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 To determine the in vitro stability and efficacy of colistin, tigecycline and levofloxacin alone or in combination with clarithromycin and/or heparin as lock solutions against biofilm-embedded Acinetobacter baumannii strains. Methods Candidate antibiotics (colistin, tigecycline and levofloxacin) were investigated in vitro, either alone or in combination with clarithromycin and/or heparin in solution. The efficacy of antibiotic lock solutions was tested in an in vitro catheter biofilm model against A. baumannii isolated from catheter-related bacteraemia. Results Candidate antibiotics at 400× MICs combined with clarithromycin (200 mg/mL) and/or heparin (1000 U/mL) were compatible. Colistin, tigecycline and levofloxacin and their combinations with clarithromycin demonstrated bactericidal activity against the biofilm-embedded A. baumannii strains. Compared with other antibiotics alone, the lock solution including only colistin was the best agent to eradicate A. baumannii embedded in the catheter model. When tested antibiotics were used in combination with clarithromycin, the combinations were significantly more effective and more rapid in reducing the live cell number or eliminating A. baumannii colonization in biofilms than each of the antibiotics alone. Conclusions Catheter lock solutions containing colistin may have the most promise for treating or preventing biofilm-producing catheter infections caused by A. baumannii. Clarithromycin was ultimately effective with the studied antibiotics to reduce live cell number or eradicate A. baumannii colonization in biofilms and could serve as an antibiotic enhancer. Our in vitro model findings now warrant clinical trials to investigate their real role in the management of catheter-related bacteraemia.

Acinetobacter baumannii is an obligately aerobic, non-motile, non-fermenting, gram-negative, opportunistic pathogen. The fact that this pathogen, which is the leading cause of nosocomial infections, is naturally resistant to many antibiotics and quickly acquires new resistance mechanisms gradually limits the antibiotic options that can be used in treatment. So, our study aims to investigate the in vitro antibacterial effects of eravacycline, a new tetracycline-class antibiotic, and compare this antibiotic with the antibiotics used in the clinic to treat the infection caused by A. baumannii. Also, eravacycline was tested in combination with meropenem or colistin against A. baumannii strains, which are resistant to colistin and meropenem. The antibiotic susceptibility of strains was determined by the microbroth dilution method. In addition, the agar dilution method determined the mutant inhibition concentration (MPC) values of the studied antibiotics. To investigate the effects of the antibiotics mentioned in our study on biofilm formation, the biofilm-forming abilities of the strains were evaluated by the crystal violet staining method. The bactericidal and synergistic effects of the studied antibiotics alone or in combination were determined by the time-dependent killing curve (TKC) method. The present antibacterial susceptibility experiments showed that 98% of the strains were multi-drug resistant (MDR). Our results in mutant inhibition studies showed that eravacycline is an antibiotic with the potential to prevent the emergence of resistant mutants with its low MPC value. When the effects of antibiotics on biofilm formation were investigated in our thesis study, it was determined that 95% of our strains formed biofilm. In biofilm inhibition experiments, it was observed that eravacycline at minimum inhibitory concentration (MIC) inhibited biofilm formation by 84% alone, 86% combined with colistin, and 85% combined with meropenem. Our combination experiments showed that 1×MIC eravacycline-meropenem and 4×MIC eravacycline-colistin combinations were synergistic against A. baumannii strains. In addition, the combination of 4×MIC eravacycline-meropenem also showed bactericidal activity at the 24th hour. No antagonist effects were detected in our combination studies. Present results reveal essential pharmacodynamic data on eravacycline, a new antibiotic for treating A. baumannii infections, which poses a global threat. Not applicable.

Background: Levofloxacin and tobramycin, alone and in combination with cefepime, were investigated for their in vitro activities and post-antibiotic effects (PAEs) on Pseudomonas aeruginosa. Methods: The in vitro activities of tobramycin and levofloxacin in combination with cefepime were determined by microbroth chequerboard technique against six P. aeruginosa strains that were isolated from patients with bacteremia. The results were interpreted by fractional inhibitory concentration index. To determine the PAEs, P. aeruginosa strains in the logarithmic phase of growth were exposed for 1 h to antibiotics, alone and in combination. Recovery periods of test cultures were evaluated using viable counting after centrifugation. Results: Three synergistic interactions were observed with cefepime-tobramycin and one with cefepime-levofloxacin combinations against tested strains.No antagonism was observed. Levofloxacin produced a PAE ranging from 1.9 to 4.5 h in a concentration-dependent manner. Similar PAEs were induced by tobramycin (ranging from 1.5 to 3.1 h). However, negative PAE values were obtained with cefepime. In combination, cefepime slightly reduced the PAE of tobramycin and levofloxacin against studied strains. Conclusion: The finding of this study may have important clinical implications for the timing of doses during therapy with cefepime, levofloxacin and tobramycin alone and in combination.