Solithromycin monotherapy for treatment of community‐acquired bacterial pneumonia: A meta‐analysis of randomised controlled trials

Abstract

Summary Objectives Solithromycin is a new monotherapy option for community‐acquired bacterial pneumonia (CABP) patients. However, the efficacy and safety of solithromycin monotherapy for the treatment of CABP remains controversial. The aim of this meta‐analysis was to evaluate the role that solithromycin played in the treatment of CABP. Methods We systematically retrieved randomised controlled trials (RCTs) compared solithromycin with other antibiotics in the treatment of CABP, which were published on PubMed, ScienceDirect, Cochrane libary and the Clinical Trials.gov before July 2018. Ultimately, a meta‐analysis of all RCTs eligible for inclusion criteria was performed. Results Three RCTs, comprising 1855 patients, were included in the meta‐analysis. There were no statistically significant differences between patients given solithromycin and those given other antibiotics with regard to early clinical response (ECR) [1855 patients, odds ratio (OR) = 1.00, 95% confidence interval (CI) 0.80 to 1.24, P = 0.99] and clinical success rates at short‐term follow‐up (SFU) (1855 patients, OR = 0.78, 95% CI 0.60 to 1.01, P = 0.06) in the intention‐to‐treat (ITT) population, as were the ECR (787 patients, OR = 0.90, 95% CI 0.64 to 1.27, P = 0.55) and clinical success rates at SFU (358 patients, OR = 0.73, 95% CI 0.41 to 1.31, P = 0.30) in microbiological intention‐to‐treat population (mITT). Similarly, with regard to the occurrence of treatment‐emergent adverse events (TEAEs), drug‐related adverse events (AEs), serious AEs, serious drug‐related AEs and mortality, no statistically significant difference between patients given solithromycin and those given other antibiotics was observed. Conclusion In the treatment of CABP, solithromycin monotherapy is an effective and safe antibiotic regimen. Other advantages (ie anti‐inflammatory effect, potent activity against expected pathogens of CABP and convenient clinical use) of solithromycin may make it a more fascinating option compared with the currently used regimens.

Ribosome Protection Proteins—“New” Players in the Global Arms Race with Antibiotic-Resistant Pathogens

“…Solithromycin (Solithera) is in phase 3 and expected to have activity against MDR Neisseria gonorrhoeae, and nafithromycin (WCK 4873) is in phase 2. While these new ketolides are not more potent per se than the current ones, they appear not to induce the expression of the corresponding ARE genes to the same degree [23,[76][77][78]. However, these new ketolides are less effective when erm genes are expressed constitutively [78,79].…”

Pharmaceutical Approaches on Antimicrobial Resistance: Prospects and Challenges

“…A fourth-generation macrolide, solithromycin, has good activity against resistant microbes, especially when compared to the previous generation macrolides. Two phase III clinical trials for CAP and one for gonorrhea have been completed for this drug [ 85 , 86 ]. However, this drug did not get approval from the US FDA because of its worrisome side effects on the liver [ 87 ].…”

Novel Therapeutic Trends in Pneumonia: Antibiotics and Mesenchymal Stem Cells

“…Solithromycin is a "fourth generation" macrolide and fluoroketolide that has yet to receive FDA approval for treatment of CAP [16,35]. Solithromycin binds the 50S ribosomal subunit near the peptide exit tunnel, prematurely terminating translation and causing frameshift errors in translation [24,36].…”

“…Solithromycin is an effective antibiotic regiment that offers additional advantages, including its anti-inflammatory effect and its potent activity against pathogens [35]. However, due to concerns related to hepatoxicity, the FDA has recommended further clinical studies to assess the safety profile in 9000 patients [16,24].…”