Meeting News

Lefamulin effective in vitro against CABP, other respiratory infections

NEW ORLEANS — Lefamulin, an investigational drug now in phase 3 trials, is effective in vitro against bacterial pneumonia and other respiratory pathogens, according to researchers who conducted several studies on the drug.

They presented several studies on the drug, which is being developed by Nabriva Therapeutics, at ASM Microbe.

Thomas M. FIle
Thomas M. File

“This is a new drug, as far as systemic availability, for treatment of patient infections both intravenously and orally, and it has a unique mechanism of action that allows it to be active against a lot of pathogens that would be resistant to other drugs, even other drugs that work at inhibiting protein synthesis,” Thomas M. File, MD, an infectious disease specialist affiliated with Summa Health System in Akron, Ohio, told Infectious Disease News. File is also an Infectious Disease News Editorial Board member.

According to the researchers, lefamulin interferes with bacterial translation when it uses an induced fit mechanism to bind to certain sites on cell ribosomes, a strategy that File said makes the drug unique.

One of the studies included 776 bacterial isolates collected from patients with community-acquired respiratory tract infections (n = 477), pneumonia (n = 282), blood infections (n = 14) or other infections (n =3).

The isolates were treated with lefamulin and other antibiotics. The new drug worked powerfully, according to the researchers, who singled out specific pathogens.

Lefamulin inhibited all 360 Streptococcus pneumoniae isolates at 0.25 µg/mL or less and all 85 Haemophilus influenzae isolates at 2 µg/mL or less. It was potent against the 85 Moraxella catarrhalis isolates, with a minimal inhibitory concentration (MIC)90 of 0.06 µg/mL, and against the 246 isolates of Staphylococcus aureus, with a MIC99 of 0.12 µg/mL.

Lefamulin’s potency was not affected by isolates’ resistance to other antibiotics, the researchers added.

Another study included 945 isolates collected from patients with community-acquired bacterial pneumonia at 62 sites in the U.S. Again, lefamulin and other antibiotics were applied to the isolates.

Lefamulin inhibited all 649 S. pneumoniae isolates at 0.5µg/mL or less and all 153 M. catarrhalis isolates at 0.12 µg/mL or less. It inhibited 93.3% of the 143 H. influenzae isolates at 2 µg/mL or less.

Again, lefamulin’s performance was not affected by resistance to other antibiotics.

“The other issue about its spectrum is that its in vitro activity doesn’t include normal gut flora such as E. coli or Bacteroides fragilis very much,” File said.

“That’s a good thing because you don’t want to affect the gut flora if you don’t have to.”

File said that lefamulin could be a valuable addition to infectious disease clinicians’ arsenals. Katie Engleman, a spokeswoman for File and the researchers, said they are awaiting data from phase 3 trials of the drug — the earliest of which are expected in the third quarter of 2017 —  before seeking FDA approval.

“Assuming it goes through … and is [FDA] approved, it will be another option for us, particularly as monotherapy for community-acquired pneumonia,” File said. – by Joe Green

References:

Paukner S, et al. In Vitro Activity of Lefamulin Against a Collection of Respiratory Pathogens from Pediatric Patients in U.S. Presented at: ASM Microbe; June 1-5, 2017; New Orleans.

Paukner S, et al. In Vitro Activity of Lefamulin Against Bacterial Pathogens Collected from Patients with Community-Acquired Bacterial Pneumonia (CAPB) – Sentry 2015 U.S. Data. Presented at: ASM Microbe; June 1-5, 2017; New Orleans.

Disclosure: File reports working as an investigator and consultant for Nabriva Therapeutics.

NEW ORLEANS — Lefamulin, an investigational drug now in phase 3 trials, is effective in vitro against bacterial pneumonia and other respiratory pathogens, according to researchers who conducted several studies on the drug.

They presented several studies on the drug, which is being developed by Nabriva Therapeutics, at ASM Microbe.

Thomas M. FIle
Thomas M. File

“This is a new drug, as far as systemic availability, for treatment of patient infections both intravenously and orally, and it has a unique mechanism of action that allows it to be active against a lot of pathogens that would be resistant to other drugs, even other drugs that work at inhibiting protein synthesis,” Thomas M. File, MD, an infectious disease specialist affiliated with Summa Health System in Akron, Ohio, told Infectious Disease News. File is also an Infectious Disease News Editorial Board member.

According to the researchers, lefamulin interferes with bacterial translation when it uses an induced fit mechanism to bind to certain sites on cell ribosomes, a strategy that File said makes the drug unique.

One of the studies included 776 bacterial isolates collected from patients with community-acquired respiratory tract infections (n = 477), pneumonia (n = 282), blood infections (n = 14) or other infections (n =3).

The isolates were treated with lefamulin and other antibiotics. The new drug worked powerfully, according to the researchers, who singled out specific pathogens.

Lefamulin inhibited all 360 Streptococcus pneumoniae isolates at 0.25 µg/mL or less and all 85 Haemophilus influenzae isolates at 2 µg/mL or less. It was potent against the 85 Moraxella catarrhalis isolates, with a minimal inhibitory concentration (MIC)90 of 0.06 µg/mL, and against the 246 isolates of Staphylococcus aureus, with a MIC99 of 0.12 µg/mL.

Lefamulin’s potency was not affected by isolates’ resistance to other antibiotics, the researchers added.

Another study included 945 isolates collected from patients with community-acquired bacterial pneumonia at 62 sites in the U.S. Again, lefamulin and other antibiotics were applied to the isolates.

Lefamulin inhibited all 649 S. pneumoniae isolates at 0.5µg/mL or less and all 153 M. catarrhalis isolates at 0.12 µg/mL or less. It inhibited 93.3% of the 143 H. influenzae isolates at 2 µg/mL or less.

Again, lefamulin’s performance was not affected by resistance to other antibiotics.

“The other issue about its spectrum is that its in vitro activity doesn’t include normal gut flora such as E. coli or Bacteroides fragilis very much,” File said.

“That’s a good thing because you don’t want to affect the gut flora if you don’t have to.”

File said that lefamulin could be a valuable addition to infectious disease clinicians’ arsenals. Katie Engleman, a spokeswoman for File and the researchers, said they are awaiting data from phase 3 trials of the drug — the earliest of which are expected in the third quarter of 2017 —  before seeking FDA approval.

“Assuming it goes through … and is [FDA] approved, it will be another option for us, particularly as monotherapy for community-acquired pneumonia,” File said. – by Joe Green

References:

Paukner S, et al. In Vitro Activity of Lefamulin Against a Collection of Respiratory Pathogens from Pediatric Patients in U.S. Presented at: ASM Microbe; June 1-5, 2017; New Orleans.

Paukner S, et al. In Vitro Activity of Lefamulin Against Bacterial Pathogens Collected from Patients with Community-Acquired Bacterial Pneumonia (CAPB) – Sentry 2015 U.S. Data. Presented at: ASM Microbe; June 1-5, 2017; New Orleans.

Disclosure: File reports working as an investigator and consultant for Nabriva Therapeutics.

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