Pediatric Annals

FROM THE GUEST EDITOR 

Rational Use of Antibiotics in an Era of Emerging Resistance

James K Todd, MD

Abstract

Doctors are men who prescribe medicines of which they know little to cure diseases of which they know less in human beings of whom they know nothing. (Voltaire)

The discovery and development of antibiotics for the treatment of bacterial infection has been heralded as one of the greatest advances in medicine in the 20th century. Although faced with growing concern regarding the emergence of antimicrobial resistance, we feel fortunate that there are few bacterial infections for which a reasonable antimicrobial alternative does not currently exist. Examples of exceptions are oral alternatives for certain systemic infections and treatment for vancomycin-resistant Enterococcus. We have been reassured by the fact that pharmaceutical companies have, so far, been relatively successful in keeping ahead of the microbial evolution of resistance.

If new antibiotics have provided the solution for emerging resistance so far, why should we worry about the future? The answer is multifactorial. First, we have been fortúnate to be able to chemically alter existing classes of antibiotics to adjust to emerging mechanisms of drug resistance (eg, ß-lactamase-resistant penicillins) or to develop new classes of antimicrobials (eg, quinolones) that engender new opportunities for chemical modification. However, there may be inherent limits - both chemical and physiologic - to the potential for new antibiotic development.

1. Strauss MB, ed. Familiar Medical Quotations, 7th ed. Boston: Little, Brown and Co.; 1968.

TABLE

Key Questions for Antibiotic Use In the 21st Century…

Doctors are men who prescribe medicines of which they know little to cure diseases of which they know less in human beings of whom they know nothing. (Voltaire)

The discovery and development of antibiotics for the treatment of bacterial infection has been heralded as one of the greatest advances in medicine in the 20th century. Although faced with growing concern regarding the emergence of antimicrobial resistance, we feel fortunate that there are few bacterial infections for which a reasonable antimicrobial alternative does not currently exist. Examples of exceptions are oral alternatives for certain systemic infections and treatment for vancomycin-resistant Enterococcus. We have been reassured by the fact that pharmaceutical companies have, so far, been relatively successful in keeping ahead of the microbial evolution of resistance.

If new antibiotics have provided the solution for emerging resistance so far, why should we worry about the future? The answer is multifactorial. First, we have been fortúnate to be able to chemically alter existing classes of antibiotics to adjust to emerging mechanisms of drug resistance (eg, ß-lactamase-resistant penicillins) or to develop new classes of antimicrobials (eg, quinolones) that engender new opportunities for chemical modification. However, there may be inherent limits - both chemical and physiologic - to the potential for new antibiotic development.

Figure. Typical evolution of new antibiotic use.

Figure. Typical evolution of new antibiotic use.

Second, new drugs usually appear better at the time of introduction than they eventually prove to be, as more clinical experience develops (Figure). Although new drugs are initially touted to be "broad spectrum," with no resistance and few adverse effects, wisdom gained through experience usually leads to much more restricted indications. The costs of this continual adjustment - both monetary and clinical - are usually high. Drug prices are justifiably high to compensate for the costs of this new drug development. But new side effects are often belatedly recognized, and the biologie vitality of microorganisms, combined with the potential of ever-increasing global genetic interchange, virtually ensures the eventual development of resistance. Even if new drugs can be developed, die process only repeats itself until we run out of therapeutic options (eg, vancomycin-resistant Enterococcus) or develop a vaccine to eliminate the disease (eg, Haemophilus influenzae type B meningitis).

There is another option! It has been shown on multiple occasions that the spread of resistance may slow and even reverse if an antibiotic's use is restricted to only proven indications. The clinical focus then shifts from a therapeutic emphasis to a diagnostic one. It can be argued that physicians and patients have been lulled by the ready availability of drug options to the assumption that over-prescription is less costly and /or more effective than a clinical strategy relying on diagnostic rigor. Have we sacrificed our clinical diagnostic skills to the empirical therapeutic trial? There is little doubt that parents, conditioned to assume that there is a prescription treatment for every illness, question our judgment when we announce, "It's only a virus." Understanding the fundamental problem points the direction to the solution; as shown in the table, we must shift our focus solely from the question of what to use, to the questions that relate more to diagnostic certainty and evidence-based therapeutic utility of antibiotics - when to start, when to alter therapy, and when to stop.

The primary goal of greater diagnostic rigor is not to save money in a managed care environment (although that will be a natural consequence of greater therapeutic precision), but rather to preserve treatment options. Physicians should learn to use a few antibiotics well and should adopt new antimicrobials only when sufficient clinical evidence documents better efficiacy, lower adverse reactions, or lower cost (with a comparable outcome). To ensure that we have effective therapeutic choices in the future, physicians must (contrary to Voltaire's cynicism) know their patients, diseases, and drugs well. We must adhere to rigorous principles of antibiotic use that minimize the further emergence of drug resistance and maintain viable treatment options for legitimate indications that improve patient outcomes.

This issue of Pediatrie Annals discusses those principles and provides clear guidelines for conservative but effective antimicrobial use in the 21st century. It focuses on (1) an understanding of the mechanisms of the antimicrobial resistance and how they are spread within bacterial populations; (2) principles for making antimicrobial treatment decisions; (3) current antibiotic choices for common bacteria; (4) the epidemiology and rationale for current physician prescribing habits; and (5) the evidence basis for antimicrobial prescription in the ambulatory setting. It is hoped that by applying these principles, we can retain our therapeutic options while improving patient outcomes.

Table

TABLEKey Questions for Antibiotic Use In the 21st Century

TABLE

Key Questions for Antibiotic Use In the 21st Century

REFERENCE

1. Strauss MB, ed. Familiar Medical Quotations, 7th ed. Boston: Little, Brown and Co.; 1968.

TABLE

Key Questions for Antibiotic Use In the 21st Century

10.3928/0090-4481-19990701-08

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