Solithromycin

Introduction : Community-acquired pneumonia is the most common infection leading to hospitalization and death in all age groups, especially in elderly populations. Increasing antibiotic resistance among the common bacterial pathogens associated with community-acquired pneumonia, especially Streptococcus pneumoniae and staphylococci, has made its empirical treatment increasingly problematic, highlighting the need for effective antibiotic therapy. Areas covered : We searched PubMed and ClinicalTrials.gov for English-language reports of phase III clinical trials conducted between 2000 and 2019 concerning the antibiotic treatment of community-acquired pneumonia...

This is a review of the macrolide and ketolide field focusing on differentiating the pharmacodynamics and especially the toxicology of the macrolides and ketolides. We emphasize the diversity in pharmacodynamics and toxicity of the macrolides and ketolides, resulting from even small structural changes, which makes it important to consider the various different compounds separately, not necessarily as a class. The ketolide, telithromycin, was developed because of rising bacterial macrolide resistance but was withdrawn postapproval after visual disturbances, syncope, myasthenia gravis, and hepatotoxicity were noted...

BACKGROUND: Solithromycin is a fourth-generation macrolide antibiotic with potential efficacy in pediatric community-acquired bacterial pneumonia. Pharmacokinetic (PK) studies of solithromycin in pediatric subjects are limited; therefore, application of minimally invasive drug sampling techniques, such as dried blood spots (DBS), may enhance the enrollment of children in PK studies. The objectives of this study were to compare solithromycin concentrations in DBS with those in liquid plasma samples (LPS) and to quantify the effects of modeling DBS concentrations on the results of a population PK model...

Neisseria gonorrhoeae, the causative agent of gonorrhoea, has rapidly evolved from an exquisitely susceptible pathogen into a 'superbug' with the capacity to exhibit an extensively drug resistant (XDR) phenotype. The threat of untreatable gonorrhoea now looms on the horizon while the arsenal of effective antimicrobial agents diminishes with time. Ceftriaxone remains the mainstay of first-line therapy as a single agent or as the backbone of a dual therapy regimen. The implementation of new assays to facilitate 'precision' treatment, based on the prediction of N...

Macrolide antibiotics bind to the exit tunnel of the ribosome and inhibit protein synthesis blocking its translocation. Thus, antibiotics including the known macrolide Erythromycin (ERY) are active against bacteria. However, at present, some bacteria show resistance to drugs, which requires the development of new powerful antibacterial agents. One possible way is to use the ERY structure, but change its side chains, while the size of the lactone ring can remain unchanged or change. In this work we consider Cethromycin (CET) and Solithromycin (SOL), which are ketolides with quinolylallyl group at C6 and aminophenyl at C11, respectively (both of them have the same lactone ring as ERY)...

BACKGROUND: Antibiotic-resistant gonorrhoea represents a global public health threat, and new therapies are needed. We aimed to compare the efficacy and safety of solithromycin, a fourth generation macrolide, with ceftriaxone plus azithromycin for the treatment of gonorrhoea. METHODS: We did an open-label, multicentre, non-inferiority trial of patients aged 15 years or older with uncomplicated untreated genital gonorrhoea at two sites in Australia and one site in the USA...

No abstract text is available yet for this article.

Solithromycin (CEM-101) is a novel fluoroketolide antimicrobial agent with activity against typical and atypical pathogens associated with community-acquired bacterial pneumonia. Using a neutropenic murine-lung infection model, the objectives of this study were to identify the pharmacokinetic/pharmacodynamic (PK/PD) index most closely associated with efficacy and the magnitude of such indices necessary for solithromycin efficacy against Streptococcus pneumoniae Plasma and epithelial lining fluid (ELF) samples for pharmacokinetics (PK) were collected serially over 24 hours from healthy mice administered single doses of solithromycin (0...

Novel antibacterial drugs that treat multidrug resistant pathogens are in high demand. We have synthesized analogs of solithromycin using Cu(I)-mediated click chemistry. Evaluation of the analogs using Minimum Inhibitory Concentration (MIC) assays against resistant Staphylococcus aureus, Escherichia coli, and multidrug resistant pathogens Enterococcus faecium and Acinetobacter baumannii showed they possess potencies similar to those of solithromycin, thus demonstrating their potential as future therapeutics to combat the existential threat of multidrug resistant pathogens...

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 randomized 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...

BACKGROUND: Solithromycin, the fourth generation of ketolides, has been demonstrated potent antibacterial effect against commonly-isolated gram-positive strains. However, Staphylococcus aureus (S. aureus) strains with a higher solithromycin MIC have already been emerged, the mechanism of which is unknown. METHODS: Antimicrobial susceptibility test was performed on 266 strains of S. aureus. The antibiotic resistance phenotype of erm-positive strain was determined by D-zone test...

PURPOSE: Macrolide antibiotics are commonly prescribed treatments for drug-resistant bacterial infections; however, many macrolides have been shown to cause liver enzyme elevations and one macrolide, telithromycin, has been pulled from the market by its provider due to liver toxicity. This work seeks to assess the mechanisms responsible for the toxicity of macrolide antibiotics. METHODS: Five macrolides were assessed in in vitro systems designed to test for bile acid transporter inhibition, mitochondrial dysfunction, and oxidative stress...

The introduction of new molecules with antimicrobial activity is an opportunity for modern antibiotic therapy in the era of rapidly growing resistance to antibiotics. Beta-lactamase-inhibiting antibiotics, cephalosporinases and carbapenemases represent a breakthrough in previous treatments for infections caused by resistant pathogens. Ceftazidime with avibactam and ceftolozane with tazobactam show exceptional efficacy in severe infections. Karbavans is a combination of meropenem and a new boron beta-lactamase inhibitor, as well as the combination of avibactam and aztreonam, are a hope for the treatment of infections caused by Klebsiella pneumoniae resistant to the majority of available antibiotics...

PURPOSE OF REVIEW: This review provides the rationale for the development of new antibiotics to treat community-acquired pneumonia (CAP). It also provides an overview of the new antibiotics targeting CAP that have recently received approval by the regulatory agencies, and those antibiotics that are in the development pipeline. RECENT FINDINGS: CAP is one of the most common reasons for hospitalization and carries a significant morbidity and risk of mortality. Increasing antibiotic resistance amongst the common bacterial pathogens associated with CAP, especially staphylococci and Streptococcus pneumoniae, has made the empiric treatment of this infection increasingly problematic...

INTRODUCTION: Several new antibiotics (ceftaroline, ceftobiprole, omadacycline, solithromycine and delafloxacin) have recently been developed. Their place in the management of community acute pneumonia (CAP) needs to be clarified. STATE OF THE ART: Because multiresistant bacteria are infrequently involved in CAP, usual regimens using third generation cephalosporins, fluoroquinolones or macrolides, alone or in combination, are effective in the overwhelming majority of cases...

No abstract text is available yet for this article.

INTRODUCTION: Solithromycin is a novel fluoroketolide developed to treat pneumonia. But, few studies evaluating its antimicrobial activity against S. pneumoniae in a mixed-infection model with anaerobes are available, while community-acquired pneumonia can involve mixed-infection of Streptococcus pneumoniae and anaerobic bacteria. This study evaluated the antimicrobial activity of solithromycin against macrolide-resistant S. pneumoniae and anaerobic bacteria with a murine pneumonia mixed-infection model...

Solithromycin is a novel fluoroketolide antibiotic which was under investigation for the treatment of community-acquired bacterial pneumonia (CABP). A phase 1 study was performed to characterize the pharmacokinetics (PK) and safety of solithromycin in children. Eighty-four subjects (median age, 6 years [age range, 4 days to 17 years]) were administered intravenous (i.v.) or oral (capsules or suspension) solithromycin (i.v., 6 to 8 mg/kg of body weight; capsules/suspension, 14 to 16 mg/kg on days 1 and 7 to 15 mg/kg on days 2 to 5)...

The gonococcal NorM efflux pump exports substrates with a cationic moiety, including quaternary ammonium compounds such as berberine (BE) and ethidium bromide (EB) as well as antibiotics such as ciprofloxacin and solithromycin. The norM gene is part of a four-gene operon that is transcribed from a promoter containing a polynucleotide tract of 6 or 7 thymidines (T's) between the -10 and -35 hexamers; the majority of gonococcal strains analyzed in this study contained a T-6 sequence. Primer extension analysis showed that regardless of the length of the poly(T) tract, the same transcriptional start site (TSS) was used for expression of norM Interestingly, the T-6 tract correlated with a higher level of both norM expression and gonococcal resistance to NorM substrates BE and EB...

Evidence is provided that solithromycin is a bactericidal against not only fast-growing chlamydial organisms but also those slowed by gamma interferon (IFN-γ) in vitro At sublethal concentrations, Sol impedes homotypic fusion of Chlamydia -containing vacuoles and reduces secretion of the type III secretion (T3S) effector IncA. Sol may therefore represent a potential new clinical treatment for Chlamydia infections. Selective perturbation of the T3S system suggests a novel mode of antibacterial action for Sol that warrants further investigation...