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 active site 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 cefquinome 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 the 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 penicillins.

Tetracycline, minocycline, tigecycline, and doxycycline are common examples of drugs in this class. They have unique activity against Rickettsia and some amoebic 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 against gram-positive bacteria such as pneumococcus (Streptococcus pneumoniae). They are often used to treat urinary tract and skin infections and respiratory infections such as bronchitis and bacterial pneumonia. Other fluoroquinolones, like ofloxacin and moxifloxacin, have additional activity against anaerobic bacteria.

Glycopeptides

Vancomycin, dalbavancin, oritavancin, telavancin, and teicoplanin are the most common glycopeptide 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 1940s, 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 infections from common bacteria are once again complicated to treat. Antibiotic resistance has become a threat to global health, and although it can occur naturally, overuse of antibiotics has hastened the phenomenon.

Antibiotics are continually in development, but their efficacy against antibiotic-resistant bacteria varies. Humans must alter their behavior to prevent further antibiotic resistance. In the meantime, research continues to identify the best use of antibiotics within and among classes and to find the safest combination therapies against specific bacteria. For example, Cresolomycin is a synthetic compound in the lincosamide antibiotic family that attacks gram-positive and gram-negative bacteria. It is more effective in treating antibiotic-resistant infections than other antibiotics in its family.

Bibliography

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Gilbert, David N., et al. The Sanford Guide to Antimicrobial Therapy. 53rd ed., pocket ed., Antimicrobial Therapy, Inc., 2023.

Mandell, Gerald L., et al., editors. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 9th ed., Churchill Livingstone/Elsevier, 2020.

Murray, Patrick R. Murray’s Basic Medical Microbiology. 2nd ed., Elsevier, 2024.

Van Bambeke, Françoise, et al. “Antibiotics That Act on the Cell Wall.” Cohen and Powderly Infectious Diseases, edited by Jonathan Cohen, et al., 4th ed., Mosby/Elsevier, 2017.

Walsh, Christopher. Antibiotics: Actions, Origins, Resistance. ASM Press, 2003.