Antibiotics anti-microbials

1. Antibiotics (anti-microbials) Dr Gareth Noble (and Dr Sue Jordan)

3. Overview 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.

4. 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

5. Classification Bacteriostatic (inhibit growth without death) or Bactericidial (Kill) Dosage related? Mechanism of action (see later) Spectrum of Activity: Broad or Narrow Chemical Structure

6. 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.

7. 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 gram-negative microbes (Broad) Note: Never confusion these terms with potency levels of the drugs or efficacy (ie. Narrow are weak, Broad are strong)

9. 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

10. 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.

11. 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

12. Interference with metabolic processes Agents are structurally similar to Para-aminobensoic 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

15. 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.

16. Administration: 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.

17. 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).

18. Table 2. Oral Administration of antibiotics

19. Adverse effects of antibiotics can be considered as: those occurring with all antibiotics (table 3); those restricted to specific agents (table 4).

25. 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.

26. 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.

27. 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.

28. 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.

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

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

31. 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