Maximizing Antimicrobial Efficacy, Minimizing Antibacterial Resistance:A Paradigm for the New Millennium.

ATEF M. SHIBL

King Saud University, Riyadh, Saudi Arabia

The emergence and spread of microbial resistance is a true global threat, affecting both industrialized and developing countries. Overuse of antibiotics in industrialized countries has contributed to an acceleration of the problem, as has underused of efficacious antibiotics in developing countries as a result of poverty and the consequent lack of effective healthcare. Misdiagnosis and defensive and unnecessary prescribing, as well as a lack of education about bacterial resistance, are important factors in the emergence of resistance.

The aim of antibiotic treatment is to maximize antimicrobial activity to prevent recurrence of infection and the creation of resistant pathogens. Pharmacokinetic characteristics and the dosing regimen of the antibiotic determine the time course of serum antibiotic concentrations. The pharmacodynamic characteristics of antibiotics are the second factor used in integrated pharmacokinetic / pharmacodynamic (PK/PD) models. The value of different PK/PD parameters in predicting eradication of causative bacterial pathogens has been investigated in various animal and clinical studies. The application of PK/PD models not only helps to optimize antibiotic treatment but may also help to prevent the spread of bacterial resistance. Other factors that may influence clinical efficacy include protein binding, variability in pharmacokinetics, and the influence of formation and closage regimen on compliance.

To minimize the prevalence of bacterial resistance, two complementary strategies are of fundamental importance. The first is to avoid antibiotics in very common situations in which they are unlikely to provide benefit. The second is to

use narrow-spectrum antibiotics as much as possible to minimize selective pressure.

The problem of antibiotic resistance is generally linked to overuse. However, the idea that resistance arises not simply from the amount of antibiotic used but also from the way in which they are used has been gaining acceptance, particularly with respect to the dosage chosen and the concentration achieved. Introduction of new antimicrobial derivatives or new classes of agent delays the resistance problem but does not solve it.

In conclusion, excessive antibiotic should be tackled by better education of prescribers; better definition of infection and a careful review of issues that encourage prolonged prescribing. Antibiotic resistance is clearly a multifactor problem, which is therefore likely to demand a multifaceted approach if it is to be controlled.