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      Bacteriemia por Klebsiella pneumoniae productora de carbapenemasa tipo KPC. Estudio comparativo y evolución en 7 años Translated title: Bacteremia caused by Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae. A retrospective study of 7 years

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          RESUMEN

          Introducción

          La bacteriemia por Klebsiella pneumoniae productora de carbapenemasa tipo KPC (Kp-KPC) se asocia a elevada mortalidad. La hipótesis de nuestro trabajo es que hubo aumento en los niveles de resistencia a diferentes antimicrobianos en Kp-KPC en bacteriemias.El objetivo del presente estudio es describir las características clínicas, microbiológicas, esquemas terapéuticos y evolución de las bacteriemias por Kp-KPC en nuestro hospital.

          Materiales y métodos

          Estudio retrospectivo y descriptivo en dos periodos: Periodo 1 (P1) 2010-2014 y periodo 2 (P2) 2015-2016. Se incluyeron pacientes ≥ 18 años con bacteriemia por Kp-KPC en un Hospital General de Agudos. Se definió como antimicrobiano activo aquel que presentaba sensibilidad en el antibiograma y en el caso particular de meropenem cuando presentaba CMI ≤ 8 mg/L y era utilizado en tratamiento combinado.

          Resultados

          Se analizaron 50 episodios (P1: 21 y P2: 29) de bacteriemia por Kp-KPC en 45 pacientes. Las siguientes variables fueron semejantes en ambos periodos: edad mediana (53 vs. 52 años); sexo masculino (45 vs. 62%); sitio de infección: bacteriemia primaria (52 vs. 45%), bacteriemia asociada a catéter (24 vs. 17%), otros (24 vs. 38%). En el P2 se registró un aumento significativo de resistencia a colistina (28 vs. 69%) (p<0,01), un aumento de aislamientos con CMI a meropenem ≥ 16 mg/L (74 vs. 97%) (p=0,02) y una disminución de resistencia a tigeciclina (29 vs. 4%) (p=0,02). La mortalidad global fue del 40 en el P1 y 32% en el P2 (p=0,7). En ningún periodo se observó diferencia en la mortalidad cuando el tratamiento dirigido fue con un antimicrobiano activo vs. dos antimicrobianos activos, así como tampoco entre los diferentes antimicrobianos utilizados.

          Conclusiones

          Se observó un aumento significativo de las bacteriemias por Kp-KPC y del nivel de resistencia a colistina y de las CMIs a meropenem. Para ambos períodos la mortalidad fué elevada.

          ABSTRACT

          Introduction

          Bacteremia caused by Klebsiella pneumoniae carbapenemase-producing strains (Kp-KPC) is associated with high mortality. The hypothesis of our work is that there was an increase in the levels of resistance to different antimicrobials in Kp-KPC isolated from bacteremia

          Materials and methods

          Retrospective and descriptive study in two periods: Period 1 (P1) 2010-2014 and period 2 (P2) 2015-2016. We included patients ≥18 years old with bacteremia caused by Kp-KPC in a General Hospital. We defined active drug (AD) if it was in vitro susceptible and in the case of meropenem if it had a MIC ≤ 8 mg/L in combination treatment.

          Results

          Fifty episodes of bacteremia caused by Kp-KPC were analyzed in 45 patients. (P1: 21 and P2: 29). The following variables were similar in both periods: median age (53 vs. 52 years); male sex (45 vs. 62%); site of infection: primary bacteremia (52 vs.45%), bacteremia associated with catheter (24 vs.17%), and other (24 vs. 38%). During P2 there was a significant increase in colistin resistance (28 vs. 69%) (p <0.01), an increase in MIC to meropenem ≥ 16 mg/L (74 and 97%) (p = 0.02), and decrease in tigecycline resistance (29 vs. 4%) (p = 0.02). The overall mortality was 40 in P1 and 32% in P2 (p=0.7). There was not difference in mortality when the definitive treatment was with an active antimicrobial vs. two active antimicrobials, as well as between the different antimicrobials used.

          Conclusions

          There was a significant increase in bacteremia caused by Kp-KPC and the level of colistin resistance and MIC to meropenem. Overall mortality was high in both periods

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          Most cited references19

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          Treatment outcome of bacteremia due to KPC-producing Klebsiella pneumoniae: superiority of combination antimicrobial regimens.

          Klebsiella pneumoniae producing Klebsiella pneumoniae carbapenemase (KPC) has been associated with serious infections and high mortality. The optimal antimicrobial therapy for infection due to KPC-producing K. pneumoniae is not well established. We conducted a retrospective cohort study to evaluate the clinical outcome of patients with bacteremia caused by KPC-producing K. pneumoniae. A total of 41 unique patients with blood cultures growing KPC-producing K. pneumoniae were identified at two medical centers in the United States. Most of the infections were hospital acquired (32; 78%), while the rest of the cases were health care associated (9; 22%). The overall 28-day crude mortality rate was 39.0% (16/41). In the multivariate analysis, definitive therapy with a combination regimen was independently associated with survival (odds ratio, 0.07 [95% confidence interval, 0.009 to 0.71], P = 0.02). The 28-day mortality was 13.3% in the combination therapy group compared with 57.8% in the monotherapy group (P = 0.01). The most commonly used combinations were colistin-polymyxin B or tigecycline combined with a carbapenem. The mortality in this group was 12.5% (1/8). Despite in vitro susceptibility, patients who received monotherapy with colistin-polymyxin B or tigecycline had a higher mortality of 66.7% (8/12). The use of combination therapy for definitive therapy appears to be associated with improved survival in bacteremia due to KPC-producing K. pneumoniae.
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            Predictors of mortality in patients with bloodstream infections caused by KPC-producing Klebsiella pneumoniae and impact of appropriate antimicrobial treatment.

            Bloodstream infections (BSIs) caused by Klebsiella pneumoniae carbapenemases (KPC)-producing K. pneumoniae (KPC-KP) are associated with high mortality rates. We investigated outcomes, risk factors for mortality and impact of appropriate antimicrobial treatment in patients with BSIs caused by molecularly confirmed KPC-KP. All consecutive patients with KPC-KP BSIs between May 2008 and May 2010 were included in the study and followed-up until their discharge or death. Potential risk factors for infection mortality were examined by a case-control study. Case-patients were those who died from the BSI and control-patients those who survived. Appropriate antimicrobial therapy was defined as treatment with in vitro active antimicrobials for at least 48 h. A total of 53 patients were identified. Overall mortality was 52.8% and infection mortality was 34%. Appropriate antimicrobial therapy was administered to 35 patients; mortality due to infection occurred in 20%. All 20 patients that received combination schemes had favourable infection outcome; in contrast, seven of 15 patients given appropriate monotherapy died (p 0.001). In univariate analysis, risk factors for mortality were age (p <0.001), APACHE II score at admission and infection onset (p <0.001) and severe sepsis (p <0.001), while appropriate antimicrobial treatment (p 0.003), combinations of active antimicrobials (p 0.001), catheter-related bacteraemia (p 0.04), prior surgery (p 0.014) and other therapeutic interventions (p 0.015) were significantly associated with survival. Independent predictors of mortality were age, APACHE II score at infection onset and inappropriate antimicrobial treatment. Among them, appropriate treatment is the only modifiable independent predictor of infection outcome. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.
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              Global dissemination of extensively drug-resistant carbapenemase-producing Enterobacteriaceae: clinical perspectives on detection, treatment and infection control.

              The prevalence of carbapenem-resistant Gram-negative bacilli is on the rise worldwide, posing a major public health threat. Previously, this was mostly a problem in Pseudomonas and Acinetobacter, but during the last decade, carbapenem resistance has escalated in medically important species such as Klebsiella pneumoniae and Escherichia coli. In particular, the rising trend in E. coli is of concern, as this may lead to almost untreatable community-acquired infections. Resistance is conferred by carbapenemases, which are beta-lactamases that can breakdown essentially all beta-lactams. Moreover, bacteria carrying these resistance determinants are often resistant to other treatment options, due to the frequent co-acquisition of non-beta-lactam resistance genes located on the same mobile genetic elements. The detection of carbapenemase-producing Enterobacteriaceae (CPE) is a challenge, because some carbapenemases produce relatively discrete levels of carbapenem resistance. Current clinical evidence for treatment guidance is limited and based on retrospective observational studies and case reports. Existing data support the use of combination therapy for treatment of severe infections caused by CPE. Combination regimens including colistin, carbapenems, tigecycline, aminoglycosides and fosfomycin have been used. Randomized controlled studies of combination regimens are ongoing and may help to determine the optimal therapy. Novel beta-lactamase inhibitors may also have a role in future treatment of these infections. Strict infection control measures including isolation or cohort care of affected patients as well as contact tracing and active screening are needed to curb the spread of CPE. In this review, we provide a clinical perspective on the management of patients infected or colonized with CPE.
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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
                08 February 2019
                February 2019
                : 32
                : 1
                : 15-21
                Affiliations
                [1 ]Unidad de Infectología, Hospital General de Agudos “Dr. Cosme Argerich”, Buenos Aires, Argentina
                [2 ]Laboratorio de Microbiología, Hospital General de Agudos “Dr. Cosme Argerich”, Buenos Aires, Argentina
                Author notes
                Correspondencia: María Inés Lespada. Unidad de Infectología, Hospital General de Agudos “Dr. Cosme Argerich”. Pi y Margall 750, C1155AHD Ciudad Autónoma de Buenos Aires. Email: milespada@ 123456gmail.com
                Article
                revespquimioter-32-15
                6372954
                e1093672-871e-480c-b754-56326704d505
                © 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/)

                History
                : 16 April 2018
                : 05 June 2018
                : 20 October 2018
                : 24 October 2018
                Categories
                Original

                klebsiellapneumoniae,carbapenemasa,kpc,bacteriemia,colistina,klebsiella pneumoniae,carbapenemase,bacteremia,colistin

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