Consequences of bacterial resistance to antimicrobial agents.

to review what current knowledge exists on the impact of antimicrobial bacterial resistance and address the methodologic obstacles to its assessment. Simply to state that a patient died of an infection caused by a resistant organism does not prove that the death was due to the resistance. To prove the statement as to cause of death, two approaches— " imputable death " and " attributable death " —are complementary and have been shown to provide comparable results. The estimation of " imputable death " requires analyzing the clinical history of a series of deaths that were caused by resistant strains of infection and to count by clinical judgment those related to the resistance. To estimate the " attributable " fraction of death or illness, the excessive risk for death or illness must be documented for patients who are infected with the resistant strains, in comparison with those who are infected with sensitive strains. The study design must control for confounders by matching the groups at inclusion or by adjustment. Among these confounders the most important are the severity of the underlying illness before onset of infection, which may be associated with both the risk for death and the risk of antibiotic resistance of the bacterium. The time at which death is evaluated is another key issue of the study design. An excessive rate of mortality may be observed during the first months of follow-up and not during a longer follow-up. Multidrug-(isoniazid and rifampicin) resistant tuberculosis (MDRTB) is associated with a more than threefold increased death if an appropriate anti-TB regimen is not used early in the course of the infection. In western countries where the prevalence of MDRTB is low and second line drugs are available, MDRTB only requires prompt detection and adequate management to limit the consequence of resistance. However, in developing countries where second line treatments are not readily available, and where 95% of worldwide tuberculosis cases occur which are responsible for 26% of the potentially avoidable death, one can predict an increasing impact of MDRTB on death in the years to come. Several studies suggest that in acute otitis media caused by Streptococcus pneu-moniae, the bacteriologic failure rate increases with penicillin G MICs. Although bacteriologic failure does not mean clinical failure, the risk for acute otitis media relapses and complications linked to resistance is poorly documented. Higher penicillin G MICs of S. pneumoniae strains observed in mastoitidis …