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Phenotypic testing for Enterobacterales that harbour ESBLs is not additive to accurate in vitro β-lactam MICs for clinical decision-making. ESBL testing is an outdated practice established in an era of higher cephalosporin breakpoints to prevent resistant Enterobacterales carrying Ambler class A β-lactamases with affinity for later-generation β-lactams from being reported as susceptible to later-generation cephalosporins, leading to clinical failures. ESBL testing is problematic because of inaccuracies when multiple classes of β-lactamases are produced by the same organism, thus limiting the testing application to specific species and resistance types. selleck compound Clinical laboratories should instead focus finite resources on accurate susceptibility testing using contemporary interpretative criteria to help guide therapeutic decisions. With continued emergence of antimicrobial resistance and in the setting of accurate susceptibility testing and current breakpoints the use of ESBL phenotypic testing is not helpful in clinical decision-making.

Optimal timing for rifampicin combination therapy in patients with staphylococcal vascular graft/endograft infection (S-VGEI) is unknown. Experts recommend adding rifampicin after lowering bacterial load by surgery and wound closure.

To assess predictors of rifampicin resistance among staphylococci isolated from patients in the Vascular Graft Infection Cohort Study.

We included prospective patients with S-VGEI diagnosis from 1 January 2002 to 30 June 2020. We retrospectively assessed determinants of rifampicin resistance using exact logistic regression and described survival with Kaplan-Meier curves.

We analysed 513

spp. among 143 predominantly male (82%) patients with a median age of 68 years (IQR 60-75). Thereof, 82 (57%) received a rifampicin combination therapy and 61 (43%) received an antimicrobial therapy without rifampicin. Among 82 patients with rifampicin, 26/26 patients with any rifampicin resistance had open wounds with a strong association of rifampicin resistance with rifampicin treatment while having open wounds (OR 37, 95% CI 6.1 to ∞). Among 75 patients with a rifampicin combination therapy and rifampicin-susceptible staphylococci at S-VGEI diagnosis, 12/12 patients with a secondary rifampicin-resistant isolate had an open wound (OR 14, 95% CI 2.1 to ∞).

Rifampicin should be started after wound closure due to increased risk of rifampicin resistance observed while having open wounds or second-look surgeries among patients with S-VGEI.

Rifampicin should be started after wound closure due to increased risk of rifampicin resistance observed while having open wounds or second-look surgeries among patients with S-VGEI.

Up to 32% of ESBL-producing Enterobacterales strains display a carbapenem-heteroresistant (cHR) phenotype but its clinical relevance is unknown.

To determine risk factors and clinical outcome associated with infection due to cHR ESBL-producing

(ESBL-EC).

A retrospective, case-control study was conducted on patients from whom a pair of clonally related

strains were isolated during separate healthcare encounters with (case) or without (control) development of cHR phenotype in the latter strain. Study groups were compared for host and microbial characteristics and carbapenem exposure. Outcome measures included ICU admission, length of hospitalization, and mortality.

Study patients (15 cases, 10 controls) were elderly (median age 74 years) with half admitted from home (52%), most (80%) having ≥3 comorbid conditions and severe functional impairment. Case patients were more likely to have 'index' ESBL-EC isolating from blood (27% versus 0%;

0.125) and have greater cumulative amount and duration of carbapenem exposure than controls. All control 'subsequent' isolates were from urine whereas five cHR case isolates were from blood or respiratory sources. More hospitalized case patients required ICU admission (23% versus 0%;

0.257) and prolonged hospital stay (>7 days) than controls (62% versus 38%%;

0.387).

Our findings deserve confirmation with a larger study population and call attention to the potential for increased morbidity with cHR ESBL-EC infections, which underscores the need to screen for cHR phenotype in patients with repeated growth of ESBL-EC, particularly from systemic sites and patients that have had extensive carbapenem exposure.

Our findings deserve confirmation with a larger study population and call attention to the potential for increased morbidity with cHR ESBL-EC infections, which underscores the need to screen for cHR phenotype in patients with repeated growth of ESBL-EC, particularly from systemic sites and patients that have had extensive carbapenem exposure.

NDM-producing Enterobacteriaceae are a major clinical concern worldwide. We characterized NDM-positive pathogens isolated from patients and assessed the dissemination patterns of the



genes in a hospital setting.

Eleven NDM-positive Enterobacteriaceae (three

, six

and two

) were isolated from nine patients over a 1 year period. Antimicrobial susceptibility was assessed by MICs. A combination of short- and long-read WGS was used for genome analysis. Clinical treatment history of patients was linked with genetic features of individual isolates to investigate the dissemination patterns of the



genes and NDM-positive strains.



in clonal

were transmitted between two patients. In other instances, an identical IncC plasmid encoding NDM-1 was transmitted between

and

isolated from the same patient, and an IncX3 plasmid, carrying



or



, was harboured in non-clonal

. Varying patterns of IS elements were identified as a critical transmission mechanism in association with



and risk of transfer of 'high mobility' resistance genes among Enterobacteriaceae.Paediatric common infection pathways have been developed in collaboration between the BSAC and national paediatric groups, addressing the management of cellulitis, lymphadenitis/lymph node abscess, pneumonia/pleural empyema, pyelonephritis, tonsillitis/peritonsillar abscess, otitis media/mastoiditis, pre-septal/post-septal (orbital) cellulitis, and meningitis. link2 Guidance for the management of a child presenting with a petechial/purpuric rash and the infant under 3 months of age with fever is also provided. The aim of these pathways is to support the delivery of high-quality infection management in children presenting to a hospital. The pathways focus on diagnostic approaches, including the recognition of red flags suggesting complex or severe infection requiring urgent intervention, approaches to antimicrobial stewardship (AMS) principles and guidance on safe and timely ambulation aligned with good practice of outpatient parenteral antimicrobial therapy (OPAT).

Identification and validation of novel therapeutic targets is imperative to tackle the rise of drug resistance in tuberculosis. An essential Mur ligase-like gene (Rv3712), expected to be involved in cell-wall peptidoglycan (PG) biogenesis and conserved across mycobacteria, including the genetically depleted

, was the primary focus of this study.

Biochemical analysis of Rv3712 was performed using inorganic phosphate release assays. The operon structure was identified using reverse-transcriptase PCR and a transcription/translation fusion vector.

mycobacterial protein fragment complementation assays helped generate the interactome.

Rv3712 was found to be an ATPase. Characterization of its operon revealed a mycobacteria-specific promoter driving the co-transcription of Rv3712 and Rv3713. The two gene products were found to interact with each other

. Sequence-based functional assignments reveal that Rv3712 and Rv3713 are likely to be the mycobacterial PG precursor-modifying enzymes MurT and GatD, respectively. An

network involving Mtb-MurT, regulatory proteins and cell division proteins was also identified.

Understanding the role of the enzyme complex in the context of PG metabolism and cell division, and the implications for antimicrobial resistance and host immune responses will facilitate the design of therapeutics that are targeted specifically to



Understanding the role of the enzyme complex in the context of PG metabolism and cell division, and the implications for antimicrobial resistance and host immune responses will facilitate the design of therapeutics that are targeted specifically to M. tuberculosis.Long before the nature of infection was recognized, or the significance of biofilms in delayed healing was understood, antimicrobial agents were being used in wound care. In the last 70 years, antibiotics have provided an effective means to control wound infection, but the continued emergence of antibiotic-resistant strains and the documented antibiotic tolerance of biofilms has reduced their effectiveness. A range of wound dressings containing an antimicrobial (antibiotic or non-antibiotic compound) has been developed. Whereas standardized methods for determining the efficacy of non-antibiotic antimicrobials in bacterial suspension tests were developed in the early twentieth century, standardized ways of evaluating the efficacy of antimicrobial dressings against microbial suspensions and biofilms are not available. Resistance to non-antibiotic antimicrobials and cross-resistance with antibiotics has been reported, but consensus on breakpoints is absent and surveillance is impossible. Antimicrobial stewardship is therefore in jeopardy. This review highlights these difficulties and in particular the efficacy of current non-antibiotic antimicrobials used in dressings, their efficacy, and the challenges of translating in vitro efficacy data to the efficacy of dressings in patients. This review calls for a unified approach to developing standardized methods of evaluating antimicrobial dressings that will provide an improved basis for practitioners to make informed choices in wound care.

Individuals with cystic fibrosis (CF) have an increased susceptibility to fungal infection/allergy, with triazoles often used as first-line therapy. Therapeutic drug monitoring (TDM) is essential due to significant pharmacokinetic variability and the recent emergence of triazole resistance worldwide.

In this retrospective study we analysed the 'real-world' TDM of azole therapy in a large CF cohort, risk factors for subtherapeutic dosing, and the emergence of azole resistance.

All adults with CF on azole therapy in a large single UK centre were included. Clinical demographics, TDM and microbiology were analysed over a 2 year study period (2015-17) with multivariate logistic regression used to identify risk factors for subtherapeutic dosing.

91 adults were treated with azole medication during the study period. A high prevalence of chronic subtherapeutic azole dosing was seen with voriconazole (60.8%) and itraconazole capsule (59.6%) use, representing significant risk factors for subtherapeutic levels. Rdinal studies are needed to understand the effects of antifungal resistance on outcome in CF and the implications of subtherapeutic dosing on resistance evolution.

Growing resistance to antimicrobials has become an important health issue of the 21st century. Many international, national and local approaches are being employed for the control and prevention of antimicrobial resistance (AMR). Among them, surveillance is reported to be the best method to reduce the spread of infection and thereby AMR. An integral component of AMR surveillance is the informatics suite for collection, storage and analysis of surveillance data.

Considering the traits of an optimal surveillance tool and constraints with existing tools, Indian Council of Medical Research (ICMR) initiated the design and development of ICMR's Antimicrobial Resistance Surveillance system (

-AMRSS). link3

-AMRSS is a web-based tool built using modular architecture. It is capable of collecting standardized data from small laboratories to generate local and nationwide reports.

-AMRSS is a robust, comprehensive, modular, extensible and intelligent open-source tool piloted in ICMR's AMR Network (31 hospitals and laboratories across India) since 2016.