In Vitro Activity of Lefamulin against S. aureus Collected Worldwide from Hospitalized Patients with Bacterial Pneumonia

Abstract

Background S. aureus (SA) is a well-recognized cause of pneumonia from both the community and hospital settings. The clinical management of SA pneumonia is complicated by the invasive infection it can cause and the high prevalence of methicillin-resistance (MR). Lefamulin (LEF) is the first semi-synthetic pleuromutilin antibiotic for IV and oral use in humans. LEF is the first semi-synthetic pleuromutilin antibiotic for IV and oral use in humans and it specifically inhibits bacterial protein synthesis. LEF is currently in Phase 3 trials for the treatment of community-acquired bacterial pneumonia (CABP). This study investigated the in vitro activity of LEF and comparators against SA strains collected from patients hospitalized with pneumonia in 2015.Methods1273 unique SA isolates were collected from hospitalized patients with pneumonia worldwide in 28 countries (33 sites) in 2015 as part of the SENTRY surveillance program. Isolates included 401 hospital-acquired (HA) SA (259 from ICU, 152 from ventilator associated pneumonia, VAP). Susceptibility testing was conducted using the CLSI broth microdilution method and susceptibility was interpreted per CLSI 2017 breakpoint criteria.ResultsLEF was the most potent compound tested, with 99.7% of all SA isolates being inhibited at a concentration of ≤0.25 mg/L (MIC50/90 values of 0.06/0.12 mg/L) and irrespective of the collection source (ICU/non-ICU, VAP/non-VAP). 31.6% of isolates (n = 402) were MRSA of which 99.3% were inhibited at a LEF concentration of ≤0.25 µg/mL (MIC50/90, 0.06/0.12 mg/L). Susceptibility rates for all SA isolates were >90% for ceftaroline, vancomycin, linezolid and doxycycline. Susceptibility to azithromycin, levofloxacin and clindamycin was limited, particularly among MRSA (see Table).ConclusionSA strains collected from patients hospitalized with pneumonia including HAP and VAP were highly susceptible to LEF regardless of the resistance phenotype to the other antibiotics tested. Due to its potent activity against resistant SA and the most prevalent typical and atypical respiratory pathogens, as well as the availability of IV and oral formulations, LEF has the potential to play a role in the empiric treatment of CABP and supports evaluation in HAP and VAP caused by SA.Disclosures S. Paukner, Nabriva Therapeutics: Employee and Shareholder, Salary; R. K. Flamm, Nabriva Therapeutics: Research Contractor, Research grant; J. Schuchert, Nabriva Therapeutics: Research Contractor, Research grant; S. P. Gelone, Nabriva Therapeutics: Employee and Shareholder, Salary; H. S. Sader, The Medicines Company: Research Contractor, Research grant