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At least 19 recordsLinked to original sources
PubMed2004

Pharmacokinetics of colistin methanesulphonate and colistin in rats following an intravenous dose of colistin methanesulphonate.

OBJECTIVES: To determine the disposition of colistin methanesulphonate (CMS) and colistin following intravenous (iv) administration of CMS in rats. METHODS: Five rats received a single iv bolus of 15 mg/kg CMS. Plasma concentrations of CMS and of colistin formed by the hydrolysis of CMS were determined by HPLC. The pharmacokinetic parameters of CMS and colistin were calculated using non-compartmental analysis. RESULTS: Total body clearance, volume of distribution at steady state and terminal half-life of CMS averaged 11.7 mL/min/kg, 299 mL/kg and 23.6 min, respectively. The mean terminal half-life of colistin was 55.7 min. Approximately 60% of the dose was eliminated via the urine in 24 h and presented as a mixture of CMS and colistin. CONCLUSIONS: Colistin appeared in plasma soon after administration of CMS, indicating rapid conversion of CMS into colistin. CMS had a shorter terminal half-life than did colistin, indicating that the disposition of the colistin generated from CMS was rate-limited by its elimination. Most of the dose was recovered in urine, half in the form of colistin. The high percentage of colistin recovered in urine was believed to be formed by hydrolysis of CMS in the bladder and in the collection vessel, and/or conversion from CMS in the kidney.

Animals↗
PubMed2004

Effect of nebulized colistin sulphate and colistin sulphomethate on lung function in patients with cystic fibrosis: a pilot study.

BACKGROUND: Pulmonary administration of colistin is one of the antimicrobial treatments used in Cystic Fibrosis (CF) patients chronically infected with Pseudomonas aeruginosa. Dry powder inhalation of colistin may be an attractive alternative to nebulization of colistin. However, nebulized colistin can cause bronchoconstriction in CF patients. Therefore, in the progress of developing a dry powder formula, the choice of the inhaler and its contents should be guided by optimal efficacy and the least possible side effects. To investigate the side effects, a study was initiated to compare the tolerability of colistin sulphate to colistin sulphomethate per nebulization in CF-patients. METHODS: Nine CF-patients chronically infected with P. aeruginosa participated in a double blind, randomized cross over study. On two visits to the outpatient clinic, patients were submitted to either nebulized colistin sulphate or colistin sulphomethate solution. Lung function tests were performed immediately before and 15 and 30 min after nebulization. RESULTS: Nebulization of colistin sulphate caused a significant larger mean decrease in lung function compared to nebulized colistin sulphomethate. A significant decrease in mean changes (SD) in FEV1 at 30 min and FVC at 15 and 30 min after nebulization compared to baseline of -7.3% (8.6%), -5.7% (7.3%) and -8.4% (7.5%) respectively was seen after colistin sulphate nebulization compared to colistin sulphomethate (P < 0.05). Seven patients were not able to complete the nebulization of colistin sulphate because of throat irritation and severe cough. CONCLUSION: Based on these results it was concluded that inhalation with nebulized colistin sulphate is not suitable for treatment of CF patients chronically infected with P. aeruginosa. Colistin sulphomethate is the drug of choice for pulmonary administration of colistin.

Administration, Inhalation↗
PubMed2006

Colistin methanesulfonate is an inactive prodrug of colistin against Pseudomonas aeruginosa.

There is a dearth of information on the pharmacodynamics of "colistin," despite its increasing use as a last line of defense for treatment of infections caused by multidrug-resistant gram-negative organisms. The antimicrobial activities of colistin and colistin methanesulfonate (CMS) were investigated by studying the time-kill kinetics of each against a type culture of Pseudomonas aeruginosa in cation-adjusted Mueller-Hinton broth. The appearance of colistin from CMS spiked at 8.0 and 32 mg/liter was measured by high-performance liquid chromatography, which generated colistin concentration-time profiles. These concentration-time profiles were subsequently mimicked in other incubations, independent of CMS, by incrementally spiking colistin. When the cultures were spiked with CMS at either concentration, there was a substantial delay in the onset of the killing effect which was not evident until the concentrations of colistin generated from the hydrolysis of CMS had reached approximately 0.5 to 1 mg/liter (i.e., approximately 0.5 to 1 times the MIC for colistin). The time course of the killing effect was similar when colistin was added incrementally to achieve the same colistin concentration-time course observed from the hydrolysis of CMS. Given that the killing kinetics of CMS can be accounted for by the appearance of colistin, CMS is an inactive prodrug of colistin with activity against P. aeruginosa. This is the first study to demonstrate the formation of colistin in microbiological media containing CMS and to demonstrate that CMS is an inactive prodrug of colistin. These findings have important implications for susceptibility testing involving "colistin," in particular, for MIC measurement and for microbiological assays and pharmacokinetic and pharmacodynamic studies.

Anti-Bacterial Agents↗
PubMed1982

A method for separating commercial colistin complex into new components: colistins pro-A, pro-B and pro-C.

Commercial colistin was separated into three major components as well as lipid components by reversed phase adsorption chromatography on Diaion HP-20 AG, a macroreticular styrene-divinylbenzene copolymer, without any inorganic salts or detergents, in aqueous-organic solvent as mobile phase. These expected components were colistins A, B and C; there were, however, appreciable differences between these components and colistins A, B and C, isolated by countercurrent distribution. The newly isolated components showed slightly higher potency than colistins A, B and C; their molecular weights, as determined by gel permeation chromatography of 2,4-dinitrophenyl derivatives on TSK-GEL G2000H (mobile phase: dimethylformamide), were also slightly higher. Accordingly, they were tentatively named colistins pro-A, pro-B and pro-C. During purification by countercurrent distribution (solvent system: sec-BuOH - n-BuOH - 0.1 N HCl, 30:6:40), colistin pro-A was converted to colistin A. Similarly, colistin pro-B was converted to colistin B, and colistin pro-C to colistin C. Therefore, we concluded that colistins A, B and C are artifacts.

Amino Acids↗
PubMed2001

In vitro pharmacodynamic properties of colistin and colistin methanesulfonate against Pseudomonas aeruginosa isolates from patients with cystic fibrosis.

The in vitro pharmacodynamic properties of colistin and colistin methanesulfonate were investigated by studying the MICs, time-kill kinetics, and postantibiotic effect (PAE) against mucoid and nonmucoid strains of Pseudomonas aeruginosa isolated from patients with cystic fibrosis. Twenty-three clinical strains, including multiresistant strains, and one type strain were selected for MIC determination. Eleven strains were resistant; MICs for these strains were >128 mg/liter. For the susceptible strains, MICs of colistin ranged from 1 to 4 mg/liter, while the MICs of colistin methanesulfonate were significantly higher and ranged from 4 to 16 mg/liter. The time-kill kinetics were investigated with three strains at drug concentrations ranging from 0.5 to 64 times the MIC. Colistin showed extremely rapid killing, resulting in complete elimination at the highest concentrations within 5 min, while colistin methanesulfonate killed more slowly, requiring a concentration of 16 times the MIC to achieve complete killing within 24 h. Colistin exhibited a significant PAE of 2 to 3 h at 16 times the MIC against the three strains after 15 min of exposure. For colistin methanesulfonate, PAEs were shorter at the concentrations tested. Colistin methanesulfonate had lower overall bactericidal and postantibiotic activities than colistin, even when adjusted for differences in MICs. Our data suggest that doses of colistin methanesulfonate higher than the recommended 2 to 3 mg/kg of body weight every 12 h may be required for the effective treatment of P. aeruginosa infections in cystic fibrosis patients.

Anti-Bacterial Agents↗
PubMed2003

Stability of colistin and colistin methanesulfonate in aqueous media and plasma as determined by high-performance liquid chromatography.

The stabilities of colistin and colistin methanesulfonate (CMS) in different aqueous media were studied by specific high-performance liquid chromatography (HPLC) methods. Colistin was stable in water at 4 and 37 degrees C for up to 60 days and 120 h, respectively. However, degradation was observed when colistin was stored in isotonic phosphate buffer (0.067 M, pH 7.4) and human plasma at 37 degrees C. The stability of CMS from three different sources in water was explored by strong-anion-exchange (SAX) HPLC for CMS and by measuring the concentrations of colistin formed from the hydrolysis of CMS. The peaks of CMS in SAX HPLC disappeared almost completely after 12 h at 37 degrees C, but appeared to remain intact for up to 2 days at 4 degrees C. Over the same period, there was no formation of colistin at 4 degrees C. In water, phosphate buffer, and plasma, there was rapid formation of colistin within 24 to 48 h at 37 degrees C from the three sources of CMS. The hydrolysis products were assumed to be a complex mixture of many different sulfomethyl derivatives, including colistin. The stability of a fourth source of CMS in Mueller-Hinton broth examined during 30 min at 37 degrees C revealed no formation of colistin. Along with previous microbiological studies, this suggested that different sulfomethyl CMSs possess intrinsic antibacterial activity. These results will be helpful for understanding the pharmacokinetics and pharmacodynamics of colistin and CMS in humans and animals.

Anti-Bacterial Agents↗
PubMed2006

Detection of residual bacitracin A, colistin A, and colistin B in milk and animal tissues by liquid chromatography tandem mass spectrometry.

Liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-MS/MS) was applied to the determination of residual bacitracin A, colistin A, and colistin B in milk and animal tissue samples. Prior to instrumental analysis, samples were subjected to acid extraction followed by solid-phase cleanup using Strata-X cartridges. Mass spectral acquisitions were performed under selective multiple reaction monitoring (MRM) mode at m/z 199 and 670 from triply charged precursors of bacitracin A (m/z 475); m/z 385 and 379 from triply charged precursors of colistin A (m/z 391); and m/z 380 and 374 from triply charged precursors of colistin B (m/z 386). Method precision was evaluated from spike recovery of samples fortified at concentrations corresponding to 2/5 of the maximum residue limits (MRLs) for each of the analytes under study. Intra-day and inter-day variations were found to range from 90.9 to 104% with relative standard deviation (RSD) <6.5%, and from 90.1 to 106% with RSD <9.1%, respectively. Limits of quantification (LOQs) were defined as the spiking concentrations at 2/5 MRL, and limits of detection (LODs) were 10-47 microg kg(-1) for bacitracin A, 1-16 microg kg(-1) for colistin A, and 6-14 microg kg(-1) for colistin B in milk and animal tissues. The presented method has good precision and high sensitivity and was applied as a fast screening protocol and a quantitative tool for monitoring of the concerned polypeptides in foods as part of a surveillance program.

Animals↗
PubMed2006

Effectiveness and nephrotoxicity of colistin monotherapy vs. colistin-meropenem combination therapy for multidrug-resistant Gram-negative bacterial infections.

A retrospective cohort study evaluated the effectiveness and nephrotoxicity of intravenous colistin monotherapy vs. colistin-meropenem combination therapy for patients with multidrug-resistant Gram-negative bacterial infections. Fourteen patients received intravenous colistin monotherapy and 57 received colistin-meropenem. No significant differences were found concerning clinical response of the infection (12/14 (85.7%) vs. 39/57 (68.4%), p 0.32) and development of nephrotoxicity (0/14 (0%) vs. 4/57 (7%), p 0.58). A favourable association was revealed between survival and treatment with colistin monotherapy compared to colistin-meropenem (0/14 (0%) vs. 21/57 (36.8%) deaths, p 0.007), even after adjusting for the variables for which significant differences were found.

Acute Kidney Injury↗
PubMed1973

Comparison of colistin-carbenicillin, colistin, and carbenicillin in Pseudomonas sepsis in monkeys.

Intravenous inoculation of 6.2 x 10(10) to 6.7 x 10(10)Pseudomonas aeruginosa organisms into rhesus monkeys 5 days after intratracheal inoculation of 2.0 to 2.5 mg of vincristine sulfate resulted in fatal sepsis in 8 of 10 untreated monkeys. When similarly infected monkeys were treated intramuscularly with 2.5 mg of colistin or 50 mg of carbenicillin per kg per day, all three monkeys in each treatment group survived; one of three monkeys receiving both antibiotics at the above doses died. Six of seven monkeys treated with 1.25 mg of colistin per kg per day and three of seven treated with 25 mg of carbenicillin per kg per day died; four of nine monkeys receiving both antibiotics at these doses died. A combination of the data obtained at both dose levels tested shows that 6 of 10, 3 of 10, and 5 of 12 monkeys, respectively, died after treatment with colistin, carbenicillin, and the colistin-carbenicillin combination. Antibacterial activity of serum from both infected and normal monkeys was not appreciably different when the two antibiotics were given singly or in combination. Under the conditions of this study and with the doses employed, the response of monkeys treated with the antibiotic combination did not differ significantly from that of monkeys treated with a single agent.

Animals↗
PubMedDate not supplied

Comparison of the binding of gram-negative bacterial endotoxin by polymyxin B sulphate, colistin sulphate and colistin sulphomethate sodium.

Polymyxins are cyclic polypeptide antibiotics. In addition to their bactericidal activity they bind lipid A and neutralize the biological effects of bacterial endotoxin. We have studied the three available polymyxin preparations: polymyxin B sulphate (PB), colistin sulphate (CS) and colistin sulphomethate sodium (CMS), and compared their endotoxin binding capacity at equivalent therapeutic dosage. Each polymyxin was bound to a column of Sepharose 4B and challenged with 5 micrograms of endotoxin from Escherichia coli O127:B8. Recovery of endotoxin in the eluate was measured by a quantitative Limulus lysate microassay. PB and CS bound 94% of the challenge dose, CMS 89% and the control column (Sepharose alone) 24%. These results suggest that parenteral CMS (the least toxic polymyxin) retains useful anti-endotoxin capacity, and that in neutropenic patients, oral polymyxin may exert both anti-endotoxin and antimicrobial effects.

Colistin↗
PubMedDate not supplied

Sensitive enzyme immunoassay of colistin and its application to detect residual colistin in rainbow trout tissue.

An antibody against colistin (CL), an antibiotic effective for gram-negative bacteria, was produced in rabbits immunized with a colistin-protein conjugate. The conjugate was prepared by a novel and convenient procedure devised to couple an amino group of CL to thiol groups of bovine serum albumin (BSA) introduced by thiol exchange reduction of its disulfide bonds with dithiothreitol, using N-(m-maleimidobenzoyloxy)succinimide (MBS) as a cross-linker. Enzyme labeling of CL with beta-D-galactosidase was performed by utilizing another cross-linker, N-(gamma-maleimidobutyryloxy)succinimide, by means of a convenient labeling method. A double antibody enzyme immunoassay of CL, which could determine as little as 30 ng/mL of CL, was developed using labeled CL and anti-CL antiserum. With this assay, drug levels were easily determined in fish tissue after CL administration. The enzyme immunoassay should provide a useful tool for detection and quantitation of residual drugs in foods and related products.

Animals↗
PubMed1976

Polyacrylic bone cement containing erythromycin and colistin. I. In vitro bacteriological activity and diffusion properties of erythromycin, colistin and erythromycin/colistin comibination.

Erythromycin and colistin demonstrate a non-antagonistic ability to inhibit the growth of a wide variety of aerobic and anaerobic bacterial isolates. When incorporated in Surgical Simplex P Radiopaque Bone Cement, fabricated cement pellets were effective in inhibiting 98% of all anaerobic and aerobic test isolates. Separate experiments indicate that each antibiotic can diffuse from polymerized cement, and that the concentration of each antibiotic is consistently above the minimum inhibitory concentration of 96% of the isolates. We conclude that erythromycin/colistin Surgical Simplex P radiopaque Bone Cement is a worthy candidate for clinical investigation.

Bone Cements↗