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Antibiotics (anti-microbials)

Dr Gareth Noble (and Dr Sue Jordan)


Kock & Pasteur over a century

Discovered cause and effect Once found, needed an agent to be created to handle them

Antibiotics = a natural substance produced by a micro-organism to kill another Antiinfectives/Anti-microbrial = any agent (natural or synthetic) that kills pathogens (microbes) Key: it needs to kill the microbial cell and not be toxic to normal healthy human cells


Antibiotics are a large and diverse group of drugs which combat infections by suppressing the growth and reproduction of bacteria. However, many bacteria are now resistant to antibiotics and some are resistant to all known agents. New drugs are continually being introduced to combat evolving patterns of resistance.

Antibiotics exploit the differences between bacterial and human cells. They prevent the renewal of the bacterial cell wall and inhibit protein formation. Note: bacteria are 'gram negative' or 'gram positive'.

Gram negative bacteria have a tough wall


Bacteriostatic (inhibit growth without death) or Bactericidial (Kill)

Dosage related?

Mechanism of action (see later)

Spectrum of Activity:

Broad or Narrow

Chemical Structure

Bacteriostatic vs Bactericidal

Bacteriostatic allows for natural immunity to deal with the microbe

Antibodies, Phagocytosis etc

Bactericidial may lead to release of toxins and microbial contents leading to subsequent illness and inflammatory responses.

Spectrum of Activity

Relates to the number of microbes that are susceptible to the action of the drug

Narrow (limited number) / Broad (wide)

Penicillin G is a narrow spectrum drug as it is only effective against gram-positive microbe Tetracyclines are effective against gram-positive and gramnegative microbes (Broad) Note: Never confusion these terms with potency levels of the drugs or efficacy (ie. Narrow are weak, Broad are strong)

Mechanism of Action:
1. Inhibition of Cell Wall Synthesis 2. Disruption of Cell Membrane 3. Inhibition of Protein Synthesis 4. Interference with Metabolic Processes
NB: Bactericidal Bacteriostatic

Inhibition of Cell Wall Synthesis

Most bacteria possess a cell wall to protect from osmotic pressures Microbe divides needs to create a new cell wall

Interrupt this leads to new microbes being susceptible to external influences Cell ruptures Microbe death

Eg. Penicillinsm cephalosporins, vancomycin and bacitracin

Disruption of the microbial cell membrane

Essentially, affect cell membrane transportation in and out Increases permeability of membrane

External influences have greater effect Microbe death

Eg. Polymyxin, Colistin

Note: These agents are more toxic systemically than those agents that inhibit cell wall synthesis.

Inhibition of Protein Synthesis

Proteins vital for growth and repair Act either at:

Site of protein synthesis (ribosome) Within the nucleus by inhibiting synthesis of nucleic acids

DNA replication / RNA synthesis = TRANSCRIPTION

Eg. Tetracyclines, aminoglycosides and macrolides (erythromycin) Exploit structural differences between microbial and human cells

High dose can lead to toxicity

Interference with metabolic processes

Agents are structurally similar to Paraaminobensoic acid (PABA) component of folic acid

Essential for nucleic acid synthesis, without it microbes can not produce the proteins for growth Exploits: microbes need to create their own folic acid, whilst we get it in our diets.

Eg Sulphonamides, Trimethoprim

Table 1 Summary of some common antibiotics

Beta-lactams (penicillins, cephalosporins)

Broad-spectrum antibiotics*. Flucloxacillin and coamoxiclav are effective against some penicillinresistant organisms.

Aminoglycosides Effective against gram negative bacteria e.g. (streptomycin, Pseudomonas. Reserved for serious infections e.g. gentamicin, tobramycin) septicaemia, meningitis, hospital-acquired pneumonia. Glycopeptides (vancomycin, teicoplanin) Tetracyclines (doxycycline, minocycline) Effective against Staphylococci resistant to other drugs, including many strains of MRSA**.

Broad-spectrum antibiotics

Macrolides (erythromycin)

Broad-spectrum antibiotics, prescribed if patient is allergic to penicillins.

Prescribed for surgical prophylaxis, bacterial vaginosis, pressure sores, leg ulcers. Effective against gram negative bacteria, gonorrhoea, gastro-intestinal infections.

Quinolones (ciprofloxacin)

Antitubercular drugs (rifampicin, isoniazid, rifabutin, streptomycin)

sulphonamides (cotrimoxazole, trimethoprin)

Reserved for treatment/ containment of tuberculosis(TB).

Co-trimoxazole is reserved for serious infections associated with HIV/AIDS. Trimethoprin is prescribed for urinary tract infections.

* Broad spectrum antibiotics are used when the infectious agent is unknown. Narrow spectrum antibiotics are prescribed when the micro-organisms have been identified from tissue samples. ** Many bacteria produce an enzyme which destroys beta lactam antibiotics. In addition to this, MRSA (methicilin-resistant Staphylococcus aureus) produces an inactivating protein which confers resistance to most other antibiotics.

Indications for antibiotics include:

Treating bacterial infections in accordance with culture and sensitivity testing or (second best) knowledge of prevalent organisms. Prophylaxis:

surgery e.g. gastro-intestinal surgery, joint replacement. meningitis contacts surgical/ dental procedures in patients with artificial heart valves or heart valve lesions.


Dose depends on many factors:

nature and severity of infection; weight, age and renal function of patient. Some doses (e.g. gentamicin, vancomycin) are determined by therapeutic monitoring of venous blood samples, extracted prior to dosing.

Severe infections require intravenous infusion.

Observe veins carefully for signs of phlebitis, particularly with penicillins and vancomycin.

Intramuscular injections are painful and avoided, unless essential, in children. A warm compress may reduce pain.
Food affects absorption (table 2).

For other routes, see individual products (BNF).

Table 2. Oral Administration of antibiotics

Antibiotic Problem


Tetracyclines, Quinolones

Absorption impaired by iron, zinc or calcium in the stomach

Oesophageal or gastric irritation

Taken either 1 hour before or 2 hours after tablets containing these minerals or dairy products.
Taken with food and a full glass of water

Doxycycline Minocycline

Ampicillin Erythromycin Rifampicin

Absorption reduced by food in the stomach Absorption reduced by high fibre diets, e.g. bran or bulk laxatives e.g. methylcellulose
Absorption impaired by antacids, particularly those containing magnesium and aluminium

Taken 1 hour before or 2 hours after meals Dose increases may be required


Most antibiotics

Antibiotic taken 1 hour before or 2 hours after antacids

Adverse effects of antibiotics can be considered as:

those occurring with all antibiotics (table 3);

those restricted to specific agents (table 4).

Table 3. Problems Associated with All Antibiotics Problem Resistance Precautions Minimise antibiotics unless bacterial sensitivity is known. Ensure adequate doses, making allowances for drug-food interactions. Complete course. Avoid spreading infection by observing hospital policies for hand-washing, asepsis, and singleuse equipment. Try to prevent contact between MRSA and vancomycin-resistant Enterococci by separating patients harbouring these bacteria. Such contact could allow development of vancomycin-resistant MRSA. Thorough patient history. Pre-therapy assessment of breathing pattern and skin to facilitate detection of any changes. Administer intravenous therapy slowly.

Hypersensitivity 1-10% of patients are hypersensitive to penicillins.


Minimise use of broad-spectrum antibiotics. Monitor fluid and electrolyte balance if diarrhoea and vomiting occur and be alert for Chlostridium difficile infections. Small frequent meals may alleviate gastrointestinal disturbance. Stomatitis may be alleviated by ice cubes and mouth care. Monitor for infections due to fungi (e.g. Candida), Pseudomonas, Enterobacteria. If aminoglycosides are administered, monitor for worsening of TB and Herpes infections. Ensure adequate doses and prompt administration. Certain antibiotics, particularly aminoglycosides, have a narrow margin between therapeutic dose and toxicity.

Therapeutic failure

Table 4. Toxicity associated with antibiotics Site Antibiotic Precaution

Brain: Convulsions Confusion

Penicillins Cephalosporins Quinolones aminoglycosides


Avoid intrathecal route. Caution in patients with histories of convulsions and/or renal failure. Avoid co-administration of quinolones and NSAIDs.
Monitor. Alternative drugs may be needed.

Peripheral nerves: pain, numbness, tingling Inner ear (hearing & balance)

Gentamicin Vancomycin Rarely: Erythromycin

Avoid other drugs affecting the ear. Avoid in pregnancy and breastfeeding, if possible. Ensure patient can hear and balance is not affected. Mobilise carefully. Monitor tinnitus. Administer intravenous therapy slowly.

Growing bones & teeth


Avoid in pregnant women & children.


Erythromycin Rifampicin Isoniazid Rarely: Tetracyclines Cephalosporins Co-amoxiclav


Undertake liver function tests if use prolonged. Avoid in people with history of alcoholism.


Be alert for severe vomiting and pain radiating to the back. Check blood glucose concentration.


Gentamicin Vancomycin Cotrimoxazole Rarely: Cephalosporins Penicillins Tetracyclines Tetracyclines, Quinolones Chloramphenicol Cotrimoxazole Rarely: Cephalosporins Aminoglycosides

Check serum creatinine and urea to assess renal function before and during therapy. Seek alternative drug in those over 65. Ensure adequate hydration, including replacing any losses due to diarrhoea and vomiting. Avoid prolonged exposure to sunlight. Use high factor, high star sunscreen Avoid in patients with history/ family history of bone marrow problems or taking other drugs potentially toxic to the marrow (e.g. carbimazole, carbamazepine, antipsychotics). Check full blood count routinely and if sore throat or fever develop.

Skin (photosensitivity) Bone marrow

Cautions and contraindications (not a complete list)

History of hypersensitivity - Patients allergic to cephalosporins are often allergic to penicillins and vice versa. Patients allergic to diuretics or celecoxib or oral hypoglycaemics may be allergic to sulphonamides. Glandular fever (Epstein-Barr virus infection), cytomegalovirus infection greatly increase the risk of developing a penicillin-induced rash.

Impaired renal function causes some drugs to accumulate e.g. penicillins, tetracyclines, vancomycin, ciprofloxacin, teicoplanin.
Impaired liver function causes some drugs to accumulate e.g. metronidazole, rifampicin. Myasthenia gravis. Aminoglycosides and quinolones exacerbate this condition.

Porphyria. Avoid sulphonamides, cephalosporins, erythromycin, flucloxacillin, rifampicin, trimethoprin Pregnancy: Penicillins are usually the antibiotics of first choice. Tetracyclines, trimethoprin, cotrimazole, glycopeptides and aminoglycosides are avoided if possible. Breastfeeding allows small amounts of antibiotic to pass from mother to infant. Hypersensitivity responses and adverse effects may occur in the infant. Breastfeeding is not advised in some severe infections.

Drug Interactions (not a complete list)

Adverse effects are cumulative when drugs causing similar problems are co-administered. For example, drugs damaging the inner ear (e.g. gentamicin, vancomycin, teicoplanin, cisplatin, furosemide), are rarely combined (table 4). Susceptible people suffer an antabuse-like reaction if they take even a small amount of alcohol with certain antibiotics, usually metronidazole or cephamandole. This results in dilatation of all the blood vessels, causing flushing, severe headache and profound hypotension. Faints, falls and cardiovascular collapse may follow.



Rifampicin and rifabutin render all oral contraceptives ineffective. All broad spectrum antibiotics increase the risk of 'pill failure' for combined oral contraceptives.

antibiotics are incompatible with other drugs when co-administered in intravenous infusions. For example, if gentamicin is combined with heparin or a penicillin, its antibiotic activity will be lost.


intensify the action of muscle relaxants such as suxamethonium. Their use must be highlighted when the patient is transferred to the anaesthetic team.
cause accumulation of other drugs e.g. digoxin, corticosteroids, anti-coagulants.


Textbook References

Karch AM (2006) Focus on Nursing Pharmacology, 3rd Edition. Lippincott Williams & Wilkins Rang et al (2003) Pharmacology, 5th Edition. Churchill Livingstone. Lilley et al (2005) Pharmacology and the Nursing Process, 4th Edition. Mosby Page et al (2002) Integrated Pharmacology, 2nd Edition. Mosby. Martini (2005) Principles of Anatomy and Physiology, Pearson Education Publishers