Abdominal abscess caused by Raoultella ornithinolytica secondary to postoperative gastric fistula: case report and review of literature.

BACKGROUND: In recent years, Raoultella ornithinolytica (R. ornithinolytica) have attracted clinical attention as a new type of pathogen. A wide range of infections with these germs is reported, and commonly found in urinary tract infections, respiratory infections, and bacteremia. CASE PRESENTATION: We report the case of an elderly woman with liver abscess, choledocholithiasis and cholangitis, who developed gastric fistula and abdominal abscess after underwent choledocholithotomy, and R. ornithinolytica were isolated from the abdominal drainage fluid. The patient was treated with meropenem and levofloxacin and had a good outcome. CONCLUSIONS: To the best of our knowledge, case of isolating R. ornithinolytica from a patient with non-viscerally abdominal abscess was extremely rare. We share a case of a woman with non-viscerally abdominal abscess secondary to postoperative gastric fistula, R. ornithinolytica was isolated from the patient's pus, and the pathogenic bacteria may originate from the gastrointestinal tract. Based on this case, We should be cautious that invasive treatment may greatly increase the probability of infection with this pathogenic bacterium.

Genomic insights of Leclercia adecarboxylata strains linked to an outbreak in public hospitals in Mexico.

BACKGROUND: Leclercia adecarboxylata is a bacteria closely related to Escherichia coli according to its biochemical characteristics and is commonly considered non-pathogenic although a growing number of publications classify it as an emerging pathogen. Fosfomycin resistance is a common trait for L. adecarboxylata encoded by fosALA gene. OBJECTIVE: To analyze genomic traits of sixteen L. adecarboxylata strains isolated from blood culture and a bottle of total parenteral nutrition. METHODS: Twenty-eight L. adecarboxylata strains isolated from blood culture and a bottle of total parenteral nutrition were identified biochemically with a Vitek ® automated system. The strains were phenotyped by their growth on Eosin Methylene Blue agar or MacConkey agar plates. Additionally, Pulsed field gel electrophoresis (PFGE) was performed to establish the clonal relationship. The genomic DNA of sixteen strains was obtained using a Qubit ® dsDNA HS Assay Kit and sequenced on an Illumina ® MiSeq instrument. Draft genomes were assembled using PROKKA and Rast. Assemblies were submitted to Resfinder and PathogenFinder from the Center for Genomic Epidemiology in order to find resistance genes and pathogenic potential. IslandViewer4 was also used to find Pathogenicity and Phage Islands. For identification of the fosA gene, manual curation and Clustal analysis was performed. A novel FosA variant was identified. Finally, phylogenetic analysis was performed using VAMPhyRE software and Mega X. RESULTS: In this paper, we report the genomes of sixteen strains of Leclercia adecarboxylata causing an outbreak associated with parenteral nutrition in public hospitals in Mexico. The genomes were analyzed for genetic determinants of virulence and resistance. A high pathogenic potential (pathogenicity index 0.82) as well as multiple resistance genes including carbapenemics, colistin and efflux pumps were determined. Based on sequence analysis, a new variant of the fosALA gene was described. Finally, the outbreak was confirmed by establishing the clonal relationship among the sixteen genomes obtained. CONCLUSIONS: Commensal strains of L. adecarboxylata may acquire genetic determinants that provide mechanisms of host damage and go unnoticed in clinical diagnosis. L. adecarboxylata can evolve in a variety of ways including the acquisition of resistance and virulence genes representing a therapeutic challenge in patient care.

Chronic Diarrhea Associated with Edwardsiella Tarda Gastroenteritis: A Case Report and Literature Review.

Edwardsiella tarda , a Gram-negative bacterium classified into the genus Enterobacteriaceae, causes self-limited gastroenteritis. Here, we report a case of E. tarda gastroenteritis in a previously healthy 12-year-old boy in whom inflammatory bowel disease was precluded by endoscopy and tissue biopsy due to 3-month history of diarrhea, abdominal pain and weight loss.

Association of Proteus mirabilis and Providencia stuartii Infections with Diabetes.

Background and Objectives: Proteus and Providencia are related genera of opportunistic pathogens belonging to the Morganellaceae family, often a cause of infections in the immunocompromised hosts, such as diabetic patients. Their clinical significance has increased due to their intrinsic resistance to polymyxins, which is often associated with acquired resistance mechanisms. In this study we evaluated the infections caused by Proteus mirabilis and Providencia stuartii in two groups of patients, with diabetes (group 1) and without diabetes (group 2) admitted to the intensive care unit and surgical wards. The infections were investigated in terms of infection type, risk factors, clinical course, predictive factors for unfavourable outcomes and antibiotic resistance profile. Materials and Methods: An observational, retrospective, cross-sectional study was conducted, comprising all patients infected with these pathogens. Bacterial identification and antibiotic sensitivity testing were performed using the Vitek2C automated system. Results: Comparison of the two groups showed that the statistically significant common infectious risk factors were found less frequently among diabetic patients when compared with non-diabetic patients, and that antimicrobial resistance was significantly lower in the diabetic patient group. However, survival rates did not differ between the two groups, drawing attention to the implications of diabetes as comorbidity. Additionally, with regard to the antibiotic resistance profile, 38.89% of P. stuartii strains isolated from diabetic patients belonged to the difficult-to-treat (DTR) phenotype, contributing to the severity of these infections compared with those caused by P. mirabilis, of which 32% were wild type strains and 0% were DTR phenotype. The DTR/extended spectrum beta-lactamase producing P. stuartii isolates more than doubled the risk of mortality, while the presence of nasogastric nutrition tripled the risk. Conclusions: P. stuartii infections that occurred in diabetic patients proved to be more difficult to treat, the majority of them being healthcare-associated bacteremias.

Human Amnion-Derived Mesenchymal Stromal Cells: A New Potential Treatment for Carbapenem-Resistant Enterobacterales in Decompensated Cirrhosis.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a severe and often fatal infection in patients with decompensated cirrhosis and ascites. The only cure for SBP is antibiotic therapy, but the emerging problem of bacterial resistance requires novel therapeutic strategies. Human amniotic mesenchymal stromal cells (hA-MSCs) possess immunomodulatory and anti-inflammatory properties that can be harnessed as a therapy in such a context. METHODS: An in vitro applications of hA-MSCs in ascitic fluid (AF) of cirrhotic patients, subsequently infected with carbapenem-resistant Enterobacterales, was performed. We evaluated the effects of hA-MSCs on bacterial load, innate immunity factors, and macrophage phenotypic expression. RESULTS: hA-MSCs added to AF significantly reduce the proliferation of both bacterial strains at 24 h and diversely affect M1 and M2 polarization, C3a complement protein, and ficolin 3 concentrations during the course of infection, in a bacterial strain-dependent fashion. CONCLUSION: This study shows the potential usefulness of hA-MSC in treating ascites infected with carbapenem-resistant bacteria and lays the foundation to further investigate antibacterial and anti-inflammatory roles of hA-MSC in in vivo models.

Severe neonatal COVID-19: Challenges in management and therapeutic approach.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), may manifest as a life-threatening respiratory infection with systemic complications. Clinical manifestations among children are generally less severe than those seen in adults, but critical cases have increasingly been reported in infants less than 1 year of age. We report a severe case of neonatal COVID-19 requiring intensive care and mechanical ventilation, further complicated by a multidrug-resistant Enterobacter asburiae super-infection. Chest X-rays, lung ultrasound, and chest computed tomography revealed extensive interstitial pneumonia with multiple consolidations, associated with persistent increased work of breathing and feeding difficulties. SARS-CoV-2 RNA was detected in respiratory specimens and stools, but not in other biological samples, with a rapid clearance in stools. Serological tests demonstrated a specific SARS-CoV-2 antibody response mounted by the neonate and sustained over time. The therapeutic approach included the use of enoxaparin and steroids which may have contributed to the bacterial complication, underlying the challenges in managing neonatal COVID-19, where the balance between viral replication and immunomodulation maybe even more challenging than in older ages.

Clinical and molecular characteristics and risk factors for patients acquiring carbapenemase-producing and non-carbapenemase-producing carbapenem-nonsusceptible-Enterobacterales bacteremia.

BACKGROUND/PURPOSE: Carbapenem-nonsusceptible Enterobacterales (CNSE) are a growing global threat. Carbapenemases are often produced by plasmids, which allow rapid transmission. This study aimed to investigate (1) the bacterial type (2) resistant genes (3) antimicrobial susceptibility and (4) risk factors for acquisition of carbapenemase-producing carbapenem-nonsusceptible Enterobacterales (CP-CNSE) and non-carbapenemase-producing carbapenem-nonsusceptible Enterobacterales (non-CP-CNSE) bacteremia. METHODS: There were a total of 113 isolates of Enterobacterales from 2013 to 2018. After excluding nonblood isolates and including only one sample from each patient, 99 isolates were analyzed and the medical charts of these patients were reviewed. Carbapenemase genes, ß-lactamase genes and antimicrobial susceptibility of the isolates were determined. Multilocus sequence typing (MLST) was performed on CP-CNSE isolates. RESULTS: CP-CNSE carried more blaSHV (P = 0.004) and were more resistant to imipenem than non-CP-CNSE (P < 0.001). In the univariate analyses, we found that CP-CNSE bloodstream infection was associated with patient <65 years of age (odds ratio, 3.90; 95% confidence interval [CI], 1.16 to 13.10; P = 0.027), mechanical ventilation at the time of bloodstream infection (BSI) (odds ratio, 3.85; 95% CI, 1.16-12.78; P = 0.028) and exposure to piperacillin/tazobactam (odds ratio, 3.96; 95% CI, 1.09-14.38; P = 0.037). However, on multivariate analyses, no independent predictor for CP-CNSE was identified in this study. CONCLUSION: CP-CNSE carried more blaSHV and were more resistant to imipenem when compared to non-CP-CNSE. No independent predictor for CP-CNSE was identified after multivariate analysis. This is the first study conducted in Taiwan comparing risk factors between CP-CNSE and non-CP-CNSE from both clinical and molecular aspects.

λ-carrageenan exacerbates Citrobacter rodentium-induced infectious colitis in mice by targeting gut microbiota and intestinal barrier integrity.

For nearly half a century, the scientific community has been unable to agree upon the safety profile of carrageenan (CGN), a ubiquitous food additive. Little is known about the mechanisms by which consumption of CGN aggravates the etiopathogenesis of murine colitis. However, analyses of gut microbiota and intestinal barrier integrity have provided a breakthrough in explaining the synergistic effect of CGN upon colitis. In Citrobacter rodentium-induced infectious murine colitis, inflammation and the clinical severity of gut tissue were aggravated in the presence of λ-CGN. Using fecal transplantation and germ-free mice experiments, we evaluated the role of intestinal microbiota on the pro-inflammatory effect of λ-CGN. Mice with high dietary λ-CGN consumption showed altered colonic microbiota composition that resulted in degradation of the colonic mucus layer, a raised fecal LPS level, and a decrease in the presence of bacterially derived short-chain fatty acids (SCFAs). Mucus layer defects and altered fecal LPS and SCFA levels could be reproduced in germ-free mice by fecal transplantation from CGN-H-fed mice, but not from germ-free CGN-H-fed mice. Our results confirm that λ-CGN may create an environment that favors inflammation by altering gut microbiota composition and gut bacterial metabolism. The present study provides evidence that the "gut microbiota-barrier axis" could be an alternative target for ameliorating the colitis promoting effect of λ-CGN.

Amino Acid-Based Diet Prevents Lethal Infectious Diarrhea by Maintaining Body Water Balance in a Murine Citrobacter rodentium Infection Model.

Infectious diarrhea is one of the most important health problems worldwide. Although nutritional status influences the clinical manifestation of various enteric pathogen infections, the effect of diet on enteric infectious diseases remains unclear. Using a fatal infectious diarrheal model, we found that an amino acid-based diet (AD) protected susceptible mice infected with the enteric pathogen Citrobacter rodentium. While the mice fed other diets, including a regular diet, were highly susceptible to C. rodentium infection, AD-fed mice had an increased survival rate. An AD did not suppress C. rodentium colonization or intestinal damage; instead, it prevented diarrhea-induced dehydration by increasing water intake. An AD altered the plasma and fecal amino acid levels and changed the gut microbiota composition. Treatment with glutamate, whose level was increased in the plasma and feces of AD-fed mice, promoted water intake and improved the survival of C. rodentium-infected mice. Thus, an AD changes the systemic amino acid balance and protects against lethal infectious diarrhea by maintaining total body water content.

First case report of acute cholangitis secondary to Cronobacter sakazakii.

INTRODUCTION: Cronobacter sakazakii is an opportunistic Gram-negative, rod-shaped bacterium which may be a causative agent of meningitis in premature infants and enterocolitis and bacteremia in neonates and adults. While there have been multiple cases of C. sakazakii infections, there have been no acute cholangitis cases reported in humans. CASE PRESENTATION: An 81-year-old male with a past medical history of basal cell carcinoma, alcoholic liver cirrhosis, transjugular intrahepatic portosystemic shunt procedure, complicated by staphylococcus bacteremia, pituitary tumor, glaucoma, and hypothyroidism presented to the emergency room with the complaint of diffuse and generalized 10/10 abdominal pain of 1 day's duration. There was a concern for pancreatitis, acute cholangitis, and possible cholecystitis, and the patient underwent a percutaneous cholecystostomy tube placement. Blood cultures from admission and biliary fluid cultures both grew C. sakazakii. The patient was treated with a carbapenem and clinically improved. CONCLUSIONS: The case study described a patient with multiple medical comorbidities that presented with C. sakazakii bacteremia and cholangitis. While this bacterium has been implicated in other infections, we believe this is the first time the bacteria is being documented to have caused acute cholangitis.

Colonization of the Caenorhabditis elegans gut with human enteric bacterial pathogens leads to proteostasis disruption that is rescued by butyrate.

Protein conformational diseases are characterized by misfolding and toxic aggregation of metastable proteins, often culminating in neurodegeneration. Enteric bacteria influence the pathogenesis of neurodegenerative diseases; however, the complexity of the human microbiome hinders our understanding of how individual microbes influence these diseases. Disruption of host protein homeostasis, or proteostasis, affects the onset and progression of these diseases. To investigate the effect of bacteria on host proteostasis, we used Caenorhabditis elegans expressing tissue-specific polyglutamine reporters that detect changes in the protein folding environment. We found that colonization of the C. elegans gut with enteric bacterial pathogens disrupted proteostasis in the intestine, muscle, neurons, and the gonad, while the presence of bacteria that conditionally synthesize butyrate, a molecule previously shown to be beneficial in neurodegenerative disease models, suppressed aggregation and the associated proteotoxicity. Co-colonization with this butyrogenic strain suppressed bacteria-induced protein aggregation, emphasizing the importance of microbial interaction and its impact on host proteostasis. Further experiments demonstrated that the beneficial effect of butyrate depended on the bacteria that colonized the gut and that this protective effect required SKN-1/Nrf2 and DAF-16/FOXO transcription factors. We also found that bacteria-derived protein aggregates contribute to the observed disruption of host proteostasis. Together, these results reveal the significance of enteric infection and gut dysbiosis on the pathogenesis of protein conformational diseases and demonstrate the potential of using butyrate-producing microbes as a preventative and treatment strategy for neurodegenerative disease.

Pyosalpinx due to Cronobacter sakazakii in an elderly woman.

BACKGROUND: Cronobacter sakazakii (C. sakazakii) is a bacterium known to cause severe neonatal infections in premature infants with the consumption of contaminated powdered milk formula. Adult infections are rare, and there have been no reports of pyosalpinx due to C. sakazakii to date. CASE PRESENTATION: We report a case of left pyosalpinx due to C. sakazakii in a sexually inactive postmenopausal woman. A 70-year-old woman presented to our hospital with left lower abdominal pain and fever. Abdominal computed tomography disclosed a cystic mass continuous with the left edge of the uterus. Urgent laparotomy revealed a ruptured left pyosalpinx with pus-like content. Left salpingo-oophorectomy, resection of the right tube, and washing of the abdominal cavity with saline were performed. Pathological examination of the left adnexa showed tubal tissue with acute inflammation and inflammatory exudate, which were compatible with pyosalpinx, and pus culture yielded C. sakazakii. CONCLUSIONS: This is the first case report of pyosalpinx due to C. sakazakii. Cronobacter sakazakii infections in adult women might occur in the elderly, whose immunity has weakened. Further accumulation of cases of C. sakazakii infection is needed to clarify the etiology and behavior of C. sakazakii in adults.

Temporal trends, risk factors and outcomes of infections due to extended-spectrum ß-lactamase producing Enterobacterales in Swiss solid organ transplant recipients between 2012 and 2018.

BACKGROUND: The burden of antimicrobial resistance is high in solid organ transplant (SOT) recipients. Among Swiss SOT recipients, we assessed temporal trends of ESBL-producing Enterobacterales (ESBL-E), identified risk factors for ESBL-E, and assessed the impact of resistance on patient outcome. METHODS: Data from the Swiss Transplant Cohort Study (STCS), a nationwide prospective cohort of SOT-recipients, were analysed. Temporal trends were described for ESBL-detection among Escherichia coli and non-Escherichia coli. In a nested case-control study, cases with ESBL-E infection were 1:1 matched (by time since transplantation, organ transplant, pathogen) to controls infected with non-ESBL-E. Factors associated with resistance and with unfavourable 30-day outcome (death, infection relapse, graft loss) were assessed. RESULTS: From 2012 to 2018, we identified 1'212 infection episodes caused by Enterobacterales in 1'074 patients, thereof 11.4% (138/1'212) caused by ESBL-E. The proportion of ESBL-production among Escherichia coli remained stable over time (p = 0.93) but increased for non-E. coli (p = 0.02) Enterobacterales. In the case-control study (n = 102), antibiotic pre-treatment was independently associated with ESBL-production (aOR = 2.6, 95%-CI: 1.0-6.8, p = 0.046). Unfavourable outcome occurred in 24/51 (47%) cases and 9/51 (18%) controls (p = 0.003). Appropriate empiric antibiotic therapy was the only modifiable factor associated with unfavourable outcome. CONCLUSIONS: In Swiss SOT-recipients, proportion of infections with ESBL-producing non-E. coli Enterobacterales increased in recent years. Antibiotic pre-treatment represents a risk factor for ESBL-E. Improving appropriateness of empiric antibiotic treatment might be an important measure to reduce unfavourable outcome, which was observed in almost half of SOT-recipients with ESBL-E infections.

Interleukin-33 signaling exacerbates experimental infectious colitis by enhancing gut permeability and inhibiting protective Th17 immunity.

A wide range of microbial pathogens is capable of entering the gastrointestinal tract, causing infectious diarrhea and colitis. A finely tuned balance between different cytokines is necessary to eradicate the microbial threat and to avoid infection complications. The current study identified IL-33 as a critical regulator of the immune response to the enteric pathogen Citrobacter rodentium. We observed that deficiency of the IL-33 signaling pathway attenuates bacterial-induced colitis. Conversely, boosting this pathway strongly aggravates the inflammatory response and makes the mice prone to systemic infection. Mechanistically, IL-33 mediates its detrimental effect by enhancing gut permeability and by limiting the induction of protective T helper 17 cells at the site of infection, thus impairing host defense mechanisms against the enteric pathogen. Importantly, IL-33-treated infected mice supplemented with IL-17A are able to resist the otherwise strong systemic spreading of the pathogen. These findings reveal a novel IL-33/IL-17A crosstalk that controls the pathogenesis of Citrobacter rodentium-driven infectious colitis. Manipulating the dynamics of cytokines may offer new therapeutic strategies to treat specific intestinal infections.

Local immune response to food antigens drives meal-induced abdominal pain.

Up to 20% of people worldwide develop gastrointestinal symptoms following a meal1, leading to decreased quality of life, substantial morbidity and high medical costs. Although the interest of both the scientific and lay communities in this issue has increased markedly in recent years, with the worldwide introduction of gluten-free and other diets, the underlying mechanisms of food-induced abdominal complaints remain largely unknown. Here we show that a bacterial infection and bacterial toxins can trigger an immune response that leads to the production of dietary-antigen-specific IgE antibodies in mice, which are limited to the intestine. Following subsequent oral ingestion of the respective dietary antigen, an IgE- and mast-cell-dependent mechanism induced increased visceral pain. This aberrant pain signalling resulted from histamine receptor H1-mediated sensitization of visceral afferents. Moreover, injection of food antigens (gluten, wheat, soy and milk) into the rectosigmoid mucosa of patients with irritable bowel syndrome induced local oedema and mast cell activation. Our results identify and characterize a peripheral mechanism that underlies food-induced abdominal pain, thereby creating new possibilities for the treatment of irritable bowel syndrome and related abdominal pain disorders.

Effect of resolvins on sensitisation of TRPV1 and visceral hypersensitivity in IBS.

OBJECTIVE: Resolvins (RvD1, RvD2 and RvE1) are endogenous anti-inflammatory lipid mediators that display potent analgesic properties in somatic pain by modulating transient receptor potential vanilloid 1 (TRPV1) activation. To what extent these molecules could also have a beneficial effect on TRPV1 sensitisation and visceral hypersensitivity (VHS), mechanisms involved in IBS, remains unknown. DESIGN: The effect of RvD1, RvD2 and RvE1 on TRPV1 activation and sensitisation by histamine or IBS supernatants was assessed on murine dorsal root ganglion (DRG) neurons using live Ca2+ imaging. Based on the results obtained in vitro, we further studied the effect of RvD2 in vivo using a murine model of post-infectious IBS and a rat model of post-inflammatory VHS. Finally, we also tested the effect of RvD2 on submucosal neurons in rectal biopsies of patients with IBS. RESULTS: RvD1, RvD2 and RvE1 prevented histamine-induced TRPV1 sensitisation in DRG neurons at doses devoid of an analgesic effect. Of note, RvD2 also reversed TRPV1 sensitisation by histamine and IBS supernatant. This effect was blocked by the G protein receptor 18 (GPR18) antagonist O-1918 (3-30 µM) and by pertussis toxin. In addition, RvD2 reduced the capsaicin-induced Ca2+ response of rectal submucosal neurons of patients with IBS. Finally, treatment with RvD2 normalised pain responses to colorectal distention in both preclinical models of VHS. CONCLUSIONS: Our data suggest that RvD2 and GPR18 agonists may represent interesting novel compounds to be further evaluated as treatment for IBS.

Cronobacter sakazakii Infection in Early Postnatal Rats Impaired Contextual-Associated Learning: a Putative Role of C5a-Mediated NF-κß and ASK1 Pathways.

This study was designed to test whether the Cronobacter sakazakii infection-impaired contextual learning and memory are mediated by the activation of the complement system; subsequent activation of inflammatory signals leads to alternations in serotonin transporter (SERT). To test this, rat pups (postnatal day, PND 15) were treated with either C. sakazakii (107 CFU) or Escherichia coli OP50 (107 CFU) or Luria bertani broth (100 µL) through oral gavage and allowed to stay with their mothers until PND 24. Experimental groups' rats were allowed to explore (PNDs 31-35) and then trained in contextual learning task (PNDs 36-43). Five days after training, individuals were tested for memory retention (PNDs 49-56). Observed behavioural data showed that C. sakazakii infection impaired contextual-associative learning and memory. Furthermore, our analysis showed that C. sakazakii infection activates complement system complement anaphylatoxin (C5a) (a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS1)) and mitogen-activated protein kinase kinase1 (MEKK1). Subsequently, MEKK1 induces pro-inflammatory signals possibly through apoptosis signal-regulating kinase-1 (ASK-1), c-Jun N-terminal kinase (JNK1/3) and protein kinase B gamma (AKT-3). In parallel, activated nuclear factor kappa-light-chain-enhancer B cells (NF-κB) induces interleukin-6 (IL-6) and IFNα-1, which may alter the level of serotonin transporter (SERT). Observed results suggest that impaired contextual learning and memory could be correlated with C5a-mediated NF-κß and ASK1 pathways.

Carbapenemase-producing Enterobacterales causing secondary infections during the COVID-19 crisis at a New York City hospital.

BACKGROUND: Patients with COVID-19 may be at increased risk for secondary bacterial infections with MDR pathogens, including carbapenemase-producing Enterobacterales (CPE). OBJECTIVES: We sought to rapidly investigate the clinical characteristics, population structure and mechanisms of resistance of CPE causing secondary infections in patients with COVID-19. METHODS: We retrospectively identified CPE clinical isolates collected from patients testing positive for SARS-CoV-2 between March and April 2020 at our medical centre in New York City. Available isolates underwent nanopore sequencing for rapid genotyping, antibiotic resistance gene detection and phylogenetic analysis. RESULTS: We identified 31 CPE isolates from 13 patients, including 27 Klebsiella pneumoniae and 4 Enterobacter cloacae complex isolates. Most patients (11/13) had a positive respiratory culture and 7/13 developed bacteraemia; treatment failure was common. Twenty isolates were available for WGS. Most K. pneumoniae (16/17) belonged to ST258 and encoded KPC (15 KPC-2; 1 KPC-3); one ST70 isolate encoded KPC-2. E. cloacae isolates belonged to ST270 and encoded NDM-1. Nanopore sequencing enabled identification of at least four distinct ST258 lineages in COVID-19 patients, which were validated by Illumina sequencing data. CONCLUSIONS: While CPE prevalence has declined substantially in New York City in recent years, increased detection in patients with COVID-19 may signal a re-emergence of these highly resistant pathogens in the wake of the global pandemic. Increased surveillance and antimicrobial stewardship efforts, as well as identification of optimal treatment approaches for CPE, will be needed to mitigate their future impact.