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      The frequency of influenza and bacterial coinfection: a systematic review and meta‐analysis

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          Abstract

          Aim

          Coinfecting bacterial pathogens are a major cause of morbidity and mortality in influenza. However, there remains a paucity of literature on the magnitude of coinfection in influenza patients.

          Method

          A systematic search of Me SH, Cochrane Library, Web of Science, SCOPUS, EMBASE, and PubMed was performed. Studies of humans in which all individuals had laboratory confirmed influenza, and all individuals were tested for an array of common bacterial species, met inclusion criteria.

          Results

          Twenty‐seven studies including 3215 participants met all inclusion criteria. Common etiologies were defined from a subset of eight articles. There was high heterogeneity in the results ( I 2  = 95%), with reported coinfection rates ranging from 2% to 65%. Although only a subset of papers were responsible for observed heterogeneity, subanalyses and meta‐regression analysis found no study characteristic that was significantly associated with coinfection. The most common coinfecting species were Streptococcus pneumoniae and Staphylococcus aureus, which accounted for 35% (95% CI, 14%–56%) and 28% (95% CI, 16%–40%) of infections, respectively; a wide range of other pathogens caused the remaining infections. An assessment of bias suggested that lack of small‐study publications may have biased the results.

          Conclusions

          The frequency of coinfection in the published studies included in this review suggests that although providers should consider possible bacterial coinfection in all patients hospitalized with influenza, they should not assume all patients are coinfected and be sure to properly treat underlying viral processes. Further, high heterogeneity suggests additional large‐scale studies are needed to better understand the etiology of influenza bacterial coinfection.

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          Most cited references42

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          Insights into the interaction between influenza virus and pneumococcus.

          Bacterial infections following influenza are an important cause of morbidity and mortality worldwide. Based on the historical importance of pneumonia as a cause of death during pandemic influenza, the increasingly likely possibility that highly pathogenic avian influenza viruses will trigger the next worldwide pandemic underscores the need to understand the multiple mechanisms underlying the interaction between influenza virus and bacterial pathogens such as Streptococcus pneumoniae. There is ample evidence to support the historical view that influenza virus alters the lungs in a way that predisposes to adherence, invasion, and induction of disease by pneumococcus. Access to receptors is a key factor and may be facilitated by the virus through epithelial damage, by exposure or up-regulation of receptors, or by provoking the epithelial regeneration response to cytotoxic damage. More recent data indicate that alteration of the immune response by diminishing the ability of the host to clear pneumococcus or by amplification of the inflammatory cascade is another key factor. Identification and exploration of the underlying mechanisms responsible for this synergism will provide targets for prevention and treatment using drugs and vaccines.
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            Etiology of Community-Acquired Pneumonia: Increased Microbiological Yield with New Diagnostic Methods

            Abstract Background The microbial etiology of community-acquired pneumonia (CAP) is still not well characterized. During the past few years, polymerase chain reaction (PCR)-based methods have been developed for many pathogens causing respiratory tract infections. The aim of this study was to determine the etiology of CAP among adults—especially the occurrence of mixed infections among patients with CAP—by implementing a new diagnostic PCR platform combined with conventional methods. Methods Adults admitted to Karolinska University Hospital were studied prospectively during a 12-month period. Microbiological testing methods included culture from blood, sputum, and nasopharyngeal secretion samples; sputum samples analyzed by real-time quantitative PCR for Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis; nasopharyngeal specimens analyzed by use of PCR; serological testing for Mycoplasma pneumoniae, Chlamydophila pneumoniae, and viruses common in the respiratory tract; and urine antigen assays for detection of pneumococcal and Legionella pneumophila antigens. Results A microbial etiology could be identified for 67% of the patients (n = 124). For patients with complete sampling, a microbiological agent was identified for 89% of the cases. The most frequently detected pathogens were S. pneumoniae (70 patients [38]) and respiratory virus (53 patients [29]). Two or more pathogens were present in 43 (35%) of 124 cases with a determined etiology. Conclusions By supplementing traditional diagnostic methods with new PCR-based methods, a high microbial yield was achieved. This was especially evident for patients with complete sampling. Mixed infections were frequent (most commonly S. pneumoniae together with a respiratory virus).
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              Seasonal influenza in adults and children--diagnosis, treatment, chemoprophylaxis, and institutional outbreak management: clinical practice guidelines of the Infectious Diseases Society of America.

              Guidelines for the treatment of persons with influenza virus infection were prepared by an Expert Panel of the Infectious Diseases Society of America. The evidence-based guidelines encompass diagnostic issues, treatment and chemoprophylaxis with antiviral medications, and issues related to institutional outbreak management for seasonal (interpandemic) influenza. They are intended for use by physicians in all medical specialties with direct patient care, because influenza virus infection is common in communities during influenza season and may be encountered by practitioners caring for a wide variety of patients.
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                Author and article information

                Journal
                Influenza Other Respir Viruses
                Influenza Other Respir Viruses
                10.1111/(ISSN)1750-2659
                IRV
                Influenza and Other Respiratory Viruses
                John Wiley and Sons Inc. (Hoboken )
                1750-2640
                1750-2659
                24 June 2016
                September 2016
                : 10
                : 5 ( doiID: 10.1111/irv.2016.10.issue-5 )
                : 394-403
                Affiliations
                [ 1 ] Department of Emergency MedicineJohns Hopkins University Baltimore MDUSA
                [ 2 ]Center for Disease Dynamics, Economics & Policy Washington DCUSA
                [ 3 ]Eastern Virginia Medical School Norfolk VAUSA
                [ 4 ]Allegheny General Hospital Pittsburgh PAUSA
                [ 5 ] Department of Emergency MedicineThe George Washington University Washington DCUSA
                Author notes
                [*] [* ] Correspondence: Eili Y. Klein, Department of Emergency Medicine, Johns Hopkins University, 5801 Smith Ave, Suite 3220, Office 265, Davis Building, Baltimore, MD 21209, USA. E‐mail: eklein@ 123456jhu.edu
                Article
                IRV12398
                10.1111/irv.12398
                4947938
                27232677
                e02b895e-cdcd-4e48-9e41-b6b7910301ef
                © 2016 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 14 May 2016
                Page count
                Pages: 10
                Funding
                Funded by: US Department of Health and Human Services
                Award ID: IDSEP130014‐01‐00
                Categories
                Systematic Review
                Systematic Review
                Custom metadata
                2.0
                irv12398
                September 2016
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.9.1 mode:remove_FC converted:18.07.2016

                Infectious disease & Microbiology
                antibiotic resistance,bacterial coinfection,influenza,meta‐analysis,mrsa,streptococcus pneumoniae

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