In this work, we synthesized a series of nine tetraalkylammonium salts derived from N ‐methyl morpholine and assessed their antibacterial efficacy against Methicillin‐Resistant Staphylococcus aureus (MRSA). The investigated morpholinium cations differ by the length of one linear alkyl chain, which ranges from 1 to 18 carbon atoms. We found that compounds with alkyl chains in the n ‐C ₁₂ H ₂₅ ‐( n ‐dodecyl) to C ₁₆ H ₃₃ ‐( n ‐hexadecyl) display the highest bactericidal effects, exhibiting Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) values of 3.9 μg/mL – surpassing the effectiveness of the commercial drug Linezolid. Conversely, compounds with shorter chains (<5 carbon atoms) are inactive against MRSA, establishing a clear structure‐activity relationship. Assays on A. salina reveal that short‐alkyl‐chain morpholinium derivatives, inactive against MRSA), are moderately toxic, while the strongest bactericides of our set demonstrate high or extreme toxicity to A. salina . Our findings underscore the potential of morpholine derivatives as a means to control Methicillin‐Resistant Staphylococcus aureus and pinpoint the need to develop safe applications for these compounds given their potential toxicity.

Background/objectives: The increasing prevalence of multidrug-resistant (MDR) bacteria, particularly Klebsiella pneumoniae, calls for the development of new antimicrobial agents. This study investigates a series of fluorinated azolium salts and their rhodium(I) complexes for antibacterial activity against clinical and reference strains of K. pneumoniae. Methods: Eleven fluorinated azolium salts and their corresponding Rh(I) complexes (22 compounds total) were synthesized and tested against several K. pneumoniae strains, including three MDR clinical isolates (U–13685, H–9871, U–13815) and ATCC reference strains. Minimum inhibitory concentrations (MICs) were determined. In silico ADMET analyses were conducted to evaluate intestinal absorption, oral bioavailability, Caco-2 permeability, carcinogenicity, solubility, and synthetic accessibility. Results: Among the Rh(I) complexes, Rh–1, Rh–3, and Rh–11 showed activity against the three MDR isolates (MIC = 62.5–250 µg/mL), while Rh–1, Rh–4, Rh–6, and Rh–11 were active against all ATCC strains (MIC = 3.9–250 µg/mL). The corresponding azolium salts displayed weak or no activity, highlighting the critical role of the metal center. ADMET predictions indicated that most Rh complexes had good intestinal absorption, and all except Rh–3, Rh–4, and Rh–9 were predicted to be orally bioavailable. Compounds Rh–1 to Rh–7 showed Caco-2 permeability, and all were classified as non-carcinogenic. Rh–8 to Rh–11 exhibited lower solubility and synthetic accessibility. Conclusions: The results underscore the potential of fluorinated Rh(I) complexes as antibacterial agents against MDR K. pneumoniae, with Rh–1 and Rh–11 emerging as promising leads based on activity and favorable predicted pharmacokinetics.

In this work, we synthesized a series of nine tetraalkylammonium salts derived from N-methyl morpholine and assessed their antibacterial efficacy against Methicillin-Resistant Staphylococcus aureus (MRSA). The investigated morpholinium cations differ by the length of one linear alkyl chain, which ranges from 1 to 18 carbon atoms. We found that compounds with alkyl chains in the n-C12H25- (n-dodecyl) to C16H33- (n-hexadecyl) display the highest bactericidal effects, exhibiting Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) values of 3.9 µg/mL - surpassing the effectiveness of the commercial drug Linezolid. Conversely, compounds with shorter chains (<5 carbon atoms) are inactive against MRSA, establishing a clear structure-activity relationship. Assays on A. salina reveal that short-alkyl-chain morpholinium derivatives, inactive against MRSA), are moderately toxic, while the strongest bactericides of our set demonstrate high or extreme toxicity to A. salina. Our findings underscore the potential of morpholine derivatives as means to control Methicillin-Resistant Staphylococcus aureus and pinpoint the need to develop safe applications for these compounds given their potential toxicity.

Background. Clostridioides difficile infection (CDI) is the leading cause of healthcare - associated diarrhea and is strongly linked to pharmacological exposure, particularly antimicrobials and proton pump inhibitors (PPIs). Objective. To evaluate the association between antimicrobial and PPI use and the risk of CDI in hospitalized patients. Materials and Methods. A retrospective observational analytical case - control study was conducted. A total of 60 hospitalized patients were included (30 cases with confirmed CDI and 30 controls without infection). Demographic, clinical, and pharmacological variables were analyzed. Associations between exposure factors and infection were estimated using crude odds ratios (OR) with 95 % confidence intervals (95 % CIs). Results. Patients with CDI were older (52.61 ± 18.81 vs. 39.62 ± 16.98 years; p = 0.0036) and received more prescribed antibiotics (4.07 ± 2.29 vs. 2.00 ± 2.42; p = 0.0012). Polyantibiotic therapy (≥3 antibiotics) was significantly associated with CDI (OR: 6.57; 95 % CI: 2.11-20.48; p = 0.0016). Prolonged PPI use (≥7 days) was also significantly associated (OR: 4.57; 95 % CI: 1.45-14.39; p = 0.015). Carbapenem (56.7 % vs. 26.7 %; p = 0.036) and clindamycin use (26.7 % vs. 6.7 %; p = 0.034) were more frequent among cases, although these associations were not statistically significant in risk estimation. Conclusions. Polyantibiotic therapy and prolonged PPI use were significantly associated with CDI. Antimicrobial exposure burden appears to be the main pharmacological determinant, while PPIs may act as a contributing factor. Incorporating CDI into pharmacovigilance systems may improve prescribing practices and enhance patient safety in hospital settings.