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Controlling antibiotic use: protecting an endangered medical resource   Back Bookmark and Share

Author : Cunney Robert, Smyth Edmond

Introduction

Few medical developments in this century have had such a profound impact on human health as the development of antibiotics. Since the first use of penicillin in 1941, it has been estimated that some 100,000 million kilograms of antibiotics have been produced world-wide.1 One study from the United States estimated that antibiotics have extended the average life span in the US by ten years. By comparison it has been estimated that curing all forms of cancer would only extend the average life span by three years.2 Prior to their introduction, diseases such as pneumonia, meningitis, bacteraemia, tuberculosis and rheumatic fever were the commonest reasons for admission to medical wards. 

In addition to their impact on these primary infectious diseases, antibiotics have also allowed us to control many opportunistic infections. Without this capacity, our ability to practice medicine in the 1990s, using advances such as cytotoxic chemotherapy, immunosuppressive drugs, transplantation and radical surgery would be compromised. However despite their profound impact on human medicine over the past fifty years this major medical resource is now under threat from overuse.

Areas of antibiotic use

It is customary to consider antibiotic use in hospital practice, general practice, veterinary practice and in developing countries separately. Although the latter two areas are probably of the greatest importance worldwide, they are beyond the scope of this review. While it is convenient to consider each of these areas as separate ecosystems it should be remembered that considerable overlap exists between them. For example we have recently demonstrated a link between use of a veterinary aminoglycoside and the presence of gentamicin resistance in Gram negative bacteria causing urinary tract infection in humans.3

While this review refers throughout to antibacterial agents, it should be noted that resistance is becoming an increasing problem with anti-viral agents (e.g. gancyclovir resistance in Cytomegalovirus), antiprotozoal agents (anti-malarial drug resistance) and anti-fungal agents (fluconazole resistance in Candida).

Problems with antibiotic use

The concerns regarding inappropriate antibiotic use can be divided into four areas: efficacy, toxicity, cost and resistance. 

Efficacy 

Studies have shown that up to 50% of antibiotic usage in both hospital and general practice is inappropriate.4,5 This is due to either;

  • antibiotic use where no infection is present, e.g. continuation of peri-operative prophylaxis for more than 24 hours after clean surgery;
  • infection which is not amenable to antibiotic therapy, e.g. antibiotics prescribed for viral upper respiratory tract infections; 
  • the wrong drug for the causative organism, e.g. the use of broad spectrum anti-Gram negative agents for community acquired pneumonia; or
  • the wrong dose or duration of therapy.
Such inappropriate use has a measurable effect on therapeutic efficacy.For example, one study showed that mortality in Gram negative septicaemia is doubled when inappropriate empiric agents were used.6 Since most initial antibiotic therapy is empiric, any attempt at improving use must tackle prescribing habits, with particular emphasis on guidelines for therapy based on clinical criteria.

Toxicity 

Inappropriate antibiotic use exposes patients to the risk of drug toxicity, while giving little or no therapeutic advantage. Antibiotics are often considered relatively safe drugs, yet direct and indirect side effects of their use are not infrequent and may be life-threatening. Allergic reactions, particularly to betalactam agents, are well recognised and have been described in reaction to antibiotic residues in food.7 Life threatening side effects from the use of antibiotics for apparently simple infections do occur. It is estimated, for example, that eight people per year in the UK die from side effects of co-trimoxazole usage in the community.8

Indirect side effects are often overlooked, especially as they may occur sometime after the antibiotic has been given. These include drug interactions (such as interference with anti-coagulant therapy), side effects associated with the administration of antibiotics (such as intravenous cannula infections) and super-infection (such as candidiasis and pseudomembranous colitis). Each of these may have a greater morbidity, and indeed mortality, than the initial infection for which the antibiotic was prescribed. 

Cost

The medical benefit of antibiotics does not come cheap. ln the hospital setting up to 50% of patients receive at least one antibiotic during their hospital stay, with surgical prophylaxis accounting for 30% of this.4 The financial cost of this can be considerable. The antimicrobial bill for our own institution is approximately IR800,000 per annum. This represents the acquisition costs of the drugs and does not include indirect costs (consumables, personnel, adverse effects etc.) which may far outweigh the cost of the individual drugs. Given that some 50% of antibiotic prescriptions may be inappropriate, it is clear that major cost savings can be realised through more judicious antibiotic prescribing. Similar costs are found in general practice where IR10,472,854 was spent on antimicrobials in the GMS alone in 1993 (the last year for which statistics are available).9

Resistance

The first penicillin resistant isolate of Staphylococcus aureus was described only two years after the introduction of penicillin. Within a decade, 90% of isolates were penicillin resistant. This pattern of antibiotic discovery and introduction, followed by exuberant use and rapid emergence of resistance has subsequently been repeated with each new class of antibiotics introduced. That bacteria can so rapidly develop resistance is due to two major evolutionary advantages. Firstly, bacteria have been in existence for some 3.8 billion years and resistance mechanisms have evolved over this time as a protective mechanism against naturally occurring compounds produced by other micro-organisms. In addition they have an extremely rapid generation time and can freely exchange genetic material encoding resistance, not only between other species but between genera. The vast quantities of antibiotics used in both human and veterinary medicine, as a result present in the environment, has led to the emergence of infection due to virtually untreatable bacteria. Multiply drug resistant tuberculosis is already wide-spread in parts of Southern Europe and has recently caused outbreaks in two hospitals in London. Vancomycin resistant enterococci and multiply drug resistant pneumococci have become a recognised problem in Irish hospitals. Vancomycin resistance in Staphylococcus aureus has already been reported on two continents. Its widespread dissemination will be catastrophic.10

Principles of control

In both the hospital and community setting, control of antibiotic use requires a team approach involving clinicians, microbiologists, pharmacists, infection control staff and administration. The cornerstone of improving antibiotic use is education, particularly in relation to prescribing habits. When prescribing antibiotics greater awareness is needed of toxicity, cost and potential emergence of resistance, as well as ensuring that it is the right drug for the right infection. This is best

   
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