title: Results from the Solithromycin International Surveillance Program (2014).
abstract: Solithromycin, a fourth-generation macrolide (a fluoroketolide with enhanced activity against macrolide-resistant bacteria due to interaction with three ribosomal sites) and the first fluoroketolide, was tested against a 2014 collection of 6,115 isolates, including Streptococcus pneumoniae (1,713 isolates), Haemophilus influenzae (1,308), Moraxella catarrhalis (577), Staphylococcus aureus (1,024), and beta-hemolytic streptococci (1,493), by reference broth microdilution methods. The geographic samples included 2,748 isolates from the United States, 2,536 from Europe, 386 from Latin America, and 445 from the Asia-Pacific region. Solithromycin was observed to be very active against S. pneumoniae (MIC50/90, 0.008/0.12 μg/ml), demonstrating 2-fold greater activity than telithromycin (MIC50/90, 0.015/0.25 μg/ml) and 16- to >256-fold greater activity than azithromycin (MIC50/90, 0.12/>32 μg/ml), with all strains being inhibited at a solithromycin MIC of ≤1 μg/ml. Against H. influenzae, solithromycin showed potency identical to that of telithromycin (MIC50/90, 1/2 μg/ml), and both of these compounds were 2-fold less active than azithromycin (MIC50/90, 0.5/1 μg/ml). All but one of the M. catarrhalis isolates were inhibited by solithromycin at ≤0.25 μg/ml. Solithromycin inhibited 85.3% of S. aureus isolates at ≤1 μg/ml, and its activity was lower against methicillin-resistant (MIC50/90, 0.06/>32 μg/ml) than against methicillin-susceptible (MIC50/90, 0.06/0.06 μg/ml) isolates. Little variation in solithromycin activity was observed by geographic region for the species tested. Solithromycin was very active against beta-hemolytic streptococci (MIC50/90, 0.015/0.03 μg/ml), and all isolates were inhibited at MIC values of ≤0.5 μg/ml. In conclusion, solithromycin demonstrated potent activity against global and contemporary (2014) pathogens that represent the major causes of community-acquired bacterial pneumonia. These data support the continued clinical development of solithromycin for the treatment of this important indication.
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA david-farrell@jmilabs.com.
authors.forename: David J
authors.initials: DJ
authors.lastname: Farrell
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Flamm
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA.
authors.forename: Helio S
authors.initials: HS
authors.lastname: Sader
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA.
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001208:Asia / Q000453:epidemiology; D017963:Azithromycin / Q000494:pharmacology; D001424:Bacterial Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology; D017714:Community-Acquired Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology; D062665:Epidemiological Monitoring; D005060:Europe / Q000453:epidemiology; D006193:Haemophilus influenzae / Q000187:drug effects / Q000254:growth & development / Q000302:isolation & purification; D006801:Humans; D007391:International Cooperation; D048628:Ketolides / Q000494:pharmacology; D007843:Latin America / Q000453:epidemiology; D018942:Macrolides / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D001936:Moraxella catarrhalis / Q000187:drug effects / Q000254:growth & development / Q000302:isolation & purification; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development / Q000302:isolation & purification; D013291:Streptococcus / Q000187:drug effects / Q000254:growth & development / Q000302:isolation & purification; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000254:growth & development / Q000302:isolation & purification; D014230:Triazoles / Q000494:pharmacology*; D014481:United States / Q000453:epidemiology
chemical_list: D000900:Anti-Bacterial Agents; D048628:Ketolides; D018942:Macrolides; D014230:Triazoles; D017963:Azithromycin; C547755:solithromycin; C106791:telithromycin