Potential Synergy Activity of the Novel Ceragenin, CSA-13, against Carbapenem-Resistant Acinetobacter baumannii Strains Isolated from Bacteremia Patients

Carbapenem-resistant Acinetobacter baumannii is an important cause of nosocomial infections, particularly in patients in the intensive care units. As chronic infections are difficult to treat, attempts have been made to discover new antimicrobials. Ceragenins, designed to mimic the activities of antimicrobial peptides, are a new class of antimicrobial agents. In this study, the in vitro activities of CSA-13 either alone or in combination with colistin (sulphate), tobramycin, and ciprofloxacin were investigated using 60 carbapenem-resistant A. baumannii strains isolated from bacteremia patients blood specimens. MICs and MBCs were determined by microbroth dilution technique. Combinations were assessed by using checkerboard technique. The MIC 50 values (mg/L) of CSA-13, colistin, tobramycin, and ciprofloxacin were 2, 1, 1.25, and 80, respectively. The MIC 90 (mg/L) of CSA-13 and colistin were 8 and 4. The MBCs were equal to or twice greater than those of the MICs. Synergistic interactions were mostly seen with CSA-13-colistin (55%), whereas the least synergistic interactions were observed in the CSA-13-tobramycin (35%) combination. No antagonism was observed. CSA-13 appears to be a good candidate for further investigations in the treatment of A. baumannii infections. However, future studies should be performed to correlate the safety, efficacy, and pharmacokinetic parameters of this molecule

Comparative In Vitro Activities of First and Second-Generation Ceragenins Alone and in Combination with Antibiotics Against Multidrug-Resistant Klebsiella pneumoniae Strains

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

In vitro activities of ceftazidime/avibactam alone or in combination with antibiotics against multidrug-resistant Acinetobacter baumannii isolates

Objectives: Infections caused by multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) are a growing problem because of the limited options for treatment. The number of antimicrobials that are currently being developed is still insufficient to control this global threat. Combination therapies of antibiotics with different antimicrobial mechanisms have been proposed as the best options for treating MDR A. baumannii infections. The objective of this study was to investigate the in-vitro effectiveness of ceftazidime/avibactam alone or in combination with antibiotics against MDR A. baumannii isolates using time-kill assays

In vitro antibacterial activity of eravacycline against multidrug-resistant Acinetobacter baumannii isolates

The antibacterial effectiveness of eravacycline was compared with various antibiotics used in Acinetobacter therapy against multidrug-resistant (MDR) Acinetobacter baumannii strains. Antibacterial susceptibility studiea was achieved by the broth microdilution method against 52 non-duplicate, A. baumanniii strains to eravacycline, tobramycin, levofloxacin, cefepime, meropenem, and colistin. Eravacycline presented greater action than the comparators of the other group, cefepime, colistin, levofloxacin, and tobramycin. While the MIC50/90 values of eravacycline were 8/16 mg/ L and those for tobramycin, levofloxacin, cefepime, meropenem, and colistin were found 256/>256, 64/ >256, 256/ >256, 128/>256, and 0.5/256 mg/L, respectively. As a result, the present study showed that eravacycline was a potent effective antibiotic against MDR A. baumannii. Eravacycline could be an effective new alternative for use in particular, for the treatment of this problematic organism

Antimicrobial activities of five endemic Hypericum species from Anatolia compared with Hypericum perforatum

Different crude extracts of some endemic Hypericum species (H. thymbrifolium, H. spectabile, H. pseudolaeve, H. neurocalycinum, H. malatyanum) and H. perforatum were analyzed using a microdilution assay for antimicrobial activity against several microorganisms. It is observed that all extracts showed activity against tested Gram positive bacteria (Staphylococcus aureus, Meticillin resistant S. aureus and Streptococcus epidermidis). The most active extracts were from H. neurocalycinum and H. malatyanum which showed potent activity with lowest MIC (4.8 mu g/mL) value against more tested Gram positive bacteria. Additionally, it was also found that some extracts of H. spectabile and H. pseudolaeve had antifungal activities against C. albicans. These endemic species were evaluated for antimicrobial activity for the first time in the literature

Effects of Various Antibiotics Alone or in Combination with Doripenem against Klebsiella pneumoniae Strains Isolated in an Intensive Care Unit

Colistin, tigecycline, levofloxacin, tobramycin, and rifampin alone and in combination with doripenem were investigated for their in vitro activities and postantibiotic effects (PAEs) on Klebsiella pneumoniae. The in vitro activities of tested antibiotics in combination with doripenem were determined using a microbroth checkerboard technique. To determine the PAEs, K. pneumoniae 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. Colistin, tobramycin, and levofloxacin produced strong PAEs ranging from 2.71 to 4.23 h, from 1.31 to 3.82 h, and from 1.35 to 4.72, respectively, in a concentration-dependent manner. Tigecycline and rifampin displayed modest PAEs ranging from 1.18 h to 1.55 h and 0.92 to 1.19, respectively. Because it is a beta-lactam, PAEs were not exactly induced by doripenem (ranging from 0.10 to 0.18 h). In combination, doripenem scarcely changed the duration of PAE of each tested antibiotic alone. The findings of this study may have important implications for the timing of doses during K. pneumoniae therapy with tested antibiotics

Antibacterial and antibiofilm activities of ceragenins againstAchromobacterspecies isolated from cystic fibrosis patients

Achromobacter species, which are recognized as emerging pathogens isolated from patients with cystic fibrosis, are capable of forming biofilm in the respiratory tract in patients and innate multidrug resistance to antimicrobials. CSAs are cationic salt derivatives that mimic the activity of antimicrobial peptides and exhibit antimicrobial activity against bacteria. In this study, the in vitro activities of various ceragenins against Achromobacter-species biofilms were investigated comparatively with a conventional antibiotic (meropenem). Biofilm-formation inhibition and biofilm-adhesion inhibition were investigated on five strong biofilm-producing strains. The lowest MIC(50)result was obtained with CSA-13. All of the tested CSAs showed significant biofilm inhibitory activity in the manner of a time- and concentration-dependent effect. To the best of our knowledge, this is the first article to evaluate the antibacterial and antibiofilm activities of tested CSAs against Achromobacter species

Antimicrobial activity of rhizomes of Ferulago trachycarpa Boiss. and bioguided isolation of active coumarin constituents

Ferulago trachycarpa (Apiaceae) is a plant used traditionally for its sedative, digestive, carminative and aphrodisiac properties with distribution in West, Southwest and South Anatolian part of Turkey. In this study the antimicrobial activities of fractionally n-hexane, dichloromethane, methanol and only methanol extracts from rhizomes of F. trachycarpa were screened against Stapylococcus aureus ATCC 6538, S. epidermidis ATCC 12228, Escherichia coli ATCC 8739, Kiebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 27853, Proteus mirabilis ATCC 14153, Enterococcus feacalis ATCC 29212 bacterial strains and fungal strains such as Candida albicans ATCC 10231, C. tropicalis ATCC 750 and C. parapsilosis ATCC 22019 by microdilution method. All extracts have been shown to possess antimicrobial activities against bacteria and fungal strains and according to the antimicrobial results, the isolation of the active constituents was made from the most active n-hexane and dichloromethane extracts. So, four pure compounds are known as coumarin derivatives, crenulatin (6-formyl-7-methoxycoumarin), suberosin (7-methoxy-6-prenylcoumarin), marmesin senecioate ((-)-prantschimgin) as dihydrofuranocoumarin derivative and ulopterol [6- (2', 3'-dihydroxy-3'-methylbuty1)-7-methoxy-coumarin] were isolated. Crenulatin (6-formyl-7-methoxycoumarin), suberosin (7-methoxy-6-prenylcoumarin), marmesin senecioate ((-)-prantschimgin) which are pure compounds demonstrated antifungal activity with 625 mg/L MIC against C. albicans and antibacterial activity with 1250 mg/L MIC against S. aureus (MRSA). These results indicate that extracts and pure compounds obtained from Ferulago trachycarpa could be a potential for pharmaceutical products which have antimicrobial activity

Evaluation of antifungal and disinfectant-resistant Candida species isolated from hospital wastewater

The present study aims to examine the in vitro antifungal susceptibility patterns ofCandidaspecies isolated from hospital wastewater, and the efficacy of widely used disinfectants (sodium hypochlorite and benzalkonium chloride) against planktonic and biofilm cells were assessed. Susceptibility testing demonstrated that the two azoles were more effective againstC. albicansthan non-albicans isolates. When we determine the efficiency of disinfectants against the planktonic cells, benzalkonium chloride did not show any activity in all the studied strains under tested conditions exceptC. albicans-1. However, sodium hypochlorite showed >= 4 log(10)killing in viable cells for different contact times. On the other hand, while 0.1% and 1% concentrations of benzalkonium chloride showed fungicidal activity against biofilm cells, sodium hypochlorite at 1% only demonstrated fungicidal activity. Those results showed that surface water is a possible transmission path for fungi in the investigated hospital region and may be a health risk, especially for the immunocompromised host

Synthesis and antibacterial activity of new hybrid derivatives of 5-sulfamoyl-1H-indole and 4-thiazolidinone groups

The synthesis of a series of new 3-phenyl-5-sulfamoyl-N-(7/8/9-(non)substituted-3-oxo-1-thia-4-azaspiro[4.4]non/[4.5]dec-4-yl)-1H-indole-2-carboxamide derivatives and their subsequent testing for antibacterial activity is described in this paper. 4-Sulfamoylbenzenediazonium chloride was synthesized from diazotization of sulfanilamide and sodium nitrite in the presence of HCl and was further allowed to condense with ethyl 2-benzylacetoacetate to produce ethyl 2-benzyl-2-(4-sulfamoylphenyl)hydrazonoacetate. This compound was cyclized to ethyl 5-sulfamoyl-3-phenyl-1H-indole-2-carboxylate employing the Fischer-indole procedure. The reaction of ethyl 5-sulfamoyl-3-phenyl-1H-indole-2-carboxylate with hydrazine hydrate yielded sulfamoyl-3-phenyl-1H-indole-2-carbohydrazide. Through a cyclization process, the spirothiazolidinone derivatives were obtained from the reaction of suitable cyclic ketones with 5-sulfamoyl-3-phenyl-1H-indole-2-carbohydrazide in the presence of thioglycolic acid/thiolactic acid. Structural elucidation of the novel compounds was achieved with the help of UV, IR,H-1 NMR, HSQC, ESI-MS, and as well as elemental analysis. Among all the synthesized compounds tested, four compounds displayed the most promising antibacterial activity. The influence of the substituents and their positions on the antibacterial activity was evaluated