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Chapter 29 Antimicrobials

Bacterial Structure

The cell wall of a bacterium is unique. Although not present in every bacterial species, it is usually a very important part of maintaining the integrity of the bacterium.

Animal and plant cells exist in a relatively constant chemical environment, but bacterial cells mostly live in an unfavourable environment. The cell wall is therefore a very important part of maintaining the integrity of the bacterium. Bacteria do not have a nucleus, but instead the genetic material exists in the form of a single chromosome that holds all the genetic information of the cell lying free in the cells. Bacteria have no mitchondria.

The function of the cell wall of a bacterium is to:

• Maintain the cell’s characteristic shape: to prevent the phosphoplipid membrane of the cell wall from adopting a spherical shape.

• Withstand considerable changes in osmolarity.

• Provide a rigid platform for structures such as flagellae.

The structure of the bacterial cell wall varies considerably between species, and classification is largely on the reaction of the bacterial cell wall to the Gram stain (named after the Danish bacteriologist Hans Christian Gram). Gram-positive bacteria retain more of the stain than Gram-negative bacteria, due to the different constituents of the cell walls.

Most of the work on wall structure has been done with Gram-positive cocci and bacilli, and with enteric bacteria (found in the intestine) and other Gram-negative rods.

Gram-Negative Bacteria

• Exhibit some flexibility in their nutritional needs, using inorganic nitrogen compounds, mineral salts and a simple carbon source for synthesis of their whole structure.

• Have a low internal osmotic pressure (see Figure 16.1, p. 124).

Gram-Positive Bacteria

• Gram-positive cocci or bacilli have more specific nutritional requirements. Several bacteria lack some synthetic abilities and require various amino acids, vitamins and accessory factors for growth

• These have a high internal osmotic pressure.

However, these characteristics do not always hold true:

• Some cocci, rickettsias, the Chlamydias and spirochaetes are Gram-negative and have exacting growth requirements.

• Mycoplasmas lack a rigid wall structure; although technically Gram-negative, they are a separate group.

Finding medication that is effective against these microorganisms is anything but straightforward.

The Bacterial Cell Wall

• Gram-Positive Bacteria

• Relatively simple wall.

• 90% of the Gram-positive cell wall comprises peptidoglycans (a polymer of sugars and amino acids) (Figure 29.1).

Figure 29.1 The structure of the bacterial cell wall.

• Gram-Negative Bacteria

• The cell wall is much more complex, consisting of layers of membranes.

• The cell wall is much thinner than the Gram-positive wall.

• Only 20% is peptidoglycans.

• The cell wall has protein components, which penetrate the layer partly or completely and form the membrane ‘mosaic’.

• The cell wall contains porins (membrane proteins that allow the passage of small molecules through the membrane).

Antimicrobial Medication

Actions

• Bactericidal: e.g. penicillins – lethal to bacteria.

• Bacteriostatic: not lethal but inhibit the ability of bacterial cells to reproduce. The body’s immune system therefore has to be efficient enough to destroy the microbe itself.

Main Antibiotic Groups

• Beta-lactams.

• Aminoglycosides.

• Tetracyclines.

• Sulphonamides.

• Beta-Lactams

• Penicillins (Figure 29.2), cephalosporins.

• Have a beta-lactam ring, which is the active part of the molecule.

• Inhibit cell wall synthesis by preventing cross-linking of peptidoglycans.

• Act on Gram-positive anaerobic bacteria, e.g. streptococci and meningococci.

• Absorbed by most tissues, except the central nervous system (CNS).

• Some patients have an allergy to penicillin.

• Low toxicity.

• Removed largely unchanged in urine.

Figure 29.2 The main antibiotic groups and azidothymidine (AZT).

• Aminoglycosides

• Gentamicin (see Figure 29.2): note the carbohydrate structure.

• Inhibit protein synthesis.

• Act on Gram-negative facultative bacteria (they can metabolize both with and without oxygen), e.g. staphylococci, Listeria and Corynebacterium spp.

• Poorly absorbed, therefore injected.

• Concentrate in renal cortex, not easily accessible to CNS and eye.

• Removed by kidney, therefore renal function must be good.

• Problems with nephrotoxicity, ototoxicity (can damage eighth cranial nerve, leading to deafness or vertigo).

• Tetracyclines

• Act on Gram-negative and Gram-positive bacteria (i.e. are broad spectrum).

• Inhibit protein synthesis (see Figure 11.6, p. 85).

• Absorption varies depending on the tetracycline.

• Bind to calcium (can therefore be incorporated into teeth and bone structure, causing discoloration of teeth and impairment of bone formation). Avoid taking with milk.

• Secreted in milk by breast-feeding women.

• Distributed to almost all tissues.

• Some are removed unchanged in the urine; others are metabolized in the liver and removed in the bile.

• Used for Chlamydia infections.

• Can cause gastrointestinal disturbances.

• Sulphonamides

• Act on Gram-negative and Gram-positive bacteria (i.e. broad spectrum).

• Work by resembling a bacterial metabolite: the sulphonamide effective blocks the metabolic process by depriving the bacteria of folic acid, which it needs for purine synthesis (see Chapter 12 ‘Purines and pyrimidines’, p. 89). DNA synthesis is therefore inhibited.

• Bacteriostatic.

• Good distribution to all tissues.

• May be partly removed unchanged by the kidneys and or metabolized in the liver.

Facts Associated with Antibiotics

• Age and health are important factors in dosage and response to the drug (see Chapter 19 ‘Pharmacodynamics: how drugs elicit a physiological effect’ p. 143).

• The kidneys eliminate most antimicrobials (very few are processed by the liver), so good renal function is vital.

• A complete course of antibiotics has to be taken to ensure that all the bacteria have been eliminated. Not taking a complete course might result in another upsurge of the bacteria and a return of the disease.

Pregnancy

This is a very important consideration in the use of antibiotics.

Treatment with Antimicrobials

Broad-spectrum drugs can be given initially but if the disease persists then a sample is taken, usually a throat swab in the case of a throat infection, or a mid-stream urine sample. Cultures are then made and tested against the appropriate antibiotic, so that a more effective antibiotic can be used.

• Main adverse reactions

Hypersensitivity

• Immediate: if extreme anaphylactic shock.

• Delayed: usually a skin rash.

Ototoxicity

Damage to the sensory cells in the cochlea and vestibular organ of the ear can lead to vertigo, ataxia and auditory disturbances, including deafness.

Prophylaxis

Although it is not advisable to give antibiotics prophylactically, this is sometimes necessary, for example when an individual has been exposed to a bacterial form of meningitis, or when an individual might be susceptible to infection after surgery to prevent septicaemia, e.g. open heart surgery.

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Chapter 29 Antimicrobials

Bacterial Structure

The cell wall of a bacterium is unique. Although not present in every bacterial species, it is usually a very important part of maintaining the integrity of the bacterium.

Animal and plant cells exist in a relatively constant chemical environment, but bacterial cells mostly live in an unfavourable environment. The cell wall is therefore a very important part of maintaining the integrity of the bacterium. Bacteria do not have a nucleus, but instead the genetic material exists in the form of a single chromosome that holds all the genetic information of the cell lying free in the cells. Bacteria have no mitchondria.

The function of the cell wall of a bacterium is to:

• Maintain the cell’s characteristic shape: to prevent the phosphoplipid membrane of the cell wall from adopting a spherical shape.

• Withstand considerable changes in osmolarity.

• Provide a rigid platform for structures such as flagellae.

The structure of the bacterial cell wall varies considerably between species, and classification is largely on the reaction of the bacterial cell wall to the Gram stain (named after the Danish bacteriologist Hans Christian Gram). Gram-positive bacteria retain more of the stain than Gram-negative bacteria, due to the different constituents of the cell walls.

Most of the work on wall structure has been done with Gram-positive cocci and bacilli, and with enteric bacteria (found in the intestine) and other Gram-negative rods.

Gram-Negative Bacteria

• Exhibit some flexibility in their nutritional needs, using inorganic nitrogen compounds, mineral salts and a simple carbon source for synthesis of their whole structure.

• Have a low internal osmotic pressure (see Figure 16.1, p. 124).

Gram-Positive Bacteria

• Gram-positive cocci or bacilli have more specific nutritional requirements. Several bacteria lack some synthetic abilities and require various amino acids, vitamins and accessory factors for growth

• These have a high internal osmotic pressure.

However, these characteristics do not always hold true:

• Some cocci, rickettsias, the Chlamydias and spirochaetes are Gram-negative and have exacting growth requirements.

• Mycoplasmas lack a rigid wall structure; although technically Gram-negative, they are a separate group.

Finding medication that is effective against these microorganisms is anything but straightforward.

The Bacterial Cell Wall

• Gram-Positive Bacteria

• Relatively simple wall.

• 90% of the Gram-positive cell wall comprises peptidoglycans (a polymer of sugars and amino acids) (Figure 29.1).

Figure 29.1 The structure of the bacterial cell wall.

• Gram-Negative Bacteria

• The cell wall is much more complex, consisting of layers of membranes.

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