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problem is especially important when there is genetic diversity among pathogens within an infected individual.


Ignoring economic considerations, patient treatment should seek to achieve the following:

(i) Make the patient healthy.

(ii) Prevent the patient from infecting others.

(iii) Prevent the spread of resistant pathogens to others.

The first aim concerns the health of the patient being treated. The second and third aims concern the effects of patient treatment on the health of others.

A single strategy cannot simultaneously best achieve all three aims. In the limit, zero treatment will usually be the best resistance management strategy. It is important to identify and justify compromises because this makes explicit problems in need of solution and is a prerequisite for evidence-based resistance management. There may come a time when resistance management strategies are required that put overall public health ahead of patient health (Foster and Grundmann, 2006). We do not think the problems of resistant pathogens are yet so dire as to require this. In our view, the current scientific challenge is to identify, among patient treatment regimens that are similarly effective at restoring health and preventing transmission, those regimens that best effect resistance management.

The aim of resistance management is to prevent clinical failures caused by high-level resistance. Resistance is often a continuous trait, and there can be varying degrees of intermediate resistance. Sometimes referred to as “tolerance,” intermediate resistance confers the ability to survive concentrations of drug below those considered therapeutic (Fig. 11.1). We define high-level resistance as that which undermines patient health by causing therapeutic failure. It is the rate of spread of high-level resistance that needs to be managed because this determines the therapeutically useful life span of a drug.

The useful life span of a drug is determined by two processes. The first is the rate at which genetic events conferring high-level resistance on an individual pathogen actually occur. For simplicity, we refer to these events as de novo mutations, but we use this to include any heritable change that confers de novo high-level resistance on a pathogen individual. For example, in bacteria, this event can be the acquisition by lateral transfer of genetic material from another species. The second process affecting the

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