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      Critical issues for Klebsiella pneumoniae KPC-carbapenemase producing K. pneumoniae infections: a critical agenda

      , , , ,
      Future Microbiology
      Future Medicine Ltd

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          Abstract

          The wide dissemination of carbapenemase producing K. pneumoniae (KPC-Kp) has caused a public health crisis of global dimensions, due to the serious infections in hospitalized patients associated with high mortality. In 2014, we aim to review clinical data on KPC-Kp at a time when a pro-active strategy (combating the problem before it is established) is no longer useful, focusing on epidemiology, patient risk profile, infection control, digestive tract colonization and treatment issues such as the role of carbapenems or carbapenem sparing strategies, colistin and resistance, dual carbapenem administration and the role of tigecycline. All these issues are illustrated prospectively to provide a forum for a Consensus strategy when not only intensive care units but also medical and surgical wards are affected by the epidemics.

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          Most cited references42

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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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              Antibiotic treatment of infections due to carbapenem-resistant Enterobacteriaceae: systematic evaluation of the available evidence.

              We sought to evaluate the effectiveness of the antibiotic treatment administered for infections caused by carbapenemase-producing Enterobacteriaceae. The PubMed and Scopus databases were systematically searched. Articles reporting the clinical outcomes of patients infected with carbapenemase-producing Enterobacteriaceae according to the antibiotic treatment administered were eligible. Twenty nonrandomized studies comprising 692 patients who received definitive treatment were included. Almost all studies reported on Klebsiella spp. In 8 studies, the majority of infections were bacteremia, while pneumonia and urinary tract infections were the most common infections in 12 studies. In 10 studies, the majority of patients were critically ill. There are methodological issues, including clinical heterogeneity, that preclude the synthesis of the available evidence using statistical analyses, including meta-analysis. From the descriptive point of view, among patients who received combination treatment, mortality was up to 50% for the tigecycline-gentamicin combination, up to 64% for tigecycline-colistin, and up to 67% for carbapenem-colistin. Among the monotherapy-treated patients, mortality was up to 57% for colistin and up to 80% for tigecycline. Certain regimens were administered to a small number of patients in certain studies. Three studies reporting on 194 critically ill patients with bacteremia showed individually significantly lower mortality in the combination arm than in the monotherapy arm. In the other studies, no significant difference in mortality was recorded between the compared groups. Combination antibiotic treatment may be considered the optimal option for severely ill patients with severe infections. However, well-designed randomized studies of specific patient populations are needed to further clarify this issue.
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                Author and article information

                Journal
                Future Microbiology
                Future Microbiology
                Future Medicine Ltd
                1746-0913
                1746-0921
                February 2015
                February 2015
                : 10
                : 2
                : 283-294
                Article
                10.2217/fmb.14.121
                25689539
                ee86d300-5f9f-44c3-bc39-57f261eae97e
                © 2015
                History

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