Get a Handle on Resistance Before It Gets a Handle on You: The PROTEKT US Surveillance Study.

COMMUNITY-ACQUIRED respiratory tract infections continue to be among the most common and important infections seen by practicing physicians. These infections involve the sinuses, the airways, and the lung, and can be caused by a wide variety of microorganisms, including viruses. As a rule, respiratory tract infections caused by viruses are self-limited and should not be treated. A notable exception is influenza, which has only recently become relatively easy to diagnose and treat. However, this discussion will be limited to resistance problems for bacterial pathogens that commonly cause community-acquired respiratory tract infections. Community-acquired respiratory tract infections that are caused by bacterial pathogens include acute exacerbations of chronic bronchitis, community-acquired pneumonia, and acute bacterial sinusitis. The most common bacterial pathogens that cause these community-acquired respiratory tract infections are the so-called "typical pathogens," such as Streptococcus pneumoniae, Hemophil us influenzae, and Moraxella catarrhalis, as well as the "atypical pathogens," such as Legionella species, Mycoplasma pneumoniae, and Chiamydia pneumoniae. The diagnosis of community-acquired respiratory tract infections has been difficult because the atypical pathogens are difficult to detect. The wide range of pathogens and the difficulty in detecting a specific pathogen has made the empirical therapy of community-acquired respiratory tract infections difficult.

Treatment of these respiratory tract infections has become increasingly difficult over the past decade due to the emergence of resistance in many of the bacterial pathogens that commonly cause such infections. For example, M catarrhalis was at one time 100% susceptible to penicillin, but for the last decade has been only 10% susceptible due to beta-lactamasemediated resistance. Similarly, H influenzae used to be 100% susceptible to amoxicillin, but for the past decade has been only 65% susceptible due to beta-lactamase-mediated resistance. More recendy, S pneumoniae has become resistant to penicillin due to altered penicillin-binding proteins. Many of these penicillin-resistant strains are also resistant to other agents, such as macrolides. Clearly, the emergence of resistance in common bacterial pathogens causing community-acquired respiratory tract infections has become a global concern.

The response to this emerging resistance has been, in part, the development of new antimicrobial agents. The development of fluoroquinolones such as levofloxacin with potent activity against these respiratory pathogens, including multi-drug-resistant S pneumoniae, is one example. Another example is the development of the ketolide class of antibiotics. The first of these agents is telithromycin. Ketolides such as telithromycin remain active against macrolide-resistant strains of S pneumoniae and will offer an additional therapeutic alternative to fluoroquinolones. However, the use of these newer agents must be monitored in order to know if and when resistance becomes a problem.

The monitoring of resistance patterns for respiratory pathogens is a critical aspect for the appropriate use of both older and newer antimicrobial agents. Clearly, newer agents should not be used if older agents are active. Resistance to these older agents, on the other hand, suggests the need for use of the newer agents. Such use, however, may in itself lead to the emergence of resistance. Thus, resistance to these newer agents also must be monitored. This need for monitoring has led to the development of the PROTEKT Surveillance Stud. PROTEKT stands for Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin. PROTEKT is a surveillance study that is prospectively collecting susceptibility data for telithromycin and other antimicrobial agents commonly used for the therapy of respiratory tract infections. PROTEKT is a global surveillance study that includes a strong presence in the United States. In the United States, data are collected by over 200 medical centers in 42 states. Each center collects data on 190 respiratory tract pathogens each year. In addition to the susceptibility data for each organism, demographic data are obtained in order to allow analysis by infection type and patient characteristics. Each isolate is also sent to a central laboratory so that the identity can be confirmed and the susceptibility testing repeated. A full range MIC is done according to NCCLS standards. Collecting these isolates means that a complete evaluation of genotypic and phenotypic resistance mechanisms can be done.

The PROTEKT US Surveillance Study now is in its second year. Data so far have shown that there is increasing resistance to beta-lactam agents and macrolides for S pneumoniae. In contrast, the resistance rates for other pathogens such as M catarrhalis and H influenzae have remained stable. Of importance and concern is the recent emergence of fluoroquinolone resistance in S pneumoniae. It is clear that S pneumoniae continues to be the most important respiratory tract pathogen in terms of resistance, morbidity and mortality. This resistance continues to increase as well as evolve, with fluoroquinolone resistance now becoming a problem. The choice of antibiotic for the therapy of community-acquired respiratory tract infections is more important now than ever before.

From the Departments of Medicine and Pathology, Vanderbilt University School of Medicine, Nashville, Tenn.

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