Tracking Susceptibility and Reducing Resistance - Fluoroquinolones at the Forefront in the Fight Against Bacterial Pathogens

29 March, 2018

Question 10

What are the mechanisms responsible for causing macrolide resistance, and do these different mechanisms translate into different clinical resistance patterns around the globe?

There are two main mechanisms responsible for the development of macrolide resistance; 23S RNA methylase coded by the erm (B) gene or efflux pump expression coded for by mef (A). In Europe, macrolide resistance has traditionally been predominantly due to the presence of the erm (B) gene, while mef genes have been seen more often in the US. Usually erm (B)-mediated resistance is more likely to be responsible for high-level macrolide resistance (MIC≥32 μg/ml).

In a Spanish analysis of 244 S. pneumoniae isolates resistant to erythromycin, 80.7% carried the erm (B) gene alone, while 18.4% carried the mef gene. And 62.2% of the isolates that were positive for the mef gene also were positive for erm (B). However, recently, the presence of both erm (B) and mef (A) genes has been seen more often in Asian countries. In the past the efflux resistance mechanism has not been considered to be as important but this is changing with studies showing an increase in isolates with both resistance mechanisms. It has been observed that from an ecological rather than clinical point of view these types of isolates have increased. This is important because isolates with both mef (A) resistance that have subsequently acquired erm (B) resistance, or vice versa, are also more resistant to other antibiotics such as penicillin and tetracyclines. These results determine a smaller amount of clinically therapeutic options available to treat patients infected with these isolates. However, it is noteworthy that such isolates do not demonstrate higher trends of resistance to levofloxacin or other fluoroquinolones in these particular isolates.