Intrauterine infection-inflammation is a major cause of early preterm birth and subsequent neonatal mortality and acute or long-term morbidity. Antibiotics can be administered in pregnancy to prevent preterm birth either prophylactically to women at high risk for preterm delivery, or to women with diagnosed intrauterine infection, prelabor rupture of membranes, or in suspected preterm labor. The therapeutic goals of each of these scenarios are different, with different pharmacological considerations, although effective antimicrobial therapy is an essential requirement. An ideal antibiotic for these clinical indications would be (a) one that is easily administered and orally bioactive, (b) has a favorable adverse effect profile (devoid of reproductive toxicity or teratogenicity), (c) is effective against the wide range of microorganisms known to be commonly associated with intra-amniotic infection, (d) provides effective antimicrobial protection within both the fetal and amniotic compartments after maternal delivery, (e) has anti-inflammatory properties, and (f) is effective against antibiotic-resistant microorganisms. Here, we review the evidence from clinical, animal, and ex vivo/in vitro studies that demonstrate that a new macrolide-derived antibiotic - solithromycin - has all of these properties and, hence, may be an ideal antibiotic for the treatment and prevention of intrauterine infection--related pregnancy complications. While this evidence is extremely encouraging, it is still preliminary. A number of key studies need to be completed before solithromycin's true potential for use in pregnancy can be ascertained.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4817400PMC
http://dx.doi.org/10.3389/fimmu.2016.00111DOI Listing

Publication Analysis

Top Keywords

antibiotic solithromycin
8
preterm birth
8
effective antimicrobial
8
ideal antibiotic
8
potent placenta-permeable
4
placenta-permeable macrolide
4
antibiotic
4
macrolide antibiotic
4
solithromycin prevention
4
prevention treatment
4

Similar Publications

Article Synopsis
  • * Of the 73 isolates, a significant majority (86.3%) showed resistance to macrolides, with notable correlations between certain serotypes and resistance genes, particularly serotype 19A and ST3111.
  • * Solithromycin and lascufloxacin were found to be highly effective antibiotics against the pneumococcal isolates regardless of their resistance genes.
View Article and Find Full Text PDF

A series of novel C11 substituted 14-membered 2-fluoro ketolides were synthesized and evaluated for their antibacterial activity against erythromycin-resistant and erythromycin-susceptible clinical isolates and strains from ATCC. The overall antibacterial spectra of the semi-synthetic antibiotics are similar to that of telithromycin (TEL) and most of them exhibited excellent activity against Gram-positive bacteria (S. epidermidis, S.

View Article and Find Full Text PDF
Article Synopsis
  • The research aimed to evaluate solithromycin's effectiveness, safety, and ability to penetrate tissues in treating ear, nose, and throat infections through three distinct studies.
  • The tissue penetration study involved 17 patients who received solithromycin before tissue removal, while the open-label study included 55 patients with various infections and assessed clinical responses post-treatment.
  • The non-inferiority study compared solithromycin to high-dose cefcapene-pivoxil in 283 patients with acute rhinosinusitis, focusing on clinical outcomes after treatment.
View Article and Find Full Text PDF

Macrolides are widely used for the long-term treatment of infections and chronic inflammatory diseases. The pharmacokinetic features of macrolides include extensive tissue distribution because of favorable membrane permeability and accumulation within lysosomes. Trastuzumab emtansine (T-DM1), a HER2-targeting antibody-drug conjugate (ADC), is catabolized in the lysosomes, where Lys-SMCC-DM1, a potent cytotoxic agent, is processed by proteinase degradation and subsequently released from the lysosomes to the cytoplasm through the lysosomal membrane transporter SLC46A3, resulting in an antitumor effect.

View Article and Find Full Text PDF

New Resistance Mutations Linked to Decreased Susceptibility to Solithromycin in Streptococcus pneumoniae Revealed by Chemogenomic Screens.

Antimicrob Agents Chemother

August 2023

Centre de Recherche en Infectiologie du Centre de Recherche du CHU de Québec and Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université Laval, Québec City, Québec, Canada.

Two strains of Streptococcus pneumoniae, one expressing the methyltransferase Erm(B) and the other negative for (B), were selected for solithromycin resistance either with direct drug selection or with chemical mutagenesis followed by drug selection. We obtained a series of mutants that we characterized by next-generation sequencing. We found mutations in various ribosomal proteins (L3, L4, L22, L32, and S4) and in the 23S rRNA.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!