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Infections
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
Two main mechanisms of resistance are described. The first mechanism is due to alteration in the 23S rRNA target by methylation of two adenine nucleotides in the RNA encoded by erm genes. At least 12 classes of erm genes have been identified by nucleic acid hybridisation analysis and nucleotide sequence comparison. The ermB gene confers co-resistance to 14-, 15-, and 16-membered-ring macrolides and lincosamides (MICs at which 90% of the isolates tested are inhibited exceeding 128 μg/ml for both three drugs), and to streptogramin B (MIC90 = 64 μg/ml). The second mechanism involves the presence of an efflux pump encoded by the mef gene, which removes drugs from the bacterial cell. The mefA gene encodes a hydrophobic 44–2kDa protein sharing homology with membrane-associated pump proteins. The mefA gene confers resistance only to 14- and 15-membered-ring macrolides (MIC90 = 8 μg/ml). Mutation of the ribosomal target of macrolides remains a rare resistance mechanism.
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.