The physical space of the MSK Library is permanently closed to visitors as of Friday, May 17, 2024. Please visit this guide for more information.
The physical space of the MSK Library is permanently closed to visitors as of Friday, May 17, 2024. Please visit this guide for more information.
Penicillins are a type of antibiotic derived from Penicillium fungi. Penicillin G (also called benzylpenicillin) was discovered by accident in 1928 by Scottish physician-scientist Alexander Fleming. While growing the bacteria Staphylococcus Aureus on an uncovered petri dish it became contaminated with mold spores. Fleming observed that the bacteria in the areas around where the mold spores were dying. He isolated the substance from the mold that was killing the bacteria and called it penicillin.
Penicillins work by preventing the formation of the bacteria's cell wall.
Natural Penicillins (1st generation)
The term "penicillin", or "natural penicillin" may refer to either of two chemical compounds:
Spectrum of Activity:
Common Generic (Brand Name) Drugs in the U.S.:
Penicillinase-Resistant Penicillins (2nd generation)
The agents in this group are also known as the antistaphylococcal penicillins. The addition of an isoxazolyl side chain to the penicillin compound protects the beta-lactam ring from acid hydrolysis by penicillinases produced by Staphylococcus spp.
Spectrum of activity:
Common Generic (Brand Name) Drugs in the U.S.:
Aminopenicillins (3rd generation)
Aminopenicillins were developed to provide further coverage against gram-negative bacteria by adding an amino group to the side chain of the basic penicillin compound.
Spectrum of activity:
Common Generic (Brand Name) Drugs in the U.S.:
Carboxypenicillins (4th generation)
Carboxypenicillins have a carboxyl group substituted for the amino group to provide an even greater gram-negative spectrum of activity, including against Pseudomonas aeruginosa.
Spectrum of Activity:
Common Generic (Brand Name) Drugs in the U.S.:
Ureidopenicillins( Antipseudomonal) Penicillins (4th generation)
Antipseudomonal penicillins are used to treat pseudomonal infections. They have the activity of penicillins and aminopenicillins, as well as additional activity against Pseudomonas, Enterococcus and Klebsiella.
Spectrum of activity:
The gram-negative coverage of this class of penicillins includes that of the carboxypenicillins, plus coverage against:
Common Generic (Brand Name) Drugs in the U.S.:
Beta-Lactamase Inhibitors
Beta-lactamases cleave break the beta-lactam ring in some penicillins, rendering the antibiotic inactive. While some beta-lactams (cloxacillin) are naturally resistant to most beta-lactamases, the other beta-lactams (amoxicillin, ampicillin, piperacillin, and ticarcillin) can be restored and widened by combining them with a beta-lactamase inhibitor.
Beta-lactamase inhibitors:
Beta-lactamase enzymes are produced by certain strains of the following bacteria:
Common Generic (Brand Name) Drugs in the U.S.:
Tetracyclines were discovered in the 1940s and the first tetracyclines were obtained or derived from Streptomyces bacteria. They inhibit protein synthesis in the microbial RNA (an important molecule that acts as a messenger for DNA). They are primarily bacteriostatic which means that they prevent bacteria from multiplying but don't necessarily kill them.
Tetracyclines are used widely in both human and veterinary medicine, for:
Because many strains of microorganisms are now resistant to some tetracyclines, culture and susceptibility testing is recommended before beginning treatment.
Cephalosporins are a large group of antibiotics derived from the mold Acremonium (previously called Cephalosporium). Cephalosporins are bactericidal (kill bacteria) and work in a similar way to penicillins. They bind to and block the activity of enzymes responsible for making peptidoglycan, an important component of the bacterial cell wall. They are called broad-spectrum antibiotics because they are effective against a wide range of bacteria.
The first cephalosporin was discovered in 1945. Since then scientists have been improving the structure of cephalosporins to make them more effective against a wider range of bacteria. Each time the structure changes, a new "generation" of cephalosporins are made. So far there are five generations of cephalosporins. All cephalosporins start with cef, ceph, or kef. Note that this classification system is not used consistently from country to country.
First generation cephalosporins refer to the first group of cephalosporins discovered. Their optimum activity is against gram-positive bacteria such as staphylococci and streptococci. They have little activity against gram-negative bacteria.
Spectrum of Activity:
Used to treat:
Common Generic (Brand Name) Drugs in the U.S.:
Second-generation cephalosporins are more active against gram-negative bacteria than first generation cephalosporins, but may be slightly less active against gram-positive cocci than 1st-generation cephalosporins.
Spectrum of activity:
Infections & Bacteria:
Some bacteria, such as most strains of Pseudomonas aeruginosa and Acinetobacter species, are resistant to second generation cephalosporins.
Common Generic (Brand Name) Drugs in the U.S.:
Cefuroxime (Ceftin, Zinacef)
Cephamycins
Second generation cephalosporins also include cephamycins. Cephamycins are drugs that were originally produced by Streptomyces but are now synthetic. Cephamycins are more active against anaerobes, such as Bacteroides species, including Bacteroides fragilis; because of this they can be used when anaerobes are suspected (eg, in intra-abdominal sepsis, decubitus ulcers, or diabetic foot infections). However, in some medical centers, these bacilli are no longer reliably susceptible to cephamycins.
There are differences between third-generation cephalosporins with regards to the bacteria they are effective against. No one third-generation cephalosporin treats all infectious disease scenarios.
Spectrum of Activity:
Infections & Bacteria
Common Generic (Brand Name) Drugs in the U.S.:
Fourth generation cephalosporins refer to the fourth group of cephalosporins discovered. They are structurally related to third-generation cephalosporins but possess an extra ammonium group, which allows them to rapidly penetrate through the outer membrane of Gram-negative bacteria, enhancing their activity. They are also active against β-lactamase producing Enterobacteriaceae which may inactivate third-generation cephalosporins.
Spectrum of activity:
Common Generic (Brand Name) Drugs in the U.S.:
Also known as: 5th generation cephalosporins
Ceftaroline is the first cephalosporin to be active against resistant gram-positive pathogens including:
Common Generic (Brand Name) Drugs in the U.S.:
There are five different quinolone classes. In addition, another class of antibiotic, called fluoroquinolones, were derived from quinolones by modifying their structure with fluorine.
Quinolones and fluoroquinolones have many things in common, but also a few differences such as what organisms they are effective against. Some people use the words quinolones and fluoroquinolones interchangeably.
Quinolones and fluoroquinolones detrimentally affect the function of two enzymes produced by bacteria (topoisomerase IV and DNA gyrase), so that they can no longer repair DNA or help in its manufacture.
Quinolones and fluoroquinolones are considered broad-spectrum antibiotics. This means that they are effective against a wide range of bacteria.
However, because of their risk of serious side effects, the FDA has advised that they are not suitable for common conditions such as sinusitis, bronchitis, and uncomplicated urinary tract infections, and should only be considered when treatment with other, less toxic antibiotics, has failed.
Quinolones and fluoroquinolones may also be used to treat unusual infections such as anthrax or plague. Doctors may also decide to use them for other types of infection when other alternative treatment options have failed or cannot be used.
Common Generic (Brand Name) Drugs in the U.S.:
Many newer fluoroquinolones have been withdrawn from the US market because of toxicity when given systemically:
Common Generic (Brand Name) Drugs in the U.S.:
| Quinolone Drug Class | Used to Treat | Additional Comments |
|---|---|---|
|
Fluoroquinolones (except moxifloxacin) |
Urinary tract infections when Escherichia coli resistance to trimethoprim/sulfamethoxazole is >15% |
Drugs of choice; however, increasing resistance of E. coli in some communities |
|
Fluoroquinolones |
Bacterial prostatitis |
|
|
Salmonella bacteremia |
||
|
Typhoid fever |
Usually effective |
|
|
Infectious diarrhea |
Effective against most bacterial causes (Campylobacter species, salmonellae, shigellae, vibrios, Yersinia enterocolitica); however, increasing resistance of Campylobacter jejuni in some regions Not used for E. coli 0157:H7 or other enterohemorrhagic E. coli Not effective against Clostridioides difficile (formerly Clostridium difficile) |
|
|
Ofloxacin |
Chlamydia trachomatis infections |
7-day course |
|
Newer fluoroquinolones |
Community-acquired pneumonia |
Other drugs preferred if patients have taken fluoroquinolones recently |
| Legionella pneumonia |
Drugs of choice (or azithromycin) |
|
|
Ciprofloxacin |
Hospital-acquired pneumonia |
Used empirically because it is effective against Pseudomonas aeruginosa Usually used with another antipseudomonal drug |
|
Long-term oral treatment of gram-negative bacillary osteomyelitis |
Because fluoroquinolones have high oral bioavailability and good bone penetration, useful for osteomyelitis |
|
|
Meningococcal prophylaxis |
||
|
Anthrax prophylaxis |
Used extensively during 2001 after bioterrorist attack in US |
Lincomycin derivatives are a small group of antibiotics that inhibit synthesis of bacterial proteins, essential for bacteria to survive.
Lincomycin derivatives are reserved for treatment of infections due to susceptible strains of pneumococci, staphylococci and streptococci. One derivative is also indicated for treatment of Plasmodium falciparum (malaria).
Macrolides are a class of antibiotics derived from Saccharopolyspora erythraea (originally called Streptomyces erythreus), a type of soil-borne bacteria. Their action is primarily bacteriostatic but may be bactericidal at high concentrations, or depending on the type of microorganism. Macrolides inhibit protein synthesis in bacteria by reversibly binding to the P site of the 50S unit of the ribosome.
Macrolides have been considered the drug of choice for group A streptococcal and pneumococcal infections when penicillin cannot be used. However, pneumococci with reduced penicillin sensitivity are often resistant to macrolides, and macrolide resistance among S. pyogenes varies globally.
Because they are active against atypical respiratory pathogens, they are often used empirically for lower respiratory tract infections, but another drug is often necessary to cover macrolide-resistant pneumococci.
Fidaxomicin has minimal to no activity against gram-negative bacteria but is bactericidal against Clostridioides difficile.
Ketolides are a new generation of macrolide antibiotics designed to overcome issues with bacterial resistance to macrolides. They are semi-synthetic antibiotics derived from erythromycin (macrolide antibiotic) and the changes give ketolides a broader spectrum of activity.
Ketolides bind to the bacterial 50S ribosomal subunit and inhibit RNA-dependent protein synthesis. They are bacteriostatic at low concentrations and bactericidal at high concentration, so basically exhibit concentration dependent killing.
Sulfonamides (sulphonamides) are a group of man-made (synthetic) medicines that contain the sulfonamide chemical group. They may also be called sulfa drugs. Many people use the term sulfonamide imprecisely to refer only to antibiotics that have a sulfonamide functional group in their chemical structure. However, there are several non-antibiotic sulfonamides that have been developed by exploiting observations made during the clinical evaluation of the antibiotic sulfonamides. These are used for a range of conditions such as diabetes and pain relief.
Sulfanilamide was the first sulfonamide developed in 1906, although it was not used as an antimicrobial agent until the late 1930s.
Sulfonamide antimicrobials are bacteriostatic (stop bacteria from reproducing but don't necessarily kill them) and work by interfering with the synthesis of folic acid in bacteria, which is essential for nucleic acid formation and ultimately DNA and RNA.
Humans obtain folic acid from their diet, but bacteria need to synthesize it. Sulfonamide antimicrobials may be combined with trimethoprim to make them bactericidal (kill bacteria), because trimethoprim acts on a different enzyme in the folic acid synthesis pathway.
Oral sulfonamides are rapidly excreted and very soluble in urine and are commonly used to treat infections of the urinary tract.
Glycopeptide antibiotics are a type of antibiotic that inhibits bacterial cell wall formation by inhibiting peptidoglycan synthesis.
None are absorbed orally, although vancomycin is effective when given orally for the treatment of Clostridium difficile-associated diarrhea because this infection is localized in the gut. Vancomycin and telavancin are given once daily, whereas dalbavancin is given once weekly or as a single infusion, and oritavancin as a single infusion.
Aminoglycosides are a class of antibiotics used mainly in the treatment of aerobic gram-negative bacilli infections, although they are also effective against other bacteria including Staphylococci and Mycobacterium tuberculosis. They are often used in combination with other antibiotics.
Aminoglycosides are thought to work by inhibiting protein synthesis inside bacteria. Kill rates of bacteria are increased when higher concentrations of aminoglycosides are present; however, the margin between a safe and a toxic dose is narrow and monitoring is often needed, although once daily dosing increases the safety window. Impairment of kidney function and hearing loss are the most common side effects of aminoglycosides. Aminoglycosides tend to be used when other less toxic antibiotics are contraindicated or ineffective.
Aminoglycosides are not well absorbed when given by mouth, so need to be given by injection by healthcare personnel.
Carbapenems are a class of beta-lactam antibiotic that are active against many aerobic and anaerobic gram-positive and gram-negative organisms.
Thienamycin was the first carbapenem to be discovered in 1976.
Carbapenems are notable for their ability to inhibit beta-lactamase enzymes (also called penicillinase) - a type of enzyme that greatly reduces the activity of antibiotics such as penicillins and cephamycins.
Of all the beta-lactam antibiotics, carbapenems possess the broadest spectrum of activity and the greatest potency against bacteria. Because of this, they are often reserved for more severe infections or used as "last-line" agents.