is macrolide antibiotic resistance a problem ?

Written by David Pascoe on December 28, 2005 in macrolides with 0 Comments

Macrolide antibiotics are an alternative to tetracycline antibiotics. Macrolides tend to be more expensive and there is less clinical history compared to tetracyclines. Macrolides inhibit bacterial protein synthesis and their association with leukocytes sees them transported into the site of an infection. As with any prescription drug the potential benefit and risk need to be assessed.

What Is the Clinical Impact of Macrolide Resistance?

Current Infectious Disease Reports 2004, 6:7-12, Current Science, Inc. ISSN 1523-3847, John R. Lonks, MD

Respiratory tract infections are treated empirically. Treatment is based on the likely pathogens and their antibiotic susceptibility. The most common respiratory tract pathogen is Streptococcus pneumoniae. In the United States, approximately 25% to 30% of S. pneumoniae are resistant to erythromycin and other macrolides. There are two mechanisms of resistance: ribosomal methylation that causes high-level resistance, and an efflux pump that causes low-level resistance. Macrolides are ineffective in animal models that use pneumococcal isolates with the methylase- or efflux-mediated resistance mechanisms. There are many case reports that describe clinical failure and isolation of a macrolide-resistant pneumococcus while a patient receives macrolide treatment. Two recent studies that included macrolide-susceptible and macrolide-resistant pneumococci showed that breakthrough bacteremia in patients receiving macrolide treatment occurred only with macrolide-resistant isolates. Study of bacteremic disease ensures the pathogenic role of the pneumococcus; however, it underestimates the true clinical impact of macrolide resistance.

Conclusion: Macrolide resistance among S. pneumoniae is increasing. In some areas of the United States, one of three S. pneumoniae are macrolide-resistant. Animal model data show the loss of efficacy of macrolide antibiotics when animals are infected with macrolide-resistant pneumococci, including those with the efflux pump (mef gene). Bacteriologic and clinical failure occurs when patients with otitis media caused by a macrolide-resistant pneumococcus are treated with a macrolide. There are many case reports of patients failing macrolide treatment who have a macrolide-resistant pneumococcus isolated from normally sterile body fluids (including blood) while receiving a macrolide. Recent studies analyzing macrolide-susceptible and macrolide-resistant pneumococcal bacteremias show that treatment failure with breakthrough bacteremia was found only when the isolate was macrolide-resistant, including those with the M phenotype (efflux pump). Study of bacteremic disease ensures the pathogenic role of the pneumococcal isolate. However, by examining only bacteremic pneumococcal disease, the true impact of treatment failures caused by macrolide resistance is underestimated.

The clinical significance of macrolide-resistant Streptococcus pneumoniae: it’s all relative.

Clin Infect Dis, 2004 Jan 1;38(1):99-103.

Nuermberger E, Bishai WR. Center for Tuberculosis Research, Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231-1001, USA.

Macrolides are currently recommended as first-line agents for the empirical treatment of community-acquired pneumonia. Heavy use of these agents for a variety of indications has resulted in an increasing incidence of macrolide resistance among pneumococcal isolates. Although several case reports and small case series have suggested that in vitro macrolide resistance is associated with treatment failure in cases of pneumococcal pneumonia, other observational data suggest that drug susceptibility testing may not correlate with treatment failure. In this article, we review current information on the mechanisms of macrolide resistance and the pharmacodynamics of macrolide therapy, together with efficacy data from animal models and clinical observations, to begin to gauge the clinical significance of macrolide resistance in Streptococcus pneumoniae. Areas for further investigation are highlighted.