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      Carbapenem resistant Klebsiella pneumoniae isolated from bloodstream infection: Indian experience

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          Abstract

          Increased incidence of multidrug resistant (MDR) Gram negative infection has resulted in high rates of morbidity and mortality. Klebsiella pneumoniae is one of the commonest MDR pathogens causing bacteraemia with limited therapeutic options such as colistin and tigecycline. Present study focused on molecular characterisation of MDR K. pneumoniae from bloodstream infection and their clinical outcome. A total of 115 K. pneumoniae from January 2015 to September 2016 were included in the study which comprised of phenotypically identified ESBL and carbapenem resistant (CR) isolates. Multiplex PCR was performed for detection of resistance genes encoding β-lactam resistance. This includes blaSHV, blaTEM, blaVEB, blaPER, blaCTX-M, blaDHA, blaCIT, blaFOX, blaACC, blaACT, blaNDM, blaOXA48-like, blaVIM and blaKPC. Co-expression of blaSHV, blaTEM and blaCTX-M was predominant with 64% (74/115) prevalence. CTX-M-1 was the variant produced by all the isolates producing CTX-M. AmpC was uncommon, seen in 5% of the isolates (6/115). Among the carbapenemases co-expression of blaNDM and blaOXA48-like was observed in 28% (32/115) and blaNDM in 19% (22/115) and blaOXA48-like in 13% (15/115). blaKPC was absent. Overall mortality was observed to be 57% (64/113) and mortality among CR K. pneumoniae (Kp) was 68% (50/73). The antibiotics that were administered for treatment of CRKp were colistin in 90% (66/73) and tigecycline in 7% (5/73) and in 99% combined with meropenem (72/73). Prevalence of community acquired and nosocomial infections were 5% (4/73) and 95% (69/73) respectively among CRKp. Minocycline and meropenem susceptibilities were comparable and hence minocycline can be a carbapenem sparing agent. The resistance to β-lactam antibiotics is steadily increasing and are plasmid mediated, their containment in healthcare setting is a challenge.

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          Development of a set of multiplex PCR assays for the detection of genes encoding important beta-lactamases in Enterobacteriaceae.

          To develop a rapid and reliable tool to detect by multiplex PCR assays the most frequently widespread beta-lactamase genes encoding the OXA-1-like broad-spectrum beta-lactamases, extended-spectrum beta-lactamases (ESBLs), plasmid-mediated AmpC beta-lactamases and class A, B and D carbapenemases. Following the design of a specific group of primers and optimization using control strains, a set of six multiplex PCRs and one simplex PCR was created. An evaluation of the set was performed using a collection of 31 Enterobacteriaceae strains isolated from clinical specimens showing a resistance phenotype towards broad-spectrum cephalosporins and/or cephamycins and/or carbapenems. Direct sequencing from PCR products was subsequently carried out to identify beta-lactamase genes. Under optimized conditions, all positive controls confirmed the specificity of group-specific PCR primers. Except for the detection of carbapenemase genes, multiplex and simplex PCR assays were carried out using the same PCR conditions, allowing assays to be performed in a single run. Out of 31 isolates selected, 22 strains produced an ESBL, mostly CTX-M-15 but also CTX-M-1 and CTX-M-9, SHV-12, SHV-5, SHV-2, TEM-21, TEM-52 and a VEB-type ESBL, 6 strains produced a plasmid-mediated AmpC beta-lactamase (five DHA-1 and one CMY-2) and 3 strains produced both an ESBL (two SHV-12, one CTX-M-15) and a plasmid-mediated AmpC beta-lactamase (DHA-1). We report here the development of a useful method composed of a set of six multiplex PCRs and one simplex PCR for the rapid screening of the most frequently encountered beta-lactamases. This method allowed direct sequencing from the PCR products.
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            Outcomes of carbapenem-resistant Klebsiella pneumoniae infection and the impact of antimicrobial and adjunctive therapies.

            Carbapenem-resistant Klebsiella pneumoniae is an emerging healthcare-associated pathogen. To describe the epidemiology of and clinical outcomes associated with carbapenem-resistant K. pneumoniae infection and to identify risk factors associated with mortality among patients with this type of infection. Mount Sinai Hospital, a 1,171-bed tertiary care teaching hospital in New York City. Two matched case-control studies. In the first matched case-control study, case patients with carbapenem-resistant K. pneumoniae infection were compared with control patients with carbapenem-susceptible K. pneumoniae infection. In the second case-control study, patients who survived carbapenem-resistant K. pneumoniae infection were compared with those who did not survive, to identify risk factors associated with mortality among patients with carbapenem-resistant K. pneumoniae infection. There were 99 case patients and 99 control patients identified. Carbapenem-resistant K. pneumoniae infection was independently associated with recent organ or stem-cell transplantation (P=.008), receipt of mechanical ventilation (P=.04), longer length of stay before infection (P=.01), and exposure to cephalosporins (P=.02) and carbapenems (P<.001). Case patients were more likely than control patients to die during hospitalization (48% vs 20%; P<.001) and to die from infection (38% vs 12%; P<.001). Removal of the focus of infection (ie, debridement) was independently associated with patient survival (P=.002). The timely administration of antibiotics with in vitro activity against carbapenem-resistant K. pneumoniae was not associated with patient survival. Carbapenem-resistant K. pneumoniae infection is associated with numerous healthcare-related risk factors and with high mortality. The mortality rate associated with carbapenem-resistant K. pneumoniae infection and the limited antimicrobial options for treatment of carbapenem-resistant K. pneumoniae infection highlight the need for improved detection of carbapenem-resistant K. pneumoniae infection, identification of effective preventive measures, and development of novel agents with reliable clinical efficacy against carbapenem-resistant K. pneumoniae.
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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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                Author and article information

                Journal
                Pathogens and Global Health
                Pathogens and Global Health
                Informa UK Limited
                2047-7724
                2047-7732
                July 02 2017
                July 04 2017
                July 02 2017
                July 04 2017
                : 111
                : 5
                : 240-246
                Affiliations
                [1 ] Department of Clinical Microbiology, Christian Medical College, Vellore, India
                [2 ] Department of Medicine, Christian Medical College, Vellore, India
                Article
                10.1080/20477724.2017.1340128
                5560201
                28670975
                0958570b-871e-4d77-8fbd-ce68c9905419
                © 2017

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