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PubMed1986

Action of colistin (polymyxin E) on the lytic cycle of the mycobacteriophage D29 in Mycobacterium tuberculosis.

The antibiotic colistin (polymyxin E) inhibited the lytic cycle of the mycobacteriophage D29 in the tubercle bacilli, but not the D29 adsorption. The protein and nucleic acid synthesis in D29-infected bacteria were not affected significantly. The inhibitory activity was reversed by washing off the antibiotic, and by addition of Ca++, but not in media made iso-osmotic by addition of NaCl or sucrose. Transmission electron microscopy revealed an asymmetric to symmetric transition in the staining profile of the cytoplasmic membrane. Though no mature phage particles were ever observed in colistin-treated, D29-infected tubercle bacilli, loosely arranged aggregates resembling phage proheads were occasionally found. Judging from the above data, it was concluded that colistin inhibited D29 lytic cycle by causing molecular displacements in the inner leaflet of the cytoplasmic membrane, and consequently, the binding sites for D29 structural proteins were not available.

Adsorption↗
PubMed2001

A simple method for the assay of colistin in human plasma, using pre-column derivatization with 9-fluorenylmethyl chloroformate in solid-phase extraction cartridges and reversed-phase high-performance liquid chromatography.

A simple, selective and sensitive high-performance liquid chromatographic (HPLC) method is described for the determination of colistin in human plasma. Derivatization with 9-fluorenylmethyl chloroformate was performed in the same solid-phase extraction C18 cartridge used for sample pre-treatment, followed by reversed-phase HPLC with fluorimetric detection. Quantification was achieved using the ratio of the summed peak areas of colistin A and B derivatives to that of the derivative of netilmicin (internal standard). Linear calibration curves were obtained within the concentrations of colistin sulfate from 0.10 to 4.0 mg/l in plasma. Accuracy was within 10% and reproducibility (RSD) was less than 10%.

Calibration↗
PubMed2002

Dry powder inhalation of antibiotics in cystic fibrosis therapy, part 1: development of a powder formulation with colistin sulfate for a special test inhaler with an air classifier as de-agglomeration principle.

The aim of this study was to investigate the pulmonary administration of antibiotics as dry powder to patients with cystic fibrosis (CF), as an alternative for nebulization. This part of the study describes the development of a powder formulation with colistin sulfate as model substance. The aim of the new dosage form was to increase pulmonary deposition, therapeutic efficiency and, by that, compliance by the CF patients. A physical powder mixture of colistin and a size fraction of lactose (106-150 microm) was prepared and the mixture was optimized with respect to colistin content (83.3%) for use in a special test inhaler. A laser diffraction apparatus with special inhaler adapter was applied for analysis of the size distribution of the aerosol cloud from the inhaler. The size distributions of the aerosol clouds from the test inhaler at flow rates between 30 and 60 l/min for the optimized formulation showed nearly the same median diameter as that for the primary drug particles. But the X(100)-value was much lower, because of an effective large particle separation from the inspiratory air by an air classifier in the test inhaler. The results suggest that dry powder inhalation might be a suitable and highly efficient alternative for nebulization of antibiotic drugs in CF therapy.

Administration, Inhalation↗
PubMed2006

Colistin: the re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections.

Increasing multidrug resistance in Gram-negative bacteria, in particular Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae, presents a critical problem. Limited therapeutic options have forced infectious disease clinicians and microbiologists to reappraise the clinical application of colistin, a polymyxin antibiotic discovered more than 50 years ago. We summarise recent progress in understanding the complex chemistry, pharmacokinetics, and pharmacodynamics of colistin, the interplay between these three aspects, and their effect on the clinical use of this important antibiotic. Recent clinical findings are reviewed, focusing on evaluation of efficacy, emerging resistance, potential toxicities, and combination therapy. In the battle against rapidly emerging bacterial resistance we can no longer rely entirely on the discovery of new antibiotics; we must also pursue rational approaches to the use of older antibiotics such as colistin.

Anti-Bacterial Agents↗
PubMed1988

Use of colistin and sorbitol for better isolation of Serratia marcescens in clinical samples.

A comparison was made of different culture media and procedures for detection of Serratia marcescens from faecal, pharyngeal and ocular swabs collected from 213 neonates. MacConkey agar and MacConkey agar with sorbitol (1%) and/or colistin (200 i.u./ml) were used both for primary isolation and after enrichment using Mossel Enterobacteriaceae broth with colistin (200 i.u./ml). The use of MacConkey agar supplemented with colistin for primary isolation improved considerably the isolation rate of S. marcescens from faecal swabs but not from pharyngeal swabs; the number of ocular isolations were insufficient to demonstrate differences between procedures. Moreover the enrichment procedures consistently increased the number of S. marcescens isolates especially from pharyngeal and ocular swabs. Use of sorbitol made detection of S. marcescens from clinical specimens easier and time- and cost-efficient.

Colistin↗
PubMed2004

Serological and molecular evidence of Rickettsia helvetica in Denmark.

Recent seroepidemiological studies and examinations of Ixodes ricinus ticks in Europe have demonstrated the presence of an emerging tick-borne infection with Rickettsia helvetica. We conducted a serosurvey in 168 Danish patients seropositive for borreliosis reflecting their exposure to I. ricinus ticks. A total of 21 patients (12.5%) had positive antibody titres to R. helvetica including 4 cases of seroconversion. None of the samples were positive for antibodies to Ehrlichia. We conclude that in humans exposed to I. ricinus ticks in Denmark the risk of acquiring rickettsial infection is for the first time demonstrated. In the same region of Denmark we collected 570 I. ricinus ticks from various sources, and examinations by PCR for Rickettsia were performed. Positive reactions were obtained in 23 ticks (4%), and R. helvetica was identified in all 13 of those for which sequencing was performed.

Animals↗
PubMed1989

Depletion of colistin in eggs following medication of laying hens.

The depletion of colistin in eggs was determined separately for the albumen, the yolk and the whole egg after oral and intramuscular administrations of colistin sulphate. Residues were assayed by an agar plate diffusion method with Bordetella bronchoseptica ATCC 4617 as test organism. Colistin residues were not detected after drug administration by the oral route, but could be detected in the yolk until eight days after intramuscular injection. The total amount excreted represented 0.9% of the dose applied.

Administration, Oral↗
PubMed2003

Treatment of multidrug-resistant Acinetobacter baumannii ventilator-associated pneumonia (VAP) with intravenous colistin: a comparison with imipenem-susceptible VAP.

We prospectively evaluated the efficacy and toxicity of intravenously administered colistin in 35 episodes of ventilator-associated pneumonia (VAP) due to multidrug-resistant Acinetobacter baumannii. Microbiological diagnosis was performed with use of quantitative culture. In 21 patients, the episodes were caused by a strain susceptible exclusively to colistin (the CO group) and were all treated with this antimicrobial intravenously. In 14 patients, the episodes were caused by strains that remained susceptible to imipenem and were treated with imipenem-cilastatin (the IM group). Acute Physiology and Chronic Health Evaluation II scores at the time of admission and Sequential Organ Failure Assessment scores at time of diagnosis were similar in both groups. VAP was considered clinically cured in 57% of cases in both groups. In-hospital mortality rates were 61.9% in the CO group and 64.2% in the IM group, and the VAP-related mortality rates were 38% and 35.7%, respectively. Four patients in the CO group and 6 in the IM group developed renal failure. Neurophysiological evaluation was performed during 12 episodes in the CO group, but it revealed no signs of neuromuscular blockade. Intravenous colistin appears to be a safe and effective alternative to imipenem for the management of VAP due to carbapenem-resistant strains of A. baumannii.

Acinetobacter Infections↗
PubMed1997

Hyphenated liquid chromatographic method for the determination of colistin residues in bovine tissues.

A selective and sensitive high-performance liquid chromatographic (HPLC) method has been developed for the measurement of colistin residues in milk and in four bovine tissues (i.e., muscle, liver, kidney, and fat). The sample treatment consists of protein precipitation using 10% (w/v) trichloroacetic acid, solid-phase purification on C18 cartridges, and precolumn derivatization of colistin with ortho-phthalaldehyde and 2-mercaptoethanol in borate buffer (pH 10.5). This latter step is performed automatically, and the resulting reaction mixture is injected into a switching HPLC system including a precolumn and an analytical column packed with end-capped LiChrospher RP18 (5 microns). Washing the precolumn and final elution onto the analytical column are conducted using acetonitrile-0.01M phosphate buffer (pH 7.0) mixtures with respective proportions of 65:35 and 68:32 (v/v). Detection is carried out by spectrofluorometry (excitation wavelength, 340 nm; emission wavelength, 440 nm). The retention times of the derivatives corresponding to the two main components of colistin (i.e., polymyxins E2 and E1) are approximately 14 and 18 min, respectively. The structural study of the derivatives corresponding to polymyxins E1 and E2 is carried out by HPLC coupled with electrospray mass spectrometry; data obtained confirms that the derivatization process occurs with the five amino groups of the analytes. Selectivity is obtained in the HPLC system versus other coadministered anti-infective drugs (beta-lactams, aminoglycosides, tetracyclines, and sulphonamides) and endogenous compounds. Quantitation is performed using the sum of the peak areas of polymyxin E1 and polymyxin E2 derivatives. Testing linearity affords correlation coefficients greater than 0.990 for calibration curves in the range of 10-500 microL/L for milk, 50-1000 micrograms/kg for muscle and fat, and 100-1000 micrograms/kg for kidney and liver. Relative standard deviation values are less than 10% at a concentration of 25 micrograms/L in milk and 100 micrograms/kg in tissues (six replicates); recoveries are higher than 60%.

Adipose Tissue↗
PubMed1997

A reassessment of the in-vitro activity of colistin sulphomethate sodium.

The in-vitro activity of colistin sulphomethate sodium was compared with that of other commonly used antimicrobial agents against 377 recent clinical isolates of Gram-negative bacteria (including 94 strains of Pseudomonas aeruginosa from patients with cystic fibrosis) and 16 organisms with defined resistance patterns. Colistin was active against most strains of P. aeruginosa (MIC90 4 mg/L), Shigella spp. (MIC90 0.5 mg/L), Salmonella spp. (MIC90 1 mg/L), Acinetobacter spp. (MIC90 2 mg/L), Citrobacter spp. (MIC90 1 mg/L), Escherichia coli (MIC90 1 mg/L), Klebsiella spp. (MIC90 8 mg/L) and Enterobacter spp. (MIC50 1 mg/L). No useful activity was demonstrated against Providentia spp. or Serratia spp. The results show that colistin remains a useful antimicrobial agent against Gram-negative bacteria, particularly those strains which are resistant to more commonly used antibiotics.

Anti-Bacterial Agents↗
PubMed2026

Evaluation of sequential phage-antibiotic therapy reveals enhanced biofilm control with meropenem and colistin in clinical MDR hypervirulent Klebsiella pneumoniae strain.

AIMS: The convergence of multidrug resistance and hypervirulence in Klebsiella pneumoniae (MDR-HvKp) has narrowed treatment options. Despite growing interest in phage-antibiotic synergy, this study evaluates the underexplored combinatorial effects of phage and antibiotics, including drug-specific interactions and sequence dependency, against the biofilm-forming MDR-HvKp clinical strain. METHODS AND RESULTS: A T5-like Klebsiella bacteriophage, Round, within the genus Webervirus, was therapeutically and genomically characterized. A biofilm-forming clinical strain, Kleb_134, was used to evaluate in vitro phage-antibiotic interactions with meropenem, colistin, and tigecycline in planktonic and biofilm models.In planktonic assays, phage combinations with meropenem and colistin resulted in a multi-log CFU reduction compared to monotherapies, whereas reduced efficacy was observed with tigecycline. In biofilm assays, pre-phage treatment followed by antibiotic exposure demonstrated the strongest biofilm reduction. Drug-specific and sequence-dependent effects were evident. Meropenem-phage combinations reduced biofilm biomass by 2.85-fold (high phage titre) and 3.8-fold (low phage titre), while colistin-phage combinations achieved reductions of 8.4-fold (high phage titre) and 2.8-fold (low phage titre). CONCLUSIONS: Sequential phage-antibiotic treatment was effective against MDR-HvKp biofilms, with pre-phage exposure enhancing antibiotic access through biofilm disruption. The bacteriostatic nature of tigecycline reduced efficacy by affecting phage replication. These findings highlight the importance of treatment sequence and antibiotic selection, and extend existing knowledge in optimizing therapeutic outcomes in MDR-HvKp infections.

Biofilms↗
PubMed2005

Evaluation of the anti-endotoxic effects of polymyxin-E (colistin) in dogs with naturally occurred endotoxic shock.

Endotoxin is a potent stimulator of the inflammatory response and is believed to initiate the pathology in gram-negative sepsis. Agents are being searched for that bind and neutralize or block the effects of endotoxin. The aim was to study the anti-endotoxic effects of polymyxin-E (colistin) in endotoxaemic dogs. The study included a total of 30 endotoxaemic dogs, which were divided into two groups (control = 15; test = 15) of both sexes, different breeds and ages. Hetastarch colloid solution (Expahes,10 mL/kg, i.v.) with lactated Ringer's solution (20 mL/kg, i.v., Q12 h) was given to all dogs. While ampicillin was administered (Alfasilin, 10 mg/kg, i.m., Q12 h) as an antibacterial to the control group, colistin (12,500 IU/kg, i.m., Q12 h) + ampicillin were administered to the test group. The clinical examination (body temperature, pulse and respiration rates, capillary filling times, peripheral pulse qualities, dehydration degrees), hematological and biochemical examinations (WBC, RBC, HGB, HCT, thrombocyte, serum urea, creatinine and TNF-alpha) were performed both before the treatment, and 2, 4, 12 and 24 h after the treatment. In comparison with the control group, it was observed that test group had shorter capillary filling time at 24 h (P < 0.001). Moreover, the degree of dehydration in test group, was significantly improved at 24 h (P < 0.01). While the differences in peripheral pulse qualities significantly differed between 0 and 2 h in controls, at 2, 4, 24 h after treatment it was found to be significantly increased when compared with 0 h in the test group. Serum TNF-alpha concentrations were statistically decreased in the test group between 0 h and other times (P < 0.01). When compared with controls, serum TNF-alpha concentrations were lower at 2, 4, 12 and 24 h in test group (P < 0.05). Results of the study indicated that polymyxin-E (colistin) has an anti-endotoxic effect and is safe for the dogs with endotoxemia at the dosage used in this study.

Ampicillin↗
PubMed1988

Comparison of the efficacy of "Trisdine" and kanamycin-colistin bladder instillations in reducing bacteriuria during intermittent catheterisation of patients with acute spinal cord trauma.

An open, prospective, randomised, comparative study of "Trisdine" and kanamycin-colistin bladder instillations in reducing significant bacteriuria during intermittent urethral catheterisation was conducted. Trisdine is an aqueous solution of chlorhexidine gluconate 0.01% with added ethylenediaminetetra-acetic acid disodium salt and TRIS buffer at final concentrations of 1.34 mMoles and 0.01 Molar respectively. All patients (15 males and 3 females) admitted with acute spinal cord trauma and bladder involvement requiring intermittent catheterisation for more than 5 days during a 12-month period were studied. There was no significant difference in the mean incidence of significant bacteriuria during intermittent catheterisation in the 7 males who had kanamycin-colistin bladder instillations compared with the 8 males who had Trisdine instillations. A comparison could not be made in the females because there were only 3 patients. Because Trisdine is more stable at ambient temperatures, is less likely to select antibiotic-resistant bacteria and is less expensive, it is concluded that Trisdine is preferable to kanamycin-colistin solution for bladder instillations during intermittent catheterisation.

Acute Disease↗
PubMed1977

Inducible high resistance to colistin in Proteus strains.

Wild-type Proteus strains are usually resistant to colistin. We have observed an increase in the level of colistin resistance in four clinical isolates of P. vulgaris, P. morganii, and P. rettgeri by prior treatment with subinhibitory concentrations of the drug. The enhanced resistance in these strains was lost after cultivating them in colistin-free medium, indicating that the enhanced resistance in the Proteus group is inducible.

Colistin↗
PubMed2006

Differentiation and distribution of colistin- and sodium dodecyl sulfate-tolerant cells in Pseudomonas aeruginosa biofilms.

During Pseudomonas aeruginosa flow cell biofilm development, the cell population differentiates into a nonmotile subpopulation which forms microcolonies and a migrating subpopulation which eventually colonizes the top of the microcolonies, resulting in the development of mushroom-shaped multicellular structures. The cap-forming subpopulation was found to develop tolerance to membrane-targeting antimicrobial agents, such as the cyclic cationic peptide colistin and the detergent sodium dodecyl sulfate. The stalk-forming subpopulation, on the other hand, was sensitive to the membrane-targeting antibacterial agents. All biofilm-associated cells were sensitive to the antibacterial agents when tested in standard plate assays. A mutation eliminating the production of type IV pili, and hence surface-associated motility, prevented the formation of regular mushroom-shaped structures in the flow cell biofilms, and the development of tolerance to the antimicrobial agents was found to be affected as well. Mutations in genes interfering with lipopolysaccharide modification (pmr) eliminated the biofilm-associated colistin tolerance phenotype. Experiments with a PAO1 strain harboring a pmr-gfp fusion showed that only the cap-forming subpopulation in biofilms treated with colistin expresses the pmr operon. These results suggest that increased antibiotic tolerance in biofilms may be a consequence of differentiation into distinct subpopulations with different phenotypic properties.

Anti-Bacterial Agents↗
PubMed1991

Variability in growth of Neisseria polysaccharea on colistin-containing selective media for Neisseria spp.

In a prospective survey of 773 healthy schoolchildren in southern Alberta, Canada, Neisseria polysaccharea was isolated from the pharynxes of only 4 (0.5%) subjects, whereas Neisseria lactamica and Neisseria meningitidis were isolated from 110 (14%) and 15 (2%) children, respectively. These strains of N. polysaccharea, together with three other sporadic isolates from Alberta, Canada, were compared with the type strain from France and strains from Spain and Germany. All strains were phenotypically identical, except that the Canadian and German strains, for which the colistin MICs were 1 mg/liter, failed to grow on Thayer-Martin medium (TMM), whereas the type strain and the Spanish strains, for which the colistin MICs were greater than 7.5 mg/liter, were not inhibited. Multilocus enzyme electrophoresis indicated that six distinct electrophoretic types were present among the seven Canadian strains. Our results show that growth on gonococcal selective media which contain colistin is a variable feature of this taxon.

Adolescent↗
PubMed2005

Quality control guidelines for testing gram-negative control strains with polymyxin B and colistin (polymyxin E) by standardized methods.

An eight-laboratory study addressed the urgent need for quality control (QC) ranges for susceptibility determination when testing colistin (polymyxin E) and polymyxin B, two polycationic peptide antimicrobial agents, against multidrug-resistant gram-negative bacilli. For Escherichia coli ATCC 25922l, the QC ranges were as follows: for colistin, 0.25 to 1 microg/ml (11 to 17 mm), and for polymyxin B, 0.25 to 2 microg/ml (13 to 19 mm). For Pseudomonas aeruginosa ATCC 27853, the QC ranges were as follows: for colistin, 0.25 to 2 microg/ml (11 to 17 mm), and for polymyxin B, 0.25 to 2 mug/ml (14 to 18 mm). More than 97% of all reported QC results were within these proposed ranges.

Anti-Bacterial Agents↗