The incidence of resistance of Streptococcus pneumoniae to the macrolide azithromycin – one of the most commonly prescribed antibiotics for treating pneumonia – was almost 50% in 2014, according to a report by Kara Keedy, PhD, executive director of microbiology at Cempra Pharmaceuticals, and her colleagues.
The researchers prospectively collected and investigated 4,567 nonreplicative community-acquired bacterial pneumonia (CABP) S. pneumoniae isolates between 2008 and 2014 in the United States, according to the report presented as a poster at IDWeek 2016. The isolates were tested for susceptibility by broth microdilution methods, according to Clinical and Laboratory Standards Institute breakpoint criteria. Macrolide resistance rates were based on azithromycin and/or clarithromycin minimal inhibitory concentrations as available, with only data on azithromycin having been collected in 2014.
CDC/Dr. Mike Miller
The overall resistance of S. pneumoniae to azithromycin exceeded 30% in all of the nine geographical divisions of the Centers for Disease Control and Prevention (CDC), with the high-level resistance of this bacterial cause of CABP to azithromycin having been greater than 25% in eight of the CDC divisions.
The co-resistance of S. pneumoniae to azithromycin and penicillin was highest in the CDC’s East South Central division in 2014. The regions with the largest percentages of isolates with high-level macrolide resistance were the East South Central (43.2%), the West South Central (38.1%), and the Mid-Atlantic (35.0%). The regions with the largest percentages of overall macrolide resistance were the West South Central (62.9%), the East South Central (56.8%), and the South Atlantic (53.2%).
The analysis also determined that the 2014 overall rate of macrolide resistance in S. pneumoniae in the United States of 48.4% is higher than it was for any of the four earlier years examined. In 2008, 2009, 2010, and 2011, those macrolide resistance rates were 39.7%, 40.2%, 37.1%, and 44.3%, respectively.
The researchers concluded that S. pneumoniae is the most common bacterial cause of CABP and that antibiotic resistance to it is “a significant clinical challenge as highlighted by” the CDC having listed it as a threatening pathogen in the urgent category. Dr. Keedy and her associates noted that in the United States, macrolides, amoxicillin/clavulanate, and respiratory fluoroquinolones are the most frequent agents prescribed to treat almost all community-acquired respiratory infections.
“Macrolide resistance in S. pneumoniae is continuing to increase in the U.S.,” the researchers reported in the poster. “Both low- and high-level macrolide resistance have been reported to cause clinical failures and other negative outcomes including longer hospital stays and higher costs.”
The study also examined the abilities of several other drugs, including the fourth-generation macrolide solithromycin, to inhibit S. pneumoniae isolates. Solithromycin does not yet have approved Clinical and Laboratory Standards Institute breakpoints, so only minimum inhibitory concentrations (MICs) were presented.
According to the study, more than 50% of S. pneumoniae isolates were inhibited by 0.008 mcg/mL solithromycin. Additionally, solithromycin had one of the lowest MICs against S. pneumoniae of all of the drugs tested in the study. The higher end of the MICs against S. pneumoniae for solithromycin and moxifloxacin was 0.25, which was lower than the higher end of the MICs for any of the other drugs tested against S. pneumoniae isolates.
Solithromycin is the first fluoroketolide in Phase III clinical development. It “shows activity against all macrolide-resistant strains of S. pneumoniae isolates, irrespective of the location in the U.S.,” according to the poster.
The data included in the poster was extracted from a global study by JMI Laboratories. Cempra funded this study. Dr. Keedy and the other authors of the poster are employees of Cempra.