Lefamulin Outlook Positive for Treatment of S. Aureas, Bacterial Pneumonia

OCTOBER 07, 2017
Thomas Castles
Recent data from 2 studies presented at ID Week 2017 in San Diego, CA support the continued clinical development of Nabriva Therapeutics’ lefamulin for the treatment of Community Acquired Bacterial Pneumonia (CABP), and infections caused by S. aureas, a well-recognized cause of pneumonia from hospital and community settings.

CABP is the number one cause of death by infectious diseases worldwide, according to a poster authored by Susanne Paukner, PhD, TITLE, and colleagues. The condition killed 3.2 million in 2015, and is projected to kill 3.5 million in 2030. Treatment is complicated by continued emerging resistance.

Lefamulin is the first semi-synthetic pleuromutilin antibiotic for intravenous and oral use in humans, and is currently being investigated as a treatment for CABP in phase 3 trials in humans. In the poster study, researchers assessed the activity of lefamulin and comparators against a contemporary set of bacterial pathogens associated with community-acquired respiratory infections collected worldwide.

“Lefamulin was the most potent compound tested, with 99.7% of all S. pneumoniae isolates being inhibited at a concentration of ≤0.25 5 mg/L (MIC50/90 values of 0.06/0.12 mg/L) and its activity was not affected by resistance to other antibiotic classes,” authors wrote.

S. pneumonia isolates were largely susceptible to levofloxacin (99.1%) and ceftriaxone (96.5%), while 34.5%, 23.3%, and 16.8% of isolates were resistant to macrolides, tetracycline and clindamycin, respectively. Lefamulin also showed potent activity against H. influenzae (MIC50/90 of 0.5/1 mg/L), including 22.0% of ß-lactamase-producing strains and M. catarrhalis (0.06/0.12 mg/L).

Overall, lefamulin demonstrated potent in vitro activity against a global collection of contemporary respiratory pathogens, which was unchanged regardless of resistance phenotype to other antibiotic classes including macrolides, ß-lactams, tetracyclines or fluoroquinolones, supporting the drug’s continued development as a treatment for respiratory tract infections, including CAPB.

Lefamulin also showed success as a treatment for S. aureus (SA), a condition for which treatment is complicated by the invasive infection it can cause and the high prevalence of methicillin resistance (MR).

In an in vitro study, also presented in a poster at IDWeek 2017, lefamulin was tested with comparators against SA strains collected from patients who were hospitalized for pneumonia in 2015.

Researchers collected 1,273 unique SA isolates from 28 countries as part of the SENTRY surveillance program. Isolates included 401 hospital-acquired SA (259 from intensive care units, 152 from ventilator associated pneumonia). Susceptibility testing was conducted using the CLSI broth microdilution method and susceptibility was interpreted per CLSI 2017 breakpoint criteria.

Again, lefamulin 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 lefamulin 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.

Overall, SA strains collected from patients hospitalized with both hospital-acquired and ventilator-acquired pneumonia were highly susceptible to lefamulin, 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, [lefamulin] has the potential to play a role in the empiric treatment of CABP and supports evaluation in [hospital acquired pneumonia] and [ventilator-acquired-pneumonia] caused by SA,” authors wrote.
 

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