nucleus of the molecule irreversibly binds to (acylates) the Ser
403 residue of the PBP active site. This irreversible inhibition of the PBPs prevents the final crosslinking (transpeptidation) of the nascent peptidoglycan layer, disrupting cell wall synthesis.
Under normal circumstances peptidoglycan precursors signal a reorganisation of the bacterial cell wall and, as a consequence, trigger the activation of autolytic cell wall
hydrolaseIn biochemistry, a hydrolase is an enzyme that catalyzes the hydrolysis of a chemical bond. For example, an enzyme that catalyzed the following reaction is a hydrolase:-Nomenclature:...
s. Inhibition of cross-linkage by β-lactams causes a build-up of peptidoglycan precursors, which triggers the digestion of existing peptidoglycan by autolytic hydrolases without the production of new peptidoglycan. As a result, the bactericidal action of β-lactam antibiotics is further enhanced.
Modes of resistance
By definition, all β-lactam antibiotics have a β-lactam ring in their structure. The effectiveness of these antibiotics relies on their ability to reach the PBP intact and their ability to bind to the PBP. Hence, there are 2 main modes of bacterial resistance to β-lactams, as discussed below.
The first mode of β-lactam resistance is due to enzymatic
hydrolysisHydrolysis is a chemical reaction during which one or more water molecules are split into hydrogen and hydroxide ions, which may go on to participate in further reactions. It is the type of reaction that is used to break down certain polymers, especially those made by step-growth polymerization...
of the β-lactam ring. If the bacteria produces the
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at...
s
β-lactamaseBeta-lactamases are enzymes produced by some bacteria and are responsible for their resistance to beta-lactam antibiotics like penicillins, cephalosporins , cephamycins, and carbapenems . These antibiotics have a common element in their molecular structure: a four-atom ring known as a beta-lactam...
or penicillinase, these enzymes will break open the β-lactam ring of the antibiotic, rendering the antibiotic ineffective. The genes encoding these enzymes may be inherently present on the bacterial
chromosomeA chromosome is an organized structure of DNA and protein that is found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions...
or may be acquired via
plasmidA plasmid is an extra-chromosomal DNA molecule separate from the chromosomal DNA which is capable of replicating independently of the chromosomal DNA. In many cases, it is circular and double-stranded...
transfer, and β-lactamase
gene expressionGene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as rRNA genes or tRNA genes, the product is a functional RNA...
may be induced by exposure to beta-lactams. The production of a β-lactamase by a bacterium does not necessarily rule out all treatment options with β-lactam antibiotics. In some instances, β-lactam antibiotics may be co-administered with a β-lactamase inhibitor. However, in all cases where infection with β-lactamase-producing bacteria is suspected, the choice of a suitable β-lactam antibiotic should be carefully considered prior to treatment. In particular, choosing appropriate β-lactam antibiotic therapy is of utmost importance against organisms with inducible β-lactamase expression. If β-lactamase production is inducible, then failure to use the most appropriate β-lactam antibiotic therapy at the onset of treatment will result in induction of β-lactamase production, thereby making further efforts with other β-lactam antibiotics more difficult.
The second mode of β-lactam resistance is due to possession of altered penicillin-binding proteins. β-lactams cannot bind as effectively to these altered PBPs, and, as a result, the β-lactams are less effective at disrupting cell wall synthesis. Notable examples of this mode of resistance include
methicillinMeticillin or methicillin is a narrow spectrum beta-lactam antibiotic of the penicillin class. It was developed by Beecham in 1959...
-resistant
Staphylococcus aureus (MRSA) and penicillin-resistant
Streptococcus pneumoniaeStreptococcus pneumoniae, or pneumococcus, is Gram-positive, alpha-hemolytic, bile soluble aerotolerant anaerobe and a member of the genus Streptococcus. A significant human pathogenic bacterium, S...
. Altered PBPs do not necessarily rule out all treatment options with β-lactam antibiotics.
Nomenclature
β-Lactams are classified according to their core ring structures.
- β-Lactams fused to saturated
In chemistry, saturation has five different meanings:#In physical chemistry, saturation is the point at which a solution of a substance can dissolve no more of that substance and additional amounts of it will appear as a precipitate...
five-membered rings:
- β-Lactams containing thiazolidine
Thiazolidines are a class of heterocyclic organic compounds with a 5-membered saturated ring with a thioether group and an amine group in the 1 and 3 positions, respectively. It is a sulfur analogue of oxazolidine....
rings are named penamPenams are a subclass of the broader β-lactam family of antibiotics and related compounds. Penams contain a β-lactam ring fused to a 5-membered ring, where one of the atoms in the ring is a sulfur and the ring is fully saturated. Penicillin is a member of this family of compounds....
s.
- β-Lactams containing pyrrolidine
Pyrrolidine, also known as tetrahydropyrrole, is an organic compound with the molecular formula C
4H
9N. It is a cyclic amine with a five-membered ring containing four carbon atoms and one nitrogen atom. It is a clear liquid with an unpleasant ammonia-like odor.Pyrrolidine is...
rings are named carbapenamA carbapenam is a β-lactam compound that is a saturated carbapenem. They exist primarily as biosynthetic intermediates on the way to the carbapenem antibiotics....
s.
- β-Lactams fused to oxazolidine
Oxazolidine is a five-membered ring compound consisting of three carbons, a nitrogen, a hydrogen, and an oxygen. The oxygen and NH are the 1 and 3 positions, respectively. In oxazolidine derivatives, there is always a carbon between the oxygen and the nitrogen . All of the carbons in oxazolidines...
rings are named oxapenams or clavamA clavam is a molecule similar to a penam, but with an oxygen substituted for the sulfur. Thus, they are also known as oxapenams.An example is clavulanic acid....
s.
- β-Lactams fused to unsaturated five-membered rings:
- β-Lactams containing 2,3-dihydrothiazole
Thiazole, or 1,3-thiazole, is a clear to pale yellow flammable liquid with a pyridine-like odor and the molecular formula C
3H
3NS...
rings are named penemA penem is a type of beta-lactam.An example is faropenem.Penems are similar in structure to carbapenems. However, where penems have a sulfur, carbapenems have another carbon.There are no naturally occurring penems; all of them are synthetically made....
s.
- β-Lactams containing 2,3-dihydro-1H-pyrrole
Pyrrole is a heterocyclic aromatic organic compound, a five-membered ring with the formula C
4H
4NH. Substituted derivatives are also called pyrroles. For example, C
4H
4NCH
3 is N-methylpyrrole...
rings are named carbapenemCarbapenems are a class of beta-lactam antibiotics with a broad spectrum of antibacterial activity. They have a structure that renders them highly resistant to beta-lactamases...
s.
- β-Lactams fused to unsaturated six-membered rings:
- β-Lactams containing 3,6-dihydro-2H-1,3-thiazine
Thiazines are organic compounds containing a ring of four carbon, one nitrogen and one sulfur atom. Chemicals that include thiazine are used for dyes, tranquilizers and insecticides....
rings are named cephemCephems are a sub-group of beta-lactam antibiotics including cephalosporins and cephamycins....
s.
- β-Lactams containing 1,2,3,4-tetrahydropyridine
Pyridine is a simple aromatic heterocyclic organic compound with the chemical formula C
5H
5N used as a precursor to agrochemicals and pharmaceuticals, and is also an important solvent and reagent. It is structurally related to benzene, wherein one CH group in the aromatic...
rings are named carbacephemA carbacephem is a type of synthetically made antibiotic, based on the structure of cephalosporin, a cephem. Carbacephems are similar to cephems but with a carbon substituted for the sulfur....
s.
- β-Lactams containing 3,6-dihydro-2H-1,3-oxazine rings are named oxacephem
An oxacephem is a molecule similar to a cephem, but with oxygen substituted for the sulfur. They are synthetically made compounds and have not been discovered in nature.An example is moxalactam.Another example is flomoxef....
s.
- β-Lactams not fused to any other ring are named monobactams.
Penicillins (Penams)
Semisynthetic penicillins are prepared starting from the penicillin nucleus
6-APA6-APA is the chemical compound -6-aminopenicillanic acid.-Use:6-APA is the core of penicillins. It is obtained from the fermentation brew of the Penicillium mold and used as the main starting block for the preparation of numerous semisynthetic penicillins.-External links:*...
.
Narrow-spectrum
- Beta-lactamase sensitive
- benzathine penicillin
- benzylpenicillin
Benzylpenicillin, commonly known as penicillin G, is the gold standard penicillin. Penicillin G is typically given by a parenteral route of administration because it is unstable in the hydrochloric acid of the stomach. Because the drug is given parenterally, higher tissue concentrations of...
(penicillin G)
- phenoxymethylpenicillin
Phenoxymethylpenicillin, commonly known as penicillin V, is the orally active form of penicillin. It is less active than benzylpenicillin, however, and is appropriate only in conditions where high tissue concentrations are not required. Phenoxymethylpenicillin exerts a bactericidal action against...
(penicillin V)
- procaine penicillin
- Penicillinase-resistant penicillins
- methicillin
Meticillin or methicillin is a narrow spectrum beta-lactam antibiotic of the penicillin class. It was developed by Beecham in 1959...
- oxacillin
Oxacillin sodium is a narrow spectrum beta-lactam antibiotic of the penicillin class.-Uses:It is effective against penicillinase enzymes, such as that produced by Staphylococcus aureus...
- nafcillin
Nafcillin sodium is a narrow spectrum beta-lactam antibiotic of the penicillin class. As a beta-lactamase-resistant penicillin, it is used to treat infections caused by Gram-positive bacteria, particularly species of staphylococci, that are resistant to other penicillins.Nafcillin is considered...
- cloxacillin
Cloxacillin is a semisynthetic antibiotic in the same class as penicillin. Cloxacillin was discovered and developed by Beecham. It is sold under a number of trade names, including Cloxapen and Orbenin....
- dicloxacillin
Dicloxacillin is a narrow spectrum beta-lactam antibiotic of the penicillin class. It is used to treat infections caused by susceptible Gram-positive bacteria. Notably, it is active against beta-lactamase-producing organisms such as Staphylococcus aureus, which would otherwise be resistant to most...
- flucloxacillin
Flucloxacillin or floxacillin is a narrow spectrum beta-lactam antibiotic of the penicillin class. It is used to treat infections caused by susceptible Gram-positive bacteria. Unlike other penicillins, flucloxacillin has activity against beta-lactamase-producing organisms such as Staphylococcus...
- β-lactamase-resistant penicillins
- temocillin
Temocillin is a β-lactamase resistant penicillin introduced by Beecham, marketed by Eumedica Pharmaceuticals as Negaban primarily for the treatment of multiresistant Gram negative bacteria.It is a carboxypenicillin.-Pharmacology:...
Extended-spectrum
- azlocillin
Azlocillin is an acylampicillin antibiotic with an extended spectrum of activity and greater in vitro potency than the carboxy penicillins.Azlocillin is similar to mezlocillin and piperacillin. It demonstrates antibacterial activity against a broad spectrum of bacteria, including Pseudomonas...
- carbenicillin
Carbenicillin is a bactericidal and bacteriolytic antibiotic belonging to the carboxypenicillin subgroup of the penicillins.
It was discovered by scientists at Beecham and marketed as Pyopen.
It has Gram-negative coverage which includes Pseudomonas aeruginosa but limited Gram-positive...
- ticarcillin
Ticarcillin is a carboxypenicillin. It is almost invariably sold and used in combination with clavulanate as Timentin. Because it is a penicillin, it also falls within the larger class of beta-lactam antibiotics...
- mezlocillin
Mezlocillin is a broad-spectrum penicillin antibiotic. It is active against both Gram-negative and some Gram-positive bacteria.-Mechanism of action:...
- piperacillin
Piperacillin is an extended spectrum beta-lactam antibiotic of the ureidopenicillin class. It is normally used together with a beta-lactamase inhibitor such as tazobactam, which is commercially available as TAZOMEDTazocin, Zobactin or Zosyn...
First generation
Moderate spectrum.
- cephalexin
- cephalothin
- cefazolin
Cefazolin , also known as cefazoline or cephazolin, is a first generation cephalosporin antibiotic.The drug is usually administrated either by intramuscular injection or intravenous infusion .-Indications:Cefazolin is mainly used to treat bacterial infections of the skin...
Second generation
Moderate spectrum with anti-
HaemophilusHaemophilus is a genus of Gram-negative, pleomorphic, coccobacilli bacteria belonging to the Pasteurellaceae family. While Haemophilus bacteria are typically small coccobacilli, they are categorized as pleomorphic bacteria because of the wide range of shapes they occasionally assume...
activity.
- cefaclor
Cefaclor, also known as cefachlor or cefaclorum , is a second-generation cephalosporin antibiotic used to treat certain infections caused by bacteria such as pneumonia and ear, lung, skin, throat, and urinary tract infections.- Indications:Cefaclor belongs to the family of antibiotics known as the...
- cefuroxime
Cefuroxime is a second-generation cephalosporin antibiotic that has been widely available in the USA as Ceftin since 1977. GlaxoSmithKline sells the antibiotic in the United Kingdom under the name Zinnat.-Indications:As for the other cephalosporins, although as a second-generation it...
- cefamandole
Cefamandole is a second-generation broad-spectrum cephalosporin antibiotic. The clinically used form of cefamandole is the formate ester cefamandole nafate, a prodrug which is administered parenterally....
Second generation cephamycins
Moderate spectrum with anti-anaerobic activity.
- cefotetan
Cefotetan is an injectable antibiotic of the cephamycin type for prophylaxis and treatment of bacterial infections. It is often grouped together with second-generation cephalosporins and has a similar antibacterial spectrum, but with additional anti-anaerobe converage.Cefotetan was developed by...
- cefoxitin
Cefoxitin is a cephamycin antibiotic developed by Merck & Co., Inc., often grouped with the second−generation cephalosporins. It is also known as Mefoxin.- Microbiology :...
Third generation
Broad spectrum.
- ceftriaxone
Ceftriaxone is a third-generation cephalosporin antibiotic. Like other third-generation cephalosporins, it has broad spectrum activity against Gram positive and Gram negative bacteria. In most cases, it is considered to be equivalent to cefotaxime in terms of safety and efficacy...
- cefotaxime
Cefotaxime is a third-generation cephalosporin antibiotic. Like other third-generation cephalosporins, it has broad spectrum activity against Gram positive and Gram negative bacteria. In most cases, it is considered to be equivalent to ceftriaxone in terms of safety and efficacy...
- cefpodoxime
Cefpodoxime , is an oral third generation cephalosporin. It is active against most Gram positive and Gram negative organisms. Notable exceptions include Pseudomonas aeruginosa, Enterococcus, and Bacteroides fragilis...
Broad spectrum with anti-
PseudomonasPseudomonas is a genus of gamma proteobacteria, belonging to the larger family of pseudomonads.Recently, 16S rRNA sequence analysis has redefined the taxonomy of many bacterial species. As a result the genus Pseudomonas includes strains formerly classified in the genera Chryseomonas and Flavimonas...
activity.
- ceftazidime
Ceftazidime is a third-generation cephalosporin antibiotic. Like other third-generation cephalosporins, it has broad spectrum activity against Gram-positive and Gram-negative bacteria. Unlike most third-generation agents, it is active against Pseudomonas aeruginosa, however it has weaker activity...
Fourth generation
Broad spectrum with enhanced activity against Gram positive bacteria and
beta-lactamaseBeta-lactamases are enzymes produced by some bacteria and are responsible for their resistance to beta-lactam antibiotics like penicillins, cephalosporins , cephamycins, and carbapenems . These antibiotics have a common element in their molecular structure: a four-atom ring known as a beta-lactam...
stability.
- cefepime
Cefepime is a fourth-generation cephalosporin antibiotic developed in 1994. Cefepime has an extended spectrum of activity against Gram-positive and Gram-negative bacteria, with greater activity against both Gram-negative and Gram-positive organisms than third-generation agents...
- cefpirome
Cefpirome is a fourth-generation cephalosporin. Trade names include Cefrom, Keiten, Broact, Cefir. Cefpirome is considered highly active against Gram-negative bacteria, including Pseudomonas aeruginosa, and Gram-positive bacteria....
Carbapenems and Penems
Broadest spectrum of beta-lactam antibiotics.
- imipenem
Imipenem is an intravenous β-lactam antibiotic developed in 1985. It has an extremely broad spectrum of activity.Imipenem belongs to the subgroup of carbapenems. It is derived from a compound called thienamycin, which is produced by the bacteria Streptomyces cattleya...
(with cilastatinCilastatin is a chemical compound which inhibits the human enzyme dehydropeptidase.Dehydropeptidase is found in the kidney and is responsible for degrading the antibiotic imipenem. Cilastatin is therefore combined intravenously with imipenem in order to protect it from dehydropeptidase and prolong...
)
- meropenem
Meropenem is an ultra-broad spectrum injectable antibiotic used to treat a wide variety of infections, including meningitis and pneumonia. It is a beta-lactam and belongs to the subgroup of carbapenem, similar to imipenem and ertapenem. Meropenem was originally developed by Sumitomo Pharmaceuticals...
- ertapenem
Ertapenem is a carbapenem antibiotic marketed by Merck as Invanz. It is structurally very similar to meropenem in that it possess a 1-β-methyl group.-Indications:...
- faropenem
Faropenem is an orally-active beta-lactam antibiotic belonging to the penem group.It is resistant to some forms of extended-spectrum beta-lactamase.It is orally available.-Forms:...
- doripenem
Doripenem is an ultra-broad spectrum injectable antibiotic. It is a beta-lactam and belongs to the subgroup of carbapenems. It was launched by Shionogi Co. of Japan under the brand name Finibax in 2005, and is being marketed outside Japan by Johnson & Johnson...
Monobactams
Unlike other beta-lactams, the monobactam contains a nucleus with no fused ring attached. Thus, there is less probability of cross-sensitivity reactions.
- aztreonam
Aztreonam is a synthetic monocyclic beta-lactam antibiotic originally isolated from Chromobacterium violaceum. It was approved by the U.S. Food and Drug Administration in 1986...
(Azactam)
- tigemonam
Tigemonam is a monobactam antibiotic....
- nocardicin A
Nocardicin A is a beta lactam antibiotic. It is produced by nocardicin-A epimerase....
- tabtoxinine-β-lactam
Beta-lactamase inhibitors
Although they exhibit negligible antimicrobial activity, they contain the beta-lactam ring. Their sole purpose is to prevent the inactivation of beta-lactam antibiotics by binding the
beta-lactamaseBeta-lactamases are enzymes produced by some bacteria and are responsible for their resistance to beta-lactam antibiotics like penicillins, cephalosporins , cephamycins, and carbapenems . These antibiotics have a common element in their molecular structure: a four-atom ring known as a beta-lactam...
s, and, as such, they are co-administered with beta-lactam antibiotics.
- clavulanic acid
Clavulanic acid is a beta-lactamase inhibitor combined with penicillin group antibiotics to overcome certain types of antibiotic resistance. It is used to overcome resistance in bacteria that secrete beta-lactamase, which otherwise inactivates most penicillins...
- tazobactam
Tazobactam is a compound which inhibits the action of bacterial beta-lactamases. It is added to the extended spectrum beta-lactam antibiotic piperacillin to produce Tazocin or Zosyn or Piprataz...
- sulbactam
Sulbactam is a molecule which is given in combination with beta-lactam antibiotics to inhibit beta-lactamase, an enzyme produced by bacteria that destroys the antibiotics...
Adverse drug reactions
Common adverse drug reactions (ADRs) for the β-lactam antibiotics include diarrhea, nausea, rash,
urticariaUrticaria are a kind of skin rash notable for dark red, raised, itchy bumps. Hives are frequently caused by allergic reactions; however, there are many non-allergic causes...
,
superinfectionIn virology, superinfection is the process by which a cell, that has previously been infected by one virus, gets coinfected with a different strain of the virus, or another virus at a later point in time. Viral superinfections of serious conditions can lead to resistant strains of the virus, which...
(including
candidiasisCandidiasis or thrush is a fungal infection of any of the Candida species, of which Candida albicans is the most common. Candidiasis encompasses infections that range from superficial, such as oral thrush and vaginitis, to systemic and potentially life-threatening diseases...
).
Infrequent ADRs include fever, vomiting,
erythemaErythema is redness of the skin, which can be caused by several things, including capillary congestion.-Causes:It can be caused by infection, massage, electrical treatment, acne medication, allergies, exercise, solar radiation , cutaneous radiation syndrome, or waxing and plucking of the hairs...
, dermatitis,
angioedemaAngioedema is the rapid swelling of the dermis, subcutaneous tissue, mucosa and submucosal tissues. It is very similar to urticaria, but urticaria, commonly known as hives, occurs in the upper dermis....
,
pseudomembranous colitisPseudomembranous colitis is an infection of the colon often, but not always, caused by the bacterium Clostridium difficile. Still, the expression "C. diff colitis" is used almost interchangeably with the more proper term of pseudomembranous colitis. The illness is characterized by...
.
Pain and inflammation at the injection site is also common for
parenteralParenteral is a route of administration that involves piercing the skin or mucous membrane. Parenteral nutrition refers to providing nutrition via the veins.-Etymology:...
ly-administered β-lactam antibiotics.
Allergy/hypersensitivity
Immunologically-mediated adverse reactions to any β-lactam antibiotic may occur in up to 10% of patients receiving that agent (a small fraction of which are truly IgE-mediated
allergicAllergy is a disorder of the immune system often also referred to as atopy. Allergic reactions occur to normally harmless environmental substances known as allergens; these reactions are acquired, predictable, and rapid. Strictly, allergy is one of four forms of hypersensitivity and is called type...
reactions, see amoxicillin rash).
AnaphylaxisAnaphylaxis is an acute systemic and severe type I hypersensitivity allergic reaction in humans and other mammals. The term comes from the Greek words ανα ana and φύλαξις phylaxis . Minute amounts of allergens may cause a life-threatening anaphylactic reaction...
will occur in approximately 0.01% of patients. There is perhaps a 5%-10% cross-sensitivity between penicillin-derivatives, cephalosporins, and carbapenems; but this figure has been challenged by various investigators.
Nevertheless, the risk of cross-reactivity is sufficient to warrant the contraindication of all β-lactam antibiotics in patients with a history of severe allergic reactions (urticaria, anaphylaxis, interstitial nephritis) to any β-lactam antibiotic.
Jarish Herxheimer reaction: Febrile reaction after first injection of penicillin in spirochetal infection. Eg; Syphilis