Treatment Of Carbapenem-resistant Enterobacteriaceae Research Articles

In-vitro synergistic activity of colistin and meropenem against clinical isolates of carbapenem resistant E.coli and Klebsiella pneumoniae by checkerboard method

ContextThe emergence of drug resistant pathogens pose major threat to hospitalized patients as well as to the community associated with increased mortality and morbidity. The treatment of carbapenem resistant enterobacteriaceae, one of the top WHO priority pathogen remains a global issue. Combination therapy with different classes of antibiotics have been tried with the aim to reduce toxicity, to increase the efficacy of the drugs and to reduce resistance. The in-vitro synergy methods have to be carried out to determine whether the combination of those antibiotics are synergistic, antagonistic or additive. AimsWe have performed in-vitro synergy testing by checkerboard method for colistin -meropenem combination to determine whether the combination of the two antibiotics were synergistic or antagonistic. Methods and materialAll the consecutive twenty five blood isolates of Escherichia coli and twenty five blood isolates of Klebsiella pneumoniae which were showing resistance to carbapenems by either disc diffusion or vitek 2 were collected over a period of 6 months and checkerboard method was performed. Statistical analysis usedThe reduction of MIC of colisin on combination with meropenem compared to MIC of colistin alone is analyzed by McNemar's chisquare test with the help of software Stata version 14 and p value < 0.05 is considered as significant. Results56% of K. pneumoniae showed synergy and 44% showed additive/indifference results. For E. coli 40% showed synergy and 60% showed additive/indifference. None of the isolates of E. coli and K. pneumoniae showed antagonism. There was more than two fold reduction in MIC of colistin (significant) on combining withmeropenem. ConclusionsThe study results support the combination therapy to treat infections by multi-drug-resistant Klebsiela pneumoniae and Escherichia coli by in-vitro checkerboard testing method which inturn will be helpful for clinicians for judicious use of antimicrobials.

Clinical characteristics of carbapenem-resistant Enterobacteriaceae infection in pediatric liver transplantation recipients

Objective: To explore the clinical features and treatment of carbapenem-resistant Enterobacteriaceae (CRE) infection in pediatric liver transplantation recipients and discuss the significance of CRE colonization by screening with rectal swabs. Methods: A total of 286 cases of pediatic liver transplantation recipients, who came from Tianjin First Central Hospital during August 1,2017 to August 1, 2018, were retrospectively investigated. The clinical characteristics, antibiotic susceptibity test, treatment outcomes and prognosis of CRE infection patients were analyzed. CRE colonization were screened by rectal swabs after liver transplantation. All cases were divided into CRE colonization group and non-CRE colonization group based on CRE colonization results. The high risk factors of CRE colonization and its relationship with CRE infection were investigated. χ(2) test was used for the comparison between groups.The single-factor analysis was used to screen risk factors. Results: The 286 cases included 132 male and 154 female cases. The age was (8±4) months.CRE infection rate after liver transplantation was 7.3% (21/286). The time of CRE infection was the 5(th) (1(th)-14(th)) days after transplantation. Abdominal infection was the most common (95.2%, 20/21), followed by bloodstream infection (12 cases) and pulmonary infection (8 cases). Infection in two or more sites accounted for 71.4% (15/21); 27 CRE strains, in which 24 strains were carbapenem-resistant Klebsiella pneumonia (88.9%), 2 strains were carbapenem-resistant Escherichia coli (7.4%) and one strain was carbapenem-resistant Enterobacter aerogenes (3.7%). The drug resistance rate of CRE strains to carbapenems, penicillin antibiotics, second-and third-generation cephalosporin was 100.0%. Medication treatment included meropenem+fosfomycin (13 cases) and meropenem+tegacycline (8 cases). The treatment was effective in 16 cases and the time was 19 (1-27) d. The 1-year survival rate among CRE infection group and non-CRE infection group were 71.4% (15/21) and 98.1% (260/265), respectively (χ(2)=37.460, P<0.01). CRE infection rate among CRE colonization group and non-CRE colonization group were 26.4% (19/72) and 0.9% (2/214), respectively (χ(2)=51.300, P<0.01). Factors before transplantation, including third-generation cephalosporin or carbapenems exposure, prolonged hospital stay within 3 months, CRE infection, and factors after transplantation, including emergency surgery, mechanical ventilation more than 24 hours (χ(2)=20.570, 6.411, 13.960, 14.600, 9.560, all P<0.01) were high risk factors for CRE colonization. Conclusions: The prognosis of CRE infection after pediatric liver transplantation is poor. Timely diagnosis and treatment are of great importance. Much attention should be paid on CRE rectal colonization and its risk factors. Screening of CRE colonization is important for early warning and control of CRE infection.

Emergence of a Plasmid-Encoded Resistance-Nodulation-Division Efflux Pump Conferring Resistance to Multiple Drugs, Including Tigecycline, in Klebsiella pneumoniae.

Transporters belonging to the chromosomally encoded resistance-nodulation-division (RND) superfamily mediate multidrug resistance in Gram-negative bacteria. However, the cotransfer of large gene clusters encoding RND-type pumps from the chromosome to a plasmid appears infrequent, and no plasmid-mediated RND efflux pump gene cluster has yet been found to confer resistance to tigecycline. Here, we identified a novel RND efflux pump gene cluster, designated tmexCD1-toprJ1, on plasmids from five pandrug-resistant Klebsiella pneumoniae isolates of animal origin. TMexCD1-TOprJ1 increased (by 4- to 32-fold) the MICs of tetracyclines (including tigecycline and eravacycline), quinolones, cephalosporins, and aminoglycosides for K.pneumoniae, Escherichia coli, and Salmonella TMexCD1-TOprJ1 is closely related (64.5% to 77.8% amino acid identity) to the MexCD-OprJ efflux pump encoded on the chromosome of Pseudomonas aeruginosa In an IncFIA plasmid, pHNAH8I, the tmexCD1-toprJ1 gene cluster lies adjacent to two genes encoding site-specific integrases, which may have been responsible for its acquisition. Expression of TMexCD1-TOprJ1 in E. coli resulted in increased tigecycline efflux and in K. pneumoniae negated the efficacy of tigecycline in an in vivo infection model. Expression of TMexCD1-TOprJ1 reduced the growth of E. coli and Salmonella but not K. pneumoniaetmexCD1-toprJ1-positive Enterobacteriaceae isolates were rare in humans (0.08%) but more common in chicken fecal (14.3%) and retail meat (3.4%) samples. Plasmid-borne tmexCD1-toprJ1-like gene clusters were identified in sequences in GenBank from Enterobacteriaceae and Pseudomonas strains from multiple continents. The possibility of further global dissemination of the tmexCD1-toprJ1 gene cluster and its analogues in Enterobacteriaceae via plasmids may be an important consideration for public health planning.IMPORTANCE In an era of increasing concerns about antimicrobial resistance, tigecycline is likely to have a critically important role in the treatment of carbapenem-resistant Enterobacteriaceae, the most problematic pathogens in human clinical settings-especially carbapenem-resistant K.pneumoniae Here, we identified a new plasmid-borne RND-type tigecycline resistance determinant, TMexCD1-TOprJ1, which is widespread among K. pneumoniae isolates from food animals. tmexCD1-toprJ1 appears to have originated from the chromosome of a Pseudomonas species and may have been transferred onto plasmids by adjacent site-specific integrases. Although tmexCD1-toprJ1 still appears to be rare in human clinical isolates, considering the transferability of the tmexCD1-toprJ1 gene cluster and the broad substrate spectrum of TMexCD1-TOprJ1, further dissemination of this mobile tigecycline resistance determinant is possible. Therefore, from a "One Health" perspective, measures are urgently needed to monitor and control its further spread. The current low prevalence in human clinical isolates provides a precious time window to design and implement measures to tackle this.

Polymyxin B and colistin—the economic burden of nephrotoxicity against multidrug resistant bacteria

Background: Polymyxin B and colistin are nephrotoxic drugs used in the treatment of carbapenem-resistant Enterobacteriaceae. The aim of this study is to evaluate the burden of costs due to polymyxin associated AKI and propose a simulated break-even price for new therapies.Methods: The pharmacoeconomic model is based on two large cross-sectional studies of polymyxin nephrotoxicity. Total direct costs in patients with and without renal failure were compared. The direct cost of each hemodialysis section (USD82.94) and daily hospital charges (USD934.85) were based on the values used in a major public hospital in the city where the clinical study was performed. The break-even price of new drugs was simulated considering eventual new drugs as effective as polymyxins, but less nephrotoxic in different percentages. Outcomes of patients after hospital discharge were not evaluated.Results: Total direct cost of the group of patients who survived without AKI was significantly lower than total direct cost of the groups either with AKI or the group who died without AKI. There was a tendency of even higher costs in those who died with AKI and dialysis. Direct cost of hemodialysis was not as important as the longer hospitalization after sepsis. Considering daily cost of polymyxin is USD60, drugs with 50% less AKI could be considered cost-beneficial if the daily cost is lower than USD160.Conclusions: AKI in patients with carbapenem-resistant Enterobacteriaceae treated with polymyxin increases both length of stay in hospital and total costs.