There has been a lot of concern amongst clinicians concerning the
in vitro literature reports of increasing pneumococcal macrolide resistance internationally. Despite the lack of
a correlative increase in clinical failures, these in vitro reports have resulted in significant changes in antibiotic
prescribing for community-acquired respiratory infections. Because of this, I feel certain issues need to be made
clear to clinicians so that they can make rational decisions as to whether there is a true need for changing prescribing
habits. First, the in vitro literature uses a wide variety of susceptibility tests and testing conditions which
Citron et al (1) have demonstrated can result in a wide variety of results in the same pneumococcal isolate. Standardization
of these tests is needed prior to valid interpretation. Secondly, and most importantly, I feel that we need actual
minimum inhibitory concentration (MIC) results for drugs (macrolides, quinolones) that penetrate the cells that
ultimately kill bacteria (WBCs) rather than breakpoints. Although NCCLS breakpoints are a good guideline for drugs
whose infection-site concentrations are approximately the same as those in the blood stream, like beta-lactams
and aminoglycosides, they are not very useful for drugs that not only concentrate at the infection sites but also
in peripheral and local phagocytic WBCs. It is these concentrations that are the relevant ones which should result
in our developing clinical breakpoints based on them. As an example, azithromycin's pneumococcal breakpoint is
2 mg/L, but Heifets (2) states that it should be 32 mg/L for MAC. As azithromycin has been shown to work just fine
for bacteria like Mycobacterium Avium Complex (MAC) with MICs as high as 32 mg/L, why would this not also be true
for pneumococcal isolates with an MIC as high as 32 mg/L (resistant by NCCLS standards). The MICs of pathogens
are needed because R (resistant) just relates to us that the MIC is above 2 mg/L, but not how far above. It is
necessary to get clinicians to think about how new drugs, or even old drugs that are not beta-lactams and aminoglycosides,
work in the human body and not take all in vitro literature as dogma.
1. Citron et al. 1996. Antimicrobial Agents Chemother 40: 2413-2415.
2. Heifets. 1996. Antimicrobial Agents Chemother 40: 1759-1767.
Guy W. Amsden, Pharm.D
Cooperstown, New York