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      Macrolide Resistance in Streptococcus pneumoniae

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          Abstract

          Streptococcus pneumoniae is a common commensal and an opportunistic pathogen. Suspected pneumococcal upper respiratory infections and pneumonia are often treated with macrolide antibiotics. Macrolides are bacteriostatic antibiotics and inhibit protein synthesis by binding to the 50S ribosomal subunit. The widespread use of macrolides is associated with increased macrolide resistance in S. pneumoniae, and the treatment of pneumococcal infections with macrolides may be associated with clinical failures. In S. pneumoniae, macrolide resistance is due to ribosomal dimethylation by an enzyme encoded by erm(B), efflux by a two-component efflux pump encoded by mef (E)/ mel( msr(D)) and, less commonly, mutations of the ribosomal target site of macrolides. A wide array of genetic elements have emerged that facilitate macrolide resistance in S. pneumoniae; for example erm(B) is found on Tn 917, while the mef (E)/ mel operon is carried on the 5.4- or 5.5-kb Mega element. The macrolide resistance determinants, erm(B) and mef (E)/ mel, are also found on large composite Tn 916-like elements most notably Tn 6002, Tn 2009, and Tn 2010. Introductions of 7-valent and 13-valent pneumococcal conjugate vaccines (PCV-7 and PCV-13) have decreased the incidence of macrolide-resistant invasive pneumococcal disease, but serotype replacement and emergence of macrolide resistance remain an important concern.

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          Sustained reductions in invasive pneumococcal disease in the era of conjugate vaccine.

          Changes in invasive pneumococcal disease (IPD) incidence were evaluated after 7 years of 7-valent pneumococcal conjugate vaccine (PCV7) use in US children. Laboratory-confirmed IPD cases were identified during 1998-2007 by 8 active population-based surveillance sites. We compared overall, age group-specific, syndrome-specific, and serotype group-specific IPD incidence in 2007 with that in 1998-1999 (before PCV7) and assessed potential serotype coverage of new conjugate vaccine formulations. Overall and PCV7-type IPD incidence declined by 45% (from 24.4 to 13.5 cases per 100,000 population) and 94% (from 15.5 to 1.0 cases per 100,000 population), respectively (P< .01 all age groups). The incidence of IPD caused by serotype 19A and other non-PCV7 types increased from 0.8 to 2.7 cases per 100,000 population and from 6.1 to 7.9 cases per 100,000 population, respectively (P< .01 for all age groups). The rates of meningitis and invasive pneumonia caused by non-PCV7 types increased for all age groups (P< .05), whereas the rates of primary bacteremia caused by these serotypes did not change. In 2006-2007, PCV7 types caused 2% of IPD cases, and the 6 additional serotypes included in an investigational 13-valent conjugate vaccine caused 63% of IPD cases among children <5 years-old. Dramatic reductions in IPD after PCV7 introduction in the United States remain evident 7 years later. IPD rates caused by serotype 19A and other non-PCV7 types have increased but remain low relative to decreases in PCV7-type IPD.
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            Structures of the bacterial ribosome at 3.5 A resolution.

            We describe two structures of the intact bacterial ribosome from Escherichia coli determined to a resolution of 3.5 angstroms by x-ray crystallography. These structures provide a detailed view of the interface between the small and large ribosomal subunits and the conformation of the peptidyl transferase center in the context of the intact ribosome. Differences between the two ribosomes reveal a high degree of flexibility between the head and the rest of the small subunit. Swiveling of the head of the small subunit observed in the present structures, coupled to the ratchet-like motion of the two subunits observed previously, suggests a mechanism for the final movements of messenger RNA (mRNA) and transfer RNAs (tRNAs) during translocation.
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              US outpatient antibiotic prescribing variation according to geography, patient population, and provider specialty in 2011.

              Appropriate antibiotic prescribing is an essential strategy to reduce the spread of antibiotic resistance. US prescribing practices have not been thoroughly characterized. We analyzed outpatient antibiotic prescribing data to identify where appropriate antibiotic prescribing interventions could have the most impact.
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                Author and article information

                Contributors
                Journal
                Front Cell Infect Microbiol
                Front Cell Infect Microbiol
                Front. Cell. Infect. Microbiol.
                Frontiers in Cellular and Infection Microbiology
                Frontiers Media S.A.
                2235-2988
                21 September 2016
                2016
                : 6
                : 98
                Affiliations
                [1] 1Departments of Medicine, Emory University Atlanta, GA, USA
                [2] 2Departments of Microbiology and Immunology, Emory University Atlanta, GA, USA
                [3] 3Departments of Epidemiology, Emory University Atlanta, GA, USA
                Author notes

                Edited by: Guangchun Bai, Albany Medical College, USA

                Reviewed by: Lesley McGee, Centers for Disease Control and Prevention, USA; Werner Albrich, Kantonsspital St. Gallen, Switzerland; Lucia Martins Teixeira, Federal University of Rio de Janeiro, Brazil

                *Correspondence: David S. Stephens dstep01@ 123456emory.edu
                Article
                10.3389/fcimb.2016.00098
                5030221
                27709102
                9eb8ccaf-1625-4ad0-bd41-6d1baec27533
                Copyright © 2016 Schroeder and Stephens.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 12 May 2016
                : 26 August 2016
                Page count
                Figures: 0, Tables: 1, Equations: 0, References: 110, Pages: 9, Words: 7746
                Categories
                Microbiology
                Mini Review

                Infectious disease & Microbiology
                streptococcus pneumoniae,antibiotic resistance,macrolide resistance,erm(b),mef(a/e)/mel(msr(d)),mega,pneumococci

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