Clearance of carbapenemase-producing Enterobacteriaceae (CPE) carriage: a comparative study of NDM-1 and KPC CPE

ObjectivesThe aim of this study was to compare clearance rates and related characteristics of patients carrying KPC-producing carbapenemase-producing Enterobacteriaceae (CPE) with those of patients carrying NDM-1-producing CPE.MethodsFrom November 2010 to October 2016, consecutive patients whose clinical or surveillance cultures yielded CPE were prospectively identified and followed in a 2700-bed tertiary referral hospital. CPE control protocols included strict single-room isolation, contact precautions and weekly surveillance cultures. CPE clearance was defined as three or more consecutive CPE-negative cultures without relapse. We compared patients carrying NDM-1 CPE and KPC and those with and without clearance. The time to CPE clearance or discharge was assessed using the Kaplan–Meier method and NDM-1 CPE and KPC CPE groups were compared.ResultsA total of 147 patients carrying CPE, 106 with NDM-1 and 41 with KPC, were included in the study. At the time of hospital discharge, 12 of the 106 patients carrying NDM-1 CPE were clear of CPE, whereas none of the KPC CPE patients were (NDM-1, 11.3% (12/106) versus KPC, 0% (0/41), p 0.02). There was no significant association between CPE clearance and factors such as an immunocompromised condition, antibiotic usage, or species of colonizing organism. Among 40 patients who were readmitted, CPE non-clearance was significantly higher in patients carrying KPC CPE (NDM-1, 36.7% (11/30) versus KPC, 80.0% (8/10), p 0.03).ConclusionsCompared with NDM-1 CPE patients, patients carrying KPC CPE had a significantly lower probability of clearance during hospitalization. Furthermore, KPC CPE carriage persisted for a substantial period of time following patient discharge.     

Mobile genetic elements associated with carbapenemase genes in South American Enterobacterales

IntroductionCarbapenem resistance in members of order Enterobacterales is a growing public health problem causing high mortality in developing and industrialized countries. Its emergence and rapid propagation worldwide was due to both intercontinental spread of pandemic strains and horizontal dissemination via mobile genetic elements (MGE) such as plasmids and transposons.ObjectiveTo describe MGE carrying carbapenem resistance genes in Enterobacterales which have been reported in South America.Search strategy and selection criteriaA search of the literature in English or Spanish published until 2019 in PubMed, Google Scholar, LILACS and SciELO databases was performed for studies of MGE in Enterobacterales reported in South American countries.ResultsSeven South American countries reported MGE related to carbapenemases. Carbapenemase-producing Klebsiella pneumoniae belonging to clonal complex 258 were the most prevalent pathogens reported; others carbapenemase-producing Enterobacterales such as Escherichia coli, Serratia marcescens, and Providencia rettgeri also have been reported. The MGE implicated in the spread of the most prevalent carbapenemase genes are Tn4401 and non-Tn4401 elements for bla_KPC and ISAba125 for bla_NDM, located in different plasmid incompatibility groups, i.e. L/M, A/C, FII and bacterial clones.ConclusionThis review indicates that, like in other parts of the world, the most commonly reported carbapenemases in Enterobacterales from South America are being disseminated through clones, plasmids, and transposons which have been previously reported in other parts of the world.     

耐碳青霉烯肠杆菌科细菌的流行病学特点以及抗生素应用策略

耐碳青霉烯肠杆菌科细菌(carbapenem-resistant Enterobacteriaceae, CRE)在全球范围内的快速增长和流行，直接影响临床治疗与患者预后，并给社会经济带来了严重负担。目前CRE临床治疗可供选择的药物有黏菌素、氨基糖苷类、替加环素和磷霉素等；美国食品药品监督局(FDA)批准的新药即头孢他啶/阿维巴坦(ceftazidime/avibactam, CAZ-AVI)、美罗培南/瓦博巴坦(meropenem/vaborbactam, MER-VAB)、亚胺培南/雷巴坦(imipenan/ribatan, AMI-LEI)和plazomicin也为CRE感染治疗提供了新的选择，但各类药物的治疗效果、新的耐药产生及不良反应各有不同，为优化临床治疗方案，提高治疗效果，本文对CRE的治疗药物的现状做一分析。     

What's new in the treatment of multidrug-resistant gram-negative infections?

Eradicating multi-drug resistant (MDR) organisms has been a major challenge in healthcare settings worldwide. Newly approved drugs and those currently in the pipeline may have a promising solution to this issue. The purposes of this review are to describe the various resistance mechanisms of Gram-negative bacteria and to provide a summary of the current literature available on the newer agents, such as ceftazidime/avibactam, ceftolozane/tazobactam, meropenem/vaborbactam, and other emerging agents used for the treatment of MDR Gram-negative infections. Given that MDR organisms confer resistance to treatment by various methods, including enzymatic degradation, efflux pumps, and porin mutation, an understanding of mechanisms of bacterial resistance combined with information on newer antimicrobial agents against MDR Gram-negative bacteria will further assist clinicians in determining the best suitable therapy for the treatment of various complicated infections.     

Osteomyelitis due to multiple carbapenemase-producing Gram-negative bacteria: The first case report of a GES-13-producing Pseudomonas aeruginosa isolate in Canada

A case of osteomyelitis in an infant following a burn injury sustained in Pakistan caused by a GES-13-producing Pseudomonas aeruginosa (the first reported in Canada) and an OXA-48 producing Klebsiella pneumoniae is described. The present case serves to highlight the importance of international travel as a risk factor for infection with carbapenemase-producing bacteria and the challenges in the laboratory detection of these organisms.     

Performance of the Rapidec®Carba NP assay for the detection of different carbapenemases in Klebsiella pneumoniae and Escherichia coli strains

PurposeThe spread of infections caused by Enterobacterales strains resistant to carbapenems is a global public health problem, and early detection of carbapenemases is very important to prevent their spread. The rapid detection of carbapenemase production with the new commercial assay Rapidec® Carba NP test is based on the biochemical detection of imipenem hydrolysis. Our study aims to evaluate the performance of the Rapidec® Carba NP test in OXA-48 positive isolates highly prevalent in our country and also in isolates with more than one carbapenemase gene that have an increased prevalence and to examine whether it can be used for confirmation of carbapenemase positivity in the routine laboratory.MethodsA total of 97 strains of 94 carbapenem-resistant Klebsiella pneumoniae and three carbapenem-resistant Escherichia coli isolated from various clinical specimens were included in the study. The results of the Rapidec® Carba NP assay were compared with those obtained by the multiplex PCR test.ResultsThe sensitivity of the Rapidec® Carba NP test was 97.8% for all carbapenemase-positive isolates. Of 90 PCR positive isolates, one OXA-48 and one OXA-48 ?+ ?NDM positive isolates were negative with Rapidec® Carba NP test.ConclusionsThe positive results detected by the Rapidec® Carba NP test make an important contribution to the early detection of carbapenemase production and infection control practices. Since two carbapenemase positive isolates were found to be negative with the Rapidec® Carba NP test in our study, it was concluded that negative results of carbapenem-resistant isolates obtained with this assay should be confirmed with an additional carbapenemase detection method to exclude false-negative results.     

耐碳青霉烯类鲍氏不动杆菌金属β-内酰胺酶检测与同源性分析

目的分析医院耐碳青霉烯类鲍氏不动杆菌(CRAB)产金属β-内酰胺酶及菌株间同源性。方法收集医院2012年8-12月临床分离的耐碳青霉烯类鲍氏不动杆菌共51株,用VITEK-2药敏分析系统进行药敏试验,用EDTA纸片协同试验筛查金属酶表型,PCR检测IMP、SIM-1、VIM、NDM-1型金属酶基因;重复序列聚合酶链反应(REP-PCR)方法分析菌株同源性。结果 51株CRAB对多种抗菌药物耐药,EDTA纸片协同试验检测金属酶仅有1株阳性,阳性率1.96%,51株CRAB经PCR检测后仅有1株携带了NDM-1型基因,未检测出IMP、SIM-1、VIM型基因;用REP-PCR法可将51株CRAB分为4个基因型(A-F),其中A型48株,占94.12%,为主要流行株;B、C、D各有1株。结论该院临床分离的CRAB株存在NDM-1型金属酶,REP-PCR法分析CRAB同源性,提示该院CRAB存在水平克隆传播,A型主要流行株。     

Comparison of clinical outcomes of patients infected with KPC- and NDM-producing Enterobacterales: a retrospective cohort study

ObjectivesWe aimed to compare clinical outcomes of patients with Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales and those with New Delhi metallo-β-lactamase (NDM)-producing Enterobacterales.MethodsWe performed a retrospective cohort study of all adult patients with KPC- or NDM-producing Enterobacterales isolates in a 2700-bed tertiary referral hospital in Seoul, South Korea, between 2010 and 2019. The primary outcome was 30-day mortality after first isolation of KPC- or NDM-producing Enterobacterales. The secondary outcome was the development of infection within 30 days by the colonizing isolates, among colonized patients. We performed Cox regression analysis for 30-day mortality and competing risk analysis for development of infection.ResultsA total of 859 patients were identified during the study period; 475 (55%) had KPC and 384 (45%) had NDM. Thirty-day mortality was significantly higher in the KPC group than in the NDM group (17% (81/475) vs 9% (33/384); p < 0.001). The KPC group developed infection within 30 days from the initial colonization after first isolation more frequently than the NDM group (8% (27/353) vs. 3% (10/295); p 0.02). Multivariable analysis revealed that independent risk factors for 30-day mortality were solid cancer (adjusted hazard ratio (aHR) 2.51; 95% confidence interval (CI) 1.66–3.79; p < 0.001), solid organ transplant (aHR 0.32; 95% CI 0.17–0.61; p < 0.001), a high APACHE II score (aHR 1.11; 95% CI 1.08–1.13; p < 0.001), KPC-producing Enterobacterales (aHR 1.69; 95% CI 1.02–2.79; p 0.04), previous carbapenem use within 3 months (aHR 1.86; 95% CI 1.26–2.75; p < 0.001) and site of KPC- or NDM-producing Enterobacterales infection at the time of the first culture (p < 0.001).DiscussionOur study suggests that KPC-producing Enterobacterales is significantly associated with poorer outcomes than NDM-producing Enterobacterales.