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.

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.

Risk factors for acquiring BMR infections: Analytical study.

INTRODUCTION: In recent years, there has been a considerable increase in the prevalence of bacteria increasingly resistant to multiple families of antibiotics, which constitutes a major problem for public health. AIM: To determine the prevalence and different risk factors for the acquisition of multi-resistant bacteria. METHODS: This is an analytical and prospective study including patients hospitalized in the Batna University Hospital during the period from January 2023 to March 2023 presenting a documented infection with isolation of sensitive or multi-resistant strains. An operating sheet based on the different risk factors for acquiring multi-resistant bacteria has been established. RESULTS: We collected 250 patients. There are 160 men and 90 women with an average age of 44 years. Of all the strains that were identified, 100 isolates were multi-resistant bacteria. ESBL-producing Enterobacteriaceae are the most frequently isolated multi-resistant bacteria. Multivariate logistic regression analysis identified four risk factors that are significantly related to the risk of acquiring multi-resistant bacteria infection: prior antibiotic therapy [P = 0,029], use of invasive medical care [P = 0,024], the nosocomial origin of the infection [P = 0,036] and the use of public toilets [P = 0,015]. CONCLUSION: Our results clearly demonstrate that the inappropriate use of antibiotics, especially broad-spectrum antibiotics, and hand-held cross-transmission play a major role in the spread of multi-resistant bacteria in our hospital.

Molecular epidemiology of multidrug-resistant Klebsiella pneumoniae, Enterobacter cloacae, and Escherichia coli outbreak among neonates in Tembisa hospital, South Africa.

Background: An outbreak of multidrug-resistant Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae infections in a neonatal ward within a tertiary hospital in South Africa resulted in the mortality of 10 patients within six months. In this work, the genomic epidemiology of and the molecular factors mediating this outbreak were investigated. Methods: Bacterial cultures obtained from clinical samples collected from the infected neonates underwent phenotypic and molecular analyses to determine their species, sensitivity to antibiotics, production of carbapenemases, complete resistance genes profile, clonality, epidemiology, and evolutionary relationships. Mobile genetic elements flanking the resistance genes and facilitating their spread were also characterized. Results: The outbreak was centered in two major wards and affected mainly neonates between September 2019 and March 2020. Most isolates (n = 27 isolates) were K. pneumoniae while both E. coli and E. cloacae had three isolates each. Notably, 33/34 isolates were multidrug resistant (MDR), with 30 being resistant to at least four drug classes. All the isolates were carbapenemase-positive, but four bla OXA-48 isolates were susceptible to carbapenems. Bla NDM-1 (n = 13) and bla OXA-48/181 (n = 15) were respectively found on IS91 and IS6-like IS26 composite transposons in the isolates alongside several other resistance genes. The repertoire of resistance and virulence genes, insertion sequences, and plasmid replicon types in the strains explains their virulence, resistance, and quick dissemination among the neonates. Conclusions: The outbreak of fatal MDR infections in the neonatal wards were mediated by clonal (vertical) and horizontal (plasmid-mediated) spread of resistant and virulent strains (and genes) that have been also circulating locally and globally.

High rates of intestinal colonization with carbapenemase producing Enterobacteriaceae in hematopoietic stem cell transplant recipients.

Carbapenem resistant Enterobacteriaceae (CRE) are major human pathogens because, these cause high number of difficult-to-treat infections. Allogeneic hematopoietic stem cell transplant (AHSCT) recipients are highly exposed to these type of bacteria. The aim of our study was to investigate prevalence of CRE colonization in AHSCT patients and to determine genes encoding carbapenem resistance. A retrospective study conducted between January 2015 and December 2019, involved 55 patients colonized with CRE strains. We determined the rate of antibiotic resistance according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the carbapenem resistance genes by PCR assays for genes encoding most frequent ß-lactamases namely, blaGES, blaKPC, blaIMI, blaNDM, blaVIM, blaIMP and blaOXA-48. Eighty-one episodes of CRE colonization were recorded in 55 patients, mainly suffering from acute leukaemia (30%) and aplastic anemia (26%). History of hospitalization was noted in 80 episodes. Prior antibiotic treatment, severe neutropenia and corticosteroid therapy were respectively found in 94%, 76% and 58% of cases. Among the 55 patients, six patients (11%) developed a CRE infection. The CRE responsible for colonization were carbapenemase producers in 90% of cases. They belonged mostly to Klebsiella pneumoniae (61/81) and Escherichia coli species (10/81). Antibiotic resistance rates were 100% for ertapenem, 53% for imipenem, 42% for amikacin, 88% for ciprofloxacin and 27% for fosfomycin. Molecular study showed that blaOXA-48 gene was the most frequent (60.5%), followed by blaNDM (58%). Thirty-five (43%) strains were co-producers of carbapenemases. In our study, we report a high rate of CRE intestinal colonization in AHSCT recipients of our center.

Carbapenem-producing Enterobacteriaceae in mothers and newborns in southeast Gabon, 2022.

Introduction: Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) pose a significant threat, leading to severe morbidity and mortality among newborns. Methods: This study, conducted at Franceville hospital's maternity and neonatology wards from February 22nd to June 20th, 2022, investigated the prevalence of CPE in 197 parturients and 203 newborns. Rectal swabs were taken from parturients before delivery and from newborns 30 minutes after birth. Blood culture samples were collected if signs of infection were observed in newborns during a 28-day follow-up. A total of 152 environmental samples were obtained, comprising 18 from sinks, 14 from incubators, 27 from cradles, 39 from maternal beds, 14 from tables and desks, four from the two baby scales and 36 from bedside furniture. Results: None of the 203 newborns were found to be CPE carriers 30 minutes after delivery. CPE carriage was found in 4.6% of mothers. When comparing colonized and uncolonized parturients, well-established risk factors for CPE carriage, such as recent hospitalization and antibiotic therapy, were more frequently observed among CPE carriers (33.3 vs 10.6% for hospitalization in the past 15 days; 55.5 vs 30.3% for hospitalization during pregnancy, and 55.5 vs 35.1% for antibiotic therapy during pregnancy). Notably, the prevalence of treatment with amoxicillin and clavulanic acid was 44.4% in CPE carriers compared to 17.0% in non-carriers. The incidence density of CPE-associated bloodstream infection was 0.49 per 100 newborns, accounting for a fatal case of CPE-associated bacteremia identified in one of the 203 newborns. Seven environmental samples returned positive for CPE (5 sinks and two pieces of furniture). Whole genome sequencing, performed on the 25 CPE isolates, revealed isolates carrying blaNDM-7 (n=10), blaNDM-5 (n=3), blaOXA181 (n=10), blaOXA48 (n=2) or blaOXA244 (n=1), along with genetic traits associated with the ability to cause severe and difficult-to-treat infections in newborns. Core genome comparison revealed nine CPE belonging to three international high-risk clones: E. coli ST410 (four mothers and a sink), two E. coli ST167 (a mother and a piece of furniture), and K. pneumoniae ST307 (a sink and a piece of furniture), with highly similar genetic backgrounds shared by maternal and environmental isolates, suggesting maternal contamination originating from the environment. Discussion: Our study reveals key findings may guide the implementation of infection control measures to prevent nosocomial infections in newborns: the prevalence of CPE carriage in one out of 20 parturients, an infection occurring in one out of 400 newborns, substantial contamination of the care environment, clinical and environmental CPE isolates possessing genetic traits associated with the ability to cause severe and challenging infections, and clonal relationships between clinical and environmental isolates suggesting CPE spread within the wards, likely contributing to the acquisition and colonization of CPE by parturients during pregnancy.

Genomic analysis of a cAmpC (CMY-41)-producing Citrobacter freundii ST64 isolated from patient.

Antibiotic resistance in Citrobacter freundii is a public health concern. This study evaluated the closed genome of a C. freundii isolated from the stool of a hospitalized patient initially related to a Salmonella outbreak. Confirmation of the isolate was determined by whole-genome sequencing. Nanopore sequencing was performed using a MinION with a Flongle flow cell. Assembly using SPAdes and Unicycler yielded a closed genome annotated by National Center for Biotechnology Information Prokaryotic Genome Annotation Pipeline. Genomic analyses employed MLST 2.0, ResFinder4.1, PlasmidFinder2.1, and VFanalyzer. Phylogenetic comparison utilized the Center for Food Safety and Applied Nutrition (CFSAN)-single nucleotide polymorphism pipeline and Genetic Algorithm for Rapid Likelihood Inference. Antimicrobial susceptibility was tested by broth microdilution following Clinical and Laboratory Standards Institute criteria. Multi-locus sequence type in silico analysis assigned the C. freundii as sequence type 64 and the blaCMY-41 gene was detected in resistome investigation. The susceptibility to antibiotics, determined using Sensititre® plates, revealed resistance to aztreonam, colistin, cefoxitin, amoxicillin/clavulanic acid, sulfisoxazole, ampicillin, and streptomycin. The genetic relatedness of the C. freundii CFSAN077772 with publicly available C. freundii genomes revealed a close relationship to a C. freundii SRR1186659, isolated in 2009 from human stool in Tanzania. In addition, C. freundii CFSAN077772 is nested in the same cluster with C. freundii clinical strains isolated in Denmark, Mexico, Myanmar, and Canada, suggesting a successful intercontinental spread.

Comparison of clinical outcomes of patients with serial negative surveillance cultures according to a subsequent polymerase chain reaction test for carbapenemase-producing Enterobacterales.

BACKGROUND: Carbapenemase-producing Enterobacterales (CPE) are of serious concern worldwide due to high morbidity and mortality. AIM: To evaluate the impact of the result of a subsequent polymerase chain reaction (PCR) test for carbapenemase after serial negative surveillance cultures on positive culture conversion in patients with three consecutive negative surveillance cultures for CPE, and to identify risk factors for conversion. METHODS: A retrospective study of patients with positive CPE cultures on CHROMagar KPC medium was performed in a Korean tertiary hospital from October 2018 to December 2022. PCR for blaKPC, blaNDM, blaIMP, blaVIM, blaGES, and blaOXA-48 was performed after three consecutive negative rectal swab cultures. Clinical characteristics and outcomes of patients were compared according to whether follow-up PCR was positive (CNPP) or negative (CNPN). FINDINGS: Of 1075 patients with positive CPE cultures, 150 (14.0%) yielded three consecutive negative rectal swab cultures. Of these, 50 (33.3%) were CNPP, and 100 (66.7%) were CNPN. Risk factors associated with a positive PCR result on multivariate analysis were: age, central venous catheter, and Escherichia coli infection. CNPP patients were more likely to have positive culture conversion for CPE than CNPN patients (39/44 (88.6%) vs 21/50 (42.0%), P<0.001). In multivariate analysis, independent risk factors for culture conversion were: a positive PCR result after surveillance cultures, diabetes mellitus, central venous catheter, and Klebsiella pneumoniae. CONCLUSION: CNPP patients have higher rates of culture conversion than CNPN patients, and a follow-up PCR test after serial negative surveillance cultures is useful in deciding whether or not to discontinue contact precautions.

Detection of Quinolone resistance Qnr genes and its association with Extended Spectrum ß-lactamase and AmpC ß-lactamase genes in Qnr Positive Enterobacteriaceae in Bangladesh.

This cross-sectional study was conducted to explore quinolone resistant Enterobacteriaceae followed by searching the prevalence of three groups of quinolone resistance genes (QnrA, QnrB and QnrS) from January 2015 to December 2015 at Dhaka Medical College hospital, Bangladesh. Then genes for ESBL and AmpC ß-lactamase were detected among Qnr positive strains for better understanding the role of these genes for multiple drug resistance. Total 340 urines, sputum, wound swab and blood samples were collected from DMCH. Total 270(79.41%) Enterobacteriaceae were isolated from 340 samples. Out of 270 Enterobacteriaceae, 225(83.33%) were quinolone (ciprofloxacin) resistant strains. Qnr genes were detected in 141(62.67%) of the 225 quinolone resistant Enterobacteriaceae. Total 187 Qnr genes [84(59.57%) QnrS, 70(49.64%) QnrB and 33(23.40%) QnrA] were detected from 141 quinolone resistant strains. Total 48(34.04%) ESBL producers were detected by DDS test and 47(33.33%) ESBL producers were positive by PCR among 141 Qnr positive strains. QnrA was co-existed with CTX-M-15. QnrB was co-existed with TEM, CTXM-15 and OXA-1. QnrS genes were also associated with TEM, CTX-M-15 and OXA-1. Among 52 cefoxitin resistant Qnr positive strains, 22(42.31%) AmpC ß-lactamase producers were detected by Modified three-dimensional test (MTDT) and 45(86.54%) AmpC ß-lactamase producers were detected by PCR. QnrA had been identified with DHA, ACC, EBC and CIT while QnrB had been identified with DHA, ACC, EBC and CIT. QnrS had also been co-existed with DHA, ACC, EBC and CIT. The results of this study provided insights into the high proportion of Qnr genes among isolated Enterobacteriaceae. Simultaneous presence of Qnr genes and genes for extended-spectrum ß-lactamase or AmpC ß-lactamase were observed in multidrug resistant Enterobacteriaceae.

Genomic landscape of NDM-1 producing multidrug-resistant Providencia stuartii causing burn wound infections in Bangladesh.

The increasing antimicrobial resistance in Providencia stuartii (P. stuartii) worldwide, particularly concerning for immunocompromised and burn patients, has raised concern in Bangladesh, where the significance of this infectious opportunistic pathogen had been previously overlooked, prompting a need for investigation. The two strains of P. stuartii (P. stuartii SHNIBPS63 and P. stuartii SHNIBPS71) isolated from wound swab of two critically injured burn patients were found to be multidrug-resistant and P. stuartii SHNIBPS63 showed resistance to all the 22 antibiotics tested as well as revealed the co-existence of blaVEB-6 (Class A), blaNDM-1 (Class B), blaOXA-10 (Class D) beta lactamase genes. Complete resistance to carbapenems through the production of NDM-1, is indicative of an alarming situation as carbapenems are considered to be the last line antibiotic to combat this pathogen. Both isolates displayed strong biofilm-forming abilities and exhibited resistance to copper, zinc, and iron, in addition to carrying multiple genes associated with metal resistance and the formation of biofilms. The study also encompassed a pangenome analysis utilizing a dataset of eighty-six publicly available P. stuartii genomes (n = 86), revealing evidence of an open or expanding pangenome for P. stuartii. Also, an extensive genome-wide analysis of all the P. stuartii genomes revealed a concerning global prevalence of diverse antimicrobial resistance genes, with a particular alarm raised over the abundance of carbapenem resistance gene blaNDM-1. Additionally, this study highlighted the notable genetic diversity within P. stuartii, significant informations about phylogenomic relationships and ancestry, as well as potential for cross-species transmission, raising important implications for public health and microbial adaptation across different environments.

Epidemiology and clinical characteristics of Morganella morganii infections: A multicenter retrospective study.

BACKGROUND: Morganella morganii is a Gram-negative, opportunistic pathogen that can cause a variety of infections, including bloodstream infections, especially in those with compromised immune systems. It is often resistant to antibiotics, making it a difficult organism to treat. Limited studies have addressed M. morganii, but the organism is becoming increasingly recognized as a public health threat. More research is needed to understand the epidemiology and virulence factors of M. morganii in Saudi Arabia, as well as to develop effective treatment strategies. METHODS: This retrospective study included all M. morganii bloodstream infections patients admitted to five tertiary care hospitals in Saudi Arabia between 2015 and 2022. RESULTS: The study population included 75 patients (45 males and 30 females) between the age of 53-72 with a 54% ICU admission rate. The most comorbidities were hypertension followed by diabetes. The most common symptoms were fever, cough, shortness of breath, vomiting, and fatigue. The study also found that M. morganii was often resistant to multiple antibiotics, including ciprofloxacin, trimethoprim/sulfamethoxazole, gentamicin, amoxicillin, nitrofurantoin, and colistin. The most common treatment for M. morganii bacteremia was carbapenems, followed by aminoglycosides, ciprofloxacin, and colistin. Source control measures, such as surgery, line removal, drainage, and tissue removal, were also used in some cases. The study found that the in-hospital mortality rate for M. morganii bacteremia was 41%. The risk of mortality was increased in patients who were admitted to the ICU, who were older than 65 years, and who had Klebsiella pneumoniae co-infection. CONCLUSION: M. morganii bacteremia is a serious infection that is often resistant to antibiotics. Elderly patients and patients with comorbidities are at increased risk of mortality. Source control measures and appropriate antibiotic therapy are important for improving outcomes.

Genomic characterization of New Delhi metallo-beta-lactamase-producing species of Morganellaceae, Yersiniaceae, and Enterobacteriaceae (other than Klebsiella) from Brazil over 2013-2022.

Over the last decade, New Delhi metallo-beta-lactamase (NDM) carbapenemase has silently spread in Brazil. In this study, we analyzed a large collection of Enterobacterales other than Klebsiella spp. received in our reference laboratory between 2013 and 2022. A total of 32 clinical isolates displaying different pulsed-field gel electrophoresis profiles, and represented by 11 species in the families Enterobacteriaceae (Citrobacter freundii, Citrobacter portucalensis, Enterobacter hormaechei, and Escherichia coli), Morganellaceae (Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, and Raoultella ornithinolytica), and Yersiniaceae (Serratia marcescens) had their whole genomes sequenced and further analyzed. Antimicrobial susceptibility was determined by disk diffusion, except for polymyxin B, assessed by broth microdilution. The blaNDM-1 allele was predominant (n = 29), but blaNDM-5 was identified in an E. coli specimen with a novel ST, and the blaNDM-7 allele was found in E. hormaechei ST45 and E. coli ST1049. Polymyxin was active against all but one Enterobacteriaceae isolate: an mcr-1-producing E. coli presenting minimal inhibitory concentration (4 mg/L). Isolates producing extended-spectrum ß-lactamases were common: cefotaximase from Munich (CTX-M)-15 (n = 10), CTX-M-2 (n = 4), and CTX-M-8 (n = 3) were detected, and the mcr-1-producing E. coli was found to co-produce both CTX-M-8 and CTX-M-55 ß-lactamases. The mcr-9 gene was found in 5/8 E. hormaechei isolates, distributed in four different sequence types, all of them presenting susceptibility to polymyxin. This study showed that NDM-producing Enterobacterales other than Klebsiella are already spread in Brazil, in diversified species, and cocarrying important resistance genes. Prompt detection and effective implementation of measures to prevent further spread are mandatory for mitigating the dissemination of NDM carbapenemase in hospital settings and preserving the already limited antimicrobial therapy options.

Use of a chromogenic medium with and without selective enrichment to screen for carbapenemase-producing Enterobacterales (CPE) from canine and feline fecal specimens during an outbreak of NDM-5-producing Escherichia coli.

Carbapenemase-producing Enterobacterales (CPE) are one of the most urgent threats to human healthcare globally. Descriptions of CPE outbreaks in veterinary hospitals suggest the need for screening strategies for CPE from companion animals. Our aim was to optimize a chromogenic agar method with and without selective enrichment to isolate CPE from companion animal feces in an ongoing outbreak of New Delhi metallo-ß-lactamse-5 Escherichia coli. A limit of detection (LOD) assay for spiked canine and feline feces was performed for both methods using a carbapenamase-producing E. coli (24213-18); the LOD (1.5 × 103 cfu/g of feces) was equivalent to that reported for human fecal specimens. We screened 1,247 companion animal fecal specimens for carriage of CPE by 1) direct plating to chromogenic agar and 2) plating to chromogenic agar following selective enrichment. Twenty-one specimens were positive for CPE by both direct culture and enrichment culture. No specimens were positive with selective enrichment and negative by direct culture. A selective enrichment step did not result in any increased recovery of CPE from companion animals, which suggests that enrichment broth may not be necessary for outbreak surveillance testing. It is important to continue to validate methods for the detection of CPE in companion animals as outbreaks become more common in veterinary facilities.

Evaluation of the French novel disc diffusion-based algorithm for the phenotypic screening of carbapenemase-producing Enterobacterales.

OBJECTIVES: The early identification of carbapenemase-producing Enterobacterales (CPE) is required to prevent their spread and initiate proper therapy. Accordingly, it is crucial to develop efficient algorithms using susceptibility testing results to discriminate non-carbapenemase producers (non-CPE) from those that require complementary tests. In 2022, to adapt its recommendations to the evolution of CPE epidemiology (increased prevalence of OXA-244 producers), the Antibiogram Committee of the French Society of Microbiology (CA-SFM) proposed a new algorithm for the screening of CPE. We compared this algorithm to the former algorithm (2015-2021). METHODS: From July 2022 to January 2023, all nonduplicate enterobacterial isolates referred to French National Reference Centre for carbapenemase detection (n = 518) were subjected to the former CA-SFM algorithm (2015 to 2021) using inhibition diameters of ertapenem, ticarcillin-clavulanate, temocillin and meropenem or imipenem, and the novel CA-SFM algorithm (since 2022) using inhibition diameters of ceftazidime-avibactam, temocillin, and meropenem or imipenem. RESULTS: Sensitivity, specificity, negative predictive value, and positive predictive value were of 80.8% (CI95 76.3%-84.6%), 66.2% (58.1%-73.5%), 59.3% (51.5%-66.6%), and 85.0% (80.7% - 88.5%) for the old CA-SFM algorithm and 97.8% (95.5%-99.0%), 45.5% (37.5%-53.7%), 89.7% (80.3%-95.2%), and 80.9% (76.9%-84.4%) for the novel CA-SFM algorithm. DISCUSSION: The novel CA-SFM algorithm possesses the best performance for the screening of CPE particularly in countries with a high prevalence of OXA-48-like producers.

Sink-traps are a major source for carbapenemase-producing Enterobacteriaceae transmission.

OBJECTIVE: We studied the extent of carbapenemase-producing Enterobacteriaceae (CPE) sink contamination and transmission to patients in a nonoutbreak setting. METHODS: During 2017-2019, 592 patient-room sinks were sampled in 34 departments. Patient weekly rectal swab CPE surveillance was universally performed. Repeated sink sampling was conducted in 9 departments. Isolates from patients and sinks were characterized using pulsed-field gel electrophoresis (PFGE), and pairs of high resemblance were sequenced by Oxford Nanopore and Illumina. Hybrid assembly was used to fully assemble plasmids, which are shared between paired isolates. RESULTS: In total, 144 (24%) of 592 CPE-contaminated sinks were detected in 25 of 34 departments. Repeated sampling (n = 7,123) revealed that 52%-100% were contaminated at least once during the sampling period. Persistent contamination for >1 year by a dominant strain was common. During the study period, 318 patients acquired CPE. The most common species were Klebsiella pneumoniae, Escherichia coli, and Enterobacter spp. In 127 (40%) patients, a contaminated sink was the suspected source of CPE acquisition. For 20 cases with an identical sink-patient strain, temporal relation suggested sink-to-patient transmission. Hybrid assembly of specific sink-patient isolates revealed that shared plasmids were structurally identical, and SNP differences between shared pairs, along with signatures for potential recombination events, suggests recent sharing of the plasmids. CONCLUSIONS: CPE-contaminated sinks are an important source of transmission to patients. Although traditionally person-to-person transmission has been considered the main route of CPE transmission, these data suggest a change in paradigm that may influence strategies of preventing CPE dissemination.

Magnitude of extended-spectrum ß-lactamase and carbapenemase producing Enterobacteriaceae among commonly vended street foods in Arba Minch town, southern Ethiopia.

BACKGROUND: The rising prevalence of extended-spectrum beta-lactamase and carbapenemase-producing Enterobacteriaceae (ESßL-PE) in street foods poses a significant risk to human health due to its epidemiological significance. Thus, the aim of this study was to determine the magnitude of foodborne Enterobacteriaceae that produce carbapenemase and ESßL, as well as their patterns of antibiotic resistance, in the studied area. METHODS: A community-based cross-sectional study was carried out from January 1st, 2023, to February 30th, 2023. One hundred randomly chosen street-vended food items (one hundred grams of each food item) were aseptically collected, and aliquots of 0.1 ml from the homogenized (25 g of samples into 225 ml of buffered peptone water (BPW)) were inoculated on MacConkey agar and Xylose Lysine Deoxycholate Agar (XLD). Enterobacteriaceae isolates were identified using various biochemical tests. ESßL and carbapenemase were first screened by indicator cephalosporins and carbapenem antibiotics, respectively. ESßL and carbapenemase were confirmed by a double-disc synergy test and modified carbapenem inactivation methods, respectively. Kirby-Bauer disc diffusion method was used for the antimicrobial-resistant test. RESULTS: A total of 112 Enterobacteriaceae belonging to six different genera were isolated. E. coli was attributed 39 (34.8%), followed by Citrobacter spp. 22 (19.6%) and K. pneumoniae 18 (16.1%), with only 8 (7.1%) isolated Salmonella spp. About 15.2% (n = 17) and 8.9% (n = 10) of Enterobacteriaceae were phenotypically confirmed to be extended-spectrum beta-lactamase (ESßL) and carbapenemase producers, respectively. The highest percentage of ESßL-producing isolates was attributed to K. pneumoniae (n = 5), E. coli (n = 4), and Enterobacter spp. (n = 3). Proteus spp. and Salmonella spp. isolates were carbapenemase-negative. All carbapenemase-positive isolates were found to be ESßL-producers. 70.6% (12/17) of ESßL-producing Enterobacteriaceae were found to be multidrug-resistant (MDR). CONCLUSION: A considerable number of multidrug-resistant ESßL and carbapenemase-producing Enterobacteriaceae were identified, suggesting that street foods may be a potential source of MDR foodborne infections. Consequently, it is important to conduct routine examinations of street food items and track trends in medication resistance.

Model-based evaluation of admission screening strategies for the detection and control of carbapenemase-producing Enterobacterales in the English hospital setting.

BACKGROUND: Globally, detections of carbapenemase-producing Enterobacterales (CPE) colonisations and infections are increasing. The spread of these highly resistant bacteria poses a serious threat to public health. However, understanding of CPE transmission and evidence on effectiveness of control measures is severely lacking. This paper provides evidence to inform effective admission screening protocols, which could be important in controlling nosocomial CPE transmission. METHODS: CPE transmission within an English hospital setting was simulated with a data-driven individual-based mathematical model. This model was used to evaluate the ability of the 2016 England CPE screening recommendations, and of potential alternative protocols, to identify patients with CPE-colonisation on admission (including those colonised during previous stays or from elsewhere). The model included nosocomial transmission from colonised and infected patients, as well as environmental contamination. Model parameters were estimated using primary data where possible, including estimation of transmission using detailed epidemiological data within a Bayesian framework. Separate models were parameterised to represent hospitals in English areas with low and high CPE risk (based on prevalence). RESULTS: The proportion of truly colonised admissions which met the 2016 screening criteria was 43% in low-prevalence and 54% in high-prevalence areas respectively. Selection of CPE carriers for screening was improved in low-prevalence areas by adding readmission as a screening criterion, which doubled how many colonised admissions were selected. A minority of CPE carriers were confirmed as CPE positive during their hospital stay (10 and 14% in low- and high-prevalence areas); switching to a faster screening test pathway with a single-swab test (rather than three swab regimen) increased the overall positive predictive value with negligible reduction in negative predictive value. CONCLUSIONS: Using a novel within-hospital CPE transmission model, this study assesses CPE admission screening protocols, across the range of CPE prevalence observed in England. It identifies protocol changes-adding readmissions to screening criteria and a single-swab test pathway-which could detect similar numbers of CPE carriers (or twice as many in low CPE prevalence areas), but faster, and hence with lower demand on pre-emptive infection-control resources. Study findings can inform interventions to control this emerging threat, although further work is required to understand within-hospital transmission sources.

Nationwide molecular epidemiology of carbapenemase-producing Citrobacter spp. in France in 2019 and 2020.

IMPORTANCE: The emergence of carbapenemase producers in Enterobacterales mostly involves Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae complex species. However, in France, we observed the emergence and the rapid dissemination of carbapenemase in Citrobacter spp. In this study, we demonstrated that a wide variety of carbapenemases is produced by many different species of Citrobacter spp. However, we clearly identify three high-risk clones of Citrobacter freundii, ST8, ST22, and ST91 that drive the spread of carbapenemase in France. This epidemiological study paves the way of further analysis that would aim to identify the virulence factors involved in this pellicular ability of these three clones to disseminate at the hospital.

Epidemiology, risk factors, and clinical outcomes of carbapenem-resistant Enterobacterales in Africa: A systematic review.

OBJECTIVES: Carbapenem-resistant Enterobacterales (CRE) commonly cause hospital-acquired infections and hospital outbreaks worldwide, with an alarming increase in Africa, necessitating review of regional CRE epidemiological trends. METHODS: A systematic review was conducted using PRISMA guidelines, searching PubMed, Scopus and Web of Science databases for studies describing CRE distribution, risk factors for CRE acquisition and clinical outcome of CRE infections in Africa. RESULTS: One-hundred and sixty-nine studies were included, with the majority from North Africa (92/169, 54.4%). Most studies (136/169; 80.4%) focused only on infection, with a total of 15666 CRE isolates (97.4% clinical infection, 2.6% colonisation). The leading bacterial species included Klebsiella (72.2%), Escherichia coli (13.5%), and Enterobacter (8.3%). The most frequently detected carbapenemases were NDM (43.1%) and OXA-48-like (42.9%). Sequence types were reported in 44 studies, with ST101 and ST147 most commonly reported in K. pneumoniae, and ST410, ST167 and ST38 in E. coli. Previous antibiotic use, prior hospitalisation, surgical procedures, indwelling devices, intensive care unit admission and prolonged hospital stay, were the most frequent factors associated with CRE infection/colonisation. Crude mortality for CRE infection was 37%. CONCLUSION: Although K. pneumoniae and E. coli remain the most frequent CRE in Africa, observed sequence types are not the commonly reported global 'high-risk' clones. The distribution of species and carbapenemases differs across African regions, while risk factors for CRE colonisation/infection, and patient outcomes are similar to those reported globally. There are limited data on CREs from parts of Africa, highlighting the need to strengthen epidemiologic surveillance programmes in the region.