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.
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http://dx.doi.org/10.3389/fimmu.2016.00111 | DOI Listing |
Front Cell Infect Microbiol
August 2024
Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Eur J Med Chem
March 2024
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 TiantanXili, Beijing 100050, China. Electronic address:
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 PDFAuris Nasus Larynx
April 2024
Department of Otorhinolaryngology, Yonaha Okanoue Hospital, Japan.
Mol Pharm
December 2023
Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
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 PDFAntimicrob 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.
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