What are types of antibiotics?

Definition

Antibiotics

are grouped by type, or class, to identify groups of similar
antibiotics that act on specific bacteria types (such as gram-negative bacilli)
and in the same manner (such as to kill cells or slow growth). The most common
method of separating antibiotics by class is according to the type of chemical
drug structure.

Beta-lactams

Penicillins and cephalosporins are two subclasses of beta-lactam antibiotics, as they share a five- or six-membered ring structure. All beta-lactams are bactericidal and work at the bacterial cell-wall level. Beta-lactams irreversibly bind as a false substrate to an activesite on the enzyme that is responsible for cell-wall peptide cross-linking; by preventing the cross-linking, beta-lactams prevent the completion of the bacterial cell wall.

Penicillin, the first beta-lactam, was identified as a mold spore,
Penicillium notatum (now called P.
chrysogenum), in 1928 by bacteriologist Alexander Fleming; the antibiotic itself was derived from P.
chrysogenum in 1941 and was active against strains of the
Staphylococcus bacterium. Although penicillin had only a
narrow, gram-positive spectrum, later penicillin-related antibiotics, such as
methicillin and ampicillin, provided expanded activity by
avoiding bacterial resistance or by acting against select gram-negative organisms,
respectively. Penicillins generally are used to treat skin, ear, respiratory, and
urinary tract infections for which bacteria remain sensitive.

Cephalosporins provide much broader-spectrum coverage within the beta-lactam class
compared with penicillins. Although their mechanism of action is like that of
penicillin, they have varied spectrums of activity because of structural
alterations. Cephalosporins are typically used to treat otitis media (ear), skin,
and urinary tract infections, but are also used in surgical prophylaxis and to
treat bone infections and pneumonia.

The activity of cephalosporins can be defined by four subtypes, or generations, to provide wide bacterial coverage. First-generation drugs, such as cephalexin and cefazolin, provide primarily gram-positive activity; second-generation cephalosporins, such as cefuroxime and cefaclor, provide gram-negative and gram-positive activity but have a range of sensitivities. Third-generation examples include ceftriaxone, cefixime, and ceftibuten; these drugs provide wide gram-negative coverage but lose much of the class gram-positive coverage. Fourth-generation drugs cefepime and cefquinone have similar gram-positive activity as early cephalosporins but have better activity against beta-lactamase-resistant bacteria, and they cross the blood-brain barrier to treat meningitis and encephalitis.

All beta-lactams are well tolerated and are associated with the mild side effects of nausea and diarrhea. However, allergy to drugs in the beta-lactam class is not uncommon and may develop with both penicillin and cephalosporin use.

Macrolides

Unlike penicillins and cephalosporins, which act on the bacterial cell-wall, macrolides interact with bacteria at protein synthesis, and they are typically bacteriostatic but may become bactericidal, depending on their concentrations and the bacteria types attacked. Macrolides such as erythromycin, clarithromycin, and azithromycin bind to the 50S section of the ribosome during bacterial protein development to change the ribosome and prevent peptide bonding. Erythromycin additionally may prevent formation of the 50S subunit itself.

Macrolides are composed of a macrocyclic lactone and are
derived from the bacterium Streptomyces
. Erythromycin, the first-in-class macrolide, has similar activity to
penicillin; conversely, the two newer macrolides have their best activity in lung
diseases, and clarithromycin is particularly effective against
Helicobacter pylori, which often causes stomach ulcers.
Macrolides are used against Staphylococcus,
Streptococcus, and Mycoplasma infections, and
they are used to treat Legionnaires’ disease, which is caused
by the Legionella bacterium. Side effects include mild nausea,
diarrhea, and stomach upset.

Tetracyclines

Like macrolides, tetracyclines are derived from Streptomyces; they are made of
four connected rings. Tetracyclines block the beginning of protein synthesis by
binding the ribosome and preventing the addition of aminoacyl tRNA (transfer
ribonucleic acid) building blocks. In addition, tetracyclines may change the
ribosome itself to prevent successful protein synthesis. Tetracyclines provide
bacteriostatic activity against a broader spectrum of bacteria than do
penicillins.

Tetracycline, minocycline, and doxycycline are common examples of drugs in this class. They have unique
activity against Rickettsia and some amebic parasites; they can
treat sinus, middle ear, urinary tract, and intestinal infections. However, a
common use of drugs in this class is to treat skin conditions such as
rosacea or moderate acne. Tetracyclines have a greater risk
of side effects, especially with prolonged use. Photosensitivity, cramps,
diarrhea, and possible bone and tooth changes may occur with tetracycline use.

Fluoroquinolones

Fluoroquinolones, unlike beta-lactams, are synthetic
rather than derived directly from a bacterial source. They are well absorbed, are distributed into bone, and can be given by mouth or intravenously. They consist of a dual ring and a fluor group that increases the antibiotic activity.

Fluoroquinolones are bactericidal against a broad spectrum
of bacteria. Fluoroquinolones act by blocking deoxyribonucleic acid (DNA) building
within the bacteria to prevent multiplication. Early examples, such as ciprofloxacin, are primarily active against gram-negative bacteria; newer agents,
including levofloxacin, keep gram-negative activity and add activity againstgram-positive
bacteria such as the pneumococcus (Streptococcus pneumoniae).
They are often used to treat urinary tract and skin infections and respiratory
infections such as bronchitis and bacterial pneumonia. Moxifloxacin, one of the newest of the fluoroquinolones, has additional activity
against anaerobic bacteria.

Glycopeptides

Vancomycin and teicoplanin are the two most common glycopeptide antibiotics, the newest class of antibiotics. Because their chemical makeup is
so large and because these drugs cannot cross a cell membrane, they affect only
gram-positive bacteria outside the cell. Each glycopeptide is made of two sugars
and one aglycone moiety with a heptapeptide core that provides antibiotic action.
Glycopeptides block the end of cell-wall peptidoglycan synthesis so that the cell
wall cannot be completed and the bacteria cannot survive. Vancomycin is useful in
the treatment of methicillin-resistant Staphylococcus aureus
(MRSA) in hospital settings; however, bacteria are also developing intermediate to
full resistance to vancomycin.

Other Antibiotics

Aminoglycoside antibiotics, discovered in 1944, contain an amino and some sugar
groups. They provide limited-spectrum coverage against gram-negative and
gram-positive agents. Aminoglycosides insert themselves
incorrectly into proteins during synthesis by binding to the ribosome. They are
particularly active against Pseudomonas aeriginosa.

Lincosamides, such as clindamycin, have greater activity against anaerobes, such
as those causing intestinal or gastric infections, and they are also used to treat
gram-positive Staphylococcus skin infections, including moderate
acne. Lincosamides are bacteriostatic and act by inhibiting protein synthesis by
the bacterial ribosome.

Impact

With the development of bacterial resistance shortly after penicillin’s introduction in the 1940’s, antibiotic drug development has greatly expanded within the beta-lactam class and beyond. However, bacterial resistance appears to be developing faster than new antibiotics are being discovered or developed in laboratories, so that infections from common bacteria are once again complicated to treat. Research continues to identify the best use of antibiotics within and among classes and to find the safest combination therapies against specific bacteria.

Bibliography

Mandell, Gerald L., John E. Bennett, and Raphael Dolin, eds. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 7th ed. New York: Churchill Livingstone/Elsevier, 2010. This thorough, two-volume textbook provides background and detailed information about all types of microbes and infectious sources. Section E in particular discusses antibiotic and other anti-infective therapies. Chapters in this section discuss efficacy, sensitivity, and pharmacologic activities of antimicrobial agents. In addition, chapters address each antibiotic type singly with specific details about mechanisms, spectrums, dosages, and combinationtherapies.

Murray, Patrick R., Ken S. Rosenthal, and Michael A. Pfaller. Medical Microbiology. 6th ed. Philadelphia: Mosby/Elsevier, 2009. Primarily describes bacteria and other infectious microbes. Later discussion presents diseases by site of infection.

Sanford, Jay P., et al. The Sanford Guide to Antimicrobial Therapy. 18th ed. Sperryville, Va.: Antimicrobial Therapy, 2010. A premier guide to antibiotic use with descriptions of agents in each class and their antibacterial activity. Text and tables document treatment options, antiresistance treatment options, drug-drug interactions, and treatment dosages and regimens.

Van Bambeke, Françoise, et al. “Antibiotics That Act on the Cell Wall.” In Cohen and Powderly Infectious Diseases, edited by Jonathan Cohen, Steven M. Opal, and William G. Powderly. 3d ed. Philadelphia: Mosby/Elsevier, 2010. Describes the mechanisms of action of antibiotics that block or kill bacteria by interacting with the bacterial cell wall. Focuses on beta-lactam and glycopeptide antibiotics. Also discusses bacterial cell-wall development, beta-lactamase-resistance development, and the latest developments in beta-lactam use. The glycopeptides discussion expands from mechanisms to treatment of vancomycin-resistant bacteria.

Walsh, Christopher. Antibiotics: Actions, Origins, Resistance. Washington, D.C.: ASM Press, 2003. Examines such topics as how antibiotics block specific proteins, how the molecular structure of drugs enables such activity, the development of bacterial resistance, and the molecular logic of antibiotic biosynthesis.