Infections are often treated with (medicinal) plants by traditional healers. Extracts from these (as well as many other) plants often exhibit antimicrobial activity in vitro. In fact, numerous bioactive compounds with antimicrobial activity have been isolated and identified from such extracts. However, very few of these compounds have been developed into clinically used antibiotics. This contrasts strongly with antimicrobial compounds from microorganisms.

Various reasons for this apparent paradox have been proposed. These include (1) insufficient potency of most antimicrobial natural products, (2) synergy required with other plant secondary metabolites for full efficacy, (3) insufficiently chemical or in vivo stability, (4) low oral bioavailability, (5) unfavorable pharmacokinetics, (6) toxicity or small therapeutic window, (7) narrow antimicrobial spectrum, (8) rapid development of resistance, (9) difficult to patent, (10) no economically viable production possible (by full synthesis, semi-synthesis, bioproduction, etc. ). In this talk, I will review and evaluate each of these, and draw some conclusions that may guide future research in this area.

Introduction

Vancomycin-resistant Enterococcus faecium (VREfm) is an increasing challenge in hospital settings. Although oritavancin has shown in vitro activity against some VREfm isolates, its clinical role remains uncertain because clinical breakpoints and outcome data are limited.

Objectives

To describe the epidemiological and microbiological features of a hospital outbreak caused by vanA-positive E. faecium.

To evaluate the in vitro activity of oritavancin.

Materials and methods

Bacterial identification was performed using MALDI-TOF mass spectrometry (bioMérieux VITEK® MS). The presence of vanA and related resistance determinants was assessed by next-generation sequencing (Oxford Nanopore Technologies).

Antimicrobial susceptibility was determined by broth microdilution using a commercial panel (ComASP® Oritavancin, Liofilchem).

Because EUCAST clinical breakpoints for oritavancin against E. faecium/VRE are not established, oritavancin MICs should be interpreted descriptively and compared with published MIC distributions rather than categorized as clinically susceptible or resistant.

Eight patients were identified as colonized with vanA-positive E. faecium. Cases clustered mainly in onco-hematology wards, suggesting nosocomial transmission in a high-risk population.

All isolates carried vanA and expressed high-level glycopeptide resistance, with:

• Vancomycin resistance (MIC ≥ 256 mg/L)

• Teicoplanin resistance (MIC ≥ 64 mg/L)

Oritavancin showed low in vitro MIC values against the outbreak isolates:

• MIC range: 0.25 mg/L

• Low MIC values were observed despite the presence of vanA. This finding is microbiologically relevant but should not be presented as evidence of clinical susceptibility in the absence of validated breakpoints and clinical outcomes.

Conclusions

Oritavancin demonstrated low in vitro MICs against the vanA-positive E. faecium outbreak isolates; however, these results should be considered descriptive because validated clinical breakpoints for this organism-drug combination are lacking.

Isolates showed high-level glycopeptide resistance, but retained low oritavancin MICs. Further PK/PD, synergy and clinical-outcome studies of oritavancin in VREfms to establish oritavancin as a standard therapeutic alternative for invasive infection are needed.

Introduction

Infections caused by carbapenemase-producing Enterobacterales, represent a major therapeutic challenge. Among them, NDM-type metallo-β-lactamases limit treatment options. Cefiderocol has emerged as one of the main therapeutic alternatives.

Eravacycline, a novel fluorocycline approved for complicated intra-abdominal infections, has demonstrated potent in vitro activity against carbapenemase-producing Enterobacterales, including KPC, NDM, and OXA-48 producing isolates. However, its clinical use should be interpreted in light of infection source, drug exposure, absence of a urinary indication, and the limited availability of outcome data in infections caused by cefiderocol-resistant NDM-producing organisms.

Objectives

To evaluate the in vitro activity of eravacycline against cefiderocol-resistant ESBL/NDM-producing Enterobacterales and to describe tetracycline-associated resistance determinants detected by whole-genome sequencing.

Materials and methods

The MIC of eravacycline was determined using gradient diffusion (Etest, bioMérieux, France), and cefiderocol MIC was determined using a commercial broth microdilution system (UMIC, Bruker, USA), in nine ESBL- and NDM-producing Enterobacterales isolates (six Escherichia coli and three Klebsiella pneumoniae). Four isolates were recovered from urine, four from rectal surveillance swabs, and one from prosthetic tissue.Isolates were sequenced by Oxford Nanopore Technologies.

Results

All nine ESBL/NDM-producing Enterobacterales isolates showed low eravacycline MICs according to the interpretive criteria applied in this study, while all were classified as cefiderocol-resistant. Genomic analysis identified multiple tetracycline-associated resistance determinants, including efflux systems or related components (acrAB-tolC, oqxAB, KpnEF, tet(A), tet(B)), transporters (emrKY), and regulatory genes (marA, evgAS). Despite the presence of these determinants, no phenotypic reduction in eravacycline activity was observed in this isolate set.

Conclusions

Eravacycline showed high in vitro activity against ESBL/NDM -producing Enterobacterales with cefiderocol resistance. The presence of tetracycline resistance genes was not associated with reduced susceptibility to eravacyline, suggesting its ability to overcome classical resistance mechanisms. These findings are clinically relevant as a hypothesis-generating observation in difficult-to-treat NDM-producing Enterobacterales.

Introduction

Resistance to cefiderocol (CFDC) among Gram-negative bacteria is multifactorial and may involve beta-lactamase activity, metallo-beta-lactamase production, alterations in siderophore uptake pathways, changes in permeability, efflux, and/or target-related mechanisms.

CFDC is a siderophore-conjugated cephalosporin with a catechol residue that allows iron binding and facilitates entry through bacterial iron acquisition systems. Therefore, the expression and functionality of iron uptake receptors may influence CFDC activity.

Several siderophore systems, including enterobactin, aerobactin, yersiniabactin and salmochelin, may be relevant under iron-limited conditions, although their contribution to CFDC susceptibility depends on bacterial species, receptor integrity, gene expression and co-existing resistance mechanisms.

Objectives

To describe whole-genome sequencing findings in CFDC-resistant NDM-producing Enterobacterales, focusing on the co-occurrence of blaNDM-5 and genes involved in siderophore/iron acquisition pathways, and to discuss their potential contribution to the observed CFDC-resistant phenotype.

Materials and methods

Five CFDC-resistant NDM-producing Enterobacterales isolates (CFDC MIC range: 4-16 mg/L) were analyzed by whole-genome sequencing. The isolates carried blaNDM-5, and genes associated with the yersiniabactin system, including irp1 and fyuA, were identified in all cases.

In addition, other siderophore-associated genes were detected in some isolates.

Results

All five CFDC-resistant NDM-producing isolates carried blaNDM-5 and the yersiniabactin-associated genes irp1 and fyuA. Additional siderophore-related genes were variably present across isolates, suggesting heterogeneity in iron acquisition repertoires.

The consistent co-occurrence of blaNDM-5 with yersiniabactin-associated loci is biologically plausible in the context of reduced CFDC activity.

Conclusions

These preliminary WGS data show a consistent co-occurrence of blaNDM-5 and yersiniabactin-associated genes among CFDC-resistant Enterobacterales isolates. The findings support the hypothesis that siderophore/iron uptake pathways may contribute to CFDC resistance in NDM-5 producers, but functional studies and comparative genomic analyses are required to establish causality.

Listeria monocytogenes is a critical foodborne pathogen, with poultry products serving as a potential reservoir. Its ability to form biofilms may aid in its persistence on processing equipment and food-contact surfaces, while antimicrobial resistance complicates efforts to control and treat infections. This study analyzed 93 L. monocytogenes isolates from poultry to assess their biofilm-forming capacity and antibiotic resistance. Biofilms were tested on polystyrene microtiter plates at 12 °C and 30 °C in a nutrient-rich medium (Brain Heart Infusion, BHI). Susceptibility to eight antibiotics relevant to clinical and food safety was tested by disk diffusion and evaluated using EUCAST breakpoints, where available. Most isolates produced detectable, typically weak biofilms at both temperatures, with some shifting to moderate biofilm formation after extended incubation at 12 °C; no strong biofilm producers were observed. This underscores the significant role of incubation time and temperature in surface colonization. Overall, the isolates remained mostly susceptible to ampicillin, penicillin G, vancomycin, tetracycline, and chloramphenicol, whereas some subpopulations exhibited resistance or low susceptibility to trimethoprim–sulfamethoxazole (TMP-SMX) and, notably, erythromycin and streptomycin. No consistent link was found between biofilm formation and antibiotic susceptibility, suggesting these traits are largely independent among these isolates. These results demonstrate that poultry-derived L. monocytogenes can form weak to moderate biofilms under the tested monoculture conditions while generally remaining susceptible to first-line antibiotics. Nevertheless, the emergence of resistance to macrolides and aminoglycosides, together with the potential for increased colonization in complex multispecies biofilms in real food processing environments, underscores the need for ongoing, integrated surveillance across animal food systems.