Dissemination of extensively drug-resistant NDM-producing Providencia stuartii in Europe linked to patients transferred from Ukraine, March 2022 to March 2023.

BackgroundThe war in Ukraine led to migration of Ukrainian people. Early 2022, several European national surveillance systems detected multidrug-resistant (MDR) bacteria related to Ukrainian patients.AimTo investigate the genomic epidemiology of New Delhi metallo-ß-lactamase (NDM)-producing Providencia stuartii from Ukrainian patients among European countries.MethodsWhole-genome sequencing of 66 isolates sampled in 2022-2023 in 10 European countries enabled whole-genome multilocus sequence typing (wgMLST), identification of resistance genes, replicons, and plasmid reconstructions. Five bla NDM-1-carrying-P. stuartii isolates underwent antimicrobial susceptibility testing (AST). Transferability to Escherichia coli of a bla NDM-1-carrying plasmid from a patient strain was assessed. Epidemiological characteristics of patients with NDM-producing P. stuartii were gathered by questionnaire.ResultswgMLST of the 66 isolates revealed two genetic clusters unrelated to Ukraine and three linked to Ukrainian patients. Of these three, two comprised bla NDM-1-carrying-P. stuartii and the third bla NDM-5-carrying-P. stuartii. The bla NDM-1 clusters (PstCluster-001, n = 22 isolates; PstCluster-002, n = 8 isolates) comprised strains from seven and four countries, respectively. The bla NDM-5 cluster (PstCluster-003) included 13 isolates from six countries. PstCluster-001 and PstCluster-002 isolates carried an MDR plasmid harbouring bla NDM-1, bla OXA-10, bla CMY-16, rmtC and armA, which was transferrable in vitro and, for some Ukrainian patients, shared by other Enterobacterales. AST revealed PstCluster-001 isolates to be extensively drug-resistant (XDR), but susceptible to cefiderocol and aztreonam-avibactam. Patients with data on age (n = 41) were 19-74 years old; of 49 with information on sex, 38 were male.ConclusionXDR P. stuartii were introduced into European countries, requiring increased awareness and precautions when treating patients from conflict-affected areas.

Plasmid genomic epidemiology of carbapenem-hydrolysing class D ß-lactamase (CDHL)-producing Enterobacterales in Canada, 2010-2021.

Carbapenems are last-resort antibiotics for treatment of infections caused by multidrug-resistant Enterobacterales, but carbapenem resistance is a rising global threat due to the acquisition of carbapenemase genes. Oxacillinase-48 (bla OXA-48)-type carbapenemases are increasing in abundance in Canada and elsewhere; these genes are frequently found on mobile genetic elements and are associated with specific transposons. This means that alongside clonal dissemination, bla OXA-48-type genes can spread through plasmid-mediated horizontal gene transfer. We applied whole genome sequencing to characterize 249 bla OXA-48-type-producing Enterobacterales isolates collected by the Canadian Nosocomial Infection Surveillance Program from 2010 to 2021. Using a combination of short- and long-read sequencing, we obtained 70 complete and circular bla OXA-48-type-encoding plasmids. Using MOB-suite, four major plasmids clustered were identified, and we further estimated a plasmid cluster for 91.9 % (147/160) of incomplete bla OXA-48-type-encoding contigs. We identified different patterns of carbapenemase mobilization across Canada, including horizontal transmission of bla OXA-181/IncX3 plasmids (75/249, 30.1 %) and bla OXA-48/IncL/M plasmids (47/249, 18.9 %), and both horizontal transmission and clonal transmission of bla OXA-232 for Klebsiella pneumoniae ST231 on ColE2-type/ColKP3 plasmids (25/249, 10.0 %). Our findings highlight the diversity of OXA-48-type plasmids and indicate that multiple plasmid clusters and clonal transmission have contributed to bla OXA-48-type spread and persistence in Canada.

Clinical and Microbiological Characteristics of Bacteremia Caused by Carbapenemase-producing Enterobacterales in Minami Ibaraki Area, Japan.

Although recent propagation of carbapenemase-producing Enterobacterales (CPE) has become a problem worldwide, the picture of CPE infection in Japan has not fully been elucidated. In this study, we examined clinical and microbiological characteristics of invasive CPE infection occurring at 8 hospitals in Minami Ibaraki Area between July 2001 to June 2017. Of 7294 Enterobacterales strains isolated from independent cases of bacteremia and/or meningitis, 10 (0.14%) were CPE (8 Enterobacter cloacae-complex, 1 Escherichia coli, and 1 Edwardsiella tarda）, all of which had the blaIMP-1 gene and susceptible to gentamicin and trimethoprim/sulfamethoxazole. These strains were isolated from 7 adult and 2 infant bacteremia (1 infant patient developed CPE bacteremia twice) after 2007. The most common portal of entry was intravenous catheters. All of the adult patients were recovered, while the infant patients eventually died. Genomic analyses showed that the 8 E. cloacae-complex strains were classified into 5 groups, each of which was exclusively detected in specific facilities at intervals of up to 3 years, suggesting persistent colonization in the facilities. This study showed that invasive CPE infection in the area was rare, caused by IMP-1-type CPE having susceptibility to various antibiotics, and nonfatal among adult patients.

Mortality factors and antibiotic options in carbapenem-resistant Enterobacterales bloodstream infections: Insights from a high-prevalence setting with co-occurring NDM-1 and OXA-48.

Bloodstream infections (BSI) caused by carbapenem-resistant Enterobacterales (CRE) are associated with a high mortality rate. This study aimed to investigate factors associated with 14-day mortality and identify a potential treatment option. A retrospective cohort study was conducted on patients with CRE-BSI in Thailand from 2015 to 2020. The multivariate Cox proportional-hazards model was employed to identify factors influencing 14-day mortality. Out of 134 diagnosed cases of CRE-BSI, the all-cause 14-day mortality rate was 35.1%. The most prevalent organism isolated was Klebsiella pneumoniae (85.8%), followed by Escherichia coli (11.9%). Among the 60 isolates tested for carbapenemase genes, the majority exhibited co-occurring blaNDM-1 and blaOXA-48 (51.7%), followed by blaOXA-48 (31.7%) and blaNDM-1 (15.0%). In the multivariate analysis, neutropenia (adjusted hazard ratio [aHR] 2.55; 95% confidence interval [95%CI] 1.28-5.06; p = 0.008), sepsis/septic shock (aHR 3.02; 95%CI 1.33-6.86; p = 0.008), and previous metronidazole exposures (aHR 3.58; 95%CI 1.89-6.71; p < 0.001) were identified as independent factors for 14-day mortality. The fosfomycin-based regimen was found to be protective (aHR 0.37; 95%CI 0.15-0.92; p = 0.032). In patients with CRE-BSI, particularly in regions with a high occurrence of co-occurring blaNDM-1 and blaOXA-48, neutropenia, sepsis/septic shock, and previous metronidazole exposures emerged as independent risk factors for mortality. Moreover, the fosfomycin-based regimen showed an improvement in the survival rate.

IMI-Type Carbapenemase-Producing Enterobacter cloacae Complex, France and Overseas Regions, 2012-2022.

We characterized a collection of IMI-like-producing Enterobacter spp. isolates (n = 112) in France. The main clone corresponded to IMI-1-producing sequence type 820 E. cloacae subspecies cloacae that was involved in an outbreak. Clinicians should be aware of potential antimicrobial resistance among these bacteria.

Bloodstream infections and multidrug resistant bacteria acquisition among burns patients in Australia and New Zealand: A registry-based study.

INTRODUCTION: This study interrogates infection related data in the Burns Registry of Australia and New Zealand (BRANZ), to examine associations of multi-drug resistant organisms (MDROs) and blood stream infection (BSI). METHODS: Data between July 2016 and June 2021 were analysed to determine prevalence, risk factors and outcomes associated with BSIs and MDROs: Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), carbapenem-resistant Pseudomonas spp. (CRP), and carbapenem-resistant Enterobacter (CRE). Data completeness and value for quality improvement activity were assessed. RESULTS: We found a low incidence (3.4%) of the resistant organisms of interest, and no change over the study period. Fequency varied between services and increased with age and size of burn. MRSA was the commonest organism in all age groups. A positive BSI result occurred in 1.6% of patients (12.1% of cultures taken) at a median time of 10.2 days post injury. Free text identification of organisms was inconsistently documented. CONCLUSIONS: The low rate and patterns of acquisition of MDROs of interest and BSIs is comparable with reports from countries with low incidence of massive burns. Wider adoption of a standardized laboratory reporting framework would help realise the potential of clinical quality registries to provide data which supports evidence based infection prevention initiatives.

Clinical and epidemiological characteristics of multi-drug resistant Enterobacterales isolated from King Fahad Hospital of the University, AlKhobar, Saudi Arabia.

Multi-drug resistant (MDR) Enterobacterales remain a major clinical problem. Infections caused by carbapenem-resistant strains are particularly difficult to treat. This study aimed to assess the clinical and epidemiological characteristics of MDR Enterobacterales isolates. A total of 154 non-repetitive clinical isolates, including Escherichia coli (n = 66), Klebsiella pneumoniae (n = 70), and other Enterobacterales (n = 18), were collected from the Diagnostic Microbiology Laboratory at King Fahad Hospital of the University. Most E. coli isolates were collected from urine specimens (n = 50, 75.8%) and resistance against the third and fourth-generation cephalosporins (ceftriaxone, ceftazidime, cefixime, and cefepime) and fluoroquinolones (ciprofloxacin and levofloxacin) was assessed. Clonal relatedness analysis using enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) revealed two clones (E. coli A and B), each comprising two strains. Most K. pneumoniae samples were collected from respiratory specimens (27.1%, 20 samples), and the strains showed overall resistance to most of the antimicrobials tested (54%‒100%). Moreover, clonal-relatedness analysis using ERIC-PCR revealed seven major clones of K. pneumoniae. These findings suggest nosocomial transmission among some identical strains and emphasize the importance of strict compliance with infection prevention and control policies and regulations. Environmental reservoirs could facilitate this indirect transmission, which needs to be investigated.

Incorporating patient, nursing and environmental factors into antimicrobial stewardship: effects of simplifying treatment from cefuroxime to ceftriaxone.

AIM: Our antimicrobial guidelines (AGs) were changed in 2021 to recommend once-daily ceftriaxone in place of three-times-daily cefuroxime as preferred cephalosporin. This analysis sought to assess the effects of this on incidence of Clostridioides difficile infection (CDI), third-generation cephalosporin-resistant Enterobacterales (3GCR-E) and resource utilisation. METHOD: Before and after analysis of 30-day CDI and 3GCR-E incidence following receipt of cefuroxime/ceftriaxone pre- and post-AG change. Total nursing time and waste production relating to cefuroxime/ceftriaxone delivery were calculated pre- and post-change. RESULTS: CDI incidence was 0.6% pre- and 1.0% post-change (adjusted odds ratio [aOR] 1.44, p=0.07) and 3GCR-E incidence 3.5% and 3.1% (aOR 0.90, p=0.33). Mean per-quarter estimated nursing administration time decreased from 2,065 to 1,163 hours (902 nurse-hour reduction) and antibiotic-related waste generation from 1,131kg to 748kg (383kg reduction). Overall days of therapy per-quarter of cefuroxime/ceftriaxone were unchanged between periods. CONCLUSION: This simplification of our AG from a three-times-daily to a once-daily antibiotic resulted in considerable savings for our hospital (roughly 1.7 full-time equivalent nurses and over a tonne of waste yearly), with no significant increases in CDI or 3GCR-E. The impact of dosing schedules on non-antibiotic-spectrum factors, such as nursing time and resource usage, is worthy of consideration when designing AGs.

Emergence of NDM-producing Enterobacterales infections in companion animals from Argentina.

Antimicrobial resistance is considered one of the most critical threat for both human and animal health. Recently, reports of infection or colonization by carbapenemase-producing Enterobacterales in companion animals had been described. This study report the first molecular characterization of NDM-producing Enterobacterales causing infections in companion animals from Argentina. Nineteen out of 3662 Enterobacterales isolates analyzed between October 2021 and July 2022 were resistant to carbapenemes by VITEK2C and disk diffusion method, and suspected to be carbapenemase-producers. Ten isolates were recovered from canine and nine from feline animals. Isolates were identified as K. pneumoniae (n = 9), E. coli (n = 6) and E. cloacae complex (n = 4), and all of them presented positive synergy among EDTA and carbapenems disks, mCIM/eCIM indicative of metallo-carbapenemase production and were also positive by PCR for blaNDM gene. NDM variants were determined by Sanger sequencing method. All 19 isolates were resistant to ß-lactams and aminoglycosides but remained susceptible to colistin (100%), tigecycline (95%), fosfomycin (84%), nitrofurantoin (63%), minocycline (58%), chloramphenicol (42%), doxycycline (21%), enrofloxacin (5%), ciprofloxacin (5%) and trimethoprim/sulfamethoxazole (5%). Almost all isolates (17/19) co-harbored blaCTX-M plus blaCMY, one harbored blaCTX-M alone and the remaining blaCMY. E. coli and E. cloacae complex isolates harbored blaCTX-M-1/15 or blaCTX-M-2 groups, while all K. pneumoniae harbored only blaCTX-M-1/15 genes. All E. coli and E. cloacae complex isolates harbored blaNDM-1, while in K. pneumoniae blaNDM-1 (n = 6), blaNDM-5 (n = 2), and blaNDM-1 plus blaNDM-5 (n = 1) were confirmed. MLST analysis revealed the following sequence types by species, K. pneumoniae: ST15 (n = 5), ST273 (n = 2), ST11, and ST29; E. coli: ST162 (n = 3), ST457, ST224, and ST1196; E. cloacae complex: ST171, ST286, ST544 and ST61. To the best of our knowledge, this is the first description of NDM-producing E. cloacae complex isolates recovered from cats. Even though different species and clones were observed, it is remarkable the finding of some major clones among K. pneumoniae and E. coli, as well as the circulation of NDM as the main carbapenemase. Surveillance in companion pets is needed to detect the spread of carbapenem-resistant Enterobacterales and to alert about the dissemination of these pathogens among pets and humans.

Plasmid-Mediated Fluoroquinolone Resistance among Enterobacterales in Africa: Systematic Review.

INTRODUCTION: According to the World Health Organization, antimicrobial resistance (AMR) is a silent global pandemic that plagues everyone. It makes therapy of infectious diseases more difficult and eventually increases morbidity and mortality. AIM: The purpose of this work is to examine existing data on plasmid-mediated quinolone resistance (PMQR), to assess the prevalence of PMQR genes in Enterobacterales, and to determine any knowledge gaps from sub-Saharan Africa. METHODOLOGY: The Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) standard was followed when conducting this systematic review. The main internet databases examined for pertinent publications were PubMed, Google Scholar, and Ajol. A set of qualifying criteria were used to evaluate the qualified articles. Using the eligibility criteria, 56 full-text articles were chosen for screening. RESULT: Thirty-two (32) articles with the majority originating from West and North Africa and only one article reporting a study carried out in Central Africa were selected for this review. Escherichia coli and Ciprofloxacin were the most reported Enterobacterales and Quinolone respectively. The PMQR genes include qnr (qnrA,qnrB, qnrC, qnrD, and qnrS), aac (6') Ib, aac (6') Ib-cr, oqxAB and qepA gene. The most prevalent PMQR gene is the aac (6') Ib-cr gene (32%) followed by qnrS (26%). CONCLUSION: This study highlighted the requirement for an efficient antimicrobial resistance surveillance system in the continent and revealed a significant incidence of PMQR genes.

INTRODUCTION: Selon l'Organisation mondiale de la santé, la résistance aux antimicrobiens (RAM) est une pandémie mondiale silencieuse qui touche tout le monde. Elle rend le traitement des maladies infectieuses plus difficile et finit par augmenter la morbidité et la mortalité. OBJECTIF: L'objectif de ce travail est d'examiner les données existantes sur la résistance plasmidique aux quinolones (PMQR), d'évaluer la prévalence des gènes PMQR chez les Enterobacterales et de déterminer d'éventuelles lacunes de connaissances en Afrique subsaharienne. MÉTHODOLOGIE: La norme Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) a été suivie lors de la réalisation de cette revue systématique. Les principales bases de données Internet examinées pour des publications pertinentes étaient PubMed, Google Scholar et Ajol. Un ensemble de critères d'admissibilité a été utilisé pour évaluer les articles qualifiés. En utilisant les critères d'éligibilité, 56 articles en texte intégral ont été choisis pour le dépistage. RÉSULTAT: Trente-deux (32) articles, dont la majorité provient d'Afrique de l'Ouest et du Nord, et un seul article rapportant une étude menée en Afrique centrale, ont été sélectionnés pour cette revue. Escherichia coli et la ciprofloxacine étaient les Enterobacterales et les quinolones les plus signalées respectivement. Les gènes PMQR comprennent les gènes qnr (qnrA, qnrB, qnrC, qnrD et qnrS), aac (6 ') Ib, aac (6 ') Ib-cr, oqxAB et qepA. Le gène PMQR le plus prévalent est le gène aac (6 ') Ib-cr (32 %), suivi de qnrS (26 %). CONCLUSION: Cette étude a souligné la nécessité d'un système efficace de surveillance de la résistance aux antimicrobiens sur le continen`t et a révélé une incidence significative des gènes PMQR. MOTS-CLÉS: Enterobacterales, Escherichia coli, Quinolone, Ciprofloxacine, PMQR, "aac(6')-Ib", "aac(6')-Ib-cr", "qnr", "qepA", "oqxAB", "résistance aux antibiotiques".

[Multi-resistant Enterobacterales and travel]. / Entérobactéries multirésistantes et voyage.

Multi-resistant Enterobacterales (MRE) are on the increase worldwide, with the main mechanism of resistance acquisition being horizontal transfer of plasmids coding for extended-spectrum betalactamase and/or carbapenemase. Low- and middle-income countries are the most affected, but surveillance in low-endemicity countries, such as Switzerland, is essential. International travel is one of the sources of MRE dissemination in the community, with the main risk factors for acquiring MRE being a stay in South or Southeast Asia and the use of antibiotics during travel. Other factors, notably animal and environmental, also explain this increase. Measures encompassing a One Health approach are therefore needed to address this issue.

Les entérobactéries multirésistantes (EMR) sont en augmentation dans le monde, avec comme mécanisme principal d'acquisition de résistance le transfert horizontal de plasmides codant pour une bêtalactamase à spectre étendu et/ou une carbapénèmase. Les pays à bas et moyens revenus sont les plus touchés, mais une surveillance dans les pays à faible endémicité, comme la Suisse, est essentielle. Les voyages internationaux sont l'une des sources de dissémination d'EMR dans la communauté, avec comme facteurs de risque principaux d'acquisition d'EMR un séjour en Asie du Sud ou du Sud-Est et l'utilisation d'antibiotiques durant le voyage. D'autres facteurs, notamment animaliers et environnementaux, expliquent aussi cette augmentation. Ainsi, il est nécessaire que des mesures englobant une approche « One Health ¼ répondent à cette problématique.

Genomic characterization of extended-spectrum ß-lactamase-producing Enterobacterales isolated from abdominal surgical patients.

Rectal swabs of 104 patients who underwent abdominal surgery were screened for ESBL producers. Sequence types (STs) and resistance genes were identified by whole-genome sequencing of 46 isolates from 17 patients. All but seven isolates were assigned to recognized STs. While 18 ESBL-producing E. coli (EPEC) strains were of unique STs, ESBL-producing K. pneumoniae (EPKP) strains were mainly ST14 or ST15. Eight patients harboured strains of the same ST before and after abdominal surgery. The most prevalent resistant genes in E. coli were blaEC (69.57%), blaCTX-M (65.22%), and blaTEM (36.95%), while blaSHV was present in only K. pneumoniae (41.30%). Overall, genes encoding ß-lactamases of classes A (blaCTX-M, blaTEM, blaZ), C (blaSHV, blaMIR, and blaDHA), and D (blaOXA) were identified, the most prevalent variants being blaCTX-M-15, blaTEM-1B, blaSHV-28, and blaOXA-1. Interestingly, blaCMY-2, the most common pAmpC ß-lactamase genes reported worldwide, and mobile colistin resistance genes, mcr-10-1, were also identified. The presence of blaCMY-2 and mcr-10-1 is concerning as they may constitute a potentially high risk of pan-resistant post-surgical infections. It is imperative that healthcare professionals monitor intra-abdominal surgical site infections rigorously to prevent transmission of faecal ESBL carriage in high-risk patients.

Carriage of antimicrobial-resistant Enterobacterales among pregnant women and newborns in Amhara, Ethiopia.

OBJECTIVES: Infections are one of the most common causes of neonatal mortality, and maternal colonization has been associated with neonatal infection. In this study, we sought to quantify carriage prevalence of extended-spectrum-beta-lactamase (ESBL) -producing and carbapenem-resistant Enterobacterales (CRE) among pregnant women and their neonates and to characterize risk factors for carriage in rural Amhara, Ethiopia. METHODS: We conducted a prospective cohort study nested in the Birhan field site. We collected rectal and vaginal samples from 211 pregnant women in their third trimester and/or during labor/delivery and perirectal or stool samples from 159 of their neonates in the first week of life. RESULTS: We found that carriage of ESBL-producing organisms was fairly common (women: 22.3%, 95% CI: 16.8-28.5; neonates: 24.5%, 95% CI: 18.1-32.0), while carriage of CRE (women: 0.9%, 95% CI: 0.1-3.4; neonates: 2.5%, 95% CI: 0.7-6.3) was rare. Neonates whose mothers tested positive for ESBL-producing organisms were nearly twice as likely to also test positive for ESBL-producing organisms (38.7% vs 21.1%, P-value = 0.06). Carriage of ESBL-producing organisms was also associated with Woreda (district) of sample collection and recent antibiotic use. CONCLUSION: Understanding carriage patterns of potential pathogens and antibiotic susceptibility among pregnant women and newborns will inform local, data-driven recommendations to prevent and treat neonatal infections.

Spread of carbapenemase-producing Morganella spp from 2013 to 2021: a comparative genomic study.

BACKGROUND: Morganella spp are opportunistic pathogens involved in various infections. Intrinsic resistance to multiple antibiotics (including colistin) combined with the emergence of carbapenemase producers reduces the number of active antimicrobials. The aim of this study was to characterise genetic features related to the spread of carbapenem-resistant Morganella spp. METHODS: This comparative genomic study included extensively drug-resistant Morganella spp isolates collected between Jan 1, 2013, and March 1, 2021, by the French National Reference Center (NRC; n=68) and European antimicrobial resistance reference centres in seven European countries (n=104), as well as one isolate from Canada, two reference strains from the Pasteur Institute collection (Paris, France), and two colistin-susceptible isolates from Bicêtre Hospital (Kremlin-Bicêtre, France). The isolates were characterised by whole-genome sequencing, antimicrobial susceptibility testing, and biochemical tests. Complete genomes from GenBank (n=103) were also included for genomic analysis, including phylogeny and determination of core genomes and resistomes. Genetic distance between different species or subspecies was performed using average nucleotide identity (ANI). Intrinsic resistance mechanisms to polymyxins were investigated by combining genetic analysis with mass spectrometry on lipid A. FINDINGS: Distance analysis by ANI of 275 isolates identified three groups: Morganella psychrotolerans, Morganella morganii subspecies sibonii, and M morganii subspecies morganii, and a core genome maximum likelihood phylogenetic tree showed that the M morganii isolates can be separated into four subpopulations. On the basis of these findings and of phenotypic divergences between isolates, we propose a modified taxonomy for the Morganella genus including four species, Morganella psychrotolerans, Morganella sibonii, Morganella morganii, and a new species represented by a unique environmental isolate. We propose that M morganii include two subspecies: M morganii subspecies morganii (the most prevalent) and M morganii subspecies intermedius. This modified taxonomy was supported by a difference in intrinsic resistance to tetracycline and conservation of metabolic pathways such as trehalose assimilation, both only present in M sibonii. Carbapenemase producers were mostly identified among five high-risk clones of M morganii subspecies morganii. The most prevalent carbapenemase corresponded to NDM-1, followed by KPC-2, and OXA-48. A cefepime-zidebactam combination was the most potent antimicrobial against the 172 extensively drug-resistant Morganella spp isolates in our collection from different European countries, which includes metallo-ß-lactamase producers. Lipid A analysis showed that the intrinsic resistance to colistin was associated with the presence of L-ARA4N on lipid A. INTERPRETATION: This global characterisation of, to our knowledge, the widest collection of extensively drug-resistant Morganella spp highlights the need to clarify the taxonomy and decipher intrinsic resistance mechanisms, and paves the way for further genomic comparisons. FUNDING: None.

Epidemiology and antimicrobial susceptibility profiles of Enterobacterales causing bloodstream infections before and during COVID-19 pandemic: Results of the Study for Monitoring Antimicrobial Resistance Trends (SMART) in Taiwan, 2018-2021.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has contributed to the spread of antimicrobial resistance, including carbapenem-resistant Enterobacterales. METHODS: This study utilized data from the Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program in Taiwan. Enterobacterales from patients with bloodstream infections (BSIs) were collected and subjected to antimicrobial susceptibility testing and ß-lactamase gene detection using a multiplex PCR assay. Statistical analysis was conducted to compare susceptibility rates and resistance genes between time periods before (2018-2019) and during the COVID-19 pandemic (2020-2021). RESULTS: A total of 1231 Enterobacterales isolates were collected, predominantly Escherichia coli (55.6%) and Klebsiella pneumoniae (29.2%). The proportion of nosocomial BSIs increased during the COVID-19 pandemic (55.5% vs. 61.7%, p < 0.05). Overall, susceptibility rates for most antimicrobial agents decreased, with Enterobacterales from nosocomial BSIs showing significantly lower susceptibility rates than those from community-acquired BSIs. Among 123 Enterobacterales isolates that underwent molecular resistance mechanism detection, ESBL, AmpC ß-lactamase, and carbapenemase genes were detected in 43.1%, 48.8% and 16.3% of the tested isolates, respectively. The prevalence of carbapenemase genes among carbapenem-resistant Enterobacterales increased during the pandemic, although the difference was not statistically significant. Two novel ß-lactamase inhibitor combinations, imipenem-relebactam and meropenem-vaborbactam, preserved good efficacy against Enterobacterales. However, imipenem-relebactam showed lower in vitro activity against imipenem-non-susceptible Enterobacterales than that of meropenem-vaborbactam. CONCLUSIONS: The COVID-19 pandemic appears to be associated with a general decrease in antimicrobial susceptibility rates among Enterobacterales causing BSIs in Taiwan. Continuous surveillance is crucial to monitor antimicrobial resistance during the pandemic and in the future.

Antimicrobial Use and Carbapenem-Resistant Enterobacterales in Korea: A Nationwide Case-Control Study With Propensity Score Matching.

BACKGROUND: Nationwide research on the association between carbapenem-resistant Enterobacterales (CREs) and antibiotic use is limited. METHODS: This nested case-control study analyzed Korean National Health Insurance claims data from April 2017 to April 2019. Based on the occurrence of CRE, hospitalized patients aged ≥ 18 years were classified into CRE (cases) and control groups. Propensity scores based on age, sex, modified Charlson comorbidity score, insurance type, long-term care facility, intensive care unit stay, and acquisition of vancomycin-resistant Enterococci were used to match the case and control groups (1:3). RESULTS: After matching, the study included 6,476 participants (1,619 cases and 4,857 controls). Multivariable logistic regression analysis revealed that the utilization of broad-spectrum antibiotics, such as piperacillin/tazobactam (adjusted odds ratio [aOR], 2.178; 95% confidence interval [CI], 1.829-2.594), third/fourth generation cephalosporins (aOR, 1.764; 95% CI, 1.514-2.056), and carbapenems (aOR, 1.775; 95% CI, 1.454-2.165), as well as the presence of comorbidities (diabetes [aOR, 1.237; 95% CI, 1.061-1.443], hemiplegia or paraplegia [aOR, 1.370; 95% CI, 1.119-1.679], kidney disease [aOR, 1.312; 95% CI, 1.105-1.559], and liver disease [aOR, 1.431; 95% CI, 1.073-1.908]), were significantly associated with the development of CRE. Additionally, the CRE group had higher mortality (8.33 vs. 3.32 incidence rate per 100 person-months, P < 0.001) and a total cost of healthcare utilization per person-month (15,325,491 ± 23,587,378 vs. 5,263,373 ± 14,070,118 KRW, P < 0.001) than the control group. CONCLUSION: The utilization of broad-spectrum antibiotics and the presence of comorbidities are associated with increasing development of CRE. This study emphasizes the importance of antimicrobial stewardship in reducing broad-spectrum antibiotic use and CRE disease burden in Korea.

Transmission of blaNDM in Enterobacteriaceae among animals, food and human.

Despite carbapenems not being used in animals, carbapenem-resistant Enterobacterales (CRE), particularly New Delhi metallo-ß-lactamase-producing CRE (NDM-CRE), are prevalent in livestock. Concurrently, the incidence of human infections caused by NDM-CRE is rising, particularly in children. Although a positive association between livestock production and human NDM-CRE infections at the national level was identified, the evidence of direct transmission of NDM originating from livestock to humans remains largely unknown. Here, we conducted a cross-sectional study in Chengdu, Sichuan Province, to examine the prevalence of NDM-CRE in chickens and pigs along the breeding-slaughtering-retail chains, in pork in cafeterias of schools, and in colonizations and infections from children's hospital and examined the correlation of NDM-CRE among animals, foods and humans. Overall, the blaNDM increases gradually along the chicken and pig breeding (4.70%/2.0%) -slaughtering (7.60%/22.40%) -retail (65.56%/34.26%) chains. The slaughterhouse has become a hotspot for cross-contamination and amplifier of blaNDM. Notably, 63.11% of pork from the school cafeteria was positive for blaNDM. The prevalence of blaNDM in intestinal and infection samples from children's hospitals was 21.68% and 19.80%, respectively. whole genome sequencing (WGS) analysis revealed the sporadic, not large-scale, clonal spread of NDM-CRE along the chicken and pig breeding-slaughtering-retail chain, with further spreading via IncX3-blaNDM plasmid within each stage of whole chains. Clonal transmission of NDM-CRE is predominant in children's hospitals. The IncX3-blaNDM plasmid was highly prevalent among animals and humans and accounted for 57.7% of Escherichia coli and 91.3% of Klebsiella pneumoniae. Attention should be directed towards the IncX3 plasmid to control the transmission of blaNDM between animals and humans.

High prevalence of multidrug-resistant Enterobacterales carrying extended-spectrum beta-lactamase and AmpC genes isolated from neonatal sepsis in Ahvaz, Iran.

OBJECTIVES: In the recent years, multidrug resistant (MDR) neonatal septicemia-causing Enterobacterales has been dramatically increased due to the extended-spectrum beta-lactamases (ESBLs) and AmpC enzymes. This study aimed to assess the antibiotic resistance pattern, prevalence of ESBLs/AmpC beta-lactamase genes, and Enterobacterial Repetitive Intergenic Consensus Polymerase Chain Reaction (ERIC-PCR) fingerprints in Enterobacterales isolated from neonatal sepsis. RESULTS: In total, 59 Enterobacterales isolates including 41 (69.5%) Enterobacter species, 15 (25.4%) Klebsiella pneumoniae and 3 (5.1%) Escherichia coli were isolated respectively. Resistance to ceftazidime and cefotaxime was seen in all of isolates. Furthermore, all of them were multidrug-resistant (resistant to three different antibiotic categories). The phenotypic tests showed that 100% of isolates were ESBL-positive. Moreover, AmpC production was observed in 84.7% (n = 50/59) of isolates. Among 59 ESBL-positive isolates, the highest percentage belonged to blaCTX-M-15 gene (66.1%) followed by blaCTX-M (45.8%), blaCTX-M-14 (30.5%), blaSHV (28.8%), and blaTEM (13.6%). The frequency of blaDHA, blaEBC, blaMOX and blaCIT genes were 24%, 24%, 4%, and 2% respectively. ERIC-PCR analysis revealed that Enterobacterales isolates were genetically diverse. The remarkable prevalence of MDR Enterobacterales isolates carrying ESBL and AmpC beta-lactamase genes emphasizes that efficient surveillance measures are essential to avoid the more expansion of drug resistance amongst isolates.

The EC-COMPASS: Long-term, multi-centre surveillance of Enterobacter cloacae complex - a clinical perspective.

BACKGROUND: Enterobacter cloacae complex (ECCO) comprises closely related Enterobacterales, causing a variety of infections ranging from mild urinary tract infections to severe bloodstream infections. ECCO has emerged as a significant cause of healthcare-associated infections, particularly in neonatal and adult intensive care. AIM: The Enterobacter Cloacae COMplex PASsive Surveillance (EC-COMPASS) aims to provide a detailed multi-centre overview of ECCO epidemiology and resistance patterns detected in routine microbiological diagnostics in four German tertiary-care hospitals. METHODS: In a sentinel cluster of four German tertiary-care hospitals, all culture-positive ECCO results between 1st January 2020 and 31st December 2022, were analysed based on Hybase® laboratory data. FINDINGS: Analysis of 31,193 ECCO datasets from 14,311 patients revealed a higher incidence in male patients (P<0.05), although no significant differences were observed in ECCO infection phenotypes. The most common sources of ECCO were swabs (42.7%), urine (17.5%), respiratory secretions (16.1%), blood cultures (8.9%) and tissue samples (5.6%). The annual bacteraemia rate remained steady at approximately 33 cases per hospital. Invasive ECCO infections were predominantly found in oncology and intensive care units. Incidences of nosocomial outbreaks were infrequent and limited in scope. Notably, resistance to carbapenems was consistently low. CONCLUSION: EC-COMPASS offers a profound clinical perspective on ECCO infections in German tertiary-healthcare settings, highlighting elderly men in oncology and intensive care units as especially vulnerable to ECCO infections. Early detection strategies targeting at-risk patients could improve ECCO infection management.