INTRODUCTION

Many bacteria have mutual relationships with humans, with both species benefiting in some way from their coexistence, for example many of the bacteria that live in the human gastrointestinal tract. These bacteria feed on nutrients from ingested food and in return carry out tasks such as producing enzymes involved in the breakdown of complex nutrients.

There are, however, bacteria that cause harm to humans, and these organisms are known as pathogens. Even some normally benign bacteria can cause harm to the human host in certain circumstances, for example when the host resistance is in some way compromised. This phenomenon is known as opportunism and the resulting infection as opportunistic infection.

The resistance of bacteria to antibiotics (p. 293) is increasingly becoming a very significant problem. The cost of resistance is measured not only in terms of failure of therapy but also in the increased costs of more expensive drugs needed to combat the resistant bacteria. In 1994, the World Health Organization Scientific Working Group on the Monitoring and Management of Bacterial Resistance to Antimicrobial Agents (Tenover and Hughes 1995) discouraged the unnecessary use of antibiotic prophylaxis in food animals and stated that ‘antimicrobial agents should not be used as a substitute for adequate hygiene in animal husbandry’.

Many conditions for which antibiotics are prescribed are either of a self-limiting nature or are viral in origin and, as such, do not require antibiotics. The causes of this inappropriate prescribing by clinicians include insufficient training or knowledge, difficulty in selection of the appropriate drug, lack of microbiological information, fear of litigation and patients’ expectations (Binyon and Cooke 2000).

TREATMENT OF INFECTIONS

The discovery of sulphonamides in the 1930s, followed by penicillin in the 1940s, heralded a new era in the treatment of infections. Since then, a large number of drugs have been produced that either kill or inhibit the growth of bacteria, fungi or viruses. These drugs, in tandem with the patient’s natural immunity, have cured many infectious diseases that previously often proved fatal. It should be noted that when immunity is impaired due to prolonged illness, old age or the use of cytotoxic drugs, infections are more difficult to eradicate. As organisms become resistant to chemotherapy, a continuing search is necessary for new drugs and modifications of those already in use.

CLASSIFICATION OF BACTERIA

Bacteria can be broadly classified according to cell shape (Fig. 15.1), that is:

Fig. 15.1 Bacteria: examples of cell shapes. (A) Cocci (spherical bacteria): 1, staphylococci; 2, streptococci; 3, diplococci. (B) 1–3, Bacilli. (C) 1, 2, Spirochaetes. (D) Actinomyces.

Subdivision of these categories is based on the Gram stain. This staining technique was developed by Christian Gram in 1884. A heat-fixed smear of bacteria undergoes a staining and counterstaining process. Gram-positive cells retain the deep purple conferred on them by the initial staining with crystal violet and iodine, whereas Gram-negative cells, which have been decolorised, exhibit the red colour of the counterstain. As a result, Gram-positive and Gram-negative cells can be readily distinguished under the microscope.

Micro-organisms are also classified as aerobes (those that can live and grow in the presence of oxygen) or as anaerobes (those that can live and grow without oxygen). These three factors:

can be used in the classification of infectious bacteria (Table 15.1).

MICROBIOLOGY

Serious infections can be life-threatening, and decisions require to be made on the most appropriate therapy. For example:

Table 15.2 Causative pathogens in some common bacterial infections

Other factors affecting the choice of antibiotic include:

It is advisable to obtain specimens for microbiological investigation before antimicrobial therapy is initiated, so that the antibiotic therapy can be reassessed or started after the organism is identified. Conventional laboratory techniques for identification require at least 18 h of incubation in appropriate media to allow detectable numbers of bacteria to grow. However, more rapid techniques help in diagnosis before culture results are available. The most valuable is a Gram-stained smear of blood or aspirate from the site of infection.

An identification of organisms from culture is followed by sensitivity tests. Filter paper discs impregnated with known concentrations of antibiotic are placed on to an agar culture plate containing the individual strain of organism isolated in the culture process. The degree of sensitivity of the organism to the antibiotic is assessed by the size of inhibition zones around the discs after further incubation. Results are reported back to the prescriber, indicating antibiotics effective in treatment.

ANTIBACTERIAL DRUGS

Antibacterial drugs act by a number of mechanisms (Fig. 15.2). They can be either bactericidal (kill bacteria) or bacteriostatic (arrest the growth of bacteria) (Box 15.1). Bacteriostatic agents, because they do not kill bacteria, rely on the host’s immune and cell defence mechanisms to clear the bacteria. If these defence mechanisms are compromised, a bactericidal drug may be preferable.

Fig. 15.2 Actions of antibacterial drugs.

METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS

Approximately 30% of the population carry the organism Staphylococcus aureus. This is a bacterium that is normally found in the nose and on skin. Although most healthy people are unaffected by it, it does have the potential to cause infection in those who have severely weakened immune systems (e.g. some ill patients in hospital).

Methicillin-resistant Staphylococcus aureus (MRSA) is a form of Staphylococcus aureus. It is transmitted in the same way and causes the same range of infections as other strains of Staphylococcus aureus. However, it has developed resistance to the more commonly used antibiotics. This makes infections caused by MRSA more difficult and costly to treat, and every effort should be made to prevent its spread.

The majority of individuals are colonised when the organism lives harmlessly on the body with no ill effects, as opposed to infected, which is when the organism penetrates tissue and causes disease.

In order to control and minimise the spread of MRSA, there must be compliance with the following:

• standard precautions (e.g. thorough hand hygiene; see p. 320)

• cleaning must be of an acceptable standard

• adherence to infection control policies (e.g. isolation, clinical waste, laundry)

• infection control training

• strict adherence to antibiotic policy

• minimal movement of patients and staff between wards, units and hospitals.

TREATMENT OF MRSA INFECTION

Patients who demonstrate clinical signs of infection will require treatment with the appropriate antibiotics. The agent used will depend on the site of infection (Table 15.3). Some of these organisms are sensitive only to vancomycin or teicoplanin. Strains may be susceptible to rifampicin, sodium fusidate, tetra-cyclines, aminoglycosides and macrolides. Treatment is guided by the sensitivity of the infecting strain. Swabs are taken from the nose and throat to establish a diagnosis (Figs 15.3 and 15.4).

Table 15.3 Decolonisation

Site	Treatment
Nasal carriage only	Nasal decolonisation only
Throat carriage	Nasal and throat decolonisation
Axilla or groin carriage	Nasal and body decolonisation

Fig. 15.3 Taking a nose swab.

Fig. 15.4 Taking a throat swab.

Nasal decolonisation

Nasal carriage treatment is to apply, with a cotton bud, mupirocin 2% nasal ointment three times daily to the inner surface of each nostril for 5 days. When mupirocin resistance is encountered, second-line treatment is with neomycin and chlorhexidine cream (Naseptin) provided that the organism is neomycin-susceptible.

Throat decolonisation

Oral hygiene is very important, as teeth and dentures may harbour MRSA. First-line treatment is oral trimethoprim (200 mg twice daily) and sodium fusidate tablets (500 mg three times daily) for 5 days. In the event of resistance or patient intolerance, an alternative is a combination of oral rifampicin (600 mg once daily) and trimethoprim 200 mg twice daily for 5 days. Rifampicin or sodium fusidate should not be used alone, because resistance may develop rapidly.

Skin decolonisation

Treatment consists of a direct application of 4% chlorhexidine to all skin using a damp disposable cloth daily for 5 days, using the chlorhexidine as a soap substitute and then rinsing it off. The hair should be washed twice during the 5-day period with 4% chlorhexidine. Alternatively, 2% triclosan or 7.5% povidone–iodine could be used. Hair conditioners and body lotions can be used after treatment if required.

Linezolid and quinupristin with dalfopristin

Linezolid and the combination of quinupristin and dalfopristin are active against MRSA, but these antibacterial drugs should be reserved for organisms resistant to other antibacterials or for patients who cannot tolerate other antibacterial drugs. Linezolid is available both orally (600 mg every 12 h) and by intravenous infusion. Thrombocytopenia, anaemia, leucopenia and pancytopenia have been reported, and weekly monitoring of full blood counts is recommended. Quinupristin with dalfopristin is available as an intravenous infusion. A novel broad-spectrum glycycline antibiotic (tigecycline) is active against Gram-positive, Gram-negative and anaerobic organisms including multidrug-resistant strains (see p. 301).

THE PENICILLINS

The penicillins are bactericidal and interfere with cell wall synthesis in growing and dividing bacteria. Lysis and cell death result from weakening of the cell wall. Penicillins are excreted in the urine in therapeutic concentrations.

The most significant and adverse effect of the penicillins is hypersensitivity, which manifests as rashes and, on occasion, anaphylaxis. Allergy to one penicillin indicates allergy to them all, because the hypersensitivity is related to the basic penicillin structure.

Excessively high serum levels due to either very high doses or to renal failure in patients given normal doses may give rise to encephalopathy, a rare but serious toxic effect due to cerebral irritation. The penicillins should not be given by intrathecal injection, as this can cause encephalopathy, which may be fatal. A second problem is accumulation of electrolyte, because most injectable penicillins contain either sodium or potassium.

Diarrhoea often occurs during oral penicillin therapy.

BENZYLPENICILLIN AND PHENOXYMETHYLPENICILLIN

Benzylpenicillin (penicillin G) is readily inactivated by gastric acid juice and is given by injection. It diffuses into most of the body tissues but does not pass the blood–brain barrier unless the meninges are inflamed; neither does it penetrate well into the pleural cavity nor into the synovial or ocular fluids. It is inactivated by bacterial beta-lactamases. Beta-Lactamases are enzymes that inactivate penicillin by attacking part of the penicillin molecule known as the beta-lactam ring. This structure is an essential part of penicillins and cephalosporins. Notable producers of beta-lactamases are staphylococci.

Benzylpenicillin is effective in a wide range of infections, including those shown in Table 15.4.

Table 15.4 Infections for which benzylpenicillin is effective

Organism	Disease
Beta-haemolytic streptococci	Septicaemia, tonsillitis
Viridans streptococci	Subacute bacterial endocarditis
Streptococcus pneumoniae	Pneumonia
Neisseria meningitidis	Meningococcal meningitis
Clostridium tetani	Tetanus
Clostridium perfringens	Gas gangrene
Treponema pallidum	Syphilis
Neisseria gonorrhoeae	Gonorrhoea
Borrelia burgdorferi	Lyme disease

Phenoxymethylpenicillin (penicillin V) has a similar but less active antibacterial spectrum. It is indicated principally for respiratory infections in children, streptococcal tonsillitis and continued treatment following benzylpenicillin injection. It is used as a prophylactic against reinfection after recovery from rheumatic fever. Phenoxymethylpenicillin is not destroyed in the stomach and is quickly but unpredictably absorbed from the small intestine. Absorption is superior when administered on an empty stomach. Phenoxymethylpenicillin is not suitable for the treatment of severe conditions in which high blood levels of penicillin are necessary.

The dose range and side effects of benzylpenicillin and phenoxymethylpenicillin are shown in Table 15.5.

Table 15.5 Benzylpenicillin and phenoxymethylpenicillin

BROAD-SPECTRUM PENICILLINS

This group includes ampicillin and amoxicillin. The main difference between ampicillin and amoxicillin is in absorption from the gut. Less than half the dose of ampicillin is absorbed from the gut, and this is decreased by the presence of food. About 40% passes into the large bowel and diarrhoea, a common side-effect, is thought to be caused by a disturbance of the large bowel flora. Amoxicillin is better absorbed, producing higher plasma and tissue concentrations, absorption not being affected by the presence of food in the stomach. Both of these drugs are inactivated by b-lactamases, including those produced by almost all staphylococci, 50% of Escherichia coli strains and 15% of Haemophilus influenzae strains. They should not be used for hospital patients without checking sensitivity.

Co-amoxiclav is a combination of amoxicillin and beta-lactamase inhibitor, clavulanic acid. The clavulanate molecules penetrate the bacterial cell and combine with the beta-lactamase molecules. This inactivates the beta-lactamases, leaving the amoxicillin free to exert a full bactericidal effect. This makes the combination active against beta-lactamase-producing bacteria that are resistant to amoxicillin: Staphylococcus aureus, Escherichia coli and Haemophilus influenzae, as well as many Bacteroides and Klebsiella species. The broad-spectrum penicillins are summarised in Table 15.7.

Table 15.7 Broad-spectrum penicillins

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