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Infections
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
Macrolides, lincosamides, ketolides, and streptogramins share overlapping binding sites on ribosomes, and have similar antimicrobial activities, as well as similar mechanisms of resistance [4]. The macrolides are a family of large cyclic molecules, all containing a macrocyclic lactone ring. The macrolide class of antibiotic agents includes compounds with 14-membered (erythromycin, clarithromycin) (Figure 17), 15-membered (azithromycin), and 16-membered (rokitamycin, spiramycin and josamycin) ring structures. Streptogramin antibiotics, such as pristinamycim or dalfopristin-quinupristin, contain two active components, type A and type B, which synergistically inhibit peptide elongation. Streptogramin B agents include quinupristin (Figure 18) and pristinamycin IA. Streptogramin A agents include dalfopristin and pristinamycim II A.
Quinupristin–Dalfopristin
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Streptogramins belong to the macrolide–lincosamide–streptogramin group of antibiotics. They constitute a family of compounds including pristinamycins, oestreomycins, and mikamycins, all isolated from Streptomyces pristinaespiralis, and virginiamycins, isolated from Streptomyces virginae (Vasquez, 1967). Streptogramins are divided into two groups (group A and group B) based on their molecular structure. Quinupristin (derived from pristinamycin IA) is a group B streptogramin, whereas dalfopristin (derived from pristinamycin IIA) is a semisynthetic derivative of a group A streptogramin. These two water-soluble streptogramins have been combined in the first parenteral streptogramin preparation commercially available at a 30:70 weight-to-weight ratio (Synercid, Aventis Pharmaceutical Products Inc., Parsippany, NJ). Quinupristin is a combination of three peptide macrolactones. Its main component (> 88%) has an empirical formula of C53H67N9O10S and a molecular weight of 1022.24 g/mol and its structural formula is shown in Figure 77.1. Dalfopristin has an empirical formula of C34H50N4O9S, a molecular weight of 690.85 g/mol (Figure 77.1).
Oxazolidinones and Streptogramins
Published in Thomas T. Yoshikawa, Shobita Rajagopalan, Antibiotic Therapy for Geriatric Patients, 2005
Stephen Marer, Shobita Rajagopalan
Streptogramins are antibiotics produced in nature by Streptomyces pristinaepiralis. They belong to the antibiotic family of macrolides-lincosamides-streptogramins (10). The streptogramin pristinamycin has been available in Europe for over 25 years for the treatment of gram-positive infections. Because it is water insoluble, it is available only for oral administration. Quinupristin and dalfopristin are both streptogramins that are derived from pristinamycin. Quinupristin is derived from pristinamycin IA, a type B streptogramin. Dalfopristin is derived from pristinamycin IIB, a type A streptogramin. The fixed-ratio 30:70 combination of quinupristin/dalfopristin is now marketed under the trade name Synercid. Because quinupristin and dalfopristin are water-soluble derivatives of pristinamycin, Synercid can be given only by the intravenous (IV) route. Synercid was released in the United States in 1999. For gram-positive organisms, it has essentially the same spectrum of activity as linezolid (with the exception of E. faecalis, which is generally resistant to quinupristin/ dalfopristin, but sensitive to linezolid), but has fewer approved indications for use.
Streptogramins for the treatment of infections caused by Gram-positive pathogens
Published in Expert Review of Anti-infective Therapy, 2021
Sophie Reissier, Vincent Cattoir
Streptogramin antibiotics are a combination of chemically unrelated compounds, namely type A and type B streptogramins, which act synergistically by inhibiting protein synthesis. Although the streptogramin compounds are separately bacteriostatic, the combination usually becomes bactericidal. Their spectrum of activity includes a broad range of aerobic and anaerobic Gram-positive bacteria, but also most of fastidious Gram-negative and atypical bacteria. This synergism also allows overcoming certain mechanisms of resistance to the individual components of the combination and may explain low rates of resistance reported so far. To date, two streptogramins are available in human medicine, oral pristinamycin, and quinupristin-dalfopristin, an injectable formulation approved since 1999 and 2000 in the US and Europe, respectively. In this study we have synthesized all the clinical studies evaluating these antibiotics. Finally, virginiamycin, an oral streptogramin, was therapeutically used in France until late 1990s and as a growth promoter for animals in many European countries until early 2000s and currently in the US.
A profile of the FDA-approved and CE/IVD-marked Aptima Mycoplasma genitalium assay (Hologic) and key priorities in the management of M. genitalium infections
Published in Expert Review of Molecular Diagnostics, 2020
Elena Shipitsyna, Magnus Unemo
Regarding management of MG infections, it is essential to follow up-to-date evidence-based national [8] and/or international guidelines [2], for diagnostics, treatment and follow-up of MG-positive patients. Test of cure (TOC) for all MG-positive patients should be performed >3–5 weeks after treatment [2,8]. Nevertheless, ideal time for TOC for MG infections in different anatomical sites and using different MG-diagnostic NAATs remains unknown and additional studies would be valuable. For macrolide- and fluoroquinolone-resistant MG cases, the streptogramin pristinamycin is the main third-line treatment recommended in Europe [2]. Pristinamycin is well-tolerated; however, it is not available or licensed in most countries internationally and it does not cure all cases as neither second- nor third-line treatment [69,70]. Currently, macrolide resistance-guided sequential therapy starting with doxycycline (presumptive therapy, and ideally first-line therapy for both non-gonococcal urethritis and CT infections) and macrolide-resistance testing followed by azithromycin (macrolide-susceptible infections) or moxifloxacin/sitafloxacin (macrolide-resistant infections) appears to give high cure rates [71,72]. Nevertheless, large-randomized controlled clinical trials (RCTs) to thoroughly evaluate and optimize the efficacy and tolerability of different algorithms and dosing regimens for treatment of MG infections are urgently needed. In these RCTs, ideally AMR emergence in also etiological agents of other STIs, e.g. gonorrhea, and bystander organisms should be studied, i.e. applying a more holistic view of the treatment of STIs.
The war against bacteria, from the past to present and beyond
Published in Expert Review of Anti-infective Therapy, 2022
Lucrezia Bottalico, Ioannis Alexandros Charitos, Maria Assunta Potenza, Monica Montagnani, Luigi Santacroce
Streptogramin antibiotics such as pristinamycin and quinupristin/dalfopristin are unique, in the sense that the producer strains synthetize two structurally unrelated antibiotics, streptogramin A, which is a cyclic hybrid peptide-polyketide macrolactone compound, and streptogramin B, which is a cyclic depsipeptide compound. The combination of these two acts synergistically to induce a rapid bacterial cell death by binding to the ribosomal exit tunnel and blocking it.