BACKGROUND:Carbapenem-resistant Enterobacterales (CRE) are increasing in the UK, but the drivers of this rise and effective treatment options remain uncertain. METHODS:Ninety-seven acute National Health Service Trusts, including 192 UK hospitals, submitted data on 8840 consecutive, non-duplicate CRE (October 2023 to September 2024) and local laboratory methods. RESULTS:Predominant CRE species were Klebsiella pneumoniae (30.6%, 2709/8840), Escherichia coli (29.3%, 2592/8840), Enterobacter cloacae complex (22.2%, 1966/8840). Overall, 21.8% (1927/8840) of CRE were collected in outpatient settings. Overall, 85.5% (7279/8513) of CRE underwent carbapenemase detection testing, with significant variation depending on species, specimen type, and baseline antibiogram. Carbapenemases detected were OXA-48-like (22.3%, 1967/8840), NDM (18.6%, 1645/8840), KPC (9.2%, 817/8840), IMP (2.0%, 178/8840), VIM (0.7%, 62/8840), multi-carbapenemase producers (4.0%, 351/8840). Overall, 51.2% (4526/8840) of CRE were tested against ≥1 novel agent. In-house antimicrobial susceptibility testing availability was common for ceftazidime-avibactam (90.7%, 88/97) and cefiderocol (73.2%, 71/97), while less common for meropenem-vaborbactam (41.2%, 40/97), imipenem-relebactam (21.6%, 21/97), aztreonam-avibactam (11.3%, 11/97). OXA-48-like- (97.6%, 1138/1166) and KPC producers (96.2%, 429/446) remained susceptible to ceftazidime-avibactam; KPC producers to meropenem-vaborbactam (99.4%, 160/161) and imipenem-relebactam (98.4%, 62/63). Cefiderocol resistance was 32.4% overall and higher among NDM- (58.4%) and multi-carbapenemase producers (50.3%). Ceftazidime-avibactam plus aztreonam synergy was performed for 17.2% (286/1658) of aztreonam-resistant metallo-β-lactamase-producers; synergy was observed in 78.7% (225/286) of cases. Colistin resistance was 10.6% (153/1445) among non-intrinsically resistant species. CONCLUSIONS:Whilst most UK CRE are tested for carbapenemases, coverage gaps persist. The community burden of CRE is increasing. Cefiderocol resistance is concerningly high, particularly among metallo-β-lactamase-producers.

Background New dosing regimens for ceftriaxone 4 g/24 hours and ceftazidime 3 g/12 hours are convenient for patients receiving OPAT. To date, these have not been clinically validated.Aim To assess the tolerability, toxicity and effectiveness of once daily ceftriaxone (4 g) and 12 hourly ceftazidime regimens (3 g twice a day) in the OPAT setting.Patients and methods From April 2018 until March 2023; demographic, clinical, microbiological and outcome data were collected on all adult patients discharged to a community-based OPAT team in East London.Results There were 487 OPAT episodes. Fifty-three (10.9%) patients received ceftriaxone 4 g once a day and 20 (4.1%) ceftazidime 3 g twice a day. In the ceftriaxone group, the commonest conditions treated were orthopaedic, neurosurgical or diabetic foot infections. OPAT was used to expedite the discharge of 45 (84.9%) patients, the remainder were admission avoidance episodes. The commonest isolate causing infection was MSSA 23 (43.4%). There were no tolerability or toxicity episodes recorded. All patients were cured and bed days saved were 1266. In the smaller twice-daily ceftazidime cohort, seven (35%) patients were treated for necrotizing otitis externa, six (30%) for bronchiectasis and six (30%) for urinary tract infections. The commonest cause of infection was P. aeruginosa, 18 (90%). One case of nephrotoxicity was recorded. All patients were cured and bed days saved were 896.Results There were 487 OPAT episodes. Fifty-three (10.9%) patients received ceftriaxone 4 g once a day and 20 (4.1%) ceftazidime 3 g twice a day. In the ceftriaxone group, the commonest conditions treated were orthopaedic, neurosurgical or diabetic foot infections. OPAT was used to expedite the discharge of 45 (84.9%) patients, the remainder were admission avoidance episodes. The commonest isolate causing infection was MSSA 23 (43.4%). There were no tolerability or toxicity episodes recorded. All patients were cured and bed days saved were 1266. In the smaller twice-daily ceftazidime cohort, seven (35%) patients were treated for necrotizing otitis externa, six (30%) for bronchiectasis and six (30%) for urinary tract infections. The commonest cause of infection was P. aeruginosa, 18 (90%). One case of nephrotoxicity was recorded. All patients were cured and bed days saved were 896.Conclusions Regimens of ceftriaxone 4 g once a day and ceftazidime 3 g twice a day were well tolerated and highly effective. If widely adopted, these regimens will save OPAT and nursing time and enable more patients to be treated.

Polymyxin antibiotics B and colistin are considered drugs of last resort for the treatment of multi-drug and carbapenem-resistant Gram-negative bacteria. With the emergence and dissemination of multi-drug resistance, monitoring the use and resistance to polymyxins imparted by mobilised colistin resistance genes (mcr) is becoming increasingly important. The Aeromonas genus is widely disseminated throughout the environment and serves as a reservoir of mcr–3, posing a significant risk for the spread of resistance to polymyxins. Recent phylogenetic studies and the identification of insertion elements associated with mcr–3 support the notion that Aeromonas spp. may be the evolutionary origin of the resistance gene. Furthermore, mcr–3-related genes have been shown to impart resistance in naïve E. coli and can increase the polymyxin MIC by up to 64-fold (with an MIC of 64 mg/L) in members of Aeromonas spp. This review will describe the genetic background of the mcr gene, the epidemiology of mcr-positive isolates, and the relationship between intrinsic and transferable mcr resistance genes, focusing on mcr–3 and mcr–3-related genes.

AbstractObjectivesThe aim of this study was to characterize an unusual case of spontaneous, community-acquired Escherichia coli meningitis in an adult presenting to a general hospital in Kenya, where initial clinical recovery was followed by reinfection with an MDR, hospital-acquired strain.Patient and methodsAn adult presented to a hospital in Kenya with meningitis symptoms. E. coli was cultured from CSF. Treatment with ceftriaxone was successful; however, the patient relapsed a few days later. E. coli was cultured from CSF and blood during the reinfection episode, though the patient died during admission. We sequenced the isolates using Illumina MiSeq and performed antimicrobial susceptibility testing, fitness and virulence assays on the bacteria.ResultsThe E. coli isolates from the two episodes were found to be distinct: the initial strain was ST88, serotype O8 H17 while the subsequent episode was caused by an ST167, serotype O101 H5 MDR strain. The ST88 strain was susceptible to all drugs except ampicillin and amoxicillin/clavulanate while the ST167 strain was MDR, including to all β-lactam drugs due to the presence of the carbapenemase gene blaNDM-5. The hospital-acquired ST167 strain was also resistant to newer drugs such as cefiderocol and eravacycline, which are currently not available locally, and had overall lower fitness and virulence in vitro compared with the initial infecting strain.ConclusionsThough less fit and virulent in vitro, the MDR strain was fatal, suggesting that host factors, rather than bacterial virulence, may have been of greater importance in this patient’s outcome.

Objectives The aim of this study was to characterize an unusual case of spontaneous, community-acquired Escherichia coli meningitis in an adult presenting to a general hospital in Kenya, where initial clinical recovery was followed by reinfection with an MDR, hospital-acquired strain. Patient and methods An adult presented to a hospital in Kenya with meningitis symptoms. E. coli was cultured from CSF. Treatment with ceftriaxone was successful; however, the patient relapsed a few days later. E. coli was cultured from CSF and blood during the reinfection episode, though the patient died during admission. We sequenced the isolates using Illumina MiSeq and performed antimicrobial susceptibility testing, fitness and virulence assays on the bacteria. Results The E. coli isolates from the two episodes were found to be distinct: the initial strain was ST88, serotype O8 H17 while the subsequent episode was caused by an ST167, serotype O101 H5 MDR strain. The ST88 strain was susceptible to all drugs except ampicillin and amoxicillin/clavulanate while the ST167 strain was MDR, including to all beta-lactam drugs due to the presence of the carbapenemase gene bla(NDM-5.) The hospital-acquired ST167 strain was also resistant to newer drugs such as cefiderocol and eravacycline, which are currently not available locally, and had overall lower fitness and virulence in vitro compared with the initial infecting strain. Conclusions Though less fit and virulent in vitro, the MDR strain was fatal, suggesting that host factors, rather than bacterial virulence, may have been of greater importance in this patient's outcome.

A hospital outbreak of carbapenem- resistant Enterobacterales was detected by routine surveillance. Whole genome sequencing and subsequent analysis revealed a conserved promiscuous blaOXA-48 carrying plasmid as the defining factor within this outbreak. Four different species of Enterobacterales were involved in the outbreak. Escherichia coli ST399 accounted for 35 of all the 55 isolates. Comparative genomics analysis using publicly available E. coli ST399 genomes showed that the outbreak E. coli ST399 isolates formed a unique clade. We developed a mathematical model of pOXA- 48- like plasmid transmission between host lineages and used it to estimate its conjugation rate, giving a lower bound of 0.23 conjugation events per lineage per year. Our analysis suggests that co- evolution between the pOXA- 48- like plasmid and E. coli ST399 could have played a role in the outbreak. This is the first study to report carbapenem- resistant E. coli ST399 carrying blaOXA- 48 as the main cause of a plasmid- borne outbreak within a hospital setting. Our findings suggest complementary roles for both plasmid conjugation and clonal expansion in the emergence of this outbreak.

Abstract Background Carbapenem resistance due to MBL production is relatively uncommon in Pseudomonas aeruginosa infections in the UK. We report a case of post-operative meningitis caused by a New-Delhi MBL-producing (NDM-1) strain, outlining the microbiological and management challenges. Patient case The patient was admitted to intensive care after craniotomy and evacuation for an intracerebral haemorrhage. Three weeks later she was febrile due to nosocomial meningitis. Purulent material evacuated from extradural and subdural spaces cultured P. aeruginosa, along with blood cultures and CSF. Susceptibility testing as per EUCAST methodology indicated the isolate was resistant to all β-lactams, aminoglycosides and quinolones but susceptible to colistin. Susceptibility to cefiderocol by disc diffusion was in the area of technical uncertainty at 21 mm (S≥22 mm). Immunochromatographic flow testing (CARBA5 NG Biotech) detected an NDM carbapenemase. WGS (Illumina) confirmed the presence of blaNDM-1 and a plethora of AMR genes responsible for the XDR phenotype {cephalosporins (blaPDC-10, blaOXA-488), aminoglycosides [aph(3')-VIa], quinolones (crpP), macrolides [mph(E), msr(E)], phenicols (catB7) and fosfomycin (fosA)}. No mutations in PBPs associated with resistance to β-lactams or iron acquisition systems involved in uptake of siderophore conjugated antibiotics were identified. The isolate belonged to ST1047, serotype 07, previously identified as a high-risk epidemic clone originating in Myanmar. Results Treatment was commenced with IV and intrathecal colistin as well as IV cefiderocol (Figure 1); a novel siderophore cephalosporin licensed for Gram-negative infections with limited treatment options. No synergy between the two drugs could be demonstrated in chequerboard assays. Although CSF sterility was achieved on three subsequent cultures with clinical response, the patient sadly died due to the underlying intracerebral injury. Four other patients subsequently became colonized with this strain and infection control measures (twice weekly screening of all patients, environmental cleaning, water testing, isolation of cases) were instituted, bringing the outbreak under control. Variable number tandem repeat analysis linked these strains to that of another patient discharged from the unit 9 months prior, but not previously reported in the UK. Conclusions The first problem encountered was a lack of evidence for the CNS penetration of cefiderocol and efficacy in the treatment of meningitis. The external ventricular drain required to administer intrathecal colistin enabled us to monitor CSF cefiderocol levels. Five CSF samples were shipped at −80°C for analysis in Germany by mass spectrometry. CSF cefiderocol levels of 1.22 μg/mL, 1.34 μg/mL, 2.39 μg/mL, 3.53 μg/mL and 3.90 μg/mL were disappointingly close to the pharmacodynamic breakpoint of 2 μg/mL and only available after treatment withdrawal. Dosing of cefiderocol was initially cautious starting at 1 g/8 h due to a creatinine clearance of 53 mL/min but later increased to 1.5 g/8 h. Further dose increases guided by serum and CSF monitoring could feasibly lead to therapeutic CSF cefiderocol levels. Clinical and pharmacological studies are needed in this area. To our knowledge this is the first attempt to treat a case of XDR neurosurgical meningitis using cefiderocol with precision treatment and achieving microbiological cure.

Abstract Objectives Cefiderocol (CFDC) is a novel siderophore cephalosporin approved in Europe for the treatment of infections caused by aerobic Gram-negative (GN) bacteria in adults with limited treatment options. The aim of the ARTEMIS study was to evaluate the in vitro activity of CFDC and comparators against recent clinical isolates collected across five countries in Europe. Here we report susceptibility data from isolates collected in the UK. Methods From January to December 2020, GN clinical isolates were collected from hospitalized patients from all infection sites (excluding the urinary tract). Duplicate isolates of the same species from a single patient were excluded. As a prespecified target, each laboratory collected 75 isolates, with: 20 Klebsiella spp., 20 other Enterobacterales, 20 Pseudomonas aeruginosa and 15 Acinetobacter baumannii isolates expected to be included. CFDC susceptibility testing was conducted using disc diffusion (with 30 μg discs) on Mueller–Hinton agar and Sensititre™ broth microdilution (BMD) panels [EUMDROXF; centrally tested at International Health Management Associates (IHMA)]. Susceptibility by disc diffusion was reported using zone diameter breakpoints (BPs) of ≥22 mm (or ≥17 mm for A. baumannii isolates, corresponding to MIC values below the pharmacokinetic/pharmacodynamic BPs of ≤2 mg/L). Comparator susceptibility was determined using custom research use only Sensititre™ BMD panels (CMP2SHIH) according to the EUCAST method for BMD. Antimicrobial susceptibility was interpreted according to EUCAST clinical BPs (v.11 2021). Results In total, 517 isolates were collected from nine UK hospitals, of which: 308 (59.6%) were Enterobacterales [including 147 (28.4%) Klebsiella spp.], 148 (28.6%) were P. aeruginosa and 33 (6.4%) were A. baumannii. The most common sites of infection were bloodstream (n = 245; 47.4%), respiratory tract (n = 158; 30.6%) and skin (n = 59; 11.4%). A high percentage of Enterobacterales (90.2%), P. aeruginosa (96.6%) and A. baumannii (96.9%) isolates were susceptible to CFDC by disc diffusion. By central laboratory testing (MIC), 99.0% of Enterobacterales, 99.3% of P. aeruginosa and 93.9% of A. baumannii isolates were susceptible to CFDC. High susceptibility rates (>85%) were also observed for all comparator agents (Table 1). A total of 32/517 (6.2%) isolates were carbapenem resistant, the majority of which (22/32, 68.8%) were susceptible to CFDC by disc diffusion.Table 1. CFDC susceptibility based on disc zone diameters; CFDC and comparator agent susceptibility based on MIC from BMD (EUCAST clinical BPs v.11, 2021) Susceptibility, n/N (%) CFDC (disc) No. isolates in ATU CFDC (MIC) MEMa C/T CZA MVB I/R CST Enterobacterales 277/307 (90.2) 40/307 (13.0) 285/288 (99.0) 295/308 (95.8) 264/308 (85.7) 298/307 (97.1) 303/308 (98.4) 286/306 (93.5) 265/307 (86.3) P. aeruginosa 143/148 (96.6) 8/148 (5.4) 144/145 (99.3) 135/148 (91.2) 140/148 (94.6) 141/148 (95.3) 137/148 (92.6) 133/147 (90.5) 142/148 (95.9) A. baumannii 31/32 (96.9) N/A 31/33 (93.9) 30/33 (90.9) N/A N/A N/A 30/33 (90.9) 30/33 (90.9) ATU, area of technical uncertainty; CFDC, cefiderocol; CST, colistin; C/T, ceftolozane/tazobactam; CZA, ceftazidime/avibactam; I/R, imipenem/relebactam; MEM, meropenem; MVB, meropenem/vaborbactam.a Isolates were defined as MEM-susceptible with a BP of ≤8 mg/L [relating to high-dose extended-infusion (2 g, 3 h infusion) MEM], based on EUCAST recommendations. Conclusions Among clinical GN isolates collected from UK hospitals in 2020, a high percentage (98.6%), including carbapenem-resistant isolates, were susceptible to CFDC by BMD. These data support the use of CFDC in patients with GN infections and limited treatment options. The differences identified between EUCAST disc diffusion and BMD using Sensititre™ panels for CFDC highlight that disc diffusion underestimates Enterobacterales susceptibility to CFDC, which is mainly a result of the area of technical uncertainty (where isolates with MIC of 2 mg/L have a zone diameter of <22 mm and are characterized as resistant). This requires further investigation to explore whether the EUCAST zone diameter BP is optimal for CFDC disc testing.

Objectives: We report the draft genome sequence of a multidrug-resistant Pseudomonas aeruginosa isolate (PA3) producing SIM carbapenemase from a patient in the United Kingdom. Methods: Isolation, identification and antimicrobial susceptibility testing were performed according to local routine microbiology protocols. Whole genomic DNA was sequenced using an Illumina HiSeq platform. The generated reads were de novo assembled using SPAdes version 3.7.1. Annotation was performed by the NCBI Prokaryote Genome Annotation Pipeline version 4.6. Sequence type, antimicrobial resistance and virulence-related genes were predicted from the sequence. Results: P. aeruginosa PA3 was resistant to most antipseudomonal ,B-lactams, aminoglycosides and quinolones but susceptible to colistin. The assembly comprised 100 contigs (> 1000 bp) with a total length of 7485 621 bp, and a total of 7190 coding sequences. The isolate belonged to sequence type (ST) 446, serotype O11 and contained bla(SIM-1) metallo-,B-lactamase in a class 1 integron structure. Conclusion: We report a bla(SIM-1) containing multidrug-resistant strain of P. aeruginosa from the UK. Moreover, the isolate was ST 446, a genetic background with potential for greater global dissemination. (C) 2022 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.

Background Preventing infantile anaemia and ensuring optimal growth and development during early childhood, particularly in resource-constrained settings, represent an ongoing public health challenge. Current responses are aligned to treatment-based solutions, instead of determining the roles of its inter-related causes. This project aims to assess and understand the complex interplay of eco-bio-social-political factors that determine infantile anaemia to inform policy, research design and prevention practices. Methods This is a longitudinal birth cohort study including four components: (1) biological, will assess known blood markers of iron homeostasis and anaemia and stool microbiota to identify and genetically analyse the participants’ flora; (2) ecological, will assess and map pollutants in air, water and soil and evaluate features of nutrition and perceived food security; (3) social, which will use different qualitative research methodologies to explore key stakeholders and informants’ perceptions related to nutritional, environmental and anaemia topics, participant observations and a participatory approach and (4) a political analysis, to identify and assess the impact of policies, guidelines and programmes at all levels for infantile anaemia in the three regions. Finally, we will also explore the role of social determinants and demographic variables longitudinally for all study participants. This project aims to contribute to the evidence of the inter-related causal factors of infantile anaemia, addressing the complexity of influencing factors from diverse methodological angles. We will assess infantile anaemia in three regions of Peru, including newborns and their mothers as participants, from childbirth until their first year of age. Ethics and dissemination Ethical approval was obtained from the Institutional Research Ethics Committee of the Instituto Nacional de Salud del Niño (Lima, Peru), CIEI-043-2019. An additional opinion has been granted by the Ethical Committee of Queen Mary University of London (London, UK). Dissemination across stakeholders is taking part as a continues part of the research process.

The discovery of penicillin over 90 years ago and its subsequent uptake by healthcare systems around the world revolutionised global health. It marked the beginning of a golden age in antibiotic discovery with new antibiotics readily discovered from natural sources and refined into therapies that saved millions of lives. Towards the end of the last century, the rate of discovery slowed to a near standstill. The lack of discovery is compounded by the rapid emergence and spread of bacterial pathogens that exhibit resistance to multiple antibiotic therapies and threaten the sustainability of global healthcare systems. Acinetobacter baumannii is an opportunistic pathogen whose prevalence and impact has grown significantly over the last 20 years. It is recognised as a barometer of the antibiotic resistance crisis due to the diverse array of mechanisms by which it can become resistant.

Repurposing old antibiotics into more effective and safer formulations is an emergent approach to tackle the growing threat of antimicrobial resistance. Herein, a peptide hydrogel is reported for the localized and sustained release of polymyxin B (PMB), a decade-old antibiotic with increasing clinical utility for treating multidrug-resistant Gram-negative bacterial infections. The hydrogel is assembled by additing PMB solution into a rationally designed peptide amphiphile (PA) solution and its mechanical properties can be adjusted through the addition of counterions, envisioning its application in diverse infection scenarios. Sustained release of PMB from the hydrogel over a 5-day period and prolonged antimicrobial activities against Gram-negative bacteria are observed. The localized release of active PMB from the hydrogel is shown to be effective in vivo for treating Pseudomonas aeruginosa infection in the Galleria mellonella burn wound infection model, dramatically reducing the mortality from 93% to 13%. Complementary antimicrobial activity against Gram-positive Staphylococcus aureus and enhanced antimicrobial effect against the Gram-negative Acinetobacter baumannii are observed when an additional antibiotic fusidic acid is incorporated into the hydrogen network. These results demonstrate the potential of the PMB-triggered PA hydrogel as a versatile platform for the localized and sustained delivery of combined antimicrobial therapies.

BACKGROUND:β-Lactam (BL)/β-lactamase inhibitor (BLI) combinations are widely used for the treatment of Gram-negative infections. Cefepime has not been widely studied in combination with BLIs. Sulbactam, with dual BL/BLI activity, has been partnered with very few BLs. We investigated the potential of cefepime/sulbactam as an unorthodox BL/BLI combination against MDR Gram-negative bacteria. METHODS:In vitro activity of cefepime/sulbactam (1:1, 1:2 and 2:1) was assessed against 157 strains. Monte Carlo simulation was used to predict the PTA with a number of simulated cefepime combination regimens, modelled across putative cefepime/sulbactam breakpoints (≤16/≤0.25 mg/L). RESULTS:Cefepime/sulbactam was more active (MIC50/MIC90 8/8-64/128 mg/L) compared with either drug alone (MIC50/MIC90 128 to >256 mg/L). Activity was enhanced when sulbactam was added at 1:1 or 1:2 (P<0.05). Reduction in MIC was most notable against Acinetobacter baumannii and Enterobacterales (MIC 8/8-32/64 mg/L). Pharmacokinetic/pharmacodynamic modelling highlighted that up to 48% of all isolates and 73% of carbapenem-resistant A. baumannii with a cefepime/sulbactam MIC of ≤16/≤8 mg/L may be treatable with a high-dose, fixed-ratio (1:1 or 1:2) combination of cefepime/sulbactam. CONCLUSIONS:Cefepime/sulbactam (1:1 or 1:2) displays enhanced in vitro activity versus MDR Gram-negative pathogens. It could be a potential alternative to existing BL/BLI combinations for isolates with a cefepime/sulbactam MIC of 16/8 mg/L either as a definitive treatment or as a carbapenem-sparing option.

The primary reason for skin graft failure and the mortality of burn wound patients, particularly those in burn intensive care centers, is bacterial infection. Several animal models exist to study burn wound pathogens. The most commonly used model is the mouse, which can be used to study virulence determinants and pathogenicity of a wide range of clinically relevant burn wound pathogens. However, animal models of burn wound pathogenicity are governed by strict ethical guidelines and hindered by high levels of animal suffering and the high level of training that is required to achieve consistent reproducible results. In this study, we describe for the first time an invertebrate model of burn trauma and concomitant wound infection. We demonstrate that this model recapitulates many of the hallmarks of burn trauma and wound infection seen in mammalian models and in human patients. We outline how this model can be used to discriminate between high and low pathogenicity strains of two of the most common burn wound colonizers Pseudomonas aeruginosa and Staphylococcus aureus, and multi-drug resistant Acinetobacter baumannii. This model is less ethically challenging than traditional vertebrate burn wound models and has the capacity to enable experiments such as high throughput screening of both anti-infective compounds and genetic mutant libraries.

AbstractA hospital outbreak of carbapenem-resistant Enterobacteriales was detected by routine surveillance. Whole genome sequencing and subsequent analysis revealed a conserved promiscuous OXA-48 carrying plasmid as the defining factor within this outbreak. Four different species of Enterobacteriales were involved in the outbreak.Escherichia coliST399 accounted for 20/55 of all the isolates. Comparative genomics with publicly availableE. coliST399 sequence data showed that the outbreak isolates formed a unique clade. The OXA-48 plasmid identified in the outbreak differed from other known plasmids by an estimated five homologous recombination events. We estimated a lower bound to the plasmid conjugation rate to be 0.23 conjugation events per lineage per year. Our analysis suggests co-evolution between the plasmid and its main bacterial host to be a key driver of the outbreak. This is the first study to report carbapenem-resistantE. coliST399 carrying OXA48 as the main cause of a plasmid-borne outbreak within a hospital setting. This study supports complementary roles for both plasmid conjugation and clonal expansion in the emergence of this outbreak.

Resistance to last-resort antibiotics is significant public health issue. Antibiotic use in animal husbandry may be a driver of resistance that can subsequently be disseminated via the food chain. This study sought to determine the level of polymyxin resistance in Gram-negative pathogens present in Australian poultry, particularly the presence of mobilizable mechanisms of polymyxin resistance. Cloacal swabs from 213 birds were taken in a point prevalence survey from six different farms at a Victorian chicken processing facility. Colistin resistant organisms were recovered by direct plating on CHROMagar COL-APSE media. Bacterial isolates were identified and analyzed by MALDI-TOF, biochemical and genotypic assays. The 213 specimens yielded 57 (26.8%) colistin-resistant Gram-negative organisms, all of which have been previously described as exhibiting intrinsic resistance to polymyxin antibiotics. The most frequent organism was identified as Hafnia paralvei (40/57; 70%). Other colistin-resistant organisms included Aeromonas hydrophila (16%), Myroides odoratus (7%), Alcaligenes faecalis (5%), and Pseudochrobactrum spp. (2%). No mobile colistin resistance (mcr) genes were detected, although the arnA gene was identified in two A. hydrophila isolates and may mediate colistin resistance in these isolates. Intrinsic polymyxin-resistant organisms are widely distributed in the food chain, with over a quarter of the birds tested yielding a polymyxin-resistant organism. However, strains containing mcr genes remain rare in Australian poultry.