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      Drug Design, Development and Therapy (submit here)

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      Delafloxacin: design, development and potential place in therapy

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          Abstract

          Delafloxacin (DLX) is a new fluoroquinolone pending approval, which has shown a good in vitro and in vivo activity against major pathogens associated with skin and soft tissue infections and community-acquired respiratory tract infections. DLX also shows good activity against a broad spectrum of microorganisms, including those resistant to other fluoroquinolones, as methicillin-resistant Staphylococcus aureus. Its pharmacokinetic properties and excellent activity in acidic environments make DLX an alternative in the treatment of these and other infections. In this manuscript, a detailed analysis of this new fluoroquinolone is performed, from its chemical structure to its in vivo activity in recently published clinical trials. Its possible place in the current antimicrobial outlook and in other infectious models is also discussed.

          Most cited references55

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          Burden of community-acquired pneumonia in North American adults.

          To determine the burden of community-acquired pneumonia (CAP) affecting adults in North America, a comprehensive literature review was conducted to examine the incidence, morbidity and mortality, etiology, antibiotic resistance, and economic impact of CAP in this population. In the United States, there were approximately 4.2 million ambulatory care visits for pneumonia in 2006. Pneumonia and influenza continue to be a common cause of death in the United States (ranked eighth) and Canada (ranked seventh). In 2005, there were >60,000 deaths due to pneumonia in persons aged>or=15 years in the United States alone. The hospitalization rate for all infectious diseases increased from 1525 hospitalizations per 100 000 persons in 1998 to 1667 per 100 000 persons in 2005. Admission to an intensive care unit was required in 10% to 20% of patients hospitalized with pneumonia. The mean length of stay for pneumonia was >or=5 days and the 30-day rehospitalization rate was as high as 20%. Mortality was highest for CAP patients who were hospitalized; the 30-day mortality rate was as high as 23%. All-cause mortality for CAP patients was as high as 28% within 1 year. Streptococcus pneumoniae continues to be the most frequently identified pathogen associated with CAP, and pneumococcal resistance to antimicrobials may make treatment more difficult. The economic burden associated with CAP remains substantial at >$17 billion annually in the United States. Despite the availability and widespread adherence to recommended treatment guidelines, CAP continues to present a significant burden in adults. Furthermore, given the aging population in North America, clinicians can expect to encounter an increasing number of adult patients with CAP. Given the significance of the disease burden, the potential benefit of pneumococcal vaccination in adults is substantial.
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            Adverse clinical and economic outcomes attributable to methicillin resistance among patients with Staphylococcus aureus surgical site infection.

            Data for 479 patients were analyzed to assess the impact of methicillin resistance on the outcomes of patients with Staphylococcus aureus surgical site infections (SSIs). Patients infected with methicillin-resistant S. aureus (MRSA) had a greater 90-day mortality rate than did patients infected with methicillin-susceptible S. aureus (MSSA; adjusted odds ratio, 3.4; 95% confidence interval, 1.5-7.2). Patients infected with MRSA had a greater duration of hospitalization after infection (median additional days, 5; P<.001), although this was not significant on multivariate analysis (P=.11). Median hospital charges were 29,455 dollars for control subjects, 52,791 dollars for patients with MSSA SSI, and 92,363 dollars for patients with MRSA SSI (P<.001 for all group comparisons). Patients with MRSA SSI had a 1.19-fold increase in hospital charges (P=.03) and had mean attributable excess charges of 13,901 dollars per SSI compared with patients who had MSSA SSIs. Methicillin resistance is independently associated with increased mortality and hospital charges among patients with S. aureus SSI.
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              Trends in US Hospital Admissions for Skin and Soft Tissue Infections

              Using data from the 2000–2004 US Healthcare Cost and Utilization Project National Inpatient Sample, we found that total hospital admissions for skin and soft tissue infections increased by 29% during 2000–2004; admissions for pneumonia were largely unchanged. These results are consistent with recent reported increases in community-associated methicillin-resistant Staphylococcus aureus infections.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2017
                20 March 2017
                : 11
                : 881-891
                Affiliations
                Department of Clinical Microbiology and Infectious Diseases, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Universidad Complutense, Madrid, Spain
                Author notes
                Correspondence: Francisco Javier Candel, Department of Clinical Microbiology and Infectious Diseases, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Universidad Complutense, Madrid, Spain, Tel +34 9 1330 3486, Email fj.candel@ 123456gmail.com
                Article
                dddt-11-881
                10.2147/DDDT.S106071
                5367733
                5290545e-4e0b-4b03-8c02-da91878463e9
                © 2017 Candel and Peñuelas. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                Categories
                Review

                Pharmacology & Pharmaceutical medicine
                delafloxacin,fluoroquinolones,methicillin-resistant staphylococcus aureus,therapy

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