Mg Of Colistin Research Articles

Radiolabeling and preclinical evaluation of technetium-99m labeled colistin

IntroductionAntibiotic resistance is a burden on the healthcare system. In present study, we have labeled an antibiotic named Colistimethate sodium (CMS) with technetium-99m (99mTc) to develop a SPECT based imaging tracer. MethodsWe standardised the labeling using 0.5–2 mg of CMS (in water) using stannous chloride dihydrate as a reducing agent followed by addition of 370 ± 74 MBq of 99mTc. A group of mice were injected intravenously (in tail vein) with 4–6 MBq of [99mTc]Tc-CMS diluted with saline and euthanized at various time intervals. microSPECT Imaging (ϒ-eye) was acquired to study the biodistribution in the healthy mice. ResultsWe standardised the labeling using 0.5 mg of colistin in 0.5 ml of saline with addition of 30 μg stannous chloride dihydrate. The retention factor value was 0.1–0.3 as compared to 0.9–1.0 for free 99mTc by TLC and retention time was found to be 14.2 ± 1.3 min as evaluated by HPLC. The biodistribution data showed uptake in lungs, spleen, and liver at 30 min but the uptake decreased in lung at 60 min. The imaging data corroborated with the biodistribution data. ConclusionsWe could successfully label [99mTc]Tc-CMS 99mTc and we could study its biodistribution in healthy mice.

Effects of Paenibacillus xylanexedens on growth performance, intestinal histomorphology, intestinal microflora, and immune response in broiler chickens challenged with Escherichia coli K88

This study investigated the effects of dietary Paenibacillus xylanexedens ysm1 supplementation on growth performance, intestinal morphology, immune response, and cecal microbiota of broiler chickens challenged with Escherichia coli K88. A total of 320 one-day-old male broiler chicks were randomly allocated to 4 treatments (8 floor pens, 10 birds/pen) including 1) negative control (NC) birds fed a basal diet and not challenged with E. coli K88; 2) positive control (PC) birds fed a basal diet and challenged with of E. coli K88; 3) P. xylanexedens ysm1 treatment (PRO) birds fed a basal diet supplemented with 1 × 109P. xylanexedens ysm1 cfu/kg feed and challenged with E. coli K88; and 4) antibiotic treatment (ANT) birds fed a basal diet supplemented with 20 mg of colistin sulphate/kg of feed and challenged with E. coli K88. The E. coli challenge decreased (P < 0.05) BWG in PC birds compared with the ANT birds on days 21 and 28. The FCR was higher (P < 0.01) in PC birds compared with the NC, PRO, and ANT birds on days 14, 21, and 28. Compared with the NC, PRO, and ANT birds on day 28, PC birds had shorter villi and higher number of goblet cells in both jejunum and ileum (P < 0.001). Irrespective of the dietary treatments, the E. coli challenge reduced the number of PCNA-positive cells in both the jejunum and ileum on day 28. Paenibacillus xylanexedens ysm1 treatment resulted in higher concentration of mucosal sIgA in the jejunum as compared to the other treatment groups on days 14 and 28. The numbers of cecal E. coli were reduced (P = 0.017) in broilers treated with P. xylanexedens ysm1 or antibiotic in comparison with the PC group on day 28. In conclusion, the present study demonstrated that dietary supplementation of this new probiotic bacteria P. xylanexedens ysm1 improved broiler performance by modulating intestinal morphology, enhancing immune response, and reducing the number of E. coli in the cecum.

Evaluation of Clinical outcomes after Tigecycline and Colistin Treatment against Multidrug-resistant Acinetobacter baumannii

Cases of multidrug-resistant Acinetobacter baumannii (MRAB) infection are increasing worldwide. Therapeutic options are limited, and these include tigecycline and colistin. However, few comparative studies have assessed the clinical effectiveness of these antibiotics. The aim of this study was to compare and evaluate the efficacy and safety of tigecycline and colistin in the treatment of an MRAB infection in order to generate optimal drug information. We retrospectively examined the electronic medical records of patients admitted to tertiary hospitals between January 2014 and March 2015. Patients were injected with colistin (colistimethate sodium) or tigecycline for at least 14 consecutive days intravenously. Data were obtained from blood samples taken at baseline and after 14days in order to evaluate the clinical efficacy and safety of these antibiotics. Eighty-four patients were treated with 50-100 mg of tigecycline per day (n=45) and 75-300 mg of colistin per day (n=39). The most frequent indications for treatment were skin and soft infection in the tigecycline group and pneumonia in the colistin group. Both antibiotics significantly decreased serum C-reactive protein (tigecycline vs. colistin = -3.4 ± 5.7 vs. -5.4 ± 7.5 mg/dL, p<0.05). The 다제내성 Acinetobacter baumannii균에서 Tigecycline과 Colistin 치료 후의 임상 결과 평가 박선희, 김혜미, 최은주, 최 인 조선대학교병원 약제부, 조선대학교 약학대학 Evaluation of Clinical outcomes after Tigecycline and Colistin Treatment against Multidrug-resistant Acinetobacter baumannii Sun Hee Park, Hye Mi Kim, Eun Joo Choi, In Choe Pharmacy Department, Chosun University Hospital, 365 Plimundaero, Dong-gu, Gwangju, 61453, Korea College of Pharmacy, Chosun University, 309 Plimundaero, Dong-gu, Gwangju, 61452, Korea 투고일자 2016.4.15; 심사완료일자 2016.5.18; 게재확정일자 2016.6.18 �교신저자 최인 Tel:062-220-3291 E-mail:iimqueen@hanmail.net Original Article

Effects of Clostridium butyricum on growth performance, immune function, and cecal microflora in broiler chickens challenged with Escherichia coli K88

This study was conducted to investigate the effects of Clostridium butyricumon growth performance, immune function, and cecal microflora in broiler chickens challenged with Escherichia coli K88. Three hundred sixty 1-d-old broiler chickens were randomly divided into 4 treatments: negative control (NC) birds were fed a basal diet and not challenged with E. coli K88; positive control (PC) birds were fed a basal diet and challenged with E. coli K88; C. butyricum treatment (CB) birds were fed a diet containing 2 × 10(7) cfu C. butyricum/kg of diet and challenged with E. coli K88; and colistin sulfate treatment (CS) birds were fed a diet containing 20 mg of colistin sulfate/kg of diet and challenged with E. coli K88. Birds fed CB had greater (P < 0.05) BW than the PC birds from 3 to 21 d postchallenge. Birds fed CB had greater (P < 0.05) serum IgA and IgY at 14 d postchallenge, greater (P < 0.05) serum IgM at 21 d postchallenge, and greater (P < 0.05) mucosal secreted IgA at 3 and 7 d postchallenge than the PC birds. Birds fed CB had greater concentrations of serum complement component 3 at 14 d postchallenge, and greater (P < 0.05) concentrations of serum complement component 4 at 3, 7, and 14 d postchallenge than the PC birds. Birds in the CS or CB treatments had less cecal E. coli population at 3, 7, and 21 d postchallenge, and less cecal Clostridium perfringens counts at 21 d postchallenge compared with the PC birds. The CB treatment increased (P < 0.05) the population of cecal Lactobacillus at 3 d postchallenge and the number of cecal Bifidobacterium at 3, 14, and 21 d postchallenge in comparison with the PC treatment. The results indicate that dietary supplementation of CB promotes growth performance, improves immune function, and benefits the cecal microflora in Escherichia coli K88-challenged chickens.

Comment on: Pharmacokinetics of inhaled colistin in patients with cystic fibrosis

Sir, Ratjen et al. recently published an important paper in JAC reporting the pharmacokinetics of colistin after inhalation of colistin methanesulphonate in patients with cystic fibrosis (CF). HPLC was used to measure the concentrations of the formed colistin. The paper raises a number of important issues that deserve comment. It is important not to use the terms colistin and colistin methanesulphonate (sodium salt, or colistimethate-Na in the paper) interchangeably. The chemistry, pharmacokinetics, pharmacodynamics and toxicity of these two entities are substantially different; most importantly, colistin is formed from colistin methanesulphonate both in vitro and in vivo. Even though some manufacturers (such as Grunenthal, Germany) label the content of injection vials of colistin methanesulphonate with ‘158 mg colistin methanesulphonate is equal to 66 mg colistin’, this labelling is misleading because it is based on antibacterial activity measured with microbiological assays and does not mean that there is 66 mg of colistin in each vial. Therefore, we strongly recommend that any pharmacokinetic calculations on colistin or colistin methanesulphonate should not be based on ‘66 mg colistin’. The HPLC assay used by Ratjen et al. was very similar to the one reported previously from another laboratory using derivatization with 9-fluorenylmethyl chloroformate on solid-phase extraction C18 cartridges; in the previously reported HPLC assay, colistin sulphate was employed to prepare calibration curves for measurement of colistin (base) in biological fluids. In the paper of Ratjen et al., it is not clear whether colistin sulphate, colistin A or colistin methanesulphonate (sodium) was used for the calibration curves of the HPLC assay. Ratjen et al. reported the amount (0.18–16.13 mg) of ‘colistin methate’ recovered in urine was equal to a mean 4.3 – 1.3% (range 0.3–24.2%) of the inhaled dose. Unfortunately, it is not clear how the concentrations of ‘colistin methate’ in urine were measured. It appears that the urinary recovery was calculated based on the recovered amount of colistin (base) and the dose of ‘66 mg colistin’. Considering the hydrolysis of colistin methanesulphonate to colistin in vivo and in vitro, such calculation of urinary recovery using the dose of ‘66 mg colistin’ is inappropriate. In addition, it is unclear whether the authors have allowed for the molecular weight difference between colistin methanesulphonate (sodium, average molecular weight 1743), colistin sulphate (average molecular weight 1403, if they used it for calibration curves for colistin) and colistin (average molecular weight 1163) when the concentrations of ‘colistin’ were calculated. Ratjen et al. used the HPLC peak for polymyxin E1 to generate calibration curves for colistin concentrations. Usually, the two major components of colistin, colistin A (polymyxin E1) and colistin B (polymyxin E2), account for more than 85% of colistin, but the ratio of these two components may vary substantially between 3:1 and 1:1. It is not clear how the authors calculated the concentrations of polymyxin E1 in the HPLC assay as the commercially available colistin sulphate is a mixture of many components. In addition, we are not aware of any literature indicating that polymyxin E2 has no antibacterial activity; hence, the claim by Ratjen et al. that ‘colistin is a pro-drug that is converted into its active component polymyxin E1’ is questionable. Indeed, polymyxin E1 is one of the constituents of colistin. It should be noted that the clearance of colistin reported by Ratjen et al. should be regarded as an apparent clearance because the amount of the inhaled dose of colistin methanesulphonate reaching the systemic circulation in the form of colistin is unknown. In summary, Ratjen et al. provided some potentially useful information on the pharmacokinetics of colistin after inhalation of colistin methanesulphonate. However, because of lack of clarity regarding the quantification of colistin in biological fluids and the pharmacokinetic analysis, caution is required when these data are used as reference for inhalation therapy of colistin methanesulphonate in CF patients.

Effects of a Dried Bacillus subtilis culture on egg quality

The effects of a dried Bacillus subtilis culture on the egg qualities of layers were studied. Nine hundred and sixty 25-wk-old Lohmann Brown layers were randomly divided into 5 groups with 192 layers in each group. Layers in group 1 were fed a control diet. The remaining groups received the control diet that contained either 20 mg of zinc bacitracin/kg and 4 mg of colistin sulfate/kg or 500, 1,000, or 1,500 mg of B. subtilis culture/ kg, respectively. The results showed improvements in egg production, feed consumption, and feed conversion (P < 0.05) of layers when 500 mg of B. subtilis culture/kg was added to the diets. The results also showed some special improvements in this group, including increases in eggshell thickness, yolk color, and Haugh unit, and decreases in yolk cholesterol concentration (P < 0.05). However, excessive doses of B. subtilis culture did not improve the performance of layers.

Use of high-performance liquid chromatography to study the pharmacokinetics of colistin sulfate in rats following intravenous administration.

The pharmacokinetics of colistin was investigated using specific high-performance liquid chromatography (HPLC) to measure the concentrations of colistin and colistin A and B in plasma and urine in five rats after administration of an intravenous bolus of 1 mg of colistin sulfate/kg of body weight. There were differences in the pharmacokinetic behaviors of unbound colistin A and B. This is the first report of the use of HPLC to study the pharmacokinetics of colistin and its two major components.

Evaluation of Culture Techniques for Isolation of Pseudomonas pseudomallei from Soil

Three selective enrichment broths and four selective agar media were evaluated for their ability to support the growth of Pseudomonas pseudomallei both at 35 degrees C and at ambient temperature (range, 20 to 32 degrees C; mean, 25 degrees C). Colony counts of 50 strains of P. pseudomallei and recovery studies with 1 soil strain in 60 simulated soil samples demonstrated that enrichment with Trypticase soy broth incorporating 5 mg of crystal violet per liter and 20 mg of colistin per liter (CVCB) and subculture to Ashdown medium supported the growth of all 50 strains and produced the highest recovery rates with the greatest suppression of other soil flora. An enrichment broth of MacConkey broth (purple) incorporating 10 mg of crystal violet per liter, 5 mg of bromcresol purple per liter, 25 mg of gentamicin per liter, and 650 mg of streptomycin per liter showed greater suppression of soil bacteria than CVCB, but it failed to support the growth of three strains of P. pseudomallei. Recovery rates were essentially the same irrespective of whether the soil samples were incubated at 35 degrees C or at ambient temperature, provided cultures were incubated in protected shade for an extended period. This is an important feature for field work in large-scale epidemiological surveys in which resources are limited.

Selective and differential medium for the primary isolation of members of the Proteeae.

A new differential and selective medium for the isolation of members of the Proteeae, PIM (Proteeae isolation medium) agar, was developed and evaluated. The medium relies on the ability of all members of the Proteeae (with the exception of a very few Morganella morganii strains) to produce a dark brown pigment in medium containing DL-tryptophan. An additional differential property, tyrosine degradation, was also demonstrated by the medium. Members of the Proteeae appeared as dark brown colonies with a halo of clearing of fine tyrosine crystals when cultured on PIM agar. Occasional strains of Citrobacter sp. and Pseudomonas aeruginosa may degrade tyrosine, but none has the ability to produce dark brown pigmentation on PIM agar. Quantitative recovery studies showed that the addition of 5 mg of clindamycin per liter suppressed gram-positive bacteria without inhibiting any strains of the Proteeae. The addition of 100 mg of colistin per liter made the medium highly selective for strains of the Proteeae, but approximately 10% of the strains were not isolated, thus making this formulation unsuitable for general surveys of the occurrence of members of the Proteeae. PIM agar should aid the investigation of episodes of cross infection caused by members of the Proteeae and the isolation of the new species of the Proteeae recently described.