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Evaluation of colistin and nalidixic acid in Todd-Hewitt broth for selective isolation of group B streptocci.

Todd-Hewitt broth (THB) containing colistin and nalidixic acid was compared with four other media with respect to efficacy of isolation of group B streptocci. It was effective as plain THB, THB with gentamicin and nalidixic acid and blood, and THB with colistin, nalidixic acid, and blood. THB with gentamicin and nalidixic acid, but without blood, was inhibitory to group B streptocci. The value of THB with colistin and nalidixic acid lies in its ability to successfully inhibit gram-negative organisms and still promote group B streptococcal growth without the addition of blood. This greatly reduces the time and expense of media preparation and permits early determination of bacterial growth, so that other means of rapidly identifying group B streptocci can be applied at the earliest possible time.

Animals↗

Microbiological activity and clinical efficacy of a colistin and rifampin combination in multidrug-resistant Pseudomonas aeruginosa infections.

The aim of the study was to assess the microbiological activity and clinical efficacy of colistin and rifampin combination against multidrug-resistant (MDR) Pseudomonas aeruginosa infections. The antimicrobial activity of the colistin/rifampin combination was evaluated using the checkerboard and time-kill curve methods against different MDR P. aeruginosa strains. The combination of rifampin and colistin resulted fully (1 strain) or partially (5 strains) synergistic for 6/7 strains and minimum inhibitory concentrations (MICs) in combination were reduced to easily obtainable therapeutic levels. The time-kill curves showed that the combination was bactericidal against the strains tested. The clinical efficacy of the combination was tested in four patients with difficult-to treat infections (sepsis or pneumonia) caused by MDR P. aeruginosa. All infections were successfully treated. Our microbiological and clinical observations suggest that the addition of rifampin to colistin may result in a synergistic bactericidal combination that may be useful in patients with infections caused by MDR P. aeruginosa which are difficult to cure.

Adult↗

Nebulizer choice for inhaled colistin treatment in cystic fibrosis.

STUDY OBJECTIVES: To develop practical ways of nebulizing colistin by determining the rate of drug output, total drug output, and particle-size distribution of two commercially available jet nebulizers, the disposable Hudson 1730 Updraft II (Hudson Respiratory Care; Temecula, CA) and the reusable Pari LC Star breath-enhanced nebulizer (Pari Respiratory Equipment; Midlothian, VA). METHODS: The nebulizers contained colistin, 75 mg, in 4 mL of isotonic solution. Particle-size distribution was measured by helium-neon laser diffraction, allowing calculation of the respirable fraction (RF), the mass of aerosol comprised of droplets < 5 microm. RESULTS: The mean (95% confidence interval [CI]) total rate of output of the Updraft II was 2.6 mg/min (2.0, 3.1; n = 4) with 1.3 mg/min (1.0, 1.5) mg/min within the RF. The rate of output of the LC Star increased in a quadratic relationship to the inspiratory flow, delivering 1.8 mg/min (0.7, 2.0; n = 4) with 1.4 mg/min (1.3, 1.6) within the RF, and 6.2 mg/min (5.6, 6.8) with 5.3 mg/min (4.8, 5.7) within the RF, at 0 L/min and 20 L/min inspiratory flows, respectively. Efficiency, as the rate of expected pulmonary deposition divided by rate of total output, was then calculated. The LC Star estimated 56% (51, 61) efficiency, with pulmonary delivery of 29% (26, 32) of the charge of the nebulizer, compared to the Updraft II at 22% (22, 23) efficiency and expected pulmonary deposition of 10% (10, 10) of the dose. CONCLUSIONS: Colistin can be successfully nebulized with both nebulizers tested. This study provides an estimate of in vivo efficiency and expected pulmonary deposition that may be used in future trials.

Adolescent↗

Selective cleavage of a peptide antibiotic, colistin by colistinase.

A colistin-inactivating enzyme, colistinase was produced by Bacillus polymyxa var. colistinus KOYAMA, a colistin-producing microorganism. The crude colistinase was fractionated as two components (colistinase I and II) by Sephadex G-50 gel filtration. Colistinase II was further purified and then, it showed as a single band in polyacrylamide disc gel electrophoresis. The molecular weight of colistinase II was about 20,000 by Sephadex G-100 gel filtration and the isoelectric point was at about 8.3. Colistinase II cleaved specifically between the 2,4-diaminobutyric acid of the side chain and 2,4-diaminobutyric acid adjacent in the cyclic peptide portion of colistin molecule.

Colistin↗

Infection prophylaxis in acute leukemia: a comparison of ciprofloxacin with trimethoprim-sulfamethoxazole and colistin.

Fifty-six patients receiving remission induction treatment for acute leukemia were studied in a randomized trial comparing ciprofloxacin with trimethoprim-sulfamethoxazole plus colistin for prevention of infections. Both groups received amphotericin B for antifungal prophylaxis. Six major infections occurred in 28 patients receiving ciprofloxacin, and 11 major infections occurred in 28 patients receiving trimethoprim-sulfamethoxazole plus colistin. No infections caused by gram-negative bacilli were seen in the ciprofloxacin group (p less than 0.02). Ciprofloxacin prevented colonization with resistant gram-negative bacilli, but 12 resistant colonizing strains were isolated from 10 patients receiving trimethoprim-sulfamethoxazole plus colistin (p less than 0.01). Ciprofloxacin was better tolerated: 23 of 28 patients were highly compliant to the drug, compared with 15 of 28 patients in the trimethoprim-sulfamethoxazole group (p less than 0.05). These results suggest that ciprofloxacin is a promising drug for the prevention of infection in patients with granulocytopenia.

Acute Disease↗

[Sensitivity to colistin: evaluation of cut-off points available in disk diffusion test].

Infections produced by multidrug resistant organisms are one of the greatest problems in health centers. Often, only polymyxines show good activity "in vitro" against the carbapenem resistant gram-negative strains; but the National Committee for Clinical Laboratory Standards (NCCLS) documents do not currently provide interpretative criteria for testing the polymyxines. The antimicrobial activity of colistin, and the correlation between the agar dilution test and disk diffusion test were evaluated against 186 gram-negative strains isolated at the Hospital de Clínicas "José de San Martín" of Buenos Aires city. All susceptibility tests were performed according to the NCCLS recommendations. Were evaluated two breakpoints, NCCLS 1981 (< or = 8 mm and > or = 11 mm), and R. Jones 2001 (< or = 11 mm and > or = 14 mm). Discrepancies on interpretative category were found (0.5% minor; 2.2% major and 4.4% very major) with NCCLS 1981, and (18.9% minor; 3.8% major and 0.5% very major) with R. Jones 2001 criteria. Conclusions. In spite of the fact that the breakpoint used by R. Jones 2001 decreases the very major error but increases the minor error, according to our results we recommend the use of MIC methods to assist the therapeutic application of colistin; however resistance to colistin was not detected with zone diameters > or = 16 mm.

Adult↗

[Usefulness of studies of susceptibility of ampicillin, carbenicillin, cefalotin and colistin as a presumptive identification system for the Aeromonas sp. group].

We have studied the restricted antibiotic susceptibility tests for 180 strains belonging to mesophilic Aeromonas sp. isolated from stools samples. Strains has been identified as follows: A. caviae (64.6%), A. hydrophila (17.7%) and A. sobria (17.7%). Antibiotics tested were ampicillin (10 micrograms), carbenicillin (100 micrograms), cephalotin (30 micrograms) and colistin (10 micrograms), by means of agar diffusion tests (disk-plate). We identified four different patterns of antibiotic susceptibility. The most frequent pattern (pattern #1) (77.8%) is characterized by susceptibility only to colistin, and was predominant among A. caviae strains (80%). Pattern #2 (susceptibility to cephalotin and colistin) was found in 18.9% of strains, being predominant in A. sobria (88.2%). We confirm the higher susceptibility of A. sobria sp. to cephalotin as well as the possibility that these different patterns might be used as screening method for species identification among mesophilic group of Aeromonas.

Aeromonas↗

[Colistin as last resort in 2 patients with pulmonary infection with multiresistant nosocomial bacteria].

A 57-year-old man requiring ventilation after gastric-tube reconstruction (due to oesophageal carcinoma) and a 16-year-old boy with thoracic trauma developed pneumonia caused by Pseudomonas aeruginosa and other pathogens. Their infections persisted during treatment with antibiotics. The antibiotic colistin was added and the clinical condition improved in both patients after 3-4 weeks. Eventually, they both were transferred to a rehabilitation clinic. The use of colistin was abandoned in the 1970s due to alleged nephro- and neurotoxicity. In recent observational studies, the drug appeared to cause fewer toxic side-effects than previously thought. Colistin is only registered for inhaled use for lung infections and for resistant pulmonary infections in patients with cystic fibrosis, but it may also be effective in the treatment of other patients with multidrug-resistant, Gram-negative bacteria.

Adolescent↗

Colistin inhibition of mannose-resistant haemagglutination by K88-positive and K99-positive escherichia coli strains. A preliminary report.

Two enteropathogenic E. coli strains isolated from a calf and a piglet succumbed to diarrhoea were studied. The bovine strain carried K99-antigen and the porcine strain was K88-positive. Both strains agglutinated pig erythrocytes in the presence of D-mannose. In the test a bacterial cell density of 3 x 10(9) per ml and doubling dilutions hereof were used. The haemagglutination titres were 16 and 128, respectively. When the bacteria were exposed to colistin before mixing with the red cells, haemagglutination was inhibited completely with 1.0 and 0.5 microgram/mg of colistin. At a colistin concentration of 0.25 microgram/ml (1/4-1/2 of the MIC's) the titres were lowered by a factor of 16-32.

Animals↗

[Pulmonary deposition of colistin aerosols in cystic fibrosis. Comparison of an ultrasonic nebulizer and a pneumatic nebulizer].

The objective of this study was to quantify the deposition in the lung of a Colistine aerosol generated using a pneumatic nebuliser (Pari LL(R) equipped with a Pari Master, Pari, Germany) and to compare this with the results obtained with an ultrasonic nebuliser (DP100, DP Medical, France) in four subjects suffering from cystic fibrosis being colonised with Pseudomonas aeruginosa. To quantify the pulmonary deposition of the aerosols we have used an indirect isotopic method which consists in assimilating the kinetics of the molecules studied with a serum albumin tagged with Technetium 99m (Tc99mm) and added to a preparation of Colistine. We have previously verified that the addition of a radioactive tracer does not change the normal distribution or dynamics of the medication within the aerosol and the radioactive counter linked to the tracer reflects the mass of the medicament. The pulmonary deposition was expressed as a percentage of the nebuliser dose. A regional analysis of the deposition (central, peripheral, superior and inferior) was carried out and in central deposition compared to the periphery (C/P) and superior compared to inferior (S/I) were calculated. With the DP100 nebuliser the pulmonary deposition of the aerosol was very reproducible from one patient to another, varying only between 9.5 to 14 percent of the nebuliser dose. With the Pari LL the fraction deposited varied more from one patient to another from 5.6 to 27% of the nebuliser dose. In three of four patients, the pulmonary deposition was superior or equal to that obtained with the ultrasonic nebuliser. The patients whose pulmonary deposition was inferior, using the pneumatic nebuliser, was the youngest in the group and co-ordinately poorly the triggering of the nebuliser with the beginning of inspiration. With the two nebulisers, the pulmonary deposition of Colisitine was very heterogeneous throughout the pulmonary parenchyma. The mean of the ratio C/P and S/I obtained in all four patients was identical (1.35 an 0.86 respectively), indicating a deposition of the aerosol which was predominantly central and inferior but was distributed equally in the peripheral parts of the lung. Pneumatic nebulisers offer a reliable alternative notably for domiciliary treatment for Colistine aerosols in patients suffering from cystic fibrosis. In younger patients who have not yet acquired good motor co-ordination, nebulisers which function continuously or are triggered by inspiration seem to be the preferred choice.

Administration, Inhalation↗

Prevalence and Genomic Characterization of mcr-Positive Enterobacteriaceae in Retail Meat in Thailand Following the Colistin Ban.

This study aimed to investigate the prevalence and characteristics of mcr-positive Enterobacteriaceae in retail meat in Thailand following the national ban on prophylactic colistin use in food producing animals. A total of 152 meat samples (103 chicken and 49 pork) were collected from supermarkets and open markets between July and September 2023. Samples were screened for mcr-1 to mcr-5 using multiplex PCR. None of the samples from supermarkets tested positive, whereas mcr genes were detected in 15.4% (6/39) and 13.3% (4/30) of chicken and pork samples, respectively, from open markets, with mcr-1 and/or mcr-3 identified. A total of 21 isolates were recovered from PCR-positive samples (11 from chicken and 10 from pork). Escherichia coli was the predominant species (n&#x2009;=&#x2009;19), followed by Klebsiella pneumoniae (n&#x2009;=&#x2009;2). All mcr-positive isolates exhibited multidrug resistance. Whole-genome sequencing was performed for 19 non-clonal isolates. One K. pneumoniae strain from a pork sample co-harbored mcr-1 and mcr-8, representing the first report of this combination in the animal sector in Thailand. In addition, virulence-associated genes, including adhesion factors, toxins, and iron acquisition systems, were identified in selected isolates. Core genome SNP-based phylogenetic analysis revealed substantial genomic diversity among the isolates, suggesting relatedness to strains reported prior to the colistin ban. These findings indicate that retail meat from open markets may serve as an important route for the transmission of mcr-positive bacteria in Thailand and highlight the urgent need to incorporate systematic retail meat surveillance into national antimicrobial resistance monitoring programs.

Animals↗

CYTOLOGICAL ASPECTS OF ANTIMICROBIAL ANTIBIOSIS. III. CYTOLOGICALLY DISTINGUISHABLE STAGES IN ANTIBIOTIC ACTION OF COLISTIN SULFATE ON ESCHERICHIA COLI.

Kaye, Jeremy J. (Cornell University Medical College, New York, N.Y.) and George B. Chapman. Cytological aspects of antimicrobial antibiosis. III. Cytologically distinguishable stages in antibiotic action of colistin sulfate on Escherichia coli. J. Bacteriol. 86:536-543. 1963.-Broth cultures of Escherichia coli were subjected to a constant concentration of colistin sulfate for varying periods of time. Controls and treated cells were fixed, dehydrated, and embedded in methacrylate, and ultrathin sections were examined in an electron microscope. Three stages in the antibiotic process were discerned. Stage 1 was characterized by a disruption of the axial orientation of the nuclear material and by an invasion of nuclear areas by tufts of material presumably of cytoplasmic origin; no loss of cellular contents could be detected cytologically. Stage 2 was characterized by the loss of nuclear material and by a loss of typical cytoplasmic granularity, an increase in cytoplasmic electron density, and an agglomeration of the cytoplasm into packed tufts of material; in contrast to the nuclear material, there was no loss of cytoplasmic material in this stage. Stage 3 was characterized by the loss of the altered cytoplasmic material but with the persistence of mesosomes, plasma membrane, and cell wall. Speculation that each and all of these changes might have resulted from an altered intracellular milieu secondary to a primary effect of the antibiotic on the plasma membrane is presented.

Anti-Bacterial Agents↗

Cytogenetic effect of colistin on human lymphocytes in vitro: chromosome aberrations, sister chromatid exchanges, mitotic index, cell cycle kinetics, and acrocentric associations.

Colistin, a peptide antibiotic, was tested at three different concentrations--71, 142, and 214 units/ml. One hundred forty-two units per milliliter corresponds to the plasma level after receiving therapeutic dose. There was a dose-dependent increase in the frequency of chromosome aberrations irrespective of the duration of treatment (T0, T24, T48). This antibiotic decreased the mitotic index and delayed the cell turn over rate indicating inhibition of DNA synthesis by it. Inhibition of DNA synthesis probably results in increase in the frequency of chromosome aberrations. Frequency of satellite associations of acrocentric chromosomes was increased with increasing concentration of the drug, but the differences at three concentrations were not significant compared to controls. There was no increase in the frequency of SCEs at any concentration or duration of treatment compared to controls. It appears that colistin induces the type of lesions that lead to chromosome aberrations and not to SCEs.

Adult↗

Dynamic ultrasound-assisted extraction of colistin from feeds with on-line pre-column derivatization and liquid chromatography-fluorimetric detection.

A dynamic ultrasound-assisted extraction (UAE) method with on-line pre-column derivatization/high performance liquid chromatography (HPLC) and fluorimetric detection is proposed for the analysis of colistin in feed. A flow injection manifold is used for the development of the extraction and derivatization steps and for interfacing them with the separation/detection step, thus providing an on-line approach with the advantage of minimum sample handling. The derivatization was performed with ortho-phthaldialdehyde and 2-mercaptoethanol. The optimum conditions for colistin extraction and formation of the fluorescent derivative have been obtained by experimental design methodology. The use of a high-intensity probe sonication makes UAE an expeditious (7 min versus > 1 h) and efficient (93.1-98.2% versus 87.5-94% of recovery) alternative as compared with extraction using an ultrasonic bath. The within-laboratory reproducibility and repeatability, expressed as percentage of relative standard deviation, were 5.2 and 5.8, respectively.

Animal Feed↗

Colistin (polymyxin E)--induced cell leakage in Mycobacterium aurum.

Addition of 100 micrograms/ml of colistin (polymyxin E) to an actively-growing culture of Mycobacterium aurum caused apparent loss of viability starting after 20 min of drug addition, whereas significant Mg++ efflux was apparent within 5 min of drug addition. Therefore, Mg++ efflux preceded cell death by at least 15 min. These data confirmed earlier reports showing that colistin interacted with the cytoplasmic membrane of mycobacteria.

Cell Membrane↗

Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections.

The emergence of multidrug-resistant gram-negative bacteria and the lack of new antibiotics to combat them have led to the revival of polymyxins, an old class of cationic, cyclic polypeptide antibiotics. Polymyxin B and polymyxin E (colistin) are the 2 polymyxins used in clinical practice. Most of the reintroduction of polymyxins during the last few years is related to colistin. The polymyxins are active against selected gram-negative bacteria, including Acinetobacter species, Pseudomonas aeruginosa, Klebsiella species, and Enterobacter species. These drugs have been used extensively worldwide for decades for local use. However, parenteral use of these drugs was abandoned approximately 20 years ago in most countries, except for treatment of patients with cystic fibrosis, because of reports of common and serious nephrotoxicity and neurotoxicity. Recent studies of patients who received intravenous polymyxins for the treatment of serious P. aeruginosa and Acinetobacter baumannii infections of various types, including pneumonia, bacteremia, and urinary tract infections, have led to the conclusion that these antibiotics have acceptable effectiveness and considerably less toxicity than was reported in old studies.

Anti-Bacterial Agents↗

Nebulized colistin in the treatment of pneumonia due to multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa.

Twenty-one patients with multidrug-resistant (MDR) Acinetobacter baumannii and Pseudomonas aeruginosa pneumonia were treated with nebulized polymyxin E (colistin). Overall clinical and microbiological response rates were 57.1% and 85.7%, respectively. Nebulized colistin may be reasonably efficacious and safe for treatment of MDR pneumonia. Its role in therapy warrants further investigation in comparative studies.

Acinetobacter Infections↗

Intravenous colistin as therapy for nosocomial infections caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii.

Sixty nosocomial infections caused by Pseudomonas aeruginosa and Acinetobacter baumannii resistant to aminoglycosides, cephalosporins, quinolones, penicillins, monobactams, and imipenem were treated with colistin (one patient had two infections that are included as two different cases). The infections were pneumonia (33% of patients), urinary tract infection (20%), primary bloodstream infection (15%), central nervous system infection (8%), peritonitis (7%), catheter-related infection (7%), and otitis media (2%). A good outcome occurred for 35 patients (58%), and three patients died within the first 48 hours of treatment. The poorest results were observed in cases of pneumonia: only five (25%) of 20 had a good outcome. A good outcome occurred for four of five patients with central nervous system infections, although no intrathecal treatment was given. The main adverse effect of treatment was renal failure; 27% of patients with initially normal renal function had renal failure, and renal function worsened in 58% of patients with abnormal baseline creatinine levels. Colistin may be a good therapeutic option for the treatment of severe infections caused by multidrug-resistant P. aeruginosa and A. baumannii.

Acinetobacter Infections↗