Carbapenem-resistant Escherichia Coli Research Articles

Rapid Dissemination of blaNDM-5 Gene among Carbapenem-Resistant Escherichia coli Isolates in a Yellow-Feather Broiler Farm via Multiple Plasmid Replicon

Although carbapenems have not been approved for animal use, carbapenem-resistant Escherichia coli (CREC) strains are increasingly being detected in food-producing animals, posing a significant public health risk. However, the epidemiological characteristics of CREC isolates in yellow-feather broiler farms remain unclear. We comprehensively investigated the genetic features of carbapenem-resistance genes among E. coli isolates recovered from a yellow-feather broiler farm in Guangdong province, China. Among the 172 isolates, 88 (51.2%) were recovered from chicken feces (88.5%, 54/61), the farm environment (51.1%, 24/47), and specimens of dead chickens (15.6%, 41/64). All CREC isolates were positive for the blaNDM-5 gene and negative for other carbapenem-resistance genes. Among 40 randomly selected isolates subjected to whole-genome sequencing, 10 belonged to distinct sequence types (STs), with ST167 (n = 12) being the most prevalent across different sources, suggesting that the dissemination of blaNDM-5 was mainly due to horizontal and clonal transmission. Plasmid analysis indicated that IncX3, IncHI2, and IncR-X1-X3 hybrid plasmids were responsible for the rapid transmission of the blaNDM-5 gene, and the genetic surrounding of blaNDM-5 contained a common mobile element of the genetic fragment designated “IS5-△ISAba125-blaNDM-5-bleMBL-trpF-dsbC”. These findings demonstrate a critical role of multiple plasmid replicons in the dissemination of blaNDM-5 and carbapenem resistance.

Global emergence of a hypervirulent carbapenem-resistant Escherichia coli ST410 clone

Carbapenem-resistant Escherichia coli (CREC) ST410 has recently emerged as a major global health problem. Here, we report a shift in CREC prevalence in Chinese hospitals between 2017 and 2021 with ST410 becoming the most commonly isolated sequence type. Genomic analysis identifies a hypervirulent CREC ST410 clone, B5/H24RxC, which caused two separate outbreaks in a children’s hospital. It may have emerged from the previously characterised B4/H24RxC in 2006 and has been isolated in ten other countries from 2015 to 2021. Compared with B4/H24RxC, B5/H24RxC lacks the blaOXA-181-bearing X3 plasmid, but carries a F-type plasmid containing blaNDM-5. Most of B5/H24RxC also carry a high pathogenicity island and a novel O-antigen gene cluster. We find that B5/H24RxC grew faster in vitro and is more virulent in vivo. The identification of this newly emerged but already globally disseminated hypervirulent CREC clone, highlights the ongoing evolution of ST410 towards increased resistance and virulence.

Carbapenem-resistant Escherichia coli exhibit diverse spatiotemporal epidemiological characteristics across the globe

Carbapenem-resistant Escherichia coli (CREC) poses a severe global public health risk. This study reveals the worldwide geographic spreading patterns and spatiotemporal distribution characteristics of resistance genes in 7918 CREC isolates belonging to 497 sequence types (ST) and originating from 75 countries. In the last decade, there has been a transition in the prevailing STs from highly virulent ST131 and ST38 to higher antibiotic-resistant ST410 and ST167. The rise of multi-drug resistant strains of CREC carrying plasmids with extended-spectrum beta-lactamase (ESBL) resistance genes could be attributed to three important instances of host-switching events. The spread of CREC was associated with the changing trends in blaNDM-5, blaKPC-2, and blaOXA-48, as well as the plasmids IncFI, IncFII, and IncI. There were intercontinental geographic transfers of major CREC strains. Various crucial transmission hubs and patterns have been identified for ST131 in the United Kingdom, Italy, the United States, and China, ST167 in India, France, Egypt, and the United States, and ST410 in Thailand, Israel, the United Kingdom, France, and the United States. This work is valuable in managing CREC infections and preventing CREC occurrence and transmission inside healthcare settings and among diverse hosts.

Synergistic antibacterial therapy for multidrug-resistant bacterial infections using multifunctional nanozymes

Multidrug-resistant (MDR) bacterial infections have become major threats to public health worldwide. To address this challenge, nanozyme with intrinsic enzyme-like activity has been used that can serve as broad-spectrum antibiotics. However, the efficacy of individual nanozyme is hindered by its limited catalytic activity and therapeutic efficiency. In this study, we develop broad-spectrum antibacterial nanocomposites, namely IrOx@PDA NPs-RSNO (IP NPs-RSNO), which demonstrate remarkable efficacy in eradicating MDR bacteria. The excellent antibacterial performance of IP NPs-RSNO is attributed to the synergistic effects of NIR photothermal property, NIR-enhanced peroxidase-like (POD-like) activity, and NIR-triggered release of NO. IP NPs-RSNO can effectively eliminate carbapenem-resistant Escherichia coli (CREC) and methicillin-resistant Staphylococcus aureus (MRSA), showing excellent therapeutic performance in treating MRSA-infected wounds. This work provides insights into the design of multifunctional nanozymes for antibacterial applications.

Evaluation of a novel chromogenic screening method for detection of carbapenem-resistant Escherichia coli.

Introduction. Early detection of carbapenem-resistant Escherichia coli (CREco), categorized as a critical priority pathogen by the World Health Organization (WHO), is crucial in optimizing therapeutic options and to thwart outbreaks in clinical settings.Gap statement. The need of the hour is a diagnostic method that can detect carbapenem resistance conferred by intrinsic or acquired carbapenem resistance mechanisms or both.Aim. The study investigates the performance of a novel screening chromogenic method for detection of CREco.Methodology. Carbapenem-susceptible (n=23) and non-susceptible (n=90) E. coli were used to investigate the efficiency of the blue chromogenic test. All of the isolates were received from a tertiary referral hospital in Silchar, India and subjected to the blue chromogenic test and observed for colour change. A colour change from colourless to blue is interpreted as a positive result. The test results were further compared with available methods for detection of carbapenem resistance conferred by carbapenemase production or other carbapenem resistance mechanisms.Results. The blue chromogenic test generated 100 % (CI: 95.98-100 %) sensitive and 100 % (CI: 85.75-100 %) specific results for the detection of CREco with no false-positive or false-negative results. Within 3 h after incubation, the test detects all CREco with carbapenemase activity. Additionally, the blue chromogenic test also positively detected E. coli harbouring carbapenemase variants and with efflux and porin activity, compared to other phenotypic-based approaches.Conclusion. The study highlights a novel method that is highly sensitive and specific, inexpensive, rapid and user-friendly for the detection of CREco. With the surge and expansion of CREco, this sensitive, specific, user-friendly and inexpensive method can be used in laboratories with limited facilities for early detection of CREco, thereby improving infection control along with averting future outbreaks.

Rectal culture could predict carbapenem-resistant organism bloodstream infection and reduce the mortality in haematological patients: A retrospective cohort study

The objective is to explore the correlation between rectal swab culture and the overall 30-d survival of hematologic patients diagnosed with carbapenem-resistant organism (CRO) bloodstream infection. A total of 434 haematological patients who were complicated with Gram-negative bacilli (GNB) bloodstream infections (BSIs) caused by Gram-negative bacteria between January 2020 and December 2021 were included in our retrospective study. Based on their drug susceptibility results, we classified patients into CRO BSIs and non-CRO BSIs cases. Through group comparison, to uncover the correlation between the positive screening of rectal swabs and reducing the mortality of CRO BSI in patients with haematological diseases. Among the 434 cases of Gram-negative bacteria bloodstream infection, 96 were identified as carbapenem-resistant bloodstream infection, which consisted of 57 cases of carbapenem-resistant Klebsiella pneumoniae (CR-KP), 19 cases of carbapenem-resistant Pseudomonas aeruginosa (CR-PA), 11 cases of carbapenem-resistant Escherichia coli (CR-CO), 5 cases of carbapenem-resistant Acinetobacter baumannii (CR-AB), and 4 cases of other Enterobacteriaceae. Before the onset of CRO bloodstream infection, rectal swab cultures were conducted on 36 patients, and the positive result rate was 75.0% (27/36), with 20 cases of CR-KP, 6 cases of CR-CO, and one case of carbapenem-resistant Enterobacter cloacae. It was observed that the rectal and blood cultures had matching outcomes in 75.0% of cases. The mortality rate within 30 d for CRO BSIs was 53.1% (51/96), while for carbapenem-resistant Enterobacteriaceae (CRE) BSIs it was 62.5% (45/72). Univariate analysis showed that 30-d mortality was significantly reduced when there were positive rectal culture results preceding bloodstream infection (P < 0.001), as well as preemptive anti-infection treatment (P < 0.001). Multivariate analysis demonstrated that preemptive adjustment to an effective antibiotic regimen, guided by positive rectal culture results, had a significant effect on decreasing 30-d mortality following CRO BSIs (P= 0.002). Furthermore, for the management of CRE BSIs, antibiotic treatments utilising ceftazidime/avibactam (CAV/AVI) may be more beneficial compared to those that use tigecycline (TGC) or polymyxin (PMB). CRO BSI, especially CRE BSI, can be life-threatening for those with haematological diseases. Utilising rectal culture can effectively identify CRO strains with high sensitivity and specificity. Adjusting antibiotic treatment based on the preemptive positive rectal culture results may significantly decrease 30-d mortality rates for haematological patients with CRO BSIs.

Carbapenem resistant Enterobacterales in the United Arab Emirates: a retrospective analysis from 2010 to 2021.

Carbapenem-resistant Enterobacterales (CRE) are spreading in the United Arab Emirates (UAE) where their dissemination is facilitated by international travel, trade, and tourism. The objective of this study is to describe the longitudinal changes of CRE as reported by the national AMR surveillance system of the UAE. In this study, we retrospectively describe CRE isolated from 317 surveillance sites, including 87 hospitals and 230 centers/clinics from 2010 to 2021. The associated clinical, demographic, and microbiological characteristics are presented by relying on the UAE national AMR surveillance program. Data was analyzed using WHONET microbiology laboratory database software (http://www.whonet.org). A total of 14,593 carbapenem resistant Enterobacterales were analyzed, of which 48.1% were carbapenem resistant Klebsiella pneumoniae (CRKp), 25.1% carbapenem resistant Escherichia coli (CREc), and 26.8% represented 72 other carbapenem resistant species. Carbapenem resistant strains were mostly associated with adults and isolated from urine samples (36.9% of CRKp and 66.6% of CREc) followed by respiratory samples (26.95% for CRKp) and soft tissue samples (19.5% for CRKp). Over the studied period carbapenem resistance rates remained high, especially in K. pneumoniae, and in 2021 were equivalent to 67.6% for imipenem, 76.2% for meropenem, and 91.6% for ertapenem. Nevertheless, there was a statistically significant decreasing trend for imipenem and meropenem resistance in Klebsiella species (p < 0.01) while the decrease in ertapenem resistance was non-significant. Concerning E. coli, there was a statistically significant decreasing trend for meropenem and imipenem resistance over the 12 years, while ertapenem resistance increased significantly with 83.8% of E. coli exhibiting ertapenem resistance in 2021. Resistance rates to ceftazidime and cefotaxime remained higher than 90% (in 2021) for CRKp and cefotaxime rates increased to 90.5% in 2021 for CREc. Starting 2014, resistance to colistin and tigecycline was observed in carbapenem resistant Enterobacterales. CRE were associated with a higher mortality (RR: 6.3), admission to ICU (RR 3.9), and increased length of stay (LOS; 10 excess inpatient days per CRE case). This study supports the need to monitor CRE in the UAE and draws attention to the significant increase of ertapenem resistance in E. coli. Future surveillance analysis should include a genetic description of carbapenem resistance to provide new strategies.

Global distribution and genomic characteristics of carbapenemase-producing Escherichia coli among humans, 2005–2023

Carbapenem-resistant Escherichia coli (CREC) has become a major public health problem worldwide. To date, there is a limited understanding of the global distribution of CREC. In this study, we performed a comprehensive genomic analysis of 7, 731 CRECs of human origin collected from different countries worldwide between 2005 and 2023. Our results showed that these CRECs were distributed in 75 countries, mainly from the United States (17.49%), China (14.88%), and the United Kingdom (14.73%). Eight carbapenemases were identified among the CRECs analyzed, including KPC, IMP, NDM, VIM, OXA, FRI, GES, and IMI. NDM was the most predominant carbapenemase (52.15%), followed by OXA (30.09%) and KPC (14.72%). Notably, all CRECs carried multiple antibiotic resistance genes (ARGs), with 178 isolates carrying mcr-1 and 9 isolates carrying tet(X). The CREC isolates were classified into 465 known sequence types (STs), with ST167 being the most common (11.5%). Correlation analysis demonstrated the significant role of mobile genetic elements in facilitating the transfer of carbapenem resistance genes. Furthermore, some CRECs from different countries showed high genetic similarity, suggesting clonal transmission exists. According to the GWAS results, the genetic difference of blaNDM-positive CRECs from China were mainly enriched in bacterial Type IV secretion system pathways compared with those from the United Kingdom and the United States. Therefore, continuous global surveillance of CRECs is imperative in the future.

Octominin: An antimicrobial peptide with antibacterial and anti-inflammatory activity against carbapenem-resistant Escherichia coli both in vitro and in vivo

The emergence of carbapenem-resistant Escherichia coli (CREC) is a global concern as its prevalence restricts treatment options and poses a considerable threat to public health. In this study, in vitro and in vivo activity of the antimicrobial peptide Octominin against CREC was investigated to reveal possible mechanisms of action. Furthermore, its safety and factors influencing its antibacterial effect were assessed. Additionally, the anti-inflammatory effects of Octominin were examined. The antimicrobial activity of Octominin against 11 strains of CREC was determined using the broth microdilution method, growth curve, and time-kill assay. Its possible mechanism of action was unraveled using the propidium iodide and N-phenyl-1-naphthylamine fluorochrome and lipopolysaccharide-binding assays. To understand the safety and stability of Octominin, its cytotoxicity, hemolysis, and antibacterial activity under various conditions (i.e, temperature, ions) were estimated. Additionally, a Galleria mellonella infection model was utilized to evaluate the efficacy of Octominin in vivo, and qRT-PCR was performed to assess its effect on the expression of proinflammatory cytokines. Octominin displayed a significant antibacterial effect, with MICs of 4-8 µg/mL and MBCs of 8-16 µg/mL. Octominin exerted its antibacterial effect by disrupting bacterial membranes. Cytotoxicity and hemolysis tests demonstrated the potential application of Octominin in vivo. The G. mellonella infection model asserted the in vivo efficacy of Octominin. Furthermore, Octominin inhibited the expression of proinflammatory cytokines. Although the temperature had little effect on its the activity, serum and ions reduced activity. Octominin is a promising alternative agent with remarkable antibacterial and anti-inflammatory effects for treating infections caused by CREC.

Co-existence of NDM-, aminoglycoside- and fluoroquinolone-resistant genes in carbapenem-resistant Escherichia coli clinical isolates from Pakistan.

Background: To determine the prevalence of antimicrobial-resistant genes in carbapenem-resistant Escherichia coli (CRECO). Methods: A total of290 carbapenem-resistant bacteria were collected from tertiary care hospitals in Lahore (Pakistan). These isolates were confirmed by VITEK 2and matrix-assisted laser desorption/ionization time of flight. The minimum inhibitory concentration was performed by VITEK 2. Sequence typing, resistant geneidentification, DNA hybridization and replicate typing were also performed. Results: 33 out of290 (11.3%) were CRECO and carried blaNDM; 69, 18and 12% were NDM-1, NDM-5and NDM-7, respectively, with 100% resistance to β-lactams and β-lactam inhibitors. ST405 and ST468 were mostly identified. NDM-ECO carried approximately 50-450kb of plasmids and 16 (55%) were associated with IncA/C. Conclusion: NDM-1-producing E. coli are highly prevalent in clinical settings.

Transmission of clones of carbapenem-resistant Escherichia coli between a hospital and an urban wastewater treatment plant

Carbapenem-resistant Enterobacterales (CRE) constitute an urgent threat to worldwide public health. The spread of CRE is facilitated by transmission via the environment. Wastewater treatment plants (WWTPs) are considered to be important sources of antibiotic resistance and hot spots of antibiotic-resistant bacteria (ARB) which can facilitate dissemination of antibiotic resistance genes. In this study, water samples were collected over one year from a WWTP in Jinan, Shandong province, China, from different functional sites in the wastewater treatment process. Carbapenem-resistant Escherichia coli (CREC) were isolated by selective cultivation and whole-genome sequenced to investigate the occurrence and characteristics of CREC in the WWTP. A total of 77 CREC isolates were included in the study and the detection rate of CREC in the WWTP water inlet was found to be 85%. An additional 10 CREC were isolated from a nearby teaching hospital during the sampling period and included for comparison to the environmental isolates. Susceptibility testing showed that all CREC were multidrug-resistant. 6 different carbapenem resistance genes (CRGs) were detected, including blaNDM-5 (n = 75), blaNDM-1 (n = 6), blaNDM-4 (n = 3), blaNDM-6 (n = 1), blaNDM-9 (n = 1), and blaKPC-2 (n = 4). 42 CREC isolates were whole-genome sequenced with Illumina short-read sequencing. 11 of these were also sequenced with Nanopore long-read sequencing. Plasmids carrying CRGs were found to belong to IncX3 (n = 35), IncFII (n = 12), IncFIA (n = 5), IncFIB (n = 2), IncC (n = 1), and IncP6 (n = 1). Clonal dissemination of CREC belonging to ST167, ST448, and ST746 was observed between different parts of the WWTP. Furthermore, isolates from the WWTP, including an isolate belonging to the high-risk ST167 strain, were found to be clonally related to CREC isolated at the hospital. The spread of CRGs is of considerable concern and strategies to prevent environmental dissemination of this contaminant urgently needs to be implemented.

Chemical composition and antibacterial activity of bee venom against multi-drug resistant pathogens.

Bee venom with an antimicrobial effect is a powerful natural product. One of the most important areas where new antimicrobials are needed is in the prevention and control of multi-drug resistant pathogens. Today, antibacterial products used to treat multi-drug resistant pathogen infections in hospitals and healthcare facilities are insufficient to prevent colonisation and spread, and new products are needed. The aim of the study is to investigate the antibacterial effect of the bee venom (BV), a natural substance, on the species of Methicillin resistantStaphylococcus aureus, Vancomycin resistantEnterococcus faecalis, Carbapenem resistantEscherichia coli, Carbapenem resistantKlebsiella pneumoniaeand Carbapenem resistantAcinetobacter baumannii. As a result of this study, it was found that MIC90and MBC90values ranged from 6.25 μg/mL - 12.5 μg/mL and numbers of bacteria decreased by 4-6 logs within 1-24 h for multi-drug resistant pathogens. In particular, Vancomycin resistantEnterococcus faecalisisolate decreased 6 log cfu/mL at 50 μg/mL and 100 μg/mL concentrations in the first hour. The effective bacterial inhibition rate of bee venom suggests that it could be a potential antibacterial agent for multi-drug resistant pathogens.Contribution:The treatment options of antibiotic-resistant pathogens are a major problem in both veterinary and human medicine fields. We have detected a high antibacterial effect against these agents in this bee venom study, which is a natural product. Apitherapy is a fashionable treatment method all over the world and is used in many areas of health. Bee venom is also a product that can be used as a drug or disinfectant raw material and can fill the natural product gap that can be used against resistant bacteria.

Local and timely antimicrobial resistance data for local and national actions: the early implementation of an automated tool for data analysis at local hospital level in Thailand.

In low- and middle-income countries (LMICs), hospitals can rarely utilize their own antimicrobial resistance (AMR) data in a timely manner. To evaluate the utility of local AMR data generated by an automated tool in the real-world setting. From 16 December 2022 to 10 January 2023, on behalf of the Health Administration Division, Ministry of Public Health (MoPH) Thailand, we trained 26 public tertiary-care and secondary-care hospitals to utilize the AutoMated tool for Antimicrobial resistance Surveillance System (AMASS) with their own microbiology and hospital admission data files via two online meetings, one face-to-face meeting and online support. All meetings were recorded on video, and feedback was analysed. Twenty-five hospitals successfully generated and shared the AMR reports with the MoPH by 28 February 2023. In 2022, the median frequency of hospital-origin bloodstream infections (BSIs) caused by carbapenem-resistant Escherichia coli (CREC) was 129 (range 0-1204), by carbapenem-resistant Klebsiella pneumoniae (CRKP) was 1306 (range 0-5432) and by carbapenem-resistant Acinetobacter baumannii (CRAB) was 4472 (range 1460-11 968) per 100 000 patients tested for hospital-origin BSI. The median number of all-cause in-hospital deaths with hospital-origin AMR BSI caused by CREC was 1 (range 0-18), by CRKP was 10 (range 0-77) and by CRAB was 56 (range 7-148). Participating hospitals found that the data obtained could be used to support their antimicrobial stewardship and infection prevention control programmes. Local and timely AMR data are crucial for local and national actions. MoPH Thailand is inviting all 127 public tertiary-care and secondary-care hospitals to utilize the AMASS. Using any appropriate analytical software or tools, all hospitals in LMICs that have electronic data records should analyse and utilize their data for immediate actions.

Epidemiology, drug resistance analysis and mortality risk factor prediction of gram-negative bacteria infections in patients with allogeneic hematopoietic stem cell transplantation

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for many malignant and refractory diseases. However, infections, as the most common complication after transplantation, often lead to poor long-term prognosis of patients. In this study, we collected electronic medical records of allo-HSCT recipients with gram-negative bacteria (GNB) infections between January 2012 and September 2021, analyzed epidemiological characteristics and antibiotic sensitivity, and determined independent risk factors for carbapenem-resistant GNB (CR-GNB) infections and death by Logistic and Cox regression models. During the 9-year period, 183 of 968 patients developed GNB infections, of which 58 died. The most common pathogen was Klebsiella pneumoniae. CR-GNB, especially carbapenem-resistant Klebsiella pneumonia (CRKP), carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Escherichia coli (CREC) had a high resistance rate to commonly used clinical antibiotics. Independent risk factors for CR-GNB infections were use of carbapenem antibiotics for >3 days one month before transplantation (OR = 3.244, 95% CI 1.428–7.369, P = 0.005), use of special immunosuppressants after transplantation (OR = 1.21, 95% CI 1.008–1.452, P = 0.041), and time of hematopoietic reconstruction >20 days (OR = 2.628, 95% CI 1.369–5.043, P = 0.004). Independent risk factors for mortality were interval between diagnosis and transplantation >180 days (HR = 2.039, 95% CI 1.05 to 3.963, P = 0.035), total bilirubin levels during infection >34.2 μmol/L (HR = 3.39, 95% CI 1.583–7.256, P = 0.002) and septic shock (HR = 5.345, 95% CI 2.655–10.761, P = 0.000). In conclusion, GNB has a high incidence and mortality in allo-HSCT recipients. Early transplantation for eligible patients, attention to liver function protection, timely identification and treatment of septic shock can help to improve the prognosis of patients.

Population genomic analysis reveals the emergence of high-risk carbapenem-resistant Escherichia coli among ICU patients in China

The increasing incidence of carbapenem-resistant Enterobacterales (CRE) mediated nosocomial infections has caused a significant public health burden globally. Currently, the prevalence and genomic characteristics of carbapenem-resistant Escherichia coli (CREC) in patients admitted to the intensive care unit (ICU) are unknown. Herein, we present a nationwide genomic investigation of CREC isolates among ICU patients in China in 2018 and 2020. In total, 113 CREC isolates were identified from 1105 samples in 25 hospitals, and investigated with phenotyping and genomics approaches. Carbapenemases were produced in 94.69% (107/113) of CREC isolates, which comprise KPC-2 (n=53, 49.53%), NDM (n=51, 47.66%), IMP-4 (n=2, 1.87%), and OXA-181 (n=1, 0.93%). Notably, CREC isolates co-carrying mcr-9 and blaNDM-5 or tet(X4) and blaNDM-5 were first identified in clinical settings. The carbapenemase genes of most isolates were located on the plasmids. The blaKPC gene was mainly mediated by IncFII plasmids (n=37, 69.81%), and blaNDM was located on the IncX3 plasmid (n=36, 70.59%). CREC isolates belonged to diverse sequence types (STs) of which ST131 was the most prevalent blaKPC-positive CREC isolates (34/113, 30.09%), while blaNDM was associated with ST617 and ST410 isolates, thereby indicating that multiple CREC clones spread in Chinese ICU patients. This study highlights the emerging threat of high-risk CREC isolates such as ST131 circulating in the ICU in China. Hence, stringent monitoring of such high-risk clones should be performed.

Risk factors and molecular epidemiology of fecal carriage of carbapenem resistant Enterobacteriaceae in patients with liver disease

BackgroundCarbapenem resistant Enterobacteriaceae (CRE) colonization is a risk factor for CRE infection. CRE infection results in an increase in mortality in patients with cirrhosis. However, minimal data regarding the prevalence and the risk factors of CRE colonization in patients with liver disease yet without liver transplantation are available. The present study aimed to investigate the prevalence, risk factors and molecular epidemiology characteristics of CRE fecal carriage among patients with liver disease.MethodsStool specimens from 574 adult inpatients with liver disease were collected from December 2020 to April 2021. CRE were screened using selective chromogenic agar medium and identified by the Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS). Antimicrobial susceptibility was determined using the broth microdilution method. Carbapenemase genes were characterized by polymerase chain reaction (PCR) and DNA sequencing. Multilocus sequence typing (MLST) was performed for Carbapenem Resistant Klebsiella pneumoniae (CR-KPN) isolates and Carbapenem Resistant Escherichia Coli (CR-ECO) isolates.ResultsThe total number of stool specimens (732) were collected from 574 patients with liver disease. 43 non-duplicated CRE strains were isolated from 39 patients with a carriage rate of 6.79% (39/574). The carriage rate was 15.60% (17/109) in patients with acute-on-chronic liver failure (ACLF). Multivariate analysis indicated that ACLF (P = 0.018), the history of pulmonary infection within past 3 months (P = 0.001) and the use of third generation cephalosporin/β-lactamases inhibitor within past 3 months (P = 0.000) were independent risk factors of CRE colonization in patients with liver disease. Klebsiella Pnuemoniae (KPN) (51.28%) and Escherichia coli (ECO) (30.77%) were main strains in these patients. All CRE strains showed high resistance to most antimicrobials except for polymyxin B and tigecycline. Most (83.72%, 36/43) of the CRE carried carbapenemase genes. blaKPC-2 was the major carbapenemase gene. The molecular epidemiology of KPN were dominated by ST11, while the STs of ECO were scattered.ConclusionsThe present study revealed that CRE fecal carriage rates were higher in patients with ACLF than in patients without liver failure. ACLF, the history of pulmonary infection within past 3 months and the use of third generation cephalosporin/β-lactamases inhibitor within past 3 months were independent risk factors of CRE colonization in patients with liver disease. Regular CRE screening for hospitalized patients with liver disease should be conducted to limit the spread of CRE strain.

Analysis of the Distribution and Antibiotic Resistance of Pathogens Causing Infections in Hospitals from 2017 to 2019.

Background Antibiotic resistance is a global public health problem, leading to high mortality and treatment costs. To achieve more efficient treatment protocols and better patient recovery, the distribution and drug resistance of pathogens in our hospital were investigated, allowing significant clinical guidance for the use of antimicrobials. Methods In this retrospective study (2017–2019), 3482 positive samples were isolated from 43,981 specimens in 2017; 3750 positive specimens were isolated from 42,923 specimens in 2018; and 3839 positive pathogens were isolated from 46,341 specimens in 2019. These samples were from various parts of the patients, including the respiratory tract, urine, blood, wound secretions, bile, and puncture fluids. The distribution and antibiotic resistance of these isolated pathogens from the whole hospital were analyzed. Results The results from pathogen isolation showed that Escherichia coli (12.8%), Staphylococcus aureus (11%), Klebsiella pneumoniae (10.8%), Pseudomonas aeruginosa (10.7%), and Acinetobacter baumannii (6.4%) represented the five main pathogenic bacteria in our hospital. Pseudomonas aeruginosa (16.2% and 17.5%) occupied the largest proportion in the central intensive care unit (central ICU) and respiratory intensive care unit (RICU), while Acinetobacter baumannii (15.4%) was the most common pathogen in the emergency intensive care unit (EICU). The resistance rate of Escherichia coli to trimethoprim and minocycline was 100%, and the sensitivity rate to ertapenem, furantoin, and amikacin was above 90%. The resistance rate of Pseudomonas aeruginosa to all antibiotics, such as piperacillin and ciprofloxacin, was under 40%. The sensitivity rate of Acinetobacter baumannii to tigecycline and minocycline was less than 30%, and the resistance rate to many drugs such as piperacillin, ceftazidime, and imipenem was above 60%. Extended-spectrum β-lactamases (ESBLs)-producing Klebsiella pneumoniae (ESBLs-KPN) and carbapenem-resistant Klebsiella pneumoniae (CRE-KPN), ESBLs-producing Escherichia coli (ESBLs-ECO) and carbapenem-resistant Escherichia coli (CRE-ECO), multidrug-resistant Acinetobacter baumannii (MDR-AB), multidrug-resistant Pseudomonas aeruginosa (MDR-PAE), and methicillin-resistant Staphylococcus aureus (MRSA) are all important multidrug-resistant bacteria found in our hospital. The resistance rate of ESBLs-producing Enterobacteriaceae to ceftriaxone and amcarcillin-sulbactam was above 95%. CRE Enterobacteriaceae bacteria showed the highest resistance to amcarcillin-sulbactam (97.1%), and the resistance rates of MDR-AB to cefotaxime, cefepime, and aztreonam were 100%. The resistance rates of MDR-PAE to ceftazidime, imipenem, and levofloxacin were 100%, and the sensitivity rate to polymyxin B was above 98%. The resistance rate of MRSA to oxacillin was 100%, and the sensitivity rate to linezolid and vancomycin was 100%. Conclusion The distribution of pathogenic bacteria in different hospital departments and sample sources was markedly different. Therefore, targeted prevention and control of key pathogenic bacteria in different hospital departments is necessary, and understanding both drug resistance and multiple drug resistance of the main pathogenic bacteria may provide guidance for the rational use of antibiotics in the clinic.

Prevalence and risk factors of carbapenem-resistant Enterobacterales positivity by active screening in intensive care units in the Henan Province of China: A multi-center cross-sectional study.

ObjectiveIn intensive care units (ICUs), carbapenem-resistant Enterobacterales (CRE) pose a significant threat. We aimed to examine the distribution, epidemiological characteristics, and risk factors for CRE positivity in ICUs.Materials and methodsThis cross-sectional study was conducted in 96 ICUs of 78 hospitals in Henan Province, China. The clinical and microbiological data were collected. A multivariable logistic regression model was used to analyze the risk factors for CRE positivity.ResultsA total of 1,009 patients were enrolled. There was a significant difference in CRE positive rate between pharyngeal and anal swabs (15.16 vs. 19.13%, P < 0.001). A total of 297 carbapenem-resistant Klebsiella pneumoniae (CR-KPN), 22 carbapenem-resistant Escherichia coli (CR-ECO), 6 carbapenem-resistant Enterobacter cloacae (CR-ECL), 19 CR-KPN/CR-ECO, and 2 CR-KPN/CR-ECL were detected. Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-beta-lactamase (NDM), and a combination of KPC and NDM were detected in 150, 9, and 11 swab samples, respectively. Multivariable logistic regression analysis determined length of ICU stay, chronic neurological disease, transfer from other hospitals, previous infection, and history of antibiotics exposure as independent risk factors for CRE positivity. Age and cardiovascular diseases were independent risk factors for mixed infections of CRE. The occurrence of CRE in secondary and tertiary hospitals was 15.06 and 25.62%, respectively (P < 0.05). Patients from tertiary hospitals had different clinical features compared with those from secondary hospitals, including longer hospital stays, a higher rate of patients transferred from other hospitals, receiving renal replacement therapy, exposure to immunosuppressive drugs, use of antibiotics, and a higher rate of the previous infection.ConclusionIn ICUs in Henan Province, CRE positive rate was very high, mostly KPC-type CR-KPN. Patients with prolonged ICU stay, chronic neurological disease, transfer from other hospitals, previous infection, and history of antibiotic exposure are prone to CRE. Age and cardiovascular diseases are susceptibility factors for mixed infections of CRE. The CRE positive rate in tertiary hospitals was higher than that in secondary hospitals, which may be related to the source of patients, antibiotic exposure, disease severity, and previous infection.

Association between Antimicrobial Consumption and the Prevalence of Nosocomial Carbapenem-Resistant Escherichia coli and Klebsiella pneumoniae in a Tertiary Hospital in Northern Taiwan.

Carbapenem-resistant Enterobacteriales has become a threat in Taiwan. This is the first local study focusing on the association between carbapenem-resistant Enterobacteriales and antimicrobial consumption. From January 2012 to December 2020, data were collected in a tertiary care hospital in Taipei, Taiwan. Antimicrobial consumption was estimated by the defined daily dose/1,000 patient-days. During the same period, the prevalence of carbapenem-resistant Escherichia coli (CREC) and carbapenem-resistant Klebsiella pneumoniae (CRKP) were collected through routine surveillance data. The following retrospective analyses were conducted: 1) analysis of antimicrobial consumption over time, (2) analysis and forecast of CREC and CRKP prevalence over time, and 3) analysis of correlation between antimicrobial consumption and the prevalence of CREC and CRKP. The consumption of piperacillin/tazobactam (β = 0.615), fluoroquinolones (β = 0.856), meropenem (β = 0.819), and doripenem (β = 0.891) increased during the observation period (P < 0.001), and the consumption of aminoglycosides (β = -0.852) and imipenem/cilastatin (β = -0.851) decreased (P < 0.001). The prevalence of CRKP rose over time (β = 0.522, P = 0.001) and correlated positively with the consumption of fluoroquinolones, levofloxacin, penicillin/β-lactamase inhibitor, piperacillin/tazobactam, meropenem, and doripenem (P < 0.05). The prevalence of CRKP and CREC both correlated negatively with consumption of aminoglycosides (P < 0.01). The prevalence of CRKP in our hospital increased as the forecast predicted based on an autoregressive integrated moving average model. This study provides alarming messages for members participating in antimicrobial stewardship programs, including the increasing prevalence of CRKP, the increasing consumption of broad-spectrum antibiotics, and the positive correlation between them.

Fingolimod Promotes Antibacterial Effect of Doripenem against Carbapenem-Resistant Escherichia coli.

The aim of this study was to determine whether fingolimod could synergize the antibacterial activity of doripenem against carbapenem-resistant Escherichia coli (CREC) and its potential as an antibiotic adjuvant for doripenem. The E. coli used in this study had the blaKPC gene and became resistant to many classes of antibiotics, particularly carbapenems. The minimum inhibitory concentrations (MICs) of fingolimod and doripenem were determined. To investigate the synergistic action between fingolimod and doripenem, synergy checkerboard, growth curve, and time-kill analyses were performed. A motility test was also performed using a semi-solid medium to determine whether fingolimod could inhibit the motility of E. coli, one of its virulence mechanisms. The expression levels of carbapenemase-, motility-, and efflux pump-related genes suppressed by fingolimod were analyzed by quantitative polymerase chain reaction (qPCR). Our study demonstrated that the combination of fingolimod and doripenem inhibited carbapenemase, biological activity and other CREC virulence factors. This study findings suggest the potential of fingolimod as an adjuvant to prevent antibiotic resistance in CREC.