Antibiotics (anti-bacterials)

• Introduction to antibiotics
• When should antibiotics be used?
• How do antibiotics work?
• Classes of antibiotics
  • Beta lactam antibiotics
  • Other classes of antibiotics
• Important issues regarding antibiotic use
  • Common side effects of antibiotics
  • How to tell if you are allergic or sensitive to antibiotics
  • Penicillin hypersensitivity
• Are antibiotics safe?
• Antibiotic interactions
• When to call your doctor

An introduction to antibiotics

Antibiotics (anti-bacterials) are defined as medications which work to kill or inhibit the growth of bacteria. Bacteria are single-cell organisms that can invade our bodies and cause disease. Antibiotics work to kill or inhibit the growth of bacteria to eliminate disease. Once the growth of bacteria is stopped, our immune system can mount a response to get rid of them.

For example, if you get a chest infection such as pneumonia, the bacteria have gotten into your lungs. They act to produce chemicals and multiply in the lung cavities, causing inflammation and discomfort. Antibiotics act to get rid of the bacteria and help your body fight the infection.

It is important to understand that antibiotics do not work against viruses. There is a difference between bacteria and viruses: a bacterium is a single-celled, living organism, whereas a virus is a piece of RNA or DNA. A virus acts to affect living cells and reproduces through the affected cell. There is no living organism to kill, thus antibiotics are ineffective.

When should antibiotics be used?

Antibiotics should be used to help fight off a bacterial infection, when your immune system may need extra help to overcome the invading organisms.

The Australian Antibiotic Guidelines have recommended that:

• We should only use antibiotics where the benefits have been scientifically proven and demonstrated;
• The correct dose of a single antibiotic should be used to treat the bacteria you are infected with. The dose should be enough to ensure that the antibiotic works, but is balanced against side effects and tolerability;
• The choice of antibiotic should be based on the results of investigations that you have had, such as blood tests;
• Antibiotic treatment should only be continued for the required period of time and not any longer.

How do antibiotics work?

Antibiotics act to either:

• • Directly kill bacteria (bactericidal); or
  • Inhibit their growth and ability to reproduce (bacteriostatic).

An antibiotic is a selective medication: it acts to kill unwanted bacteria, but not the other cells in your body. Each class of antibiotic is characterised by its own defined mechanism of action. It can affect bacteria in many different ways. For example, an antibiotic may act to stop a bacterium from producing its own cell wall – this stops the bacteria from reproducing properly and it dies off.

To interfere with bacteria growing and reproducing in the body, antibiotics interfere with certain processes that bacteria use to grow and survive. These include:

• Preventing the bacteria from producing necessary proteins by binding to the building blocks that build the proteins;
• Interfering with the production of metabolic processes such as production of folic acid, an essential vitamin that bacteria depend on to survive;
• Obstructing production of the bacteria’s cell wall, which results in an ineffective wall that does not protect the bacterium and allow it to function properly;
• Blocking both RNA and DNA synthesis.

Classes of antibiotics

Beta lactam antibiotics

The group of beta lactam antibiotics includes penicillins, cephalosporins, carbapenems and monobactams. They are characterised by a special beta lactam ring structure made of four major components. Beta lactams antibiotics inhibit the growth of bacteria by targeting the bacterial cell wall. Molecules in the bacterial cell wall are linked by bridges. This whole process is controlled by certain enzymes, which are inactivated by beta lactam antibiotics.

Penicillins

These are divided into groups depending on how many classes of bacteria they are active against.  

Narrow spectrum penicillins

Narrow spectrum penicillins are only active against certain bacteria, including gram-positive bacteria such as Staphylococcus aureus and Streptococci. Examples include:

• Benzylpenicillin (penicillin G) is administered through the veins and remains the treatment of choice for susceptible infections;
• Procaine penicillin is a form of penicillin available to inject into the muscles of affected patient. This penicillin is combined with a compound to delay its absorption into the bloodstream;
• Benzathine penicillin is also given as an injection into the muscles;
• Phenoxymethylpenicillin (penicillin V) can be given orally, but should be taken at least an hour before food, because food impairs its absorption.

Widespread resistance to penicillins has developed over the many years since its discovery. However, it is still the antibiotic choice for susceptible organisms.

There are some penicillins in this group that have activity against a strain of bacteria called Staphylococcus aureus, which produces enzymes called beta lactamases to destroy other penicillins. These include dicloxacillin, flucloxacillin and methicillin. They can be taken orally, but are best absorbed when the stomach is empty.

Moderate spectrum penicillins

Moderate spectrum penicillins (amoxycillin and ampicillin) have a similar range of activity as narrow spectrum penicillin, but are more active against extra bacteria such as those responsible for chest infections and urinary tract infections.

Broad spectrum penicillins

Broad spectrum penicillins consist of a special compound combined with penicillin. This protects the medication against destruction by the beta lactamase enzyme produced by some bacteria. A commonly used medication that belongs in this group is Augmentin Duo Forte (amoxycillin and potassium clavulanate), which can be used to treat chest infections. However, these medications should be reserved for treatment of infections due to bacteria that are resistant to other antibiotics due to production of beta lactamases.

Cephalosporins

These antibiotics are divided into four major groups. In general, the first group of cephalosporins are quite active against gram-positive bacteria. These bacteria commonly cause skin infections and possible wound infections. The third and fourth groups of agents have better activity against gram-negative bacteria, which commonly cause urinary tract infections and some chest infections. However, these agents must be used carefully to avoid producing resistant strains of bacteria.

First generation cephalosporins

These include cephalexin, cephalothin and cefaclor.

Second generation cephalosporins

Second generation antibiotics aren’t as commonly used as compared to the first or third generation antibiotics. These include cefamandole and cefuroxime.

Third generation cephalosporins

Third generation cephalosporins include cefotaxime, ceftriaxone, ceftazidime and cefpodoxime. These antibiotics are effective in infections such as meningitis because they penetrate the fluid around the brain and spinal cord.

Fourth generation cephalosporins

Antibiotics such as cefepime fall under the fourth and broadest generation of cephalosporins. This is a very broad spectrum antibiotic, with activity against a wide range of bacteria. Use of cefepime is often limited to the hospital, where it may be used to treat serious infections that have failed to respond to other therapies.

Carbapenems

These include: meropenem, imipenem and ertapenem. This class of antibiotics has a broad spectrum of activity and are effective against many bacteria. However, they should be reserved for resistant infections. They are expensive antibiotics to use. Carbapenems have a chemical structure which makes them highly resistant to enzymes produced by bacteria to counteract them, such as beta lactamases. However, increasing use of carbapenems has led to increased resistance and development of infections due to organisms such as methicillin resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE).

Monobactams

This class of  beta lactam antibiotics has good activity against gram-negative bacteria.

Other classes of antibiotics

Aminoglycosides

Members of this group of antibiotics include:

• Gentamicin;
• Tobramycin;
• Amikacin;
• Paromomycin;
• Framycetin;
• Streptomycin;
• Neomycin.

Aminoglycosides work by stopping the bacteria from making their proteins, thus preventing them from growing and reproducing effectively. They are a group of antibiotics that are highly effective against gram-negative organisms. However, the use of these antibiotics should depend upon the known susceptibility patterns of bacteria encountered. Your doctor will make sure they are used appropriately.

Important side effects of these medications include effects on the ears and kidneys. Your kidney function and auditory function should be monitored while on these antibiotics. Your doctor may request blood tests to be performed while you are taking these antibiotics, to ensure that the level they reach in the blood is adequate.

Glycopeptides

Antibiotics that fall within the group of glycopeptides include vancomycin and teicoplanin. These drugs act by preventing the bacteria from making the walls of their cells and also by impairing synthesis of RNA. Both antibiotics are very active against resistant gram-positive organisms. However, they have poorer activity against gram-negative bacteria.

The role of these antibiotics lies especially in treating serious infections due to organisms which are resistant to other antibiotics, such as MRSA, and severe infections in patients hypersensitive to penicillins.

Vancomycin and teicoplanin can be given through the veins, or orally through the mouth. It is often given through the veins as a slow infusion. This is because it is occasionally associated with the ‘red man syndrome’. Although they are available orally, they have poor oral absorption.

Lincosamides

Of the lincosamide group of antibiotics, clindamycin is the most commonly used. Lincomycin is also available and both antibiotics have good activity against gram-positive organisms. They act by preventing bacteria from producing proteins needed for their growth and reproduction.

These drugs are often used as second line therapy, if you have allergies to other antibiotics or are intolerant to conventional therapy. They can also be used where resistant organisms are encountered.

Macrolides

The macrolide group of antibiotics includes erythromycin, roxithromycin, azithromycin and clarithromycin. They also act by preventing bacteria from producing proteins needed for their growth and reproduction. Depending on the concentration the medications are administered at, they may be bacteriostatic or bactericidal. They are most commonly used to treat chest infections acquired in the community.

They have a range of activity targeting gram-positive and -negative bacteria, and other organisms likely to cause chest infections such as Legionella, Mycoplasma and Chlamydia species. Erythromycin, azithromycin and clarithromycin are also active against Bordetella (Bordetella pertussis is associated with whooping cough). Clarithromycin can be used in combination with other drugs (penicillin antibiotics such as amoxycillin and a proton pump inhibitor) in the treatment of Helicobacter pylori infection. This bacteria has been shown to be implicated in causing ulcers in the stomach and intestine.

When using these types of antibiotics, erythromycin and clarithromycin may affect enzymes that are involved in drug metabolism. This means that if you are prescribed these antibiotics, your doctor should be aware of all the medications you are currently taking and stop or reduce the dose of any medications that may be interacting. Some people have complained of side effects such as vomiting and diarrhoea with erythromycin. There has been a trend towards using those antibiotics that are better tolerated (e.g. roxithromycin and clarithromycin).

Nitroimidazoles

Nitroimidazoles include metronidazole, tinidazole and nitrothiazoles. These antibiotics have a special nitro group and are active against bacteria that do not need any oxygen to survive – i.e. anaerobes and protozoa such as Trichomonas vaginalis, Giardia lamblia and Entamoeba histolytica. Anaerobes are commonly seen in infections such as bacterial vaginosis.

Nitroimidazoles are changed to their active forms inside the bacteria. This produces free radicals and other compounds that are toxic to the cell, causing cell death.

If you are one these medications, you should not take alcohol simultaneously – these drugs may prevent the breakdown and metabolism of alcohol in your body, causing an unpleasant reaction when mixed with alcohol.

Quinolones

Quinolones block DNA synthesis in bacteria by interfering with the action of the bacterial enzyme DNA gyrase. They include ciprofloxacin, moxifloxacin, ofloxacin and norfloxacin.

They have a broad spectrum of activity against gram-negative bacteria. They are well absorbed orally and are the only oral agents active against Pseudomonas aeruginosa. This is a type of bacteria that often affects patients who have an impaired immune system. Pseudomonas rarely causes infection in healthy people but it is a major cause of infections acquired in hospital.

This group of antibiotics is commonly used to treat urinary and gastrointestinal (intestines, stomach, bowel) infections. Quinolones are antibiotics that should be reserved for treatment of resistant infections or where an oral drug with their spectrum of activity is required. Inappropriate use can lead to development of resistant bacteria, rendering bacteria that present a challenge for antibiotic treatment.

Rifamycins

These include rifampicin and rifabutin, which are antibiotics with a strong spectrum of activity against gram-positive organisms and mycobacteria. Mycobacteria are those bacteria that can cause diseases such as tuberculosis, infection of lymph nodes (lymphadenitis) and chest infections. There has been rapid development of resistance to these drugs when used alone, thus they are used in combination with other antibiotics. This group of antibiotics works by preventing bacteria from producing RNA and necessary proteins.

Rifamycins are mainly used in tuberculosis and mycobacterium infections such as certain skin infections, in combination with other drugs. It is used with other agents to treat gram-positive infections, especially MRSA infections, and also for prophylaxis against bacterial meningitis to treat susceptible contacts.

Rifamycins are antibiotics that can activate many enzymes. This results in many potential drug interactions, thus care must be taken when administering this medication with other drugs also metabolised by the same antibiotic system. These include blood thinning agents, the oral contraceptive pill, corticosteroids and oral drugs used in the treatment of diabetes.

Sulphonamides and trimethoprim

Sulfamethoxazole is the only commonly used sulphonamide, and is combined with the antibiotic trimethoprim to form the compound cotrimoxazole. It inhibits the formation of tetrahydrofolic acid, which is important for bacteria to form purines. Sulphonamides are broad spectrum antibiotics, active against many organisms.

Due to the sulphonamide component in sulphonamides, some people may experience adverse effects or be allergic to this antibiotic.

The main indication for trimethoprim is in the treatment of susceptible urinary tract infections. Cotrimoxazole should be restricted to situations where trimethoprim alone is ineffective or the infective organisms demonstrate resistance.

Tetracyclines

These antibiotics include tetracycline, doxycycline, minocycline and rolitetracycline. Tetracyclines act by stopping bacteria from producing necessary proteins. They have a broad spectrum of activity, active against both gram-positive and gram-negative bacteria, protozoa and many anaerobes (bacteria that can survive without oxygen).

They are commonly used to treat chest infections acquired in the community, such as bronchitis, ear infections including otitis media and sinusitis. Tetracyclines may also be used to treat patients with genital tract infections, acne and as malaria prophylaxis.

The preferred tetracycline in most situations is doxycycline, as it has a longer half life and can be taken once a day. Its use is limited by its side effects on the skin and the ears.

If you are pregnant, tetracyclines should be used with caution during pregnancy. They are contraindicated after the first eighteen weeks of pregnancy due to possible effects on the baby’s teeth. These antibiotics are also best avoided in children less than 8-12 years old, due to potential effects on tooth development.

Important issues regarding antibiotic use

An important issue regarding antibiotic use is emerging resistance with some bacteria. You may contribute to this problem by not finishing off courses of antibiotics because you feel better, using other people’s antibiotics to treat your cold or flu, or insisting on getting antibiotics to treat a cold or flu. Increasing resistance is demonstrated particularly in organisms such as methicillin resistant Staphylococcus aureus (MRSA), Streptococcus pneumoniae and vancomycin-resistant enterococci (VRE). They have demonstrated increasing resistance over the years and now even broader reserve antibiotics may not be effective against some highly resistant strains.

It is important to know when an antibiotic is needed – most colds and flus are caused by viruses and do not require treatment with antibiotics. Unnecessary prescription of antibiotics is associated with unnecessary side effects, potential drug reactions and increased costs.

Before taking antibiotics, you should tell your doctor if you have a history of hypersensitivity or allergic response to the drug that you are being prescribed.

If you have any co-existing medical conditions or organ impairment (e.g. liver failure or kidney failure), this can result in altered drug levels and your doctor may need to adjust the dose.

Common side effects of antibiotics

All antibiotics are associated with their own side effects. In general, antibiotics can affect the bacteria that live in your intestines, causing side effects such as nausea, vomiting and diarrhoea.

The most common groups of antibiotics associated with hypersensitivity reactions are the beta lactam antibiotics. You should tell your doctor exactly what happens when you take an antibiotic, if you think you have an allergic reaction. True allergic reactions are supported by symptoms such as a drop in blood pressure, trouble breathing, rashes, swelling of the skin, lips and throat.

How to tell if you are allergic or sensitive to antibiotics

Antibiotic hypersensitivity is usually diagnosed on the basis of your history and appropriate investigations, including skin testing and oral challenges. It is difficult to accurately confirm antibiotic hypersensitivity, as there are no skin or blood tests available that offer 100% accuracy in regards to drug allergies. It has been reported that there is a false negative rate of 3-20% in patients with true penicillin allergy, due to changing penicillin skin test reagent mixes.

Penicillin hypersensitivity

Most beta lactam antibiotics that are associated with a hypersensitivity reaction commonly result in symptoms such as rash, fever, serum sickness-like reactions, and breakdown of cells. True anaphylactic responses to penicillin occur in about one out of 10 000 courses administered, with 10% of these reactions being fatal. Most anaphylactic reactions occur in patients without a history of penicillin allergy. However, you should always make sure you tell your doctor if you have a history of allergic reactions to penicillin or any other of the antibiotics. Studies have shown that between 3% – 10% of patients with a penicillin allergy may also be allergic to other beta lactam antibiotics such as cephalosporins and carbapenems.

Are antibiotics safe?

Most antibiotics are safe if you do not have a history of allergic reaction and you do not have any organ failure. Just like any other medication, they have to be prescribed in the correct doses and for the correct length of time. Your doctor will make sure that you are given appropriate doses of antibiotics to treat your condition.

There may be an increase in the toxic side effects of one antibiotic by another drug, due to interactions that occur when both medications are given at the same time. Some antibiotics that may be associated with increased side effects when given with other medications include aminoglycosides, cephalosporins and some tetracyclines. These antibiotics are usually given with caution, especially if you have any pre-existing medical problems.

Antibiotic interactions

If you are on multiple medications, there is an increased risk of drug interactions occurring. These can be divided into those that occur during the absorption stage (most commonly), due to existing medical conditions and impaired excretion of drugs, or due to enzyme inhibition or induction.

Interactions with antibiotics occurring when absorbed

Some drugs such as antacids and anti-diarrhoeal medications can combine with other medications such as tetracyclines and clindamycin. This results in the formation of complexes, which delays the absorption of these antibiotics into the gastrointestinal tract. If this is the case, it is best that you avoid taking these drugs at the same time.

Other drugs may have effects on the lining of your stomach and intestine, which affects the rate of and total absorption of antibiotics administered.

Antibiotics that affect the levels of enzymes in the body

Some drugs are potent enzyme inhibitors or inducers, which can alter the level of antibiotics present in the blood stream. You should consult your doctor before taking any medications, to rule out potential drug interactions.

When to call your doctor

You should consult your doctor if you have any questions about the types of antibiotics you are on, or are experiencing any side effects whilst on the antibiotics. If you have any co-existing medical problems, or are pregnant, they will be able to provide you with advice on which antibiotics are suitable. You should also see the doctor if your symptoms are not improving, or you do not feel any better after taking a course of antibiotics.

For further information about antibiotics talk to your doctor.

References

1. Antibiotic Expert Group. Therapeutic Guidelines – Antibiotic, Melbourne: Therapeutic Guidelines Limited; 2006
2. Bochner F, Buckely N, Calabretto H. et al, editors. Australian Medicines Handbook, Adelaide, S.Aust: Australian Medicines Handbook Pty Ltd; 2007
3. Mayer G. Antibiotics – Protein Synthesis, Nucleic Acid Synthesis and Metabolism, [online] 2005 [cited 1st March 2007] Available from: URL link
4. Mims Australia. MIMS Issue 1: 2007, CMPMedica Australia Pty Ltd; 2006
5. O’Connor L. Antibiotics, Lecture series, Department of Microbiology, University of Western Australia, Australia;2002
6. Pai M, Momary K, Rodvold K. Antibiotic drug interactions, Med Clin North Am 2006;90(6):1223-55
7. Rang H, Dale M, Ritter J. Pharmacology, Edinburgh: Churchill Livingstone; 2000
8. Walsh C. Antibiotics:actions, origins, resistance Washington, D.C.:ASM Press; 2003