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      Fosfomycin in the pediatric setting: Evidence and potential indications

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          Abstract

          To date, there has been little experience in using fosfomycin in children. However, its broad spectrum of action and excellent safety profile have renewed interest in this antibiotic, especially for treating infections by multidrug-resistant bacteria. The main indication for fosfomycin in pediatrics is currently community-acquired lower urinary tract infection. Given its good activity against bacteria, fosfomycin can also be useful in urinary infections caused by extended-spectrum beta-lactamase-producing enterobacteria. Fosfomycin presents very good dissemination to tissues including bone and is therefore an option in the combined therapy of osteomyelitis, especially in cases produced by methicillin-resistant Staphylococcus aureus (MRSA) or in cases with beta-lactam allergies. Fosfomycin can also be employed in combination for multidrug-resistant Gram-negative bacteremia (especially carbapenemase-producing enterobacteria), S. aureus (if there is a high suspicion of MRSA or complicated infections) and vancomycin-resistant Enterococcus spp. Other infections in which fosfomycin could be part of a combined therapy include staphylococcal endocarditis (in case of beta-lactam allergy or MRSA), central nervous system infections (mainly by MRSA, S. epidermidis, Listeria and resistant pneumococcus), nosocomial pneumonia and infections associated with mechanical ventilation.

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          Risk factors and outcomes for multidrug-resistant Gram-negative bacteremia in the NICU.

          To assess the risk factors antibiotic therapy and outcomes of multidrug-resistant (MDR) Gram-negative bacilli (GNB) bacteremia in NICU patients.
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            Fosfomycin: Pharmacological, Clinical and Future Perspectives

            Fosfomycin is a bactericidal, low-molecular weight, broad-spectrum antibiotic, with putative activity against several bacteria, including multidrug-resistant Gram-negative bacteria, by irreversibly inhibiting an early stage in cell wall synthesis. Evidence suggests that fosfomycin has a synergistic effect when used in combination with other antimicrobial agents that act via a different mechanism of action, thereby allowing for reduced dosages and lower toxicity. Fosfomycin does not bind to plasma proteins and is cleared via the kidneys. Due to its extensive tissue penetration, fosfomycin may be indicated for infections of the CNS, soft tissues, bone, lungs, and abscesses. The oral bioavailability of fosfomycin tromethamine is <50%; therefore, oral administration of fosfomycin tromethamine is approved only as a 3-gram one-time dose for treating urinary tract infections. However, based on published PK parameters, PK/PD simulations have been performed for several multiple-dose regimens, which might lead to the future use of fosfomycin for treating complicated infections with multidrug-resistant bacteria. Because essential pharmacological information and knowledge regarding mechanisms of resistance are currently limited and/or controversial, further studies are urgently needed, and fosfomycin monotherapy should be avoided.
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              Mortality and morbidity in community-acquired sepsis in European pediatric intensive care units: a prospective cohort study from the European Childhood Life-threatening Infectious Disease Study (EUCLIDS)

              Background Sepsis is one of the main reasons for non-elective admission to pediatric intensive care units (PICUs), but little is known about determinants influencing outcome. We characterized children admitted with community-acquired sepsis to European PICUs and studied risk factors for mortality and disability. Methods Data were collected within the collaborative Seventh Framework Programme (FP7)-funded EUCLIDS study, which is a prospective multicenter cohort study aiming to evaluate genetic determinants of susceptibility and/or severity in sepsis. This report includes 795 children admitted with community-acquired sepsis to 52 PICUs from seven European countries between July 2012 and January 2016. The primary outcome measure was in-hospital death. Secondary outcome measures were PICU-free days censured at day 28, hospital length of stay, and disability. Independent predictors were identified by multivariate regression analysis. Results Patients most commonly presented clinically with sepsis without a source (n = 278, 35%), meningitis/encephalitis (n = 182, 23%), or pneumonia (n = 149, 19%). Of 428 (54%) patients with confirmed bacterial infection, Neisseria meningitidis (n = 131, 31%) and Streptococcus pneumoniae (n = 78, 18%) were the main pathogens. Mortality was 6% (51/795), increasing to 10% in the presence of septic shock (45/466). Of the survivors, 31% were discharged with disability, including 24% of previously healthy children who survived with disability. Mortality and disability were independently associated with S. pneumoniae infections (mortality OR 4.1, 95% CI 1.1–16.0, P = 0.04; disability OR 5.4, 95% CI 1.8–15.8, P < 0.01) and illness severity as measured by Pediatric Index of Mortality (PIM2) score (mortality OR 2.8, 95% CI 1.3–6.1, P < 0.01; disability OR 3.4, 95% CI 1.8–6.4, P < 0.001). Conclusions Despite widespread immunization campaigns, invasive bacterial disease remains responsible for substantial morbidity and mortality in critically ill children in high-income countries. Almost one third of sepsis survivors admitted to the PICU were discharged with some disability. More research is required to delineate the long-term outcome of pediatric sepsis and to identify interventional targets. Our findings emphasize the importance of improved early sepsis-recognition programs to address the high burden of disease. Electronic supplementary material The online version of this article (10.1186/s13054-018-2052-7) contains supplementary material, which is available to authorized users.
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                Author and article information

                Journal
                Rev Esp Quimioter
                Rev Esp Quimioter
                Sociedad Española de Quimioterapia
                Revista Española de Quimioterapia
                Sociedad Española de Quimioterapia
                0214-3429
                1988-9518
                07 June 2019
                May 2019
                : 32
                : Suppl 1
                : 55-61
                Affiliations
                [0001]Servicio de Pediatría, Enfermedades Infecciosas y Patología Tropical. Hospital Universitario La Paz, Madrid
                [0002]Red Española de Investigación Traslacional en Infectología Pediátrica (RITIP)
                Author notes
                Correspondence: Fernando Baquero-Artigao, Servicio de Pediatría, Enfermedades Infecciosas y Patología Tropical. Hospital Universitario La Paz. Paseo de la Castellana, 261. 28046 Madrid. Tfno.: 917277443. E-mail: fbaqueroartigao@ 123456gmail.com
                Article
                revespquimioter-32-suppl-1-55
                6555161
                31131593
                dbbffe2f-9a13-4b9f-b713-81727b5234cb
                © The Author 2019

                The article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) ( https://creativecommons.org/licenses/by-nc/4.0/)

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                Current Key Topics in Fosfomycin

                fosfomycin,pediatrics,children,newborns,beta-lactam resistance

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