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Updated 11 February 2013

Antibiotics

Antibiotics have been one of the greatest success stories of modern medicine. An antibiotic is any substance that interferes with the ability of bacteria to function normally.

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Antibiotics have been one of the greatest success stories of modern medicine.

An antibiotic is any substance that interferes with the ability of bacteria to function normally. It cures disease by killing (bactericidal) or injuring (bacteriostatic) bacteria, allowing the body's own immune system to
overcome the infection.

The first antibiotic was penicillin, discovered accidentally from a mould culture. Today, over 100 different antibiotics are available to cure bacterial infections from minor discomforts to life-threatening infections.

Although antibiotics are useful in a wide variety of infections, it is important to realise that antibiotics only treat bacterial infections. Many common infections are caused by viruses. Antibiotics do not kill viruses, while many bacterial infections do not need to be treated with antibiotics. This is why you are not prescribed antibiotics for many infections.

When you have been prescribed antibiotics, it is essential that you complete the prescribed course. Even though you may feel better before your medicine is entirely finished, follow through and take the entire course. If an antibiotic is stopped in mid-course, the bacteria may be partially treated and not completely killed, causing the bacteria to develop the ability to defend themselves against the effect of the antibiotic. This can cause a serious problem if those stronger bacteria grow enough to cause a re-infection.

Antibiotic resistance
When bacteria develop the ability to defend themselves against the effect of an antibiotic, they are said to have acquired antibiotic resistance - one of the foremost concerns in modern medicine.

Simply put, if an antibiotic develops resistance the micro-organism is either not responding or responding minimally to an antibiotic to which that micro-organism used to respond earlier.

The existence of antibiotic-resistant bacteria creates the danger of life-threatening infections that don't respond to antibiotics.

There are several reasons for the development of antibiotic-resistant bacteria. Besides not finishing prescribed courses, one of the most important is antibiotic overuse. This includes the common practice of prescribing antibiotics for the common cold or flu. Even though antibiotics do not affect viruses, many people expect to get a prescription for antibiotics when they visit their doctor. Although the common cold is uncomfortable, antibiotics do not cure it, nor change its course. You can help reduce the development of resistant bacteria by not asking for antibiotics for a common cold or flu.

How do antibiotics work?
Different antibiotics have different ways of fighting bacteria. For example, they can work by:

  • Inhibiting the bacterium to form a cell wall or changing the cell wall structure of bacteria - The bacteria literally ruptures due to the penetration of fluids through the cell wall. Examples include penicillin (and its derivatives ampicillin and cloxacillin), cephalosporin and vancomycin.
  • Interfering with protein production - Proteins are needed to ensure the manufacturing of new bacteria to replace old, dying bacteria. Some antibiotics interfere with the ability of bacteria to make proteins that are used to build important parts of the cell. Examples include tetracycline, aminoglycosides and macrolides.

  • Interfering with DNA synthesis - These antibiotics interfere with the production of new chromosomes, the cell's genetic information. Examples include quinolones.

Which antibiotic?
The choice of antibiotic used is made by considering the condition itself and the susceptibility of the organism causing the illness. Other factors may also be considered when choosing an antibiotic - medication cost, dosing schedule, allergies and common side effects are often taken into account. Patterns of infection in your community may also be considered.
The major antibiotics

  1. Penicillins

Examples: Amoxil, Megapen, Suprapen, Augmentin

Penicillin weakens the bacterial cell wall and allows water to enter the cell, causing cells to burst.

Penicillins are bactericidal and are not toxic to human cells which have no cell wall.

Resistance against penicillin is the result of an enzyme (â-lactamase) produced in the bacteria that destroy a vital part of penicillin’s structure.

Benzylpenicillin or Penicillin G is the most potent penicillin available, but has a relatively narrow spectrum of action. It is not given orally and is â-lactamase sensitive, meaning that resistance is common.

Ampicillin and Amoxicillin has an extended spectrum compared to the earlier penicillins. Both have a broader spectrum of action while still being â-lactamase sensitive. It can be given orally or parenterally (by injection or intravenous infusion (drip)).

Amoxicillin is probably the most widely used antibiotic in South Africa. It is well absorbed when taken by mouth and is often combined with clavulanic acid which protects the antibiotic against the effect of â-lactamase. This combination is called co-Amoxiclav.

Flucloxacillin and cloxacillin are â-lactamase resistant, but have a narrow spectrum of action. It is particularly useful in the treatment of soft tissue infections.

Adverse effects with penicillins are relatively unusual. Allergy occurs in about 0.7% of patients ranging from mild skin reactions to potentially fatal anaphylaxis. Candida infections, better known as thrush, may develop if a probiotic is not used simultaneously. Ampicillin and amoxicillin may induce diarrhoea in some patients.

The use of penicillin may decrease the effectiveness of oral contraceptives.

  1. Cephalosporins

Examples: Orelox, Prozef, Lorabid

Cephalosporins are broad spectrum antibiotics with structural similarities to penicillin. It has a mechanism of action similar to that of the penicillins – a mechanism disrupting cell wall structural integrity - and has a bactericidal action.
The cephalosporins are grouped into different generations according to their antimicrobial properties. The initial cephalosporins were designated first generation while later, more extended spectrum cephalosporins were classified as second generation cephalosporins. Each newer generation of cephalosporins has significantly greater antimicrobial properties than the preceding generation. Fourth generation cephalosporins, however, have true broad spectrum activity.
Due to the similarity in chemical structure to penicillin an estimated 10 – 20% of patients with a penicillin allergy are also allergic to cephalosporins. As is the case with penicillins, candida infections and diarrhoea may also occur.

Interesting fact
Cephalosporin compounds were first isolated from cultures of Cephalosporium acremonium from a sewer in Sardinia in 1948 by Italian scientist Giuseppe Brotzu. He noticed that these cultures produced substances that were effective against Salmonella typhi -  the cause of typhoid fever.

  1. Carbapenems

Examples: Tienam, Meronem

The carbapenems, imipenem and meropenem, are a class of antibiotics with a very broad spectrum of action. They act as antimicrobials through inhibiting cell wall synthesis of bacteria. It remains very stable in the presence of â-lactamase and its use is generally limited to severe nosocomial (hospital-acquired) infections.

Meropenem is furthermore useful in the treatment of bacterial meningitis. It is more stable to renal inactivation than is the case with Imipenem. Imipenem is rapidly degraded by renal enzymes when administered alone and is always co-administered with cilastin – a specific enzyme inhibitor – to prevent inactivation. Cilastin itself does not have any antibacterial effect.

Meropenem may be less likely than imipenem to induce seizures, but until further experience is gained, caution is advised when prescribing this to patients with neurological disorders.

Adverse effects

    • hypersensitivity – those allergic to penicillin should not take these drugs
    • gastrointestinal effects
    • central nervous system effects including seizures

Interesting Fact Due to imipenem’s broad spectrum of action it is often referred to as “Gorilla-cillin”.

  1. Monobactams

Example: Azactam

The monobactams are narrow-spectrum antibiotics with structural similarities to penicillin. Aztreonam is the only commercially available monobactam.

Aztreonam has activity against gram-negative organisms only. It is stable against many â-lactamases, making it useful in the treatment of sepsis due to resistant gram-positive organisms.

Adverse effects:

  • nausea, vomiting, diarrheoa, abdominal cramps
  • mouth ulcers, altered taste
  • flushing
  • hypersensitivity reactions (specially if allergic to other beta-lactam antibiotics)
  • rashes, injection-site reactions
  • hypotension, seizures, confusion, dizziness, headache
  • halitosis
  1. Aminoglycosides

Examples: Garamycin, Amikin, Nebcin
Aminoglycosides are a bactericidal group of antibiotics that lead to abnormal protein production in bacteria and also cause cell membrane damage.

These antibiotics are poorly absorbed orally and are therefore not given by mouth

The first antibiotic remedy for tuberculosis, streptomycin, first used some 60 years ago is an aminoglycoside. It is now rarely used in the developed world.

Aminoglycosides are administered parenterally (gentamicin and amikacin being most often used) or applied topically for local effect (gentamicin, tobramycin and neomycin) – often in ear and eye ointments.

Aminoglycosides have a narrow therapeutic window and toxicity including oto- and nephrotoxicity (ear- and kidney toxicity) occurs if not monitored closely.

These antibiotics may also enhance the effect of muscle relaxants.

Interesting fact
Streptomycin is also used as a pesticide, to combat the growth of bacteria, fungi, and algae in certain fruit, vegetables, seed, and ornamental crops while controlling algae in ornamental ponds and aquaria. As is the case with its medical application, extensive use can be associated with the development of resistance.

  1. Macrolides

Examples: Ilosone, Zithromax, Klacid

The macrolide group of antibiotics are broad-spectrum and functions by inhibiting bacterial protein synthesis. They are bacteriostatic at usual doses, but bactericidal in high doses.

It is reported that resistance to this group of antibiotics develops rapidly.

Macrolide antibiotics such as Erythromycin are used as an alternative to penicillin in penicillin-allergic patients.

Newer generation macrolide antibiotics such as clarithromycin and azithromycin have a broader spectrum of use than erythromycin with fewer adverse effects. An added advantage is that they can even be given once daily.

Gastrointestinal upsets common with erythromycin are less common with the newer macrolide antibiotics.

Erythromycin (and to a lesser extent clarithromycin) inhibits certain enzymes in the human body which can increase the effect of a wide range of other drugs such as warfarin, some epileptic drugs, and so forth. The combination of macrolides and statins (drugs used for lowering cholesterol including simvastatin and pravastatin) is not advisable and can lead to debilitating muscular weakness, spasms, cramps and stiffness.

Interesting fact
The drug tacrolimus (Prograf), which is used as an immuno-suppressant and not as an antibiotic, is also a macrolide.

  1. Lincosamides

Example: Dalacin

Although chemically distinct from erythromycin, clindamycin, the major lincosamide is similar in its mode of action and is also bacteriostatic.

It functions by selectively inhibiting bacterial protein synthesis.

Lincosamides is rapidly absorbed and penetrates most tissues well, except the central nervous system.

It is particularly effective in penetrating bone tissue making it effective in the treatment of osteomyelitis.

Diarrhoea as a side effect is common, while pseudomembrane colitis, a serious and potentially fatal inflammatory condition of the large bowel common in middle aged woman also occurs. It is caused by a super infection with a strain of Clostridium difficile - a strain resistant to clindamycin – and the toxin it secretes. This toxin damages the intestinal mucosal lining.

Although this condition may occur with any antibiotic, it is especially common after treatment with clindamycin and this severely limits its use. It is recommended that patients discontinue use if diarrhoea develops.

Skin reactions are also often observed with the use of lincosamides.

Clindamycin have been reported to cause oesophageal (throat) irritation – this can however be avoided by taking the antibiotic with adequate amounts of fluid.

Interesting fact
Clindamycin can be used to treat malaria and is also effective as a topical treatment for acne.

  1. Streptogramins

Example: Synercid

Streptogramins antibiotics act by inhibiting bacterial protein synthesis. The two streptogramins found in Synercid, quinupristin and dalfopristin, act synergistically and are more effective than each component alone.

Dalfopristin inhibits the early phase of protein synthesis and quinupristin inhibits the late phase of protein synthesis.

The combination should be reserved for treating infections which have failed to respond to other antibacterials (for example meticillin-resistant Staphylococcus aureus, MRSA) or for patients who cannot be treated with other antibacterials.

These drugs should under no circumstances be co-administered with drugs that prolong cardiac QT interval. These include cisapride, terfenadine, quinadine and lidocaine.

Adverse effects:

  • joint or muscle aches
  • nausea, diarrhea or vomiting
  • rash or itching
  • headache
  1.  Sulphonamides and trimetoprim

Example: Purbac

Suphonamides are rarely used alone today. On its own it’s primarily used for the treatment of urinary tract infections.

A combination of a sulphonamide with another similar antifolate drug (e.g. trimetoprim) adds to the spectrum of antibacterial activity.

Sulphonamides are bacteriostatic and functions by acting as an inhibitor of bacterial folic. The human body do not manufacture folate and humans are thus not unaffected.

Trimetoprim is also bacteriostatic and has a similar spectrum to the sulphonamides. It is widely used for urinary tract infections and also for respiratory tract infections.

Co-trimoxazole, a combination of a sulphonamide (sulphamethoxazole) and trimetoprim, is still widely used today. Therapeutic effectiveness is however decreasing due to the emergence of widespread resistance.

Gastro-intestinal side effects, headache and nausea can be a result of both components of co-trimoxazole, while a skin rash, allergy and fever are less common. Allergic reactions are mostly a result of a sulphur allergy.

To reduce the risk of crystalluria a high fluid intake of 1.5 L/day is recommended in patients receiving sulphonamides.

  1. Quinolones

Examples:Ciprobay, Utin, Tavanic, Tequin, Avelon

The quinolones are a family of broad-spectrum bactericidal antibiotics that act by inhibiting DNA gyrase, preventing recoiling of DNA after replication and thereby interfering with the reproduction of bacterial DNA.

Quinolones are effective, but generally expensive drugs. Resistance to quinolones is furthermore becoming more common.

In general quinolones are used as reserve drugs and not for first-line treatment, partially due to the above-mentioned financial implications and the risk of resistance.

Nalidixic acid was the first quinolone identified. It has no systemic antibacterial effect, but is effectively used as a urinary antiseptic for lower urinary tract infections.

Ciprofloxacin is one of the most widely used antibiotics currently available and has a broad spectrum of activity. It is also used as prophylactic treatment for those who came into contact with patients who had meningococcal meningitis.

In some countries ciprofloxacin eye drops are used as treatment for patients with corneal ulcers.

Adverse effects

  • gastro-intestinal upsets
  • tendonitis and possible damage to growing cartilage – it is therefore not indicated for children, young teenagers and pregnant woman.
  • potential nerve damage – Therapy should be discontinued if a patient experiences symptoms of pain, burning, tingling or numbness
  • a lowered seizure threshold has also been noticed and is therefore contra-indicated in epileptics
  • photosensitivity may also be a troublesome side effect   

Interesting fact
Fluoroquinolones may block the neurotransmitter GABA, and this may cause confusion in the elderly. Many elderly patients have been found wandering around, confused, after being treated with fluoroquinolones.

  1. Tetracyclines

Examples: Tetralysal, Doxitab, Cyclimycin, Roxy

The tetracyclines are bacteriostatic and act by interfering with bacterial protein synthesis.

Tetracyclines are indicated for use against many bacterial infections, but because of increased bacterial resistance have been superseded by more effective agents for many infections. Lately tetracyclines are mainly used to treat acne. It is also commonly used as malaria prophylaxis.

Tetracycline and oxytetracyclin have short half-lives, while doxycyline has a longer half-life, allowing it to be used as little as once daily.

Tetracyclines:

  • may cause discolouration and deformity in growing teeth and is not recommended during pregnancy and in children younger than 12 years of age;
  • bind avidly to heavy metal ions and the antibiotic may be inactivated or absorption greatly reduced if taken with milk, antacids containing aluminium, iron or zinc, or with iron supplements;
  • may cause photosensitivity of the skin, and those taking it are recommended to avoid sun exposure or intense light;
  • may lead to dry and flaky skin if overused in the treatment of acne vulgaris.

Adverse effects

  • gastro-intestinal upsets, nausea and vomiting
  • candida super infection - a probiotic used concomitantly is recommended
  • tinnitus
  • oesophageal irritation and ulceration is a threat with doxycycline and doses should be taken with adequate amounts of fluids, while sitting in an upright position and well before retiring

Interesting fact

Nubian mummies studied in the 1990s were found to contain significant levels of tetracycline. There is evidence that the beer consumed by these people before they were mummifiedummies could have been the source of significant tetracycline levels.

  1. Metronidazole

Example: Flagyl

Metronidazole is a prodrug, meaning that the drug is metatabolised into its active form only after oral administration. Metronidazole disrupts the helical structure of DNA and inhibits bacterial protein synthesis and replication.

It is well absorbed after oral or rectal administration and can also be given intravenously or as a topical application. It is widely distributed in the body (including into abscess cavities) and is metabolised by the liver.

Metronidazole is used against anaerobic organisms. It is, amongst others, useful in the treatment of some dental infections, particularly dental abscess, against protozoal infections and in patients with stomach ulcers as part of the treatment of Helicobacter pylori, a bacterium responsible for the formation of peptic ulcers.

Adverse effects

  • nausea, anorexia and a metallic taste in the mouth
  • drowsiness, dizziness, headache
  • possibly teratogenic if taken in the first trimester of
  • reduces efficacy of contraceptive pill

Interesting fact
Consuming alcohol while using metronidazole causes a disulfiram-like reaction, similar to that observed with the medication prescribed for alcoholics, with effects that can include nausea, vomiting, flushing of the skin, accelerated heart rate, shortness of breath, and even death. Consumption of alcohol should be avoided by patients during systemic metronidazole therapy and for at least 24 hours after completion of treatment.

Drug interactions
Metronidazole may inhibit the metabolism of warfarin leading to higher levels of warfarin in the body.          

  1. Nitrofuran derivatives

Nitrofurantoin

Example: Macrodantin

Nitrofurantoin is used as a urinary antiseptic and to treat Gram-negative infections in the lower urinary tract. Resistance has been reported to develop relatively quickly.

The drug is taken orally and is well absorbed. It is excreted unchanged in the urine and is only antimicrobial when concentrated in the urine – it has no systemic antibacterial effect.

At the concentrations achieved in urine, nitrofurantoin is bactericidal.

The mechanism of action of nitrofurantoin is unique and complex. The drug works by damaging bacterial DNA.

Nutrofurantoin should not be combined with quinolone antibiotics as they are mutually antagonistic and possibly reduce the effect of both substances.

Adverse effects

  • gastrointestinal upsets, anorexia, nausea and vomiting. If taken with food or milk  these symptons can be greatly reduced.
  • allergy (including respiratory effects)
  • central nervous system effects include headache and dizziness

Interesting fact
Nitrofurantoin colours urine a dark orange-brown - this is completely harmless.

  1. Steroid Antibacterials

Fusidic Acid

Example: Fucidin

Fusidic acid is bacteriostatic and inhibits bacterial replication. It is often used topically in creams and eye drops (Fucithalmic), but may also be given systemically as tablets or injections (Fucidin).

Fucidic acid is a narrow-spectrum antibiotic active only against S. aureus. The most important use of fusidic acid clinically is its activity against Methicillin Resistant Staphylococcus Aureus (MRSA), a sometimes-fatal hospital-acquired 'super bug'. Many strains of MRSA remain sensitive to fusidic acid, but because resistance develops easily, fusidic acid must never be used on its own to treat MRSA and should be combined with another antimicrobial such as rifampicin.  It is not affected by â-lactamase.

It is given orally or parenterally and can be used alone or also with flucloxacillin to reduce the development of resistance. It is well absorbed and widely distributed, including to bone (useful in osteomyelitis). It is metabolised in the liver.

Adverse effects

  • Gastrointestinal upsets include vomiting, diarrhoea, epigastric pain and anorexia. Gastric discomfort can be minimised by taking the drug with meals.
  • Liver-toxicity is the main serious effect. This is however usually reversible on discontinuing treatment.
  • On rare occasions skin reactions and rashes my occur.
  1. Glycopeptide antibacterials

Vancomycin and teicoplanin

Examples: Targocid, Vancocin

The glycopeptide antibiotics vancomycin and teicoplanin are bactericidal and interfere with bacterial cell wall formation. They are only effective against Gram-positive organisms.

Vancomycin and teicoplanin are most often used restrictively intravenously to treat serious or resistant S. aureus infections and for prophylaxis of endocarditis in penicillin-allergic patients.

In some cases vancomycin is given orally to treat pseudomembrane colitis. Although it is not absorbed systemically after oral administration, is has a local effect making it effective in the treatment of this condition.

Adverse effects
Vancomycin has plasma concentration-dependent toxicity and monitoring of plasma concentrations is essential. This is not necessary for teicoplanin, which is much less toxic.

Effects include:

  • nephrotoxicity
  • ototoxicity
  • allergy
  • histamine release (after rapid injection of vancomycin: ‘red man syndrome’).

Interesting fact
Vancomycin was first isolated from a soil sample collected from the interior jungles of Borneo by a missionary. The compound was initially labelled compound 05865, but was eventually given the generic name, vancomycin (derived from the word "vanquished").

  1. Amphenicols

Chloramphenicol

Example: Chlorcol

Chloramphenicol is a broad-spectrum, mainly bacteriostatic, antibiotic that acts by inhibiting bacterial protein synthesis. It is well absorbed and widely distributed, including to the CNS. It is metabolised in the liver.

It was introduced in clinical practice in 1949 and was the first antibiotic to be manufactured synthetically on a large scale.

Although chloramphenicol is an effective broad spectrum antibiotic effective against a wide variety of microorganisms, its uses are limited by its serious toxicity. The major indication is to treat bacterial meningitis caused by susceptible organisms. It is also specifically used for Rickettsia. It is however still very widely used in low income countries, because it is exceedingly cheap.

In the West, the main use of chloramphenicol is in eye drops or ointment for bacterial conjunctivitis.

Adverse effects

  • A rare and potential fatal form of anaemia that is probably immunological in origin. This is seldom reversible and onset may be during or weeks to months after therapy. Because of this chloramphenicol should be reserved for severe infections caused by susceptible organisms only.
  • Reversible bone marrow depression caused by its effect on protein synthesis in      
    humans.
  • Other adverse effects include gastrointestinal effects and hypersensitivity reactions.
  • Chloramphenicol is associated with an increased risk of childhood leukaemia

Interesting fact
Chloramphenicol has recently been discovered to be a life-saving cure for chytridiomycosis in frogs. Chytridiomycosis is a fungal disease that has been blamed for the extinction of a third of the 120 frog species lost since 1980.

Interesting fact
Grey-baby syndrome - intravenous chloramphenicol use has been associated with the so called grey-baby syndrome. This phenomenon occurs in newborn infants, because they do not yet have fully functional liver enzymes, allowing chloramphenicol to remain unmetabolised in the body. This causes several adverse effects, including hypotension and cyanosis. The condition can be prevented by using chloramphenicol at the recommended doses and monitoring blood levels in mothers.

  1. Oxazolidinones

Linezolid

Example: Zyvoxid

Linezolid, an oxazolidinone antibacterial, is active against multi-resistant bacteria including gram-positive bacteria including meticillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci.

It is the first commercially available oxazolidinone antibiotic and is usually reserved for the treatment of serious bacterial infections where older antibiotics have failed due to antibiotic resistance. Conditions such as skin infections or nosocomial pneumonia where methicillin or penicillin resistance is found are indicators for linezolid use.

Linezolid works by inhibiting the initiation of bacterial protein synthesis.

Initially there was hope that bacteria would be unable to develop resistance to it. However, in 2001 Staphylococcus aureus was first identified as being resistant to linezolid. Resistance to linezolid can develop with prolonged treatment or if the dose is less than that recommended.

Adverse effects

  • skin reactions
  • loss of appetite, diarrhoea, nausea, constipation
  • fever

Interesting fact Linezolid is a weak monoamine oxidase inhibitor (MAOI) and cannot be used with tyramine containing foods or pseudoephedrine.

  1. Aminocyclitols

Example: Trobicin

Spectinomycin interrupts protein synthesis in bacteria. It is given by injection to treat gonorrhoea, especially in patients who are allergic to penicillins.

Adverse effects

  • Pain, itching or skin reactions at injection site
  • Dizziness, headache, insomnia
  • Nausea
  • Fever, chills
  1. Fosfomycin

Example: Urizone

Fosfomycin is a broad-spectrum indicated as a single-dose therapy in the treatment of acute uncomplicated lower urinary tract infections caused by sensitive E.Coli in women and girls over 5 years of age. It is also used for prophylaxis in diagnostic and surgical transurethral procedures in adult men.

Absorption of the dose is delayed and reduced by food, resulting in reduced blood and urinary concentration. The dose should be taken 2 hours before the next meal.

Avoid using together with metoclopramide (maxolon/clopamon) as this reduces the effect of the drug.

Adverse effect

  • gastrointestinal disturbances
  • skin reactions
 
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