Interaction Of Colistin Research Articles

Antimicrobial Contribution of Chitosan Surface-Modified Nanoliposomes Combined with Colistin against Sensitive and Colistin-Resistant Clinical Pseudomonas aeruginosa.

Colistin is a re-emergent antibiotic peptide used as a last resort in clinical practice to overcome multi-drug resistant (MDR) Gram-negative bacterial infections. Unfortunately, the dissemination of colistin-resistant strains has increased in recent years and is considered a public health problem worldwide. Strategies to reduce resistance to antibiotics such as nanotechnology have been applied successfully. In this work, colistin was characterized physicochemically by surface tension measurements. Subsequently, nanoliposomes coated with highly deacetylated chitosan were prepared with and without colistin. The nanoliposomes were characterized using dynamic light scattering and zeta potential measurements. Both physicochemical parameters fluctuated relatively to the addition of colistin and/or polymer. The antimicrobial activity of formulations increased by four-fold against clinical isolates of susceptible Pseudomona aeruginosa but did not have antimicrobial activity against multidrug-resistant (MDR) bacteria. Interestingly, the free coated nanoliposomes exhibited the same antibacterial activity in both sensitive and MDR strains. Finally, the interaction of colistin with phospholipids was characterized using molecular dynamics (MD) simulations and determined that colistin is weakly associated with micelles constituted by zwitterionic phospholipids.

Synergistic Activities of Colistin with Tigecycline Combination Against Clinical Isolates of Carbapenem-resistant Acinetobacter baumannii

OBJECTIVES: To determine in vitro antimicrobial susceptibility and synergistic activity of colistin in combination with tigecycline against clinical strains of carbapenem- resistant Acinetobacter baumannii (CRAB).MATERIAL AND METHODS: Colistin and tigecycline minimum inhibitory concentrations (MICs) of 12-clinical CRAB isolates were determined by broth microdilution. Checkerboard testing was performed to assess the interaction of the colistin-tigecycline combination. Fractional inhibitory concentration indexes (ΣFIC) in the range of 0.5 to 1.0, > 1.0 to < 4.0 and ≥ 4.0 are considered as additive, indifferent, and antagonistic effects, respectively.RESULTS: All CRAB isolates were susceptible to colistin. Three out of 12 CRABs were susceptible to tigecycline based on a pharmacokinetic-pharmacodynamics (PK-PD) breakpoint (MICs ≤ 0.25 μg/mL). The MIC of both antimicrobials was decreased in most of the CRAB isolates in the checkerboard synergy testing. The interaction of colistin and tigecycline combination revealed both additive and indifferent effects in five and seven of the 12-CRAB isolates, respectively. Neither synergism nor antagonism of colistin and tigecycline combination was demonstrated.CONCLUSION: No synergistic effect between colistin and tigecycline against CRAB isolates was detected. However, the combination of these two drugs is likely to result in a decrease in the MIC of both drugs. Further studies with a larger sample to determine the in vitro synergistic activity of colistin and tigecycline combination are required.

Synergistic Activities of Colistin with Tigecycline Combination Against Clinical Isolates of Carbapenemresistant Acinetobacter baumannii

OBJECTIVES: To determine in vitro antimicrobial susceptibility and synergistic activity of colistin in combination with tigecycline against clinical strains of carbapenem- resistant Acinetobacter baumannii (CRAB). MATERIAL AND METHODS: Colistin and tigecycline minimum inhibitory concentrations (MICs) of 12-clinical CRAB isolates were determined by broth microdilution. Checkerboard testing was performed to assess the interaction of the colistin-tigecycline combination. Fractional inhibitory concentration indexes (ΣFIC) in the range of 0.5 to 1.0, > 1.0 to < 4.0 and ≥ 4.0 are considered as additive, indifferent, and antagonistic effects, respectively. RESULTS: All CRAB isolates were susceptible to colistin. Three out of 12 CRABs were susceptible to tigecycline based on a pharmacokinetic-pharmacodynamics (PK-PD) breakpoint (MICs ≤ 0.25 μg/mL). The MIC of both antimicrobials was decreased in most of the CRAB isolates in the checkerboard synergy testing. The interaction of colistin and tigecycline combination revealed both additive and indifferent effects in five and seven of the 12-CRAB isolates, respectively. Neither synergism nor antagonism of colistin and tigecycline combination was demonstrated. CONCLUSION: No synergistic effect between colistin and tigecycline against CRAB isolates was detected. However, the combination of these two drugs is likely to result in a decrease in the MIC of both drugs. Further studies with a larger sample to determine the in vitro synergistic activity of colistin and tigecycline combination are required. Keywords: in vitro, synergism, tigecycline, colistin, checkerboard method DOI: 10.31524/bkkmedj.2019.02.005

Drug and nanoparticle mediated rapid naked eye water test for pathogens detection

Inspired by the interaction of colistin with lipopolysaccharides (LPS) of the bacterial outer membrane, we describe a simple, cost effective and rapid assay for the detection of bacterial contamination in water samples. Colistin, a bactericidal drug, has been used by us in a receptor configuration for detection of pathogenic microorganisms without involving any tedious sample preparation step. The approach employs the cationic antibiotic drug for dual purpose, firstly, as a primary binder for pathogens and secondly, as an aggregator for negatively charged Gold nanoparticles (GNPs). The former consists of colistin binding to bacteria in water that renders GNPs free in solution thus depicting red color and the latter shows colistin driven aggregation of GNPs producing blue colored solution. The assay works in a two-step procedure that involves addition of colistin and GNPs to the water sample before results can be visualized based on color change. The assay is sensitive at a concentration up to 10 bacterial cells·mL−1 in a time frame of 5 min without requiring any expensive reagents and instruments.

Interaction of Colistin and Colistin Methanesulfonate with Liposomes: Colloidal Aspects and Implications for Formulation

Interaction of colistin and colistin methanesulfonate (CMS) with liposomes has been studied with the view to understanding the limitations to the use of liposomes as a more effective delivery system for pulmonary inhalation of this important class of antibiotic. Thus, in this study, liposomes containing colistin or CMS were prepared and characterized with respect to colloidal behavior and drug encapsulation and release. Association of anionic CMS with liposomes induced negative charge on the particles. However, degradation of the CMS to form cationic colistin over time was directly correlated with charge reversal and particle aggregation. The rate of degradation of CMS was significantly more rapid when associated with the liposome bilayer than when compared with the same concentration in aqueous solution. Colistin liposomes carried positive charge and were stable. Encapsulation efficiency for colistin was approximately 50%, decreasing with increasing concentration of colistin. Colistin was rapidly released from liposomes on dilution. Although the studies indicate limited utility of colistin or CMS liposomes for long duration controlled-release applications, colistin liposomes were highly stable and may present a potential opportunity for coformulation of colistin with a second antibiotic to colocalize the two drugs after pulmonary delivery.

Synergy of colistin with rifampin and trimethoprim/sulfamethoxazole on multidrug-resistant Stenotrophomonas maltophilia

Stenotrophomonas maltophilia is characterized by intrinsic resistance to a variety of antimicrobials. Therapeutic options are often limited particularly after the emergence of isolates resistant to trimethoprim/sulfamethoxazole. The application of colistin for infections caused by multidrug-resistant Gram-negative pathogens is limited due to its toxicity. In order to evaluate the activity of the interaction of colistin with rifampin or trimethoprim/sulfamethoxazole on S. maltophilia, 24 different isolates resistant to trimethoprim/sulfamethoxazole were in vitro exposed over-time to the combination of 1× and 4×MIC of colistin with 2μg/ml of rifampin or 2/38μg/ml of trimethoprim/sulfamethoxazole. The applied concentrations for rifampin and trimethoprim/sulfamethoxazole reflect their mean serum levels. Synergy of colistin and rifampin was documented after the first two hours of bacterial growth for approximately 60% of isolates and it occurred with both applied concentrations of colistin. The interaction of colistin and rifampin prevented regrowth observed when single colistin was applied. Synergy of colistin and trimethoprim/sulfamethoxazole was mainly found when colistin was applied at a concentration of 4×MIC involving 41.7% of isolates after 24 h of growth. In the presence of trimethoprim/sulfamethoxazole bacterial regrowth, observed when single colistin was applied, was prevented. It is concluded that growth of multidrug-resistant S. maltophilia is significantly inhibited by the interaction of colistin and rifampin and to a lesser extent of colistin and trimethoprim/sulfamethoxazole. These results merit further study in both the animal model and the clinical setting.

Interaction of colistin with lipids in liposomes and monolayers

Colistin is an antibiotic member of the polymixin family, showing a high amphipathic character. Its mechanism of action has been related to its ability to disrupt phospholipid bilayers of the bacterial membrane. Due to its hydrophobic properties colistin can interact both with the polar heads and the alkyl chains of the phospholipids. Moreover, it has a polycationic structure, so its interactions with phospholipids should be highly dependent on the electric charge of the lipid and the ionisation state of polymixin molecule. In the present paper we report on physicochemical studies to define the type and characteristics of these interactions. The surface activity of colistin has been shown to be highly dependent on the pH of the medium, the less protonated forms being more stable at the air–water interface. Interaction with phospholipid monolayers shows the same tendency. Colistin is also able to form mixed monolayers with phospholipids with small deviations from ideality. Physicochemical studies carried out with fluorescent probes indicate the presence of pure colistin aggregates that can coexist with mixed micelles composed of colistin/phospholipids. In no case did the interaction cause significative changes in the transition temperature of phospholipids.