Emergence Of Carbapenem-resistant Enterobacteriaceae Research Articles

Management of Carbapenem-Resistant Enterobacteriaceae Bloodstream Infections: An Experience from a Tertiary Care Centre in Oman

The emergence of Carbapenem-resistant Enterobacteriaceae (CRE)is a public health concern worldwide. It is associated with increased mortality due to limited antibiotics available to treat CRE infections. The aim of this study was to understand the epidemiology of CRE infections, associated mortality, and available treatment options. All patients with CRE isolated in blood culture were identified between December 2011 and October 2019. Risk factors and mortality associated with each risk factor at 14 and 30 days were determined.55 cases of CRE bloodstream infections were isolated, with a median age of 56 years. Eighty-four percent of patients received treatment in the ICU. All cases were caused by Klebsiella pneumonia. The rate of resistance to the tested antibiotics was as follows: meropenem 92% (50/54), imipenem 75% (40/53), etrapenam 95% (19/20), Amikacin 71% (37/52), cotrimoxazole 73% (40/53), Gentamicin 47% (25/53) and colistin 7% (3/41). Major risk factors associated were the presence of a urinary catheter (84%), central venous catheter (78%), mechanical ventilation (74%) and post-surgery (67%). Mortality at 14 days and 30 days was 41%, and 52%, respectively. Univariate analysis showed that 14 days mortality was higher in patients with central venous catheter (P=0.01). Charlson's comorbidity index was associated with an increased risk of death at 30 days (P=0.04). There was no statistically increased survival in those treated with combination therapy at 30 days (P=0.5). The mortality of CRE infections seems to be high and optimal therapy is not yet well defined. Combination therapy is not associated with increased survival in this cohort of patients.

Carbapenem-resistant Enterobacteriaceae infection in children less than one year old in an Asian medical center.

The emergence of carbapenem-resistant Enterobacteriaceae (CRE) is a threat to public health worldwide. This study aimed to determine the risk factors and outcomes for CRE colonization and infection in infants. Children aged <1 year hospitalized with CRE pathogens isolated from January 2016 to June 2019 were retrospectively analyzed. Demographic and clinical data were examined. A total of 48 infections were identified in 70 infants aged <1 year, and 66.7% (32/48) of these infants were born preterm. The infection rate in infants aged <1 month was higher than that of others (P=0.005). The most commonly isolated CRE was Klebsiella pneumoniae (60.4%, 29/48), followed by Enterobacter cloacae complex (18.8%, 9/48). Sputum (37.5%, 18/48), blood (27.1%, 13/48), and urine (25.0%, 12/48) were the most common clinical samples. Urinary tract infection was common in infants aged 6-12 months. CRE infection was associated with mechanical ventilation (P=0.037), central venous catheter (CVC) insertion (P=0.034), and congenital heart disease (P=0.027). The hospital stay of patients with CRE infection was longer (median, 75 days; SD, 66.4 days), and their all-cause mortality (6.4%) was higher than those with colonization. CRE infection was common in infants aged <1 month, and patients usually had longer hospitalization. Carbapenemase production was not common. Mechanical ventilation, CVC insertion, and congenital heart disease were associated with a higher risk of CRE acquisition in infants aged <1 year.

The Predominance of Klebsiella aerogenes among Carbapenem-Resistant Enterobacteriaceae Infections in Japan.

The emergence of carbapenem-resistant Enterobacteriaceae (CRE) is an important public health issue worldwide, not only due to the potential of these pathogens for widespread dissemination, but also due to the limited antimicrobial therapy options, and the elevated mortality rates associated with these infections. As with other multidrug-resistant organisms (MDROs), active surveillance via timely testing, early diagnosis, and contact isolation is an important strategy to control the occurrence and spread of CRE bacteria. Here we summarize the epidemiology of CRE infections in Japan from 2015 to 2019. Data were extracted from a public dataset collected by the nationwide surveillance system via the National Institute of Infectious Diseases (NIID) of Japan. The annual number of reported CRE infections has remained relatively stable, with a tendency to increase in the last two years (1671 cases reported in 2015 and 2333 cases reported in 2019). The majority of patients who presented CRE infections over this five year period were older than 65 years (~80%, mean age 75), 60% of them were men, and mortality rates were around 3.5%. Importantly, about 60% of infections are caused by both Enterobacter cloacae and Klebsiella aerogenes (previously known as Enterobacter aerogenes), the former being the most common pathogen in 2015 and 2016 (~30%), and the latter the leading pathogen since 2017 (~40%). The most common carbapenemase isolated was the IMP carbapenemase type. Further studies are needed to determine the prevalence of CRE colonization, especially in the healthcare setting, and to elucidate the mechanisms behind the local predominance of Klebsiella aerogenes and Enterobacter cloacae.

Detection of intestinal colonization by carbapenem-resistant Enterobacteriaceae (CRE) among patients admitted to a tertiary care hospital in Egypt

BackgroundThe irrational use of carbapenems in the last years lead to the emergence of carbapenem-resistant Enterobacteriaceae (CRE). This study aimed at determining the prevalence of CRE intestinal carriage among admitted patients in a tertiary care hospital in Egypt, to characterize carbapenemase-producing genes and to identify possible risk factors of CRE colonization. One hundred rectal swabs were collected from patients within 48 h of hospital admission. Culture was done on chromogenic media and then identification and antibiotic susceptibility testing were done using Vitek 2 compact system. Carbapenemase production was confirmed by Rapidec Carba NP test and by multiplex PCR for blaOXA-48-like, blaNDM-like, blaVIM-like, blaIMP-like and blaKPC-like.ResultsA total number of 36 CRE isolates were recovered from 28 patients. Thus, the prevalence of CRE colonization was 28%. Escherichia coli (83%), followed by Klebsiella pneumoniae (17%) were the main species. History of recent hospitalization and prior antibiotic intake were statistically significant risk factors predisposing to CRE colonization. Rapidec Carba NP gave positive results in 29/36 CRE isolates, whereas seven isolates gave negative results; six of them harbored blaOXA-48-like. Overall, the blaOXA-48-like was detected in 24/36 (66.7%), followed by blaNDM-like in 11/36 (30.6%) and lastly blaVIM-like in 1/36 (2.8%).ConclusionsOur findings confirm that CRE colonization is disseminating in our healthcare facility, a fact that should be considered as possible pathogens causing infections in high risk patients. Strict infection control measures should be applied to all CRE carriers at hospital admission and a proper antimicrobial stewardship program should be followed in clinical settings.

Changing Patterns of Causative Pathogens over Time and Efficacy of Empirical Antibiotic Therapies in Acute Cholangitis with Bacteremia.

To select appropriate empirical antibiotics, updates on the changes in pathogens are essential. We aimed to investigate the changes in pathogens and their antibiotic susceptibility in acute cholangitis (AC) with bacteremia over a period of 15 years. Furthermore, the efficacy of empirical antibiotic therapies and the risk factors predicting antibiotic-resistant pathogens (ARPs) were analyzed. A total of 568 patients with AC and bacteremia who were admitted to Daegu Catholic University Medical Center from January 2006 to December 2020 were included. Their medical records were retrospectively reviewed. In addition, the data were grouped and analyzed at 3-year intervals under the criteria of Tokyo Guideline 2018. During the study period, 596 pathogens were isolated from blood cultures of 568 patients. The three most common pathogens were Escherichia coli (50.5%), Klebsiella species (24.5%), and Enterococcus species (8.1%). The proportion of vancomycin-resistant Enterococci (VRE) has increased since the mid-2010 (0.0% to 4.3%, p=0.007). There was emergence of carbapenem-resistant Enterobacteriaceae (CRE) in 2018 to 2020, albeit not statistically significant (1.3%, p=0.096). Risk factors predicting ARP were healthcare-associated infection, history of previous biliary intervention, and the severity of AC. For patients with these aforementioned risk factors, imipenem was the most effective antibiotic and piperacillin-tazobactam was also effective but to a lesser degree (susceptibility rates of 92.1% and 75.0%, respectively). The proportion of VRE has increased and CRE has emerged in AC. In addition, healthcare-associated infection, history of previous biliary intervention, and the severity of AC were independent risk factors predicting ARP. For patients with these risk factors, the administration of imipenem or piperacillin-tazobactam should be considered.

Phylogenetically Diverse Escherichia coli Strains from Chicken Coharbor Multiple Carbapenemase-Encoding Genes (bla NDM -bla OXA-blaIMP).

Carbapenem-resistant Enterobacteriaceae (CRE) has been a public health risk in several countries, and recent reports indicate the emergence of CRE in food animals. This study was conducted to investigate the occurrence, resistance patterns, and phylogenetic diversity of carbapenem-resistant E. coli (CREC) from chicken. Routine bacteriology, PCR detection of E. coli species, multiplex PCR to detect carbapenemase-encoding genes, and phylogeny of CRE E. coli were conducted. The results show that 24.36% (19/78) were identified as CREC based on the phenotypic identifications of which 17 were positive for the tested carbapenemases genes. The majority, 57.99% (11/19), of the isolates harbored multiple carbapenemase genes. Four isolates harbored all blaNDM, blaOXA, and blaIMP, and five and two different isolates harbored blaNDM and blaOXA and blaOXA and blaIMP, respectively. The meropenem, imipenem, and ertapenem MIC values for the isolates ranged from 2 μg/mL to ≥256 μg/mL. Phylogenetic grouping showed that the CREC isolates belonged to five different groups: groups A, B1, C, D, and unknown. The detection of CREC in this study shows that it has become an emerging problem in farm animals, particularly, in poultry farms. This also implies the potential public health risks posed by CRE from chicken to the consumers.

Coexistence of two blaCTX-M-14 genes in a blaNDM-5-carrying multidrug-resistant Escherichia coli strain recovered from a bloodstream infection in China

The emergence of carbapenem-resistant Enterobacteriaceae has become a serious public-health threat. Here we report the complete genome sequence of a multidrug-resistant (MDR) Escherichia coli carrying blaNDM-5 and two copies of blaCTX-M-14 recovered from a bloodstream infection in China. Whole-genome sequencing of E. coli strain 2D was performed both using Oxford Nanopore MinION and Illumina NovaSeq 6000 platforms. De novo hybrid assembly of short Illumina reads and long MinION reads was performed using Unicycler. In silico multilocus sequence typing (MLST), antimicrobial resistance genes and plasmid replicons were identified from the genome sequence. Core genome MLST (cgMLST) analysis between E. coli 2D and all ST354 E. coli strains retrieved from the NCBI GenBank database was performed using BacWGSTdb 2.0 server. The complete genome sequence of E. coli 2D consists of six contigs comprising 5 363 300 bp, including one chromosome and five plasmids, and was assigned to ST354. Six antimicrobial resistance genes were identified, including blaNDM-5 located in a 46 161-bp IncX3 plasmid and two copies of the blaCTX-M-14 gene located both in the chromosome and in a 96 499-bp IncB plasmid. The closest relative of E. coli 2D was another isolate recovered from Lebanon, which differed by 162 cgMLST loci. This study reports the first genome sequence of a MDR E. coli carrying blaNDM-5 and two copies of blaCTX-M-14 in China. These data may help to understand the antimicrobial resistance mechanisms and transmission dynamics of carbapenem-resistant Enterobacteriaceae in clinical settings.

Effect of Mushroom against Extended Spectrum Beta Lactamase (ESBL) Producing Microorganisms

According to the WHO global report, ESBL (Extended-Spectrum Beta-Lactamase)-producing microorganisms is the most common cause of urinary tract infection; hospital-acquired infection as well as a foodborne infection. These include Escherichia coli, Salmonella, Shigella and Vibrio cholera. The carbapenems which include doripenem, ertapenem, imipenem and meropenem are the known choice of medication for life-threatening infections which is caused by ESBL-producing microorganisms. Recently there is the emergence of carbapenem-resistant Enterobacteriaceae and Pseudomonas which makes treatment an obstacle for the medical personnel for various infections. Natural products have been reported to be emerged as a potential possibility to be explored as antimicrobial drugs. The plant extracts could serve as an alternate source of resistance modifying agents owing to the wide variety of secondary metabolites (eg. flavonoids, phenols, tannins, alkaloids, etc). Mushroom are have been considered as a source that attracts the researchers to explore its properties as it has been established with various bioactive components that possess many health beneficial effects such as antimicrobial and antifungal compounds. In this paper, we summarizes the information available in the literature on the ESBL, mushroom and current treatment, with a special focus on the three different types of mushrooms (Fistulina hepatica, Leucopaxillus giganteus and Pleurotus Ostreatus) against spectrum beta-lactamase (ESBL) producing microorganisms. Electronic databases including SciFinder, Web of Science, Science Direct, PubMed, and Google Scholar were screened using the following keywords: “antibacterial, antimicrobial, mushroom, ESBL, Enterobacter, Fistulina hepatica, Leucopaxillus giganteus and Pleurotus Ostreatus”. We intend to enhance understanding in the field and promote further work on the development of phytocomponent based antimicrobial compounds.

Six-year trends of resistance characteristics in carbapenem-resistant Klebsiella pneumoniae isolated from Malaysia

Background: The emergence of carbapenem-resistant Enterobacteriaceae (CRE) has been labelled as a “Global threat” and Klebsiella pneumoniae remains the most common CRE species encountered in many parts of the world including Malaysia. Resistant to carbapenem is mainly caused by the production of carbapenemases; however, non-carbapenemase-producing CRKP (NCP-CRKP) have also been reported in many part of the world. In this study, we aimed to determine the trends of genotypic and phenotypic characteristics of CRKP isolated from a tertiary teaching hospital within a 6-year period. Methods and materials: A total of 312 CRKP isolated from April 2013 to March 2019 were included in this study. The isolates were subjected to broth microdilution for the determination of the minimum inhibitory concentration of carbapenems. Pulsed field gel electrophoresis (PFGE) were performed to determine the genetic linkage among the isolates and the presence of carbapenemase genes such as blaKPC, blaNDM, blaIMP, blaVIM and blaOXA-48 variants were determined using PCR and sequencing. Results: Overall, PFGE analysis showed great genetic diversity among the isolates. The number of CRKP peaked in 2015 and a few episodes of potential transmissions have been observed based on the genotyping analysis. The isolates collected in 2015 also showed high level of resistance to imipenem and meropenem (> MIC 32 mg/L). A unique trend in the distribution of carbapenemase genes throughout the 6-year period have been observed with blaNDM and blaOXA-48 variants remained the two major carbapenemase detected. In addition, co-existence of carbapenemase genes in CRKP and an increase of NCP-CRKP have also been observed. In general, all the NCP-CRKP collected from 2013–2019 were ESBL-producer and majority of them were resistant to many agents of cephalosporins. Deletion or alteration of porins among the isolates has been investigated; however, only minority of the isolates showed the deletion of outer membrane proteins (OMPs). Conclusion: This study indicated the genetic events which might have been contributed to clone emergence and adaptation to the hospital environment. The significant rise in NCP-CRKP is worrying and could be associated with heterogeneous mechanisms due to antibiotic exposure and selection.

Emergence of Carbapenem-Resistant Enterobacteriaceae in a Tertiary Care Hospital in Southern Thailand†

Carbapenem-resistant Enterobacteriaceae (CRE) is emerging as a major problem in healthcare settings globally, including Thailand, due to limited therapeutic options. We reported the detection, antimicrobial susceptibility profiles, and the presence of carbapenemase genes of CRE isolates obtained from Songklanagarind Hospital between July 2012 and June 2015. A total of 273 non-duplicated CRE isolates was recovered from 248 patients. The predominant organism was Klebsiella pneumoniae (183 [67.0 %]), followed by Escherichia coli (38 [13.9 %]). The susceptibility to 13 antibiotics was performed by disk diffusion assay. Most of the CRE isolates remained susceptible to amikacin. Minimum inhibitory concentrations (MIC) of carbapenems were determined by E-test. The MIC50 and MIC90 were varied among genera and species. Multiplex PCRs for the carbapenemase genes blaIMP, blaVIM, blaOXA-48, blaNDM-1, blaKPC, and blaGES were performed. One hundred and seventy-eight out of these 273 CRE isolates (65.2 %) harbored either single or multiple carbapenemase genes. One hundred and fifty nine isolates harbored the blaNDM-1 gene (113 K. pneumoniae, 25 E. coli, 17 E. cloacae, 2 Citrobacter freundii, 1 Enterobacter aerogenes, and 1 Pantoea agglomerans), 7 isolates carried blaIMP (4 K. pneumoniae, 2 C. freundii, and 1 E. cloacae), 7 isolates possessed blaOXA-48 (1 K. pneumoniae, 5 E. coli, and 1 E. aerogenes), whereas 3 and 2 isolates harbored blaNDM-1 and blaIMP (2 K. pneumoniae and 1 E. cloacae) and blaNDM-1 and blaOXA-48 (1 E. coli and 1 E. cloacae), respectively. In conclusion, this study revealed the detection of CRE, with the majority of K. pneumoniae harboring blaNDM-1 in this setting.

Molecular Epidemiology of Carbapenemases in Enterobacteriales from Humans, Animals, Food and the Environment.

The Enterobacteriales order consists of seven families including Enterobacteriaceae, Erwiniaceae, Pectobacteriaceae, Yersiniaceae, Hafniaceae, Morganellaceae, and Budviciaceae and 60 genera encompassing over 250 species. The Enterobacteriaceae is currently considered as the most taxonomically diverse among all seven recognized families. The emergence of carbapenem resistance (CR) in Enterobacteriaceae caused by hydrolytic enzymes called carbapenemases has become a major concern worldwide. Carbapenem-resistant Enterobacteriaceae (CRE) isolates have been reported not only in nosocomial and community-acquired pathogens but also in food-producing animals, companion animals, and the environment. The reported carbapenemases in Enterobacteriaceae from different sources belong to the Ambler class A (blaKPC), class B (blaIMP, blaVIM, blaNDM), and class D (blaOXA-48) β-lactamases. The carbapenem encoding genes are often located on plasmids or associated with various mobile genetic elements (MGEs) like transposons and integrons, which contribute significantly to their spread. These genes are most of the time associated with other antimicrobial resistance genes such as other β-lactamases, as well as aminoglycosides and fluoroquinolones resistance genes leading to multidrug resistance phenotypes. Control strategies to prevent infections due to CRE and their dissemination in human, animal and food have become necessary. Several factors involved in the emergence of CRE have been described. This review mainly focuses on the molecular epidemiology of carbapenemases in members of Enterobacteriaceae family from humans, animals, food and the environment.

An Outbreak of New Delhi Metallo--Lactamase-5 (blaNDM-5)–Producing Escherichia coli in Companion Animals in the United States

Background: The emergence of carbapenem-resistant Enterobacteriaceae (CRE) in companion animals will be a game changer for infection prevention and control strategies in veterinary and human healthcare facilities. CRE have emerged as an important cause of human healthcare-associated infections and are a major clinical and public health problem. Although reports of CRE from animals are still very rare, they have been documented in China, Europe, and the United States. Methods: In April 2019, a passive veterinary surveillance system identified the blaNDM-5 gene in an E. coli isolated from a dog in Philadelphia in July 2018. CRE are reportable to the Philadelphia Department of Public Health (PDPH), and in May 2019, the Matthew J. Ryan Veterinary Hospital at the University of Pennsylvania (MJRVH) reported a cluster of carbapenem-resistant E. coli (CR-E. coli) isolated from 14 animals to the PDHP. This cluster of 17 isolates, that all contained a blaNDM-5 gene, was the first report of a CR-E. coli outbreak at a US veterinary facility. The first isolate, E. coli 24213-18, was sequenced on the Pacific Biosciences (PacBio) Sequel Sequencer and has been uploaded to GenBank. Whole genome sequencing was performed on all 17 isolates using the Illumina MiSeq platform. Antimicrobial resistance genes were identified from the National Center for Biotechnology Information Pathogen Detection Isolates Browser using AMRFinder. Results: PacBio sequencing confirmed E. coli ST167 and identified a circular IncFII plasmid of 139,547 bp that contained the blaNDM-5 gene, along with many additional resistance genes. In June 2019, a retrospective review of hospital records was completed and showed that, from July 2018, 17 CR- E. coli were isolated from 14 animals. Conclusions: Control of CRE infections in human healthcare settings is challenging because the organisms colonize the gastrointestinal tract and can go undetected. The same issue is to be expected with companion animals. Healthcare-associated spread of CRE E. coli in a veterinary facility emphasizes the importance of rapidly identifying and characterizing carbapenem-resistant isolates from animals. Methods to control the spread of CRE in veterinary medical settings have not yet been studied, and related investigations will be critically important to limit the transmission of these pathogens in animal populations. The risk of transmission of CRE from animals to people is currently poorly understood. CRE will be a major challenge across all health fields as these organisms become more prevalent in the community. It is likely that a ‘One Health’ approach to surveillance, infection prevention, and antimicrobial stewardship will be required to limit the spread and potential global dominance of CRE.Funding: NoneDisclosures: None

Treatment of Multi-Drug Resistant Gram-Negative Bacterial Pathogenic Infections

The multidrug-resistant Gram-negative bacteria (MDR-GNB) infections in severely infected patients present numerous difficulties in terms of treatment failure where antibiotics cannot arrest such drug resistant bacteria. Based on the patient’s medical history and updated microbiological epidemiology data, an effective empirical treatment remains critical for optimal results to safeguard human health. The aim of this manuscript is to review management of MDR-Gram negative pathogenic bacterial infections. Quick diagnosis and narrow antimicrobial spectrum require rapid and timely diagnosis and effective laboratories in accordance with antimicrobial stewardship (AS) principles. Worldwide, there is an increased emergence of Carbapenem-resistant Enterobacteriaceae (CRE), Pseudomonas aeruginosa, and Acinetobacter baumannii. Recently, novel therapeutic options, such as meropenem/vaborbactam, ceftazidime/avibactam, ceftolozane/tazobactam, eravacycline and plazomicin became accessible to effectively counteract severe infections. Optimally using these delays the emergence of resistance to novel therapeutic agents. Further study is required, however, due to uncertainties in pharmacokinetic/pharmacodynamics optimization of dosages and therapeutic duration in severely ill patients. The novel agents should be verified for (i) action on carbapenem resistant Acinetobacter baumannii; (ii) action on CRE of β-lactam/β-lactamase inhibitors dependence on type of carbapenemase; (iii) emergence of resistance to novel antibacterials and dismiss selective pressure promoting development of resistance. Alternative treatments should be approached alike phage therapy or antibacterial peptides. The choice of empirical therapy is complicated by antibiotic resistance and can be combated by accurate antibiotic and their combinations usage, which is critical to patient survival. Noteworthy are local epidemiology, effective teamwork and antibiotic stewardship to guarantee that medications are utilized properly to counter the resistance.

The in vitro activity of polymyxin B and tigecycline alone and combination with other antibiotics against carbapenem-resistant Enterobacter cloacae complex isolates, including high-risk clones.

The emergence of carbapenem-resistant Enterobacteriaceae (CRE) has become a significant problem for global public health. Currently, treatments program is minimal. This study aimed to evaluate the molecular mechanisms of carbapenem-resistant Enterobacter cloacae complex isolates (CREC) infections. Methods: Resistance genes were detected using PCR with specific primers. Multilocus sequence typing (MLST) was also performed. Furthermore, we evaluated the effects of polymyxin B (PMB) and tigecycline (TGC) antibiotics (Abs) alone and in combination with meropenem (MEM), amikacin (AMK), and levofloxacin (LEV) against CREC isolates. The results were then compared with in vitro synergy testing results obtained from time-kill assays (TKAs), and the microdilution checkerboard method. The synergistic efficiency of PMB + TGC was also evaluated. Abs use clinically achievable concentrations to determine the antibacterial effects of the Ab. Similar sequence type (ST) classifications had a comparably resistant phenotype; PMB-based combination therapy is better than TGC-based combination therapy. we found that the combination of PMB + AMK is promising for the treatment of AMK-sensitive CREC. The high-risk ST93 carrying the bla KPC-2 gene should be monitored.

A review of -multidrug-resistant Enterobacteriaceae in a neonatal unit in Johannesburg, South Africa

BackgroundMulti-drug resistant organisms are an increasingly important cause of neonatal sepsis.AimThis study aimed to review neonatal sepsis caused by multi-drug resistant Enterobacteriaceae (MDRE) in neonates in Johannesburg, South Africa.MethodsThis was a cross sectional retrospective review of MDRE in neonates admitted to a tertiary neonatal unit between 1 January 2013 and 31 December 2015.ResultsThere were 465 infections in 291 neonates. 68.6% were very low birth weight (< 1500 g). The median age of infection was 14.0 days. Risk factors for MDRE included prematurity (p = 0.01), lower birth weight (p = 0.04), maternal HIV infection (p = 0.02) and oxygen on day 28 (p < 0.001). The most common isolate was Klebsiella pneumoniae (66.2%). Total MDRE isolates increased from 0.39 per 1000 neonatal admissions in 2013 to 1.4 per 1000 neonatal admissions in 2015 (p < 0.001). There was an increase in carbapenem-resistant Enterobacteriaceae (CRE) from 2.6% in 2013 to 8.9% in 2015 (p = 0.06). Most of the CRE were New Delhi metallo—β lactamase- (NDM) producers.The all-cause mortality rate was 33.3%. Birth weight (p = 0.003), necrotising enterocolitis (p < 0.001) and mechanical ventilation (p = 0.007) were significantly associated with mortality. Serratia marcescens was isolated in 55.2% of neonates that died.ConclusionsThere was a significant increase in MDRE in neonatal sepsis during the study period, with the emergence of CRE. This confirms the urgent need to intensify antimicrobial stewardship efforts and address infection control and prevention in neonatal units in LMICs. Overuse of broad- spectrum antibiotics should be prevented.

Is systematic fecal carriage screening of extended-spectrum beta-lactamase-producing Enterobacteriaceae still useful in intensive care unit: a systematic review

BackgroundExtended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) are disseminating worldwide leading to increased hospital length of stay and mortality in intensive care units (ICU). ESBL-E dissemination was first due to outbreaks in hospital settings which led to the implementation of systematic fecal carriage screening to improve hygiene procedures by contact precautions. ESBLs have since spread in the community, and the relevance of contact precautions is questioned. ESBL-E dissemination led to an overuse of carbapenems triggering the emergence of carbapenem-resistant Enterobacteriaceae. Empirical antimicrobial therapy based on ESBL-E fecal carriage has been proposed but is debated as it could increase the consumption of carbapenems among ESBL-E carriers without any clinical benefit. Finally, selective decontamination among ESBL-E fecal carriers is evoked to decrease the risk for subsequent ESBL-E infection, but its efficacy remains debated. We propose to systematically review the evidence to recommend or not such systematic ESBL-E fecal carriage screening in adult ICU.MethodsEvery article focusing on ESBL-E and ICU available on the MEDLINE database was assessed. Articles were included if focusing on cross-transmission, efficacy of hygiene procedures, link between ESBL-E colonization and infection or guidance of empirical therapy or selective decontamination efficacy.ResultsAmong 330 articles referenced on PubMed, 39 abstracts were selected for full-text assessment and 25 studies were included. Systematic screening of ESBL-E fecal carriage to guide contact precautions do not seem to decrease the rate of ESBL-E cross-transmission. It has a very good negative predictive value for subsequent ESBL-E infections but a positive predictive value between 40 and 50% and so does not help to spare carbapenems. Cessation of ESBL-E carriage systematic screening could decrease the use of carbapenems in ICU without any clinical harm. Nevertheless, further studies are needed to validate these results from monocentric before-after study. Selective decontamination strategy applied to ESBL-E fecal carriers could be helpful, but available data are conflicting.ConclusionCurrent knowledge lacks of high-quality evidence to strongly recommend in favor of or against a systematic ESBL-E fecal carriage screening policy for ICU patients in a non-outbreak situation. Further evaluation of selective decontamination or fecal microbiota transplantation among ESBL-E fecal carriers is needed.

Contribution of acrB upregulation & OmpC/Ompk36 loss over the presence of blaNDM towards carbapenem resistance development among pathogenic Escherichia coli & Klebsiella spp.

Background & objectives:The global spread of carbapenem-resistant Enterobacteriaceae (CRE) is an emerging clinical problem. Hence, in this study, the plausible role of extended-spectrum beta-lactamases (ESBLs)/carbapenemases, OmpC/Ompk36, acrB and their combinations was explored among CRE.Methods:The minimum inhibitory concentration (MIC) of meropenem, enzyme-phenotypes (ESBLs/IR and metallo-beta-lactamase (MBL)/non-MBL carbapenemase), genotypes (blaTEM, blaSHV and blaCTX-M; blaNDM and blaVIM; blaKPC and blaOXA-48-like variants), acrB and outer membrane protein (OMP) expressions were analyzed with a total of 101 non-duplicate clinical isolates, obtained from various samples of patients visiting two tertiary care units of Eastern India during May 2013 - October 2016. This included Escherichia coli (n=36) and Klebsiella pneumoniae (n=65), categorized into two groups, namely Group I (resistant to all carbapenems; n=93; E. coli=34 and Klebsiella spp.=59) and Group II (non-resistant to all the carbapenems; n=8; E. coli=2 and Klebsiella spp.=6).Results:Though 88.17 per cent of Group I isolates exhibited ESBL property, the presence of carbapenemase activity (70.96%) and that of blaNDM gene (42/66: 63.63%) indicated their contributions towards the emergence of CRE. Further, porin loss and/or efflux pump activation among ESBL/carbapenemase-producing isolates heightened the MIC of meropenem from 64 to 256 mg/l (range exhibited by only ESBL/carbapenemase-producing isolates) to >256 mg/l.Interpretation & conclusions:These findings implied the major contribution of porin loss and/or efflux pump activation over the presence of ESBLs/carbapenemases in imparting carbapenem resistance in pathogenic bacteria.

Full title: Identification of potential drug targets against carbapenem resistant Enterobacteriaceae (CRE) strains using in silico gene network analysis

In the era where issue of antibiotic resistance is increasing at an alarming rate and resistance to most antibiotics has occurred, carbapenems have been the choice of drug against most infection because of its unique structure. However due to lack of antibiotic policy carbapenems too have achieved resistance and led to the emergence of carbapenem resistant Enterobacteriaceae (CRE). Members of Enterobacteriaceae family produce New Delhi metallo-beta-lactamase (NDM), a type of carbapenemase that can cleave carbapenems. Therefore, new anti-microbial targets need to be identified and for this purpose a holistic model is designed in this approach in order to find out the influential genes that are liable in imparting carbapenem resistance owing to the presence of NDM. In this research approach, firstly genes associated with resistance owing to NDM are collected from NCBI database. A total of 419 genes from E. coli that have been obtained from NCBI were subjected to STRING for protein-protein interaction analysis. Out of 419 genes, only 59 genes showed interaction. STRING gave 1679 functional partners at different confidence levels. In the next stage, clustering analysis of the 1679 functional partners was done using MCODE app of Cytoscape software which generated 71 clusters. Topological properties of the 804 functional partners obtained from the 71 clusters were done using Network Analyser plugin of Cytoscape software. 797 functional partners were streamlined and they were subjected to functional enrichment analysis by DAVID Database. This database finally gave 21 genes from 15 clusters, thus indicating that these 15 genes might have a crucial role in the development of carbapenem resistance owing to NDM. These genes can be targeted for designing new anti-microbial drugs in future by the way of gene silencing or altering the genetic expression.

Clinical benefit of ertapenem compared to flomoxef for the treatment of cefotaxime-resistant Enterobacteriaceae bacteremia.

ObjectivesCefotaxime-resistant Enterobacteriaceae (CE) infections are intractable, with limited treatment options. Though carbapenems are frequently prescribed for CE infections, the emergence of carbapenem-resistant Enterobacteriaceae is of huge concern. Flomoxef is effective against CE in vitro, and some clinical data on its demonstrated effectiveness against CE bloodstream infections (BSIs) exists.Patients and methodsWe conducted a retrospective study on adults with BSI caused by flomoxef-susceptible CE to investigate the efficacy of flomoxef compared with that of ertapenem. The outcome was evaluated with propensity score-based matching and logistic regression analysis.ResultsDemographic and clinical characteristics of patients treated with flomoxef (n = 58) or ertapenem (n = 188) were compared. In the multivariate analysis, severe sepsis (adjusted odds ratio [AOR] = 3.84; 95% confidence interval [CI], 1.16–12.78; p = 0.03), high BSI mortality score (AOR = 5.59; 95% CI, 2.37–13.21; p < 0.01), ultimately or rapidly fatal comorbidity (AOR = 10.60; 95% CI, 3.43–32.75; p < 0.01), and pneumonia (AOR = 10.11; 95% CI, 3.43–29.81; p < 0.01) were independently associated with 28-day mortality. Using propensity scores, 58 flomoxef-treated patients were matched to 116 ertapenem-treated patients. There were no intergroup differences in BSI severity, comorbidity, or BSI sources. The 28-day mortality rates (20.7% vs 13.8%, p = 0.28) did not differ significantly. However, hospitalization length was shorter in the ertapenem group (10.2 ± 8.5 vs. 14.6 ± 9.4 days, p < 0.01).ConclusionAlthough similar outcomes were observed between the groups, ertapenem therapy was associated with a shorter hospitalization time in adults after CE BSI.

Emergence of carbapenem-resistant Enterobacteriaceae in Orange County, California, and support for early regional strategies to limit spread

The east-to-west spread of carbapenem-resistant Enterobacteriaceae (CRE) represents an opportunity to explore strategies to limit spread in nonendemic areas. We evaluated CRE emergence and regional support for containment strategies. A 17-question cross-sectional survey was administered to infection prevention programs in Orange County, CA (31 hospitals serving 3 million residents), between January and September 2014. Questions addressed newly detected hospital- and community-onset CRE cultures (2008-2013), current CRE control strategies, and support for prevention strategies for a hypothetical regional intervention. Among 31 hospitals, 21 (68%, representing 17 infection prevention programs) completed the survey. CRE was scarcely detected between 2009-2010; within 4 years, 90% of hospitals reported CRE, with 2.5-fold higher community-onset than hospital-onset CRE. Between 2011 and 2013, annual CRE incidence increased 4.7-fold (1.4-6.3 cases/10,000 admissions). Support for a regional CRE prevention bundle was unanimous. Although 22% bathed patients positive for CRE with chlorhexidine gluconate and 11% actively screened for CRE, 86% and 57%, respectively, would consider these strategies in a regional intervention. CRE epidemiology in Orange County parallels early progression previously seen in now-endemic areas, representing an opportunity to consider interventions to prevent endemic spread. Many facilities would consider proactive strategies, such as chlorhexidine bathing, in the setting of a regional collaborative.