Atypical pneumonia - Emerging treatments

Lefamulin

A first-in-class pleuromutilin antibiotic available in oral and intravenous formulations. It inhibits bacterial protein synthesis via interactions with the A- and P- sites of the peptidyl transferase center of the 50S subunit. Lefamulin offers a unique spectrum of activity covering Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus (including MRSA), beta-hemolytic streptococci (including Streptococcus pyogenes and Streptococcus agalactiae), and Enterococcus faecium (including vancomycin-resistant enterococci). It also covers Legionella pneumophila, Chlamydia pneumoniae, and Mycoplasma pneumoniae, the most common atypical organisms that cause community-acquired pneumonia.[86][87][88] The safety and efficacy of lefamulin has been evaluated in two phase 3 clinical trials where it was found to be noninferior to moxifloxacin (with or without linezolid) in terms of primary efficacy end points (early clinical response, investigator assessment of clinical response). It was considered safe and well tolerated.[89][90] However, it has the potential to cause QT interval prolongation and should not be used in patients with known prolongation of the QT interval, ventricular arrhythmias, or who are on other drugs that prolong the QT interval. Lefamulin is approved by the Food and Drug Administration (FDA) for the treatment of community-acquired pneumonia in adults; however, its exact place in management is not clear yet.

Delafloxacin

A new fluoroquinolone antibiotic approved by the FDA for the treatment of adults with community-acquired pneumonia caused by designated susceptible bacteria. It covers L pneumophila, C pneumoniae, and M pneumoniae, the most common atypical organisms that cause community-acquired pneumonia. The approval is based on results from a phase 3 study that found it was noninferior to moxifloxacin.[91]

Omadacycline

A new modernized tetracycline antibiotic (aminomethylcycline) with broad-spectrum activity, designed to overcome tetracycline resistance. It covers L pneumophila, C pneumoniae, and M pneumoniae, the most common atypical organisms that cause community-acquired pneumonia. It is available in oral and intravenous formulations. Like other antibiotics in the tetracycline class, omadacycline may cause discoloration of deciduous teeth, and inhibition of fetal bone growth when administered during pregnancy. It has been found to be noninferior to moxifloxacin in terms of efficacy in adults with community-acquired pneumonia.[92] Omadacycline is approved by the FDA for the treatment of community-acquired pneumonia in adults; however was refused approval for this indication in Europe in October 2018.

Solithromycin

In a randomized controlled trial oral solithromycin, a macrolide, was noninferior to oral moxifloxacin for the treatment of patients with community-acquired bacterial pneumonia.[93] Studies demonstrate that the efficacy, tolerability, and safety profile make it a promising treatment.[94][95] Solithromycin is currently in phase 3 development for the treatment of community-acquired bacterial pneumonia.