Objectives: The ceragenins, or CSAs, were designed to mimic the activities of antimicrobial peptides and represent a new class of antimicrobial agent. The aim of this study was to comparatively investigate the antimicrobial activities of first/second generation ceragenins and various antibiotics against multidrug-resistant (MDR) Klebsiella pneumoniae, including colistin-resistant bacteria. Also, the synergistic effects of two ceragenins with colistin or meropenem were investigated with six K. pneumoniae strains presenting different resistant patterns. Methods: Minimal inhibition concentrations (MICs) were determined by the microdilution method according to the CLSI. Antibiotic combination studies were evaluated by the time–kill curve method. Results: MIC₅₀ and MIC₉₀ values of tested ceragenins ranged from 8 to 32 mg/L and 16 to 128 mg/L. Overall, among the ceragenins tested, CSA-131 showed the lowest MIC₅₀ and MIC₉₀ values against all microorganisms. The MICs of the ceragenins were similar or better than tested antibiotics, except for colistin. Synergistic activities of CSA-131 in combination with colistin was found for strains both at 1× MIC and 4× MIC. No antagonism was observed with any combination. Conclusions: First-generation ceragenins CSA-13 and CSA-44 and second-generation ceragenins CSA-131, CSA-138 and CSA-142 have significant antimicrobial effects on MDR K. pneumoniae. Mechanisms allowing resistance to clinical comparator antibiotics like colistin did not impact the activity of ceragenins. These results suggest that ceragenins may play a role in treating infections that are resistant to known antibiotics.

Objectives: Achromobacter xylosoxidans is an emerging pathogen in cystic fibrosis (CF). Relatively little is known about its clinical impact and optimal management. In the present study, the in vitro bactericidal activities of meropenem, either alone or in combination with colistin, levofloxacin, or chloramphenicol, were assessed using A. xylosoxidans strains isolated from CF patients. The synergistic interactions of these combinations were also investigated. Methods: Minimal inhibitory concentrations (MICs) were determined by microbroth dilution. Bactericidal and synergistic effects of the tested antibiotic combinations were assessed by using the time-kill curve technique. Results: Based on the time-kill curves, we found that meropenem-colistin combinations have bactericidal and synergistic activities for 24 h against A. xylosoxidans strains, both at 1 × MIC and 4 × MIC. Although synergistic interactions were seen with meropenem-levofloxacin combinations, no bactericidal interactions were observed. Additionally, the meropenem-chloramphenicol combinations were found to be neither bactericidal nor synergistic. No antagonism was observed with any combination tested. Conclusions: This study’s findings could have important implications for empirical or combination antimicrobial therapy with tested antibiotics.

Objectives: Antimicrobial resistance is a major problem in the treatment of infectious diseases. Therefore, it is important to develop new and effective antimicrobial agents. For this purpose, a new series of compounds with a 2,4-dihydro-3H-1,2,4-triazole-3-thione structure was synthesized. Materials and Methods: 2,4-dihydro-3H-1,2,4-triazole-3-thione compounds (T1-T8) were synthesized by heating thiosemicarbazide derivatives under alkaline conditions. Infrared (IR), 1 H-NMR, and 13 C-NMR spectroscopic methods were used to elucidate the chemical structures of the compounds. The antimicrobial activity of the compounds against eight bacterial strains (five Gram-negative and three Gram-positive) and two fungal strains was evaluated using the microdilution method. Results: Compounds T4, carrying a benzoyl group, and T6, carrying a phenethyl group, showed the best antibacterial activity against Enterococcus faecalis ATCC 29212, with minimum inhibitory concentrations (MICs) of 41.79 mg/L and 81.25 mg/L, respectively. Compound T6 also demonstrated the strongest antibacterial activity against Staphylococcus epidermidis ATCC 12228, with an MIC of 40.62 mg/L. Antifungal activity assays revealed that compounds T4, T6, and T8 were the most potent against Candida albicans ATCC 90028, with MIC values of 40.62-83.59 mg/L, and that T6, T7, and T8 were the most potent against Candida glabrata ATCC 90030, with MIC values of 40.62-162.5 mg/L. Conclusion: Among the compounds, T6 appears to exhibit significant antimicrobial activity against both Gram-positive bacteria (e.g., E. faecalis ATCC 29212 and S. epidermidis ATCC 12228) and fungi (e.g.

Background/Objectives: Stenotrophomonas maltophilia (SM) is a significant cause of hospital-acquired infections in immunocompromised and critical care patients. This study investigates the impact of combining ceftazidime/avibactam (CZA) with conventional antibiotics on SM obtained from various sources in planktonic and biofilm cell cultures. Methods: Using broth microdilution, the MICs of different antibiotics, including CZA, were determined on 37 SM strains. CZA’s bactericidal and synergistic effectiveness were examined through in vitro time–kill curve tests with tigecycline (TGC), chloramphenicol (CHL), levofloxacin (LVX), colistin (CS), and amikacin (AMK). In addition, synergistic activity was investigated against SM biofilm cell cultures, and antibiotic Mutant Prevention Concentrations (MPCs) were tested against SM isolates. Results: Compared to ceftazidime (CAZ), CZA was four times more efficient against 37 SM strains. Unlike TGC and CHL, CS, AMK, and CZA had 2–4 times higher MBCs than MICs. All studied antibiotics were bactericidal at 1× or 4× MIC doses against SM bacteria, except for CZA. The combinations of CZA with LVX and CZA with AMK or CS demonstrated synergistic effects in four out of seven (57%) strains and in three out of seven (43%) strains, respectively, when tested at doses equivalent to the MIC. Moreover, all antibiotic combinations with CZA showed a synergistic effect at dosages four times the MIC. Additionally, CZA and the tested drugs synergistically inhibited SM biofilm formation, and MPC values were 8–16 times the MIC. Conclusions: The results of this study indicate that combining CZA with LVX and CS was more effective against SM strains. These combinations might provide alternatives for treating SM pathogens in both planktonic and biofilm cell cultures.

Coagulase-negative staphylococci (CoNS), particularly Staphylococcus epidermidis and Staphylococcus capitis , are significant opportunistic pathogens associated with biofilm-related infections and antimicrobial resistance. Although bacteriophage therapy is a promising alternative to antibiotics, human skin-derived phages targeting clinically important CoNS remain poorly characterized. Four bacteriophages were isolated from facial skin swabs of healthy volunteers, and two (phages Se_20 and Se_42) were selected for detailed characterization. Biological characteristics, antibacterial activity, genomic features, and preliminary in vivo activity were evaluated. Both phages exhibited lytic activity against clinically relevant CoNS and reduced planktonic bacterial counts by > 3 log₁₀ CFU/mL within 4–6 h. They showed strain-dependent antibiofilm activity, inhibiting biofilm formation by up to 88.6% and reducing preformed biofilm biomass by up to 86.3%. Both exhibited a latent period of 25 min, while the burst sizes were 142 PFU/cell for Se_20 and 70 PFU/cell for Se_42. Genome analyses confirmed that phages were lytic and lacked virulence factors, antimicrobial resistance genes, and tRNA/rRNA genes. In the Galleria mellonella infection model, phage treatment increased larval survival without detectable toxicity. This study demonstrates that the human skin microbiome is a valuable source of lytic bacteriophages against CoNS and supports their further preclinical evaluation as alternative antimicrobial candidates for biofilm-associated infections.