Antibiotics: Types and Side Effects

• What are Antibiotics?
• Antibiotic resistance
• Antibiotics classification
• Penicillins
• Cephalosporins
• Fluoroquinolones
• Tetracyclines
• Macrolides
• Aminoglycosides

by eMedExpert staff
Medical references reviewed: August, 2018

What are Antibiotics?

The word "antibiotics" comes from the Greek anti ("against") and bios ("life"). The noun “antibiotic” was suggested in 1942 by Dr. Selman A. Waksman, soil microbiologist 4.

An antibiotic is a drug that kills or slows the growth of bacteria. Antibiotics belong to a class of antimicrobials, a larger group which also includes anti-virals, anti-fungals, and anti-parasitic drugs. Antibiotics are chemicals produced by or derived from microorganisms (i.e. bugs or germs such as bacteria and fungi). The first antibiotic was discovered by Alexander Fleming in 1928. This discovery was a significant breakthrough in medical science.

Antibiotics are used to treat a variety of bacterial infections. Antibiotics cure infectious diseases by killing or injuring bacteria. Bacteria are single-celled organisms, and are natural and normal part of life. Pathogenic bacteria cause disease when they are able to gain access to vulnerable parts of the body and multiply rapidly.

Bactericidal and Bacteriostatic Antibiotics

Some antibiotics are bactericidal, meaning that they work by killing bacteria. Other antibiotics are bacteriostatic, meaning that they work by stopping bacteria multiplying.

Different types of antibiotics affect different bacteria in different ways. For example, an antibiotic might inhibit a bacterium's ability to turn glucose into energy, or its ability to construct its cell wall. When this happens, the bacterium dies instead of reproducing.

Broad-spectrum and Narrow-spectrum Antibiotics

Some antibiotics can be used to treat a wide range of infections and are known as broad-spectrum antibiotics. Others are only effective against a few types of bacteria and are called narrow-spectrum antibiotics.

Antibiotic resistance

Antibiotics are extremely important in medicine, but unfortunately bacteria are capable of developing resistance to them. Antibiotic-resistant bacteria are bacteria that are not killed effectively by antibiotics. When bacteria are exposed to the same medication over and over, the bacteria change and are no longer affected by the drug.

There are several ways how bacteria become antibiotic-resistant. For example, they have an internal mechanism of changing their structure so the antibiotic no longer works, they develop ways to inactivate or neutralize the antibiotic. Also bacteria can transfer the genes coding for antibiotic resistance between them, making it possible for bacteria never exposed to an antibiotic to acquire resistance. The problem of antibiotic resistance becomes more serious when antibiotics are used to treat disorders for which they are ineffective.

Resistance to antibiotics represents a serious and growing problem, because some infectious diseases are becoming hard to treat. Resistant bacteria do not respond to the antibiotics and continue to cause the illness. Some resistant bacteria can be treated with more powerful medicines, but some infections are difficult to cure even with novel drugs.

Antibiotics Classification

Although there are several systems for classification of antibiotics, the most useful is based on chemical structure. Antibiotics within a structural class will generally have similar patterns of effectiveness, toxicity, and allergic potential.

The main classes of antibiotics are:

• Beta-Lactams
• Penicillins
• Cephalosporins
• Macrolides
• Fluoroquinolones
• Tetracyclines
• Aminoglycosides

Most commonly used types of antibiotics are: Aminoglycosides, Penicillins, Fluoroquinolones, Cephalosporins, Macrolides, and Tetracyclines. While each class is composed of multiple drugs, each drug is unique in some way.

Penicillins

The penicillins are the oldest class of antibiotics. Penicillins are bicyclic penam compounds and share their chemical structure with the cephalosporins.

Penicillins are generally bactericidal, inhibiting the formation of the bacterial cell wall. Penicillins are used to treat skin infections, dental infections, ear infections, respiratory tract infections, urinary tract infections, and gonorrhea.

There are four types of penicillins:

• The natural penicillins are based on the original penicillin-G structure. Natural penicillins are active against gram-positive streptococci, staphylococci, and some gram-negative bacteria such as meningococcus.
• Penicillinase-resistant penicillins (e.g. methicillin, oxacillin) are active against beta-lactamase producing bacteria, that inactivates most penicillin antibiotics.
• Aminopenicillins such as ampicillin and amoxicillin are effective against a wider range of bacteria and have a better oral absorption.
• Extended-spectrum penicillins (e.g. mezlocillin, piperacillin, ticarcillin).

Penicillins side effects

Penicillins are generally very safe drugs with minimum toxicity. Their most common side effect is diarrhea. Nausea, vomiting, and upset stomach are also common. In rare cases penicillins can cause immediate or delayed allergic reactions which manifest as skin rashes, fever, angioedema, and anaphylactic shock. Severe hypersensitivity reactions are more common after injections than after oral formulations.

Neurotoxicity. Very high doses of penicillins, especially in patients with renal impairment, may cause convulsions5.

All penicillins are classed as Pregnancy category B.

Cephalosporins

Cephalosporins have a mechanism of action identical to that of the penicillins. However, the basic chemical structure of the penicillins and cephalosporins differs in other respects, resulting in different spectrum of antibacterial activity. Like the penicillins, cephalosporins have a beta-lactam ring structure that interferes with synthesis of the bacterial cell wall and so are bactericidal. Cephalosporins are derived from cephalosporin C which is produced from Cephalosporium acremonium.

Cephalosporins are used to treat pneumonia, strep throat, tonsillitis, staph infections, bronchitis, otitis media, various types of skin infections, gonorrhea, urinary tract infections Cephalosporin antibiotics are also commonly used for surgical prophylaxis. Cephalexin can also be used to treat bone infections.

Cephalosporins are extremely diverse class of antibiotics, they are grouped into "generations" by their antimicrobial properties. Each newer generation has a broader spectrum of activity than the one before.

• The first generation cephalosporins have quite similar spectrums of activity. They have excellent coverage against most gram-positive pathogens but variable to poor coverage against most gram negative pathogens. The first generation includes:
  • cephalothin
  • cefazolin
  • cephapirin
  • cephradine
  • cephalexin
  • cefadroxil
• The second generation cephalosporins have expanded gram negative spectrum in addition to the gram positive spectrum of the first generation cephalosporins. Cefoxitin and cefotetan have good activity against Bacteroides fragilis. Enough variation exists between the second generation cephalosporins in regard to their spectrums of activity against most species of gram negative bacteria, that susceptibility testing is generally required to determine sensitivity. The second generation includes:
  • cefaclor
  • cefamandole
  • cefonicid
  • ceforanide
  • cefuroxime
• The third generation cephalosporins have much expanded gram negative activity. However, some members of this group have decreased activity against gram-positive organisms. They have the advantage of convenient dosage regimen, but they are expensive. The third generation includes:
  • cefcapene
  • cefdaloxime
  • cefditoren
  • cefetamet
  • cefixime
  • cefmenoxime
  • cefodizime
  • cefoperazone
  • cefotaxime
  • cefpimizole
  • cefpodoxime
  • ceftibuten
  • ceftriaxone
• The fourth generation cephalosporins are extended-spectrum agents with similar activity against gram-positive organisms as first-generation cephalosporins. They also have a greater resistance to beta-lactamases. Many fourth generation cephalosporins can cross blood brain barrier and are effective in meningitis. The fourth generation includes:
  • cefclidine
  • cefepime
  • cefluprenam
  • cefozopran
  • cefpirome
  • cefquinome

Cephalosporins side effects

Cephalosporins are remarkably safe class of antibiotics and usually cause few adverse effects. Common side effects include: diarrhoea, nausea, mild stomach cramps or upset. Approximately 5–10% of patients with allergic hypersensitivity to penicillins will also have cross-reactivity with cephalosporins. Thus, cephalosporin antibiotics are contraindicated in people with a history of allergic reactions (urticaria, anaphylaxis, interstitial nephritis, etc) to penicillins or cephalosporins.

Hematologic toxicity. Thrombocytopenia, neutropenia, abnormalities of platelet function and coagulation have been reported with certain cephalosporins 6.

Cephalosporin antibiotics are classed as Pregnancy category B.

Fluoroquinolones

Fluoroquinolones (fluoridated quinolones) are the newest class of antibiotics. Their generic name often contains the root "floxacin". They are synthetic compounds, and are not derived from bacteria.

The earliest first-generation medications are referred as quinolones, and newer generations as fluoroquinolones. The older quinolones are not well absorbed and are used to treat mostly urinary tract infections. The fluoroquinolones are broad-spectrum agents with excellent oral bioavailability. Because of their high absorption fluoroquinolones can be administered not only intravenously but orally as well.

Fluoroquinolones are used to treat urinary tract infections, skin infections, and respiratory infections (such as sinusitis, pneumonia, bronchitis), pulmonary infections in cystic fibrosis.

Fluoroquinolones are bactericidal and kill bacteria by inhibiting bacterial enzyme DNA gyrase.

Fluoroquinolone family includes:

• clinafloxacin
• ciprofloxacin
• gatifloxacin
• levofloxacin
• lomefloxacin
• ofloxacin
• sparfloxacin
• trovafloxacin

Fluoroquinolones side effects

Fluoroquinolones are generally well tolerated and have acceptable level of safety. The most common side effects include nausea, vomiting, diarrhea, abdominal pain. More serious but less common side effects are central nervous system disturbances (headache, confusion, dizziness, tremor), phototoxicity (more common with lomefloxacin and sparfloxacin), prolongation of the QT interval7, tendinopathy and tendon rupture8, and convulsions9.

Fluoroquinolones should be avoided when possible in pregnant women and children.

Tetracyclines

Tetracyclines are an old class of antibiotics. They got their name for their chemical structure which contains four hexagonal rings. Tetracyclines are derived from a species of Streptomyces bacteria.

Tetracycline antibiotics are bacteriostatic agents and work by inhibiting the bacterial protein synthesis via interaction with the 30S subunit of the bacterial ribosome. Tetracyclines are effective against a wide variety of microorganisms, including spirochetes, atypical bacteria, rickettsia, and amebic parasites.

Current applications of tetracyclines include treatment of peptic ulcer disease as part of a multi-drug regimen, infections of the respiratory tract, cholera, Rocky Mountain spotted fever, Lyme disease, typhus, prophylaxis of traveler’s diarrhea, malaria prophylaxis. Their most common current use is in the treatment of acne vulgaris and rosacea.

Tetracycline antibiotics are:

• doxycycline
• minocycline
• oxytetracycline
• tetracycline

Tetracyclines side effects

Common side effects associated with tetracyclines include stomach cramps, diarrhea, nausea, vomiting, esophageal ulceration, sore mouth or tongue. Tetracyclines can cause skin photosensitivity, which increases the risk of sunburn under exposure to UV light. This may be of particular importance for those intending to take on holidays long-term doxycycline as a malaria prophylaxis.

Rarely, tetracyclines may cause allergic reactions. Very rarely severe headache and vision problems may be signs of dangerous secondary intracranial hypertension.

Tetracycline antibiotics should not be used in children under the age of 8, and specifically during periods of tooth development. Tetracyclines are classed as pregnancy category D. Tetracyclines may cause the gray to yellow discoloration of actively forming teeth and deposition in growing bones.

Macrolides

The macrolide antibiotics owe their name to a macrocyclic lactone ring in their chemical structure. They are derived from Streptomyces bacteria.

The macrolides target bacterial ribosomes and prevent protein production and are mainly bacteriostatic agents.

Erythromycin, the prototype of this class, has a spectrum and use similar to penicillin. Newer members of the group, azithromycin and clarithyromycin, are particularly useful for their excellent lung penetration. Macrolide antibiotics are used to treat respiratory tract infections (such as pharyngitis, sinusitis, and bronchitis), genital, gastrointestinal tract, and skin infections.

Macrolide antibiotics are:

• azithromycin
• clarithromycin
• dirithromycin
• erythromycin
• roxithromycin
• troleandomycin

Macrolides side effects

Macrolides are usually tolerated quite well. Most common adverse effects include nausea, vomiting, abdominal discomfort, and diarrhea. They have been rarely associated with reversible deafness and allergic reactions (including angioedema, anaphylaxis, and dermatologic reactions)12. Oral erythromycin may be highly irritating to the stomach and when given by injection may cause severe thrombophlebitis. Macrolide antibiotics should be used with caution in patients with liver dysfunction.

More information about the side effects of macrolides.

Pregnancy category B: Azithromycin, erythromycin.
Pregnancy category C: Clarithromycin, dirithromycin, troleandomycin.

Aminoglycosides

Aminoglycosides are derived from various species of Streptomyces.

In 1943, Selman Waksman, together with his co-workers, discovered that a bacterium Streptomyces griseus produced an antibiotic substance which they named "streptomycin." Selman Waksman was awarded the Nobel Prize in Physiology or Medicine in 1952 for his discovery of streptomycin.

The aminoglycosides are bactericidal and work by binding to the 30S subunit of the bacterial ribosome, thus stopping bacteria from making proteins.

Aminoglycoside antibiotics are used to treat infections caused by gram-negative bacteria. Aminoglycosides may be used in combination with with penicillins or cephalosporins to ensure better antimicrobial coverage. Aminoglycosides work quite well, but bacteria can become resistant to them. Since aminoglycosides are broken down easily in the stomach, they can't be given by mouth and must be injected. Generally, aminoglycosides are given for short time periods.

Aminoglycoside grope includes:

• amikacin
• gentamicin
• kanamycin
• neomycin
• streptomycin
• tobramycin

Aminoglycosides side effects

The major irreversible toxicity of aminoglycosides is ototoxicity10 (damage to the ear and hearing). Among them, streptomycin and gentamicin are primarily vestibulotoxic, whereas amikacin, neomycin, dihydrosterptomycin, and kanamicin are primarily cochleotoxic.

Another significant concern with aminoglycoside antibiotics is nephrotoxicity11 (kidney damage). Renal damage is related to the accumulation of high concentrations of aminoglycoside antibiotic in the renal cortex.

Further reading

• Antibiotics for Strep Throat
• Antibiotics for Ear Infections
• Antibiotics for Chlamydia

References & Resources

• 1. The Merck Manual of Medical Information. Mark H. Beers et al., eds. 2nd Home Edition. Whitehouse Station, NJ: Merck; 2003.
• 2. Antibiotics: MedlinePlus. U.S. National Library of Medicine
• 3. Physicians' Desk Reference. 59th ed. Montvale, N.J.: Thomson PDR, 2005.
• 4. Waksman SA. Mycologia Vol. 39, No. 5 (Sept.-Oct. 1947): 565-569.
• 5. Barrons RW, Murray KM, Richey RM. Populations at risk for penicillin-induced seizures. Ann Pharmacother. 1992 Jan;26(1):26-9. PubMed
• 6. Thompson JW, Jacobs RF. Adverse effects of newer cephalosporins. Drug Saf. 1993 Aug;9(2):132-42. PubMed
• 7. Briasoulis A, Agarwal V, Pierce WJ. QT prolongation and torsade de pointes induced by fluoroquinolones: infrequent side effects from commonly used medications. Cardiology. 2011;120(2):103-10. PubMed
• 8. Kim GK. The Risk of Fluoroquinolone-induced Tendinopathy and Tendon Rupture. J Clin Aesthet Dermatol. 2010 Apr;3(4):49-54. PubMed
• 9. Kushner JM, Peckman HJ, Snyder CR. Seizures associated with fluoroquinolones. Ann Pharmacother. 2001 Oct;35(10):1194-8. PubMed
• 10. Selimoglu E. Aminoglycoside-induced ototoxicity. Curr Pharm Des. 2007;13(1):119-26. PubMed
• 11. Lopez-Novoa JM, Quiros Y, Vicente L, Morales AI, Lopez-Hernandez FJ. New insights into the mechanism of aminoglycoside nephrotoxicity. Kidney Int. 2011 Jan;79(1):33-45. PubMed
• 12. Periti P, Mazzei T, Mini E, Novelli A. Adverse effects of macrolide antibacterials. Drug Saf. 1993 Nov;9(5):346-64.

Published: May 05, 2007
Last updated: March 22, 2018