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Bacterial heteroresistance is defined when a seemingly susceptible population of bacteria contains one or more resistant subpopulations. This behaviour has been seen in a variety of bacteria and with many different antibiotics. Heteroresistance is largely unrecognized during clinical diagnosis, because it is hard to accurately test for in a clinical lab using standard antibacterial test methodologies. Overlooking heteroresistance may contribute to inaccurate definitions of antibiotic susceptibility and could lead to poorer patient outcomes, undermining global antimicrobial stewardship. Awareness of the clinical impact of heteroresistance should be better represented in antimicrobial susceptibility test guidance, so clinicians can better spot heteroresistance when present and adjust dosing or treatment plans if necessary. Development of viable clinical tests for heteroresistance should be made a research priority, allowing us to better understand, test and treat heteroresistant bacteria.

Chronic sub-inhibitory antimicrobial exposures may shape antibiotic resistance (AMR) dissemination at the animal, food and environment interface. Polyether ionophore coccidiostats remain widely used in poultry production, yet their influence on AMR dissemination at sub-inhibitory exposure is unclear. To determine whether sub-minimum inhibitory concentration (MIC) polyether ionophores enhance resistance plasmid transfer in vitro and to characterize their effects on gut microbiota and resistome dynamics in vivo during and after administration. We investigated the effects of representative polyether ionophores at sub-MICs on resistance spreading phenotypes in vitro and gut resistome dynamics in VREfm-challenged broilers. In vitro plasmid conjugation and related phenotypes were quantified, and in vivo caecal microbiota and resistome were profiled by 16S rRNA gene sequencing and shotgun metagenomics. Sub-MIC polyether ionophores increased plasmid conjugation, copy number and biofilm formation in Enterococcus spp., whereas no comparable effects were observed in Escherichia coli. In vivo, salinomycin temporarily disrupted caecal microbiota development and, at Day 20, suppression of indigenous taxa (e.g. Faecalibacterium) was accompanied by a transient surge in VREfm colonization and vanA abundance; resistome expansion was non-persistent. After salinomycin cessation, recovery of beneficial genera like Akkermansia was associated with reduction of the total resistance gene burden towards pre-treatment baseline by Day 42. Polyether ionophores can promote resistance dissemination phenotypes in vitro, but gut ecological resilience may limit long-term impacts after cessation of exposure under recommended dosing conditions. The transient resistome surge during the treatment suggests increased shedding and potential environmental dissemination via manure, warranting surveillance and risk assessment.

Pseudomonas aeruginosa readily evolves antimicrobial resistance through regulatory plasticity and stress-adaptive pathways. Clinically, antibiotics lacking intrinsic antipseudomonal activity are often favoured with the assumption that they avoid selective pressure on P. aeruginosa. Whether subinhibitory exposure to such 'non-antipseudomonal antibiotics' (NAPA) can nevertheless select for canonical resistance pathways remains incompletely defined. Three P. aeruginosa strains (ATCC 27853 and two bloodstream isolates) were serially passaged over 14 days in the presence of ertapenem, ceftriaxone or moxifloxacin at one-third the baseline MIC. MICs for antipseudomonal antibiotics (meropenem, ceftazidime, ciprofloxacin) were measured at serial time points and after a 3-day antibiotic-free recovery (Day 14). Whole-genome sequencing was performed longitudinally to identify mutations. NAPA exposure led to reproducible elevations in antipseudomonal MICs: ertapenem triggered up to a 29-fold increase in meropenem MIC, ceftriaxone up to a 31-fold rise in ceftazidime MIC and moxifloxacin up to a 12-fold increase in ciprofloxacin MIC. Elevated MICs persisted on Day 14 despite absence of further antibiotic pressure. Genomic analysis revealed convergent evolution of mutations in efflux regulator genes (nfxB, nalC, nalD, amrR) and the β-lactamase-regulating gene dacB, emerging during periods of MIC escalation and mapping to regulatory pathways governing efflux and AmpC expression. Subinhibitory exposure to antibiotics without intrinsic antipseudomonal activity reproducibly selected for heritable multidrug-resistant phenotypes in P. aeruginosa. Convergent mutations arose in regulatory genes classically associated with direct antipseudomonal antibiotic pressure, demonstrating that resistance architectures can be selected independent of target engagement and underscoring the potential for collateral resistance under antibiotic stress.

Aerosolized colistin has been increasingly used to treat multidrug-resistant gram-negative infections, particularly in the intensive care unit (ICU), as an alternative to intravenous colistin, which is limited by nephrotoxicity and poor pulmonary penetration. Systemic colistin use has been linked to the emergence of resistance, but the impact of inhaled colistin on resistance development remains unclear. We conducted a time-series analysis using monthly data from April 2014 to December 2023 in the ICUs of a 2700-bed tertiary-care hospital comprising 108 adult ICU beds. Monthly antibiotic use and the incidence of colistin-resistant Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii from respiratory specimens were analysed using vector autoregressive (VAR) or vector error correction models (VECMs), depending on the presence of stationarity and cointegration. In bivariate VAR analyses, aerosolized colistin use was positively associated with subsequent increases in colistin-resistant K. pneumoniae and A. baumannii, with significant effects observed across multiple lags. In multivariate VAR models including other antibiotic classes, the temporal association persisted for K. pneumoniae. Sensitivity analyses using VECM also showed significant associations for E. coli, K. pneumoniae, P. aeruginosa and A. baumannii. In an additional analysis of non-respiratory specimens, aerosolized colistin was also significantly associated with colistin-resistant A. baumannii. Aerosolized colistin use was temporally associated with increased resistance in major gram-negative pathogens, particularly K. pneumoniae and A. baumannii. These findings highlight the need for cautious use of inhaled colistin and support its inclusion in targeted antimicrobial stewardship efforts, given its potential contribution to the emergence of resistance.

Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) are leading causes of urinary tract infections (UTIs). In Morocco, carbapenem resistance data are scarce and largely hospital-based. We investigated carbapenem-resistant E. coli and K. pneumoniae isolates from community settings in Morocco. In this prospective multicentre study, we analysed 1296 non-duplicate E. coli and K. pneumoniae isolates recovered from outpatients with community-acquired UTIs (CA-UTIs) across 12 Moroccan cities (January 2022-December 2023). Antimicrobial susceptibility testing was performed following EUCAST guidelines. All phenotypically carbapenem-resistant isolates (n = 54, 13 E. coli, et 41 K. pneumoniae) were subjected to whole-genome sequencing (WGS) using Illumina technology to identify resistance determinants, mobile genetic elements and clonal lineages. E. coli predominated [n = 1000, 77.2% (95% CI: 74.8-79.4)] while K. pneumoniae accounted for 22.8% [n = 296 (95% CI: 20.6-25.2)]. Carbapenem resistance rates were significantly higher in K. pneumoniae than in E. coli [ertapenem: 21.1% (95% CI: 16.6-26.4) versus 2.4% (95% CI: 1.6-3.6); imipenem: 15.0% (CI: 11.2-19.6) versus 1.9% (95% CI: 1.2-3.0)].WGS revealed a high clonal diversity [eight sequence types (ST) in E. coli and 12 in K. pneumonnie]. Carbapenemase-mediated resistance was predominant in K. pneumoniae (notably bla NDM-14, bla NDM-7, bla NDM-5 and bla OXA-48). By contrast, E. coli primarily exhibited efflux and permeability defect mechanisms with sporadic carbapenemase-encoding gene carriage (bla NDM or bla OXA-48). The K. pneumoniae international high-risk clone ST147 producing NDM-14 was dominant (n = 23 isolates), followed by ST307 (n = 4), whereas ST410 was the most frequently identified among E. coli (n = 5). Carbapenem-resistant E. coli and K. pneumoniae in community UTIs in Morocco, are driven by multiple clones. These findings underscore the urgent need to expand community-based AMR surveillance beyond hospital settings.

Antimicrobial resistance (AMR) is a growing global health threat to humans, domestic animals and wildlife. In response, the WHO endorsed the AMR Global Action Plan in 2015 to guide the development of national action plans (NAPs). NAPs articulate priorities, sectoral roles and implementation strategies to address AMR. Although the wildlife sector has been noted to be minimally included in these documents, the extent and nature of its inclusion remain unclear. This is concerning given wildlife's role at the human-animal-environment interface in AMR dynamics. To assess the extent and context of wildlife inclusion in AMR NAPs. We reviewed 177 AMR NAPs available in the WHO library. Each document was searched for the terms 'wildlife' or 'wild', and the extracted excerpts were analysed using an inductive thematic analysis to determine the context in which wildlife was referenced. Wildlife was minimally included in the analysed NAPs, with only 11% (20/177) containing wildlife-related references. Fifty-eight mentions were identified across documents, appearing within One Health definitions, proposed actions, document headings and governance structures. Surveillance was the most proposed wildlife-related activity; however, detailed implementation strategies were absent. Uganda was the only country whose NAP explicitly incorporated a wildlife-associated institution within its governance framework. Wildlife is minimally included in AMR NAPs, with references predominantly conceptual rather than operational. The absence of defined implementation mechanisms undermines effective One Health integration and risks weakening comprehensive AMR responses.

Antimicrobial resistance (AMR) is a global public health crisis affecting human health, animal health, plant health, and the environment. In 2015, all WHO Member States endorsed the Global Action Plan on AMR and committed to develop multi-sectoral national action plans (NAPs) under a 'One Health' approach. To accelerate the implementation of AMR NAPs, the WHO introduced a costing and budgeting tool in 2021 to support prioritization of interventions, identification of activities financed through existing budgets, estimation of implementation costs and assessment of funding gaps. To assess the impacts resulting from the use of the costing and budgeting tool at national level in WHO African region (AFRO) Member States. National AMR focal points from the human, animal, agriculture and environmental sectors in 15 WHO African Region Member States trained on the tool completed a questionnaire using Google Forms via a secure web-based survey link. Eleven countries reported mobilizing funding using costed data generated through the tool. Costed NAPs informed policy decisions in seven countries and improved stakeholder collaboration in funding efforts. However, the use of the tool revealed significant challenges, including insufficient domestic financing and lack of congruence of donor priorities with national needs. Costing One Health AMR NAPs serves as an important catalyst for realistic budgeting and resource planning including resource mobilization to ensure both effective implementation and the long-term sustainability of AMR interventions.

Antimicrobial resistance (AMR) poses a major threat to effective treatment and global health security, with disproportionate impacts in low- and middle-income settings. In Central Africa, health system fragility, limited surveillance capacity and weak multisectoral coordination heighten vulnerability. Despite momentum following the WHO Global Action Plan, the status of AMR governance, One Health coordination and financing in the subregion remains insufficiently characterized. To systematically assess AMR governance in Central Africa (2015-2025), focusing on policy frameworks, One Health coordination and financing mechanisms. We conducted a PRISMA 2020-compliant systematic review registered in PROSPERO (CRD420251082393). Six databases were searched, along with grey literature, including national policy documents, institutional reports and consultations with AMR focal points. Eligible sources addressed AMR policy, coordination, surveillance and funding. Of the 4464 records identified, 27 documents were included (19 peer-reviewed articles, one report, seven national action plans). Evidence was concentrated in Cameroon, with limited data from other countries. National action plans aligned with global standards were identified in six countries, while none were available for Equatorial Guinea or the Republic of Congo. Across the region, governance was characterized by partial policy alignment but weak implementation, limited operationalization of One Health, fragmented surveillance and reliance on external funding. Key constraints included inadequate laboratory capacity, weak stewardship systems and insufficient domestic financing. AMR governance in Central Africa has progressed at the policy level but remains operationally constrained. Bridging the gap between policy and implementation requires strengthened institutionalization of One Health, improved accountability and sustainable domestic investment.

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This multicentre study aimed to assess performance of the EUCAST disc diffusion (DD) and MIC methods for linezolid susceptibility testing in a genetically diverse strain collection. Nordic clinical microbiology laboratories (n = 83) were invited to test a blinded collection of well-characterized Enterococcus faecalis (n = 10) and Enterococcus faecium (n = 10) strains using the EUCAST DD and gradient tests [Etest and MIC Test strips (MTS)] from two manufacturers (bioMerieux and Liofilchem). Results were compared to reference broth microdilution (BMD) MICs and genotype (presence/absence of linezolid resistance determinants). Forty-five laboratories provided DD, and 41 gradient test results. Comparing DD with reference MICs and genotype yielded overall categorical agreements (CA) of 87.0% and 97.8%, respectively. Essential agreement (EA) was 99.7% for Etest (bias +10.0%) and 84.5% for MTS (bias +71.0%). Susceptibility categorization with Etest and MTS showed CA of 90.5% and 84.1% with reference MICs, and 82.9% and 98.6% with genotype, respectively. Most discrepancies involved strains with borderline linezolid MICs (4-8 mg/L) and known linezolid resistance mechanisms. Linezolid exposure of strains with MIC 4 mg/L carrying transferable resistance genes (optrA or poxtA), led to MIC increasing above the clinical breakpoint. Etest and EUCAST DD had the highest CAs with linezolid reference MIC. EUCAST DD method and MTS gradient test consistently detected strains with confirmed resistance mechanisms. Our findings highlight the potential clinical implications of resistance determinants in MIC borderline strains and support the need for an area of technical uncertainty or a warning in breakpoint tables for linezolid in enterococci.

Antimicrobial resistance is considered one of the most dangerous threats to public health globally. In the last decade, several antimicrobial agents were developed for the treatment of infections with multidrug-resistant Gram-negative bacteria, especially carbapenem-resistant isolates. The aim of this study was to investigate the in vitro activity of the siderophore cephalosporin cefiderocol (FDC) and four comparator beta-lactam-beta-lactamase-inhibitor combinations (ceftazidime/avibactam, ceftolozane/tazobactam, imipenem/relebactam and meropenem/vaborbactam) against 401 clinical isolates of Gram-negative pathogens collected in Germany between 2019 and 2020. Genetic determinants of resistance were investigated by PCR and/or whole-genome sequencing. Furthermore, the ComASP test kit for cefiderocol minimum-inhibitory concentration (MIC) determination was compared to the EUCAST reference method broth microdilution. The cefiderocol resistance rate of Pseudomonas aeruginosa was 1.5% while resistance to the comparator agents ranged from 19.7% to 40.9%. Among both Acinetobacter baumannii and Stenotrophomonas maltophilia isolates the MIC50 value of cefiderocol was six or more log2 steps lower than the ones of the comparator agents. Seven isolates (three Escherichia coli, one Klebsiella pneumoniae, one P. aeruginosa and two A. baumannii) revealed cefiderocol MICs > 2 mg/L. While different beta-lactamase genes were detected in these isolates, they were most probably not solely responsible for cefiderocol resistance. MICs produced by ComASP test kits were comparable to the results of broth microdilution in E. coli, K. pneumoniae, P. aeruginosa and S. maltophilia (categorical agreement > 95%; essential agreement > 91%). Overall, cefiderocol activity against P. aeruginosa, A. baumannii and S. maltophilia was higher compared to the other agents tested.

Klebsiella pneumoniae is a major cause of healthcare-associated infections in Romania, where carbapenem resistance rates exceed 63%. The dissemination of clones co-producing multiple carbapenemases poses a critical challenge to infection control and antimicrobial management. To describe the molecular characteristics of carbapenem-resistant K. pneumoniae (CRKp) isolates and to assess their epidemiological relevance in a Romanian tertiary-care hospital. Non-duplicate CRKp isolates collected between July 2023 and May 2025 were included. Identification and antimicrobial susceptibility testing were performed according to EUCAST 2025 criteria. Isolates with reduced carbapenem susceptibility underwent WGS using Oxford Nanopore technology. MLST, resistome, virulome and plasmid profiling were analysed. A total of 101 CRKp isolates were included. In 55.4% (n = 56) of strains the resistance genotype displayed both bla NDM-5 and bla OXA-48-like genes. WGS identified ST383 as the dominant sequence type (n = 31; 30.7%), with 93.5% (29/31) of ST383 clones co-harbouring bla NDM-5 and bla OXA-48 along with bla CTX-M-15 genes, primarily located on mosaic resistance-virulence plasmids, with evidence of chromosomal integration. Cefiderocol susceptibility was 90.3% by broth microdilution. All tested ST383 isolates remained susceptible to aztreonam-avibactam. ST383 emerged as the dominant carbapenemase-producing K. pneumoniae lineage and represents the first documented identification in Romania of strains co-harbouring bla NDM-5 and bla OXA-48, highlighting the emergence of a high-risk clone with substantial dissemination potential.

Antimicrobial resistance (AMR) is a serious and growing public health concern driven by multiple factors. Urinary tract infection (UTI) is one of the infections commonly associated with AMR, and more than 80% of UTIs are caused by Escherichia coli. MDR E. coli is a significant problem that requires urgent intervention, particularly in complicated UTIs (cUTIs) with underlying comorbidities. Although prevalence rates of MDR E. coli vary globally, it remains a critical clinical and economic challenge on every continent. The majority of MDR E. coli strains produce ESBLs, followed by AmpC enzymes, making them generally resistant to penicillins, cephalosporins and aztreonam. While there are some therapeutic options for uncomplicated UTIs (uUTIs), choices are limited for cUTIs, with carbapenems being the mainstay of treatment. However, carbapenem resistance is on the rise, severely impeding clinical regimens. With very few options available, combinations of antimicrobial agents for synergistic activity are increasingly relied upon for carbapenem-resistant E. coli. This situation has compelled the search for novel antimicrobial agents, which are slowly entering the market, although not as quickly as AMR is spreading worldwide. Current focus is shifting towards alternative antimicrobial therapies that exhibit broad-spectrum bactericidal activity and immunomodulatory effects, considered for both preventive and therapeutic strategies. A multi-disciplinary approach combining novel antimicrobials, innovative therapies and robust infection control measures will be essential to effectively manage MDR E. coli in uUTIs and cUTIs and mitigate the global threat of antibiotic resistance.

Contemporary multicentre data on carbapenemase distribution among carbapenem-resistant Enterobacterales (CRE) in Lebanon remain limited. This study aimed to characterize the distribution of carbapenemase enzyme families among clinical CRE isolates collected from Lebanese hospitals. A multicentre study was conducted across 14 hospitals representing different Lebanese regions between March and October 2025. CRE isolates were centrally processed using standardized phenotypic microbiological methods and interpreted according to the 2025 European Committee on Antimicrobial Susceptibility Testing breakpoints. Carbapenemase identification was performed using NG-Test® CARBA-5. Agreement between phenotypic prediction and rapid immunochromatographic testing was evaluated. A total of 59 non-duplicate CRE isolates from individual patients were included. New Delhi metallo-β-lactamase (NDM) was the predominant carbapenemase enzyme family (64.4%), followed by OXA-48-like enzymes (23.7%), with co-production observed in 10.2% of isolates. Among carbapenem-resistant Escherichia coli (34 isolates), NDM predominated (73.5%). In contrast, carbapenem-resistant Klebsiella pneumoniae (15 isolates) more frequently harboured OXA-48-like enzymes (53.3%), although NDM-producing isolates were also identified (33.3%). No NDM-producing isolate was susceptible to ceftazidime-avibactam, whereas OXA-48-like producers retained higher susceptibility (71.4%). Phenotypic carbapenemase prediction showed high agreement with NG-Test® CARBA-5 results (κ = 0.89), including 100% sensitivity for metallo-β-lactamase detection. NDM was the predominant carbapenemase among CRE isolates recovered from participating Lebanese hospitals, while Oxacillinase-48 carbapenemase (OXA-48)-like enzymes remained common. These findings highlight the importance of carbapenemase-specific characterization, as therapeutic options differ according to the underlying resistance mechanism. Rapid carbapenemase detection using NG-Test® CARBA-5, coupled with phenotypic prediction, may support resistance mechanism-guided therapy, antimicrobial stewardship and surveillance efforts.

In the UK, over 16% of antibiotic prescriptions are for skin infections. New approaches are required to treat and prevent such infections, and new therapeutic modalities should be investigated. Epidermicin NI01 is a first-in-class bacteriocin with potent activity and a novel mode of action against MRSA and Streptococci, leading causes of community and healthcare acquired skin infections and a significant burden of antimicrobial resistance (AMR). The activity of NI01 in a model of MRSA skin infection was assessed during this study. Immunosuppressed male CD1 mice were wounded dorsally using tape-stripping and S. aureus strain USA300 was topically applied. Topical q24 h administration of vehicle (0.5% HMPC) or NI01 (4 dosing regimens in 0.5% HPMC) or 50 mg of Bactroban 2% (mupirocin) or Fucidin 2% (fusidic acid) was initiated at 24 h post-infection (hpi). At 96 hpi, infected skin was recovered for quantitative skin burden analysis. There were no adverse effects observed due to infection or treatment. No reduction in skin burden was seen in the 3% NI01 mono-dose group. Treatments resulted in significant log10 reductions in cfu/g tissue of 2.82 (Fucidin), 2.48 (3% NI01 q24) and 2.47 (Bactroban). The MIC of NI01 for S. aureus strain USA300 was 4 mg/L before the study and ex vivo. These in vivo activity data warrant further development of NI01 for topical therapy of infections caused by drug-resistant priority pathogens. Clinical use could spare conventional antibiotics for serious and systemic infections and would support stewardship efforts to reduce mupirocin resistance in S. aureus.

Enterococcus faecium and Staphylococcus aureus are opportunistic bacterial pathogens with a demonstrated capacity to develop antimicrobial resistance and cause serious life-threatening infections, underscoring the urgent need for new therapeutic options. Here, we have synthesized and characterized the activities of an 8-hydroxyquinoline-based ionophore antibiotic (ionophoroantibiotic; IP antibiotic), designated 'IP-antibiotic 12.' Using multidrug-resistant strains of E. faecium and S. aureus, in vitro investigations revealed that IP-antibiotic 12 exhibits bactericidal activity, demonstrates a low propensity for resistance emergence, increases the susceptibility of particular strains to select antibiotics, possesses a favorable toxicity profile, and dysregulates bacterial metal homeostasis. IP-antibiotic 12 demonstrated therapeutic efficacy against multidrug-resistant S. aureus skin infection, as a direct-acting topical antimicrobial and antibiotic adjunct when co-administered with oral linezolid. Interestingly, it was not efficacious in murine models of systemic and pulmonary infection. These results highlight the potential of IP-antibiotic 12 as a novel therapeutic against multidrug-resistant gram-positive bacteria and provide a foundation for the development of next-generation IP-antibiotics with enhanced in vivo therapeutic efficacy.

Klebsiella has recently been recognized as a potential host of mobile tigecycline-resistant gene tet(X4), posing a serious threat to public health. However, the occurrence of other tet(X) variants in Klebsiella remains uncommon. We identified a novel tet(X5) variant in one Klebsiella pneumoniae and two Klebsiella quasipneumoniae isolates recovered from retail meat in Hainan, China and investigated its phenotypic resistance, genetic context and transferability. Antimicrobial susceptibility was determined by broth microdilution. Whole-genome sequencing, utilizing both Illumina and Nanopore platforms, facilitated the complete characterization of the genome sequence and plasmid structure. Resistance gene analysis revealed a novel tet(X5) variant encoding a 385-amino acid protein, designated Tet(X5.5), which exhibited 97.6% identity with the reference Tet(X5) protein. A total of 21 amino acid substitutions were identified, primarily located in the N- and C-terminal regions. Functional assays confirmed that expression of tet(X5.5) increased the tigecycline MIC in E. coli DH5α from 0.125 to 4 mg/L (32-fold). In K. pneumoniae 241CM75B, the tet(X5.5) gene was located on two conjugative plasmids: an ∼170 kb IncFIBK/IncFIIK8 hybrid plasmid and an ∼74 kb IncFIIpCRY plasmid. The other two isolates carried identical IncFIIpCRY plasmids. Conjugation assays confirmed that all tet(X5.5)-carrying plasmids were self-transmissible to E. coli C600, with transfer frequencies ranging from 10-6 to 10-5. Genetic analysis revealed that tet(X5.5) was embedded within an ISCR2-mediated transposon structure that was conserved across distinct plasmid backbones. This study reports a novel transferable tet(X5) variant in Klebsiella, underscoring the risk of foodborne transmission and the necessity for integrated surveillance across clinical and agricultural settings.

MRSA decolonization strategies are widely implemented to reduce the risk of invasive infections but rely heavily on the use of chlorhexidine. Reduced chlorhexidine susceptibility has been reported after widespread use in hospital settings. The objective of the study is to assess chlorhexidine susceptibility among clinical MRSA isolates and to investigate potential induction of reduced susceptibility following chlorhexidine exposure. Ninety-five MRSA isolates from 77 patients of the University Hospital Zurich, treated between October 2021 and September 2022, were included. Chlorhexidine MICs were determined using the broth microdilution method, and subsequently MBCs were assessed. WGS was performed using the Illumina technology. Ten isolates with MBC values ≥8 mg/L were selected for cyclic exposure experiments using sub-inhibitory chlorhexidine concentrations and for analysis of genes associated with reduced chlorhexidine susceptibility. Longitudinal isolates from seven patients were analysed to assess in-host evolution. Most isolates showed chlorhexidine MICs of 2 mg/L (76.6%, 60/77) and MBCs of 4 mg/L (68.8%, 53/77). ST8 was the most represented MLST among the isolates tested (23.1%). None of the 10 isolates with MBCs ≥8 mg/L demonstrated further reductions in chlorhexidine susceptibility following repeated sub-lethal exposure. Although resistance-associated genes were detected, no phenotypic impact on chlorhexidine susceptibility was observed. Longitudinal analysis of seven patients revealed stable MIC and MBC values despite prolonged carriage and chlorhexidine exposure. These findings indicate the absence of inducible or clinically relevant reduced susceptibility to chlorhexidine among MRSA isolates in this setting, despite repeated exposure.

Carbapenem resistance is a growing public health crisis with regional variability in incidence. We characterized the susceptibility of carbapenem-resistant Gram-negative rods (CR-GNRs) from the Pacific Northwest to five reserve beta-lactam agents including cefiderocol and aztreonam-avibactam. A panel of 162 CR-GNRs from unique patients were tested against cefiderocol, aztreonam-avibactam, ceftazidime-avibactam, meropenem-vaborbactam and ceftolozane-tazobactam, with a subset of isolates derived from patients with bacteraemia (n = 55). Whole-genome sequencing (WGS) was performed on representative Stenotrophomonas maltophilia isolates displaying a range of cefiderocol MICs (n = 9). Among all isolates, the MIC50 and MIC90 to cefiderocol was 0.25 and 4 mg/L, respectively, compared with 4 and >64 mg/L for aztreonam-avibactam. Overall, 98.3% of S. maltophilia (n = 60), 91.2% of Enterobacterales (n = 34) and 88.5% of Pseudomonas aeruginosa (n = 26) isolates were susceptible to cefiderocol, while 78.6% of other non-fermenters had MICs ≤4 mg/L. Aztreonam-avibactam and cefiderocol exhibited similar activity against Enterobacterales and S. maltophilia, but aztreonam-avibactam was less active against other organisms. WGS of S. maltophilia isolates with elevated cefiderocol MICs identified disruptive mutations in PBP-encoding genes (mrcB/PBP1b and pbpC/PBP1c) that were not observed in highly susceptible isolates. The bacteraemia cohort had many comorbidities and a 29% 30 day all-cause mortality. In this cohort, cefiderocol demonstrated the highest in vitro activity as extrapolated from MICs, followed by ceftazidime-avibactam, aztreonam-avibactam, meropenem-vaborbactam and ceftolozane-tazobactam, respectively. Cefiderocol exhibited the greatest in vitro activity against various CR-GNRs species in a Pacific Northwest population enriched for severely ill patients. Susceptibility to other agents was more variable among tested organisms.