Antibiotics: types and side effects

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

The word "antibiotics" comes from the Greek anti ("against") and bios ("life"). An antibiotic is a drug that kills or slows the growth of bacteria. Antibiotics are one class of antimicrobials, a larger group which also includes anti-viral, anti-fungal, and anti-parasitic drugs. Antibiotics are chemicals produced by or derived from microoganisms (i.e. bugs or germs such as bacteria and fungi). The first antibiotic was discovered by Alexander Fleming in 1928 in a significant breakthrough for medical science. Antibiotics are among the most frequently prescribed medications in modern medicine.

Antibiotics are used to treat many different bacterial infections. Antibiotics cure disease by killing or injuring bacteria. Bacteria are simple one-celled organisms that can be found, by the billions, all around us: on furniture and counter-tops, in the soil, and on plants and animals. They are a natural and needed part of life. Bacteria cause disease and infection when they are able to gain access to more vulnerable parts of our bodies and multiply rapidly. Bacteria can infect many parts of the body: eyes, ears, throat, sinuses, lungs, airways, skin, stomach, colon, bones, genitals.

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

Each different type of antibiotic affects 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.

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.

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

Bacteria have number of ways how they become antibiotic-resistant. For example, they possess 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 from those which have. The problem of antibiotic resistance is worsened when antibiotics are used to treat disorders in which they have no efficacy (e.g. antibiotics are not effective against infections caused by viruses), and when they are used widely as prophylaxis rather than treatment.

Resistance to antibiotics poses a serious and growing problem, because some infectious diseases are becoming more difficult to treat. Resistant bacteria do not respond to the antibiotics and continue to cause infection. Some of these resistant bacteria can be treated with more powerful medicines, but there some infections that are difficult to cure even with new or experimental drugs.

Although there are several classification schemes for antibiotics, based on bacterial spectrum (broad versus narrow) or route of administration (injectable versus oral versus topical), or type of activity (bactericidal vs. bacteriostatic), the most useful is based on chemical structure. Antibiotics within a structural class will generally have similar patterns of effectiveness, toxicity, and allergic potential.

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.

The penicillins are the oldest class of antibiotics. Penicillins have a common chemical structure which they share with the cephalopsorins. Penicillins are generally bactericidal, inhibiting formation of the cell wall. Penicillins are used to treat skin infections, dental infections, ear infections, respiratory tract infections, urinary tract infections, gonorrhea.

There are four types of penicillins:

• The natural penicillins are based on the original penicillin-G structure. Penicillin-G types are effective against gram-positive strains of streptococci, staphylococci, and some gram-negative bacteria such as meningococcus.
• Penicillinase-resistant penicillins, notably methicillin and oxacillin, are active even in the presence of the bacterial enzyme that inactivates most natural penicillins.
• Aminopenicillins such as ampicillin and amoxicillin have an extended spectrum of action compared with the natural penicillins. Extended spectrum penicillins are effective against a wider range of bacteria.

Penicillins are among the least toxic drugs known. The most common side effect of penicillin is diarrhea. Nausea, vomiting, and upset stomach are also common. In rare cases penicillins can cause immediate and delayed allergic reactions - specifically, skin rashes, fever, and anaphylactic shock. Penicillins are classed as category B during pregnancy.

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 some difference in the 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, staph infections, tonsillitis, 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 among the most diverse classes 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 include: Their spectrums of activity are quite similar. They possess generally excellent coverage against most gram-positive pathogens and variable to poor coverage against most gram negative pathogens. The first generation cephalosporins include:
  • cephalothin
  • cefazolin
  • cephapirin
  • cephradine
  • cephalexin
  • cefadroxil
• The second generation cephalosporins. In addition to the gram positive spectrum of the first generation cephalosporins, these agents have expanded gram negative spectrum. Cefoxitin and cefotetan also 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 cephalosporins include:
  • 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 dosing schedules, but they are expensive. The third generation cephalosporins include:
  • 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 than the third generation cephalosporins. Many fourth generation cephalosporins can cross blood brain barrier and are effective in meningitis. The fourth generation cephalosporins include:
  • cefclidine
  • cefepime
  • cefluprenam
  • cefozopran
  • cefpirome
  • cefquinome

Cephalosporins generally cause few side effects. Common side effects associated these drugs 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. Cephalosporin antibiotics are classed as pregnancy category B.

Fluoroquinolones (fluoridated quinolones) are the newest class of antibiotics. Their generic name often contains the root "floxacin". They are synthetic antibiotics, and not derived from bacteria. Fluoroquinolones belong to the family of antibiotics called quinolones. The older quinolones are not well absorbed and are used to treat mostly urinary tract infections. The newer fluroquinolones are broad-spectrum bacteriocidal drugs that are chemically unrelated to the penicillins or the cephaloprosins. Because of their excellent absorption fluroquinolones can be administered not only by intravenous but orally as well.

Fluoroquinolones are used to treat most common urinary tract infections, skin infections, and respiratory infections (such as sinusitis, pneumonia, bronchitis).

Fluoroquinolones inhibit bacteria by interfering with their ability to make DNA. This activity makes it difficult for bacteria to multiply. This effect is bacteriocidal.

Commonly used fluoroquinolones include

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

Fluoroquinolones are well tolerated and relatively safe. The most common side effects include nausea, vomiting, diarrhea, abdominal pain. Other more serious but less common side effects are central nervous system effects (headache, confusion and dizziness), phototoxicity (more common with lomefloxacin and sparfloxacin). All drugs in this class have been associated with convulsions. Fluoroquinolones are classed as pregnancy category C.

Tetracyclines got their name because they share a chemical structure that has four rings. They are derived from a species of Streptomyces bacteria. Tetracycline antibiotics are broad-spectrum bacteriostatic agents, that inhibit bacterial protein synthesis. Tetracyclines may be effective against a wide variety of microorganisms, including rickettsia and amebic parasites.

Tetracyclines are used in the treatment of infections of the respiratory tract, sinuses, middle ear, urinary tract, skin, intestines. Tetracyclines also are used to treat Gonorrhoea, Rocky Mountain spotted fever, Lyme Disease, typhus. Their most common current use is in the treatment of moderately severe acne and rosacea.

The most commonly prescribed tetracycline antibiotics are:

• tetracycline
• doxycycline
• minocycline
• oxytetracycline

Drugs in the tetracycline class become toxic over time. Expired drugs can cause a dangerous syndrome resulting in damage to the kidneys.

Common side effects associated with tetracyclines include cramps or burning of the stomach, diarrhea, 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 doxycyline 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. Use during pregnancy may cause alterations in bone development.

The macrolide antibiotics are derived from Streptomyces bacteria, and got their name because they all have a macrocyclic lactone chemical structure. The macrolides are bacteriostatic, binding with bacterial ribosomes to inhibit protein synthesis. 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 high level of lung penetration. Macrolide antibiotics are used to treat respiratory tract infections (such as pharyngitis, sinusitis, and bronchitis), genital, gastrointestinal tract, and skin infections.

The most commonly prescribed macrolide antibiotics are:

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

Side effects associated with macrolides include nausea, vomiting, and diarrhea; infrequently, there may be temporary auditory impairment. Azithromycin has been rarely associated with allergic reactions, including angioedema, anaphylaxis, and dermatologic reactions. Oral erythromycin may be highly irritating to the stomach and when given by injection may cause severe phlebitis. Macrolide antibiotics should be used with caution in patients with liver dysfunction. Pregnancy category B: Azithromycin, erythromycin. Pregnancy category C: Clarithromycin, dirithromycin, troleandomycin.

Aminoglycoside antibiotics are used to treat infections caused by gram-negative bacteria. Aminoglycosides may be used along with penicillins or cephalosporins to give a two-pronged attack on the bacteria. 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.

The aminoglycosides are drugs which stop bacteria from making proteins. This effect is bacteriocidal.

The most commonly-prescribed aminoglycosides:

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

When injected, their side effects include possible damage to the ears and to the kidneys. This can be minimized by checking the amount of the drug in the blood and adjusting the dose so that there is enough drug to kill bacteria but not too much of it.