FDA approves new antibiotic to treat community-acquired bacterial pneumonia.

The U.S. Food and Drug Administration today approved Xenleta (lefamulin) to treat adults with community-acquired bacterial pneumonia.

Community-acquired pneumonia occurs when someone develops pneumonia in the community (not in a hospital). Pneumonia is a type of lung infection that can range in severity from mild to severe illness and can affect people of all ages. According to data from the Centers from Disease Control and Prevention, each year in the United States, about one million people are hospitalized with community-acquired pneumonia and 50,000 people die from the disease.

Lefamulin: Review of a Promising Novel Pleuromutilin Antibiotic.


lefaThis semi-synthetic compound inhibits the synthesis of bacterial protein, which is required for bacteria to grow. It acts by binding to the peptidyl transferase center, or PTC, on the bacterial ribosome in such a way that it interferes with the interaction of protein production at two key sites known as the “A” site and the “P” site, resulting in the inhibition of bacterial proteins and the cessation of bacterial growth. Its binding occurs with high affinity, high specificity and at molecular sites that are different than other antibiotic classes.


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lefa activity

The safety and efficacy of Xenleta, taken either orally or intravenously, was evaluated in two clinical trials with a total of 1,289 patients with CABP. In these trials, treatment with Xenleta was compared to another antibiotic, moxifloxacin with or without linezolid. The trials showed that patients treated with Xenleta had similar rates of clinical success as those treated with moxifloxacin with or without linezolid.

The most common adverse reactions reported in patients taking Xenleta included diarrhea, nausea, reactions at the injection site, elevated liver enzymes and vomiting. Xenleta has the potential to cause a change on an ECG reading (prolonged QT interval). Patients with prolonged QT interval, patients with certain irregular heart rhythms (arrhythmias), patients receiving treatment for certain irregular heart rhythms (antiarrhythmic agents), and patients receiving other drugs that prolong the QT interval should avoid Xenleta. In addition, Xenleta should not be used in patients with known hypersensitivity to lefamulin or any other members of the pleuromutilin antibiotic class, or any of the components of Xenleta. Based on findings of fetal harm in animal studies, pregnant women and women who could become pregnant should be advised of the potential risks of Xenleta to a fetus. Women who could become pregnant should be advised to use effective contraception during treatment with Xenleta and for two days after the final dose.

Xenleta received FDA’s Qualified Infectious Disease Product (QIDP) designation. The QIDP designation is given to antibacterial and antifungal drug products intended to treat serious or life-threatening infections under the Generating Antibiotic Incentives Now (GAIN) title of the FDA Safety and Innovation Act. As part of QIDP designation, Xenleta was granted Priority Review under which the FDA’s goal is to take action on an application within an expedited time frame.

The FDA granted the approval of Xenleta to Nabriva Therapeutics.

A key global challenge the FDA faces as a public health agency is addressing the threat of antimicrobial-resistant infections. Among the FDA’s other efforts to address antimicrobial resistance, is the focus on facilitating the development of safe and effective new treatments to give patients more options to fight serious infections.

 References and further reading:

Lefamulin Review of a Promising Novel PleuromutilinAntibioticIn vitro activity of the novel pleuromutilin lefamulin (BC-3781) and effect of efflux pump inactivation on multidrug-resistant and extensively-drug resistant Neisseria gonorrheae

Jacobbson S, Paukner S, Golparian D, et al.

Antimicrob Agents Chemother 2017 Sept 11. pii: AAC.01496-17. doi: 10.1128/AAC.01497-17. [Epub ahead of print]

Pleuromutilins: Potent drugs for resistant bugs – mode of action and resistance

Paukner S, Riedl R

Cold Spring Harb Perspect Med 2017 Jan 3; 7(1): pii: a027110. doi: a027110.

In vitro activities of lefamulin and other antimicrobial agents against macrolide-susceptible and macrolide-resistant Mycoplasma pneumoniae from the United States, Europe, and China

Waites KB, Crabb DM, Duffy LB, et al.

Antimicrob Agents Chemother 2017 Feb; 61(2): pii: e02008-16.doi: 10.1128/AAC.02008-16.

In Vitro Activity of Lefamulin Tested against Streptococcus pneumoniae with Defined Serotypes, Including Multidrug-Resistant Isolates Causing Lower Respiratory Tract Infections in the United States.

Mendes RE, Farrell DJ, Flamm RK, et al.

Antimicrob Agents Chemother 2016 Jun 20; 60(7): 4407-11.

Simultaneous assessment of the pharmacokinetics of a pleuromutilin, lefamulin, in plasma, soft tissues and pulmonary epithelial lining fluid

Zeitlinger M, Schwameis R, Burian A, et al.

J Antimicrob Chemother 2016 Apr; 71(4): 1022-6.

Population pharmacokinetic analyses for BC-3781 using phase 2 data from patients with acute bacterial skin and skin structure infections

Rubino CM, Xue B, Bhavnani SM, et al.

Antimicrob Agents Chemother 2015 Jan; 59(1): 282-8.

Structural insights into species-specific features of the ribosome from the pathogen Staphylococcus aureus

Eyala Z, Matzova D, Krupkina M, et al.

Proc Natl Acad Sci U S A. 2015 Oct 27; 112(43): E5805–E5814.

Lefamulin Review of a Promising Novel PleuromutilinAntibiotic