The use and resistance to antibiotics in the community

Abstract

The frequency of resistance to antibiotics among common community-acquired pathogens, and the number of drugs to which they are resistant have been increasing worldwide. The relationship between antibiotic usage and resistance is strongly supported by data from several studies. Countries with the highest per capita antibiotic consumption have the highest resistance. The emergence of penicillin-resistant Streptococcus pneumoniae is related to high consumption of antibiotics in general, as well as to increased use of aminopenicillins and/or probably to wider use of oral cephalosporins. Increased consumption of macrolides, especially the long-acting ones, correlates significantly with the level of macrolide resistance of group A streptococci and S. pneumoniae while increased use of oral cephalosporins might be associated with the increase of β-lactamase-producing strains of Moraxella catarrhalis. Trimethoprim/sulphamethoxazole resistance is strongly associated with resistance to penicillin. A rise in consumption of fluoroquinolones is consonant with a higher rate of resistance to quinolones of S. pneumoniae, Escherichia coli and other Gram-negative bacteria. Paediatric bacterial isolates are more often resistant to various antimicrobial agents than isolates from adult patients; this higher resistance rate may be due to more frequent antimicrobial treatments in children, and extensive child to child transmission. Reliable data on antimicrobial consumption and resistance should form a basis for national policies devised to reduce the resistance of microorganisms to antibiotics.

Introduction

Antibiotics are given to humans and animals for therapy and prophylaxis of infectious diseases. They are also used in animals for growth promotion and, to a lesser extent, in agriculture for plant protection and in industry [1]. In humans, 80–90% of antimicrobial drugs are used in outpatients and the rest in the hospitals [1], [2], [3], [4]. It is estimated that 20–50% of all antibiotic use is questionable [1]. The consequences of antibiotic overuse and misuse include increased risk of adverse side effects, higher cost and higher rate of antimicrobial resistance of community pathogens. What distinguishes antimicrobial agents from other drugs, is that each antimicrobial agent used may have potential significant effect on, the world microbial ecology. Antibiotics affect both pathogens and the normal flora. In theory any antibiotic can select resistant strains as long as the local concentration of the drug exceeds the minimal inhibitory concentration (MIC) for the susceptible bacterial population but is below the MIC for the resistant clone. To what extent disturbances occur depends on the spectrum of the agent, dose, route of administration, pharmacokinetic and pharmacodynamic properties, and in vivo inactivation of the agent [5]. Incomplete absorption of orally administered drugs may influence the intestinal microflora, and secretion of an antimicrobial agent by the intestinal or vaginal mucosa, bile, salivary glands or eccrine or apocrine sweat glands may interfere with the normal flora at different habitats. As a consequence, antibiotic-resistant microorganisms may increase in numbers, and they also might serve as reservoirs for resistance genes. One antibiotic may select for resistance to one or more structurally unrelated antibiotics, because resistance may be genetically linked (via co-selection of multi-resistance plasmids and other resistance traits) [6]. Some antimicrobial agents are more selective for resistance than others [7]. Besides selective antibiotic pressure, transferable resistance (clonal spread or horizontal resistance gene transfer) is the major determinant of resistance development [8]. There are several ways to study the relationship between antibiotic usage and the incidence of bacterial resistance. Pharmacoepidemiology, mathematical modelling, pharmacokinetic and microbiological analysis of several body sites that normally harbour dense microbial flora are the methods used to study the evaluation and prediction of the ecological impact of antibiotics on the human microflora, as well as the use and the effects of drugs in human populations [9].

It is irrefutable that antibiotic use promotes resistance development. However, quantifying the specific contribution of antibiotic use to resistance poses some problems. Evidence is accumulating that social, economic and genetic factors also have impact on the establishment, maintenance and spread of resistance traits.

The likelihood of selecting resistance in the community depends on many factors. The key factors are shown in Table 1.