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Total structures of colistin minor components.

Structural characterization of the colistin (CL) components were carried out using Frit-fast atom bombardment liquid chromatography/mass spectrometry (Frit-FAB LC/MS), tandem mass spectrometry (MS/MS) and the amino acid analysis proposed by MARFEY, and the total structures of 4 minor components including the absolute configuration of the constituent amino acids were proposed. The structures of the minor components were the same as those of the main component colistin A or B except that L-leucine is replaced by L-valine or L-isoleucine.

Anti-Bacterial Agents↗

Isolation and structural characterization of colistin components.

Preparative-scale separation of colistin sulphate bulk sample was carried out on a preparative poly(styrene-divinylbenzene) stationary phase. Isocratic elution with acetonitrile-sodium sulphate solution (0.7% m/v; pH adjusted to 2.5 with TFA) - water (16:50:34, % v/v/v) was carried out at a flow rate of 4.0 ml min(-1). Six colistin components were isolated and characterized using 1H and 13C NMR. The molecular weights were confirmed by mass spectrometry. The structures of 2 components were determined for the first time. Polymyxin E7 was identified as having the same composition as polymyxin E1, except that the fatty acid moiety was 7-methyloctanoic acid. Isoleucine polymyxin E8 was characterized as having the same composition as isoleucine polymyxin E1 with 7-methylnonanoic acid as the fatty acid moiety.

Anti-Bacterial Agents↗

Isolation and properties of a streptococcal hemolysin formed in the presence of colistin.

The strains of beta-hemolytic streptococci capable of producing streptolysin S, Su and Blackmore, were found to be useful in acquiring CIH (colistin-induced hemolysin), while C203U strain, which produces only streptolysin O, was ineffective in this respect. In these experimental series, much amounts of coccal cells from exponential phase of culture were necessary for obtaining good results and for its reproducibility. Further experiments showed that an oligoribonucleotide, rich in guanylic residu, separated by DEAE-cellulose column chromatography could be favourably compared with RNase-core in production of CIH in the medium. Yield of this hemolysin was fully dependent upon the concentration of K+ (100 mM), Mg2+ (10 mM) ions and maltose (5 mM) contained in the reaction medium, respectively. When one of three components was omitted, CIH was not obtained, even though colistin and oligoribonucleotide were present. Additionally, crude preparation of CIH was fractionated on DEAE-cellulose column, resulting in isolation of two peaks (F-I and F-II) with hemolytic activity. Considering the response of two hemolytic fractions to various inhibitors and activators, F-II is likely to correspond to streptolysin S, while F-I may, at least, be a segment differed from the streptolysin, S and O.

Colistin↗

Treatment of nosocomial meningitis due to a multidrug resistant Acinetobacter baumannii with intraventricular colistin.

We report a case of serious nosocomial meningitis due to a multidrug-resistant Acinetobacter baumannii in a 23-year-old woman who had a posterior fossa craniotomy with upper cervical laminectomy for excision of a meningioma at the level of foramen magnum. Post-operatively, she had neck pain with continuous fever and deterioration in the level of consciousness and convulsions. The CSF was turbid and had neutrophil pleocytosis. A multidrug-resistant Acinetobacter baumannii was isolated from the blood and CSF. The patient failed high doses of imipenem, ciprofloxacin and systemic colistin but responded well to intraventricular injections of colistin 125,000 units twice daily for 3 weeks. No apparent side effects were noticed. We have reviewed other similar cases reported in the literature.

Acinetobacter Infections↗

Colistin, meropenem and rifampin in a combination therapy for multi-drug-resistant Acinetobacter baumannii multifocal infection. A case report.

A 16 year-old girl underwent a multifocal (lungs, skin, soft tissues) infection due to multiresistant Acinetobacter baumannii after a car crash. To treat such a severe disease we used a combination therapy of colistin (2 millions Units twice/day), rifampicin (600 mg/day), meropenem (1 g 3 times a day) after a synergistic activity test was performed (checkerboard method on Mueller-Hinton broth and 5x10(5) cfu/mL inoculum). After 24 days, when a significant clinical improvement was gained, the 3-drugs combination therapy was replaced with i.v. levofloxacin 500 mg twice/day but, after 10 days of quinolones therapy, fever started again and the same multidrug resistant (MDR) A. baumannii was isolated from the skin grafts, central venous catheter tip and bronchial alveolar lavage. A combination therapy with colistin and meropenem was therefore started and definitive defervescence was obtained after 10 days. This therapy was continued for 70 days even if the patient was apyretic because A. baumannii was still present in the skin secretions. After 109 days of hospitalization in our intensive care unit, the patient was transferred to a rehabilitative unit. This case shows how useful is, in selected cases, rediscovering old antibiotic drugs, specially when they are adopted as a combination therapy, and highlights the importance of the clinical microbiological laboratory as it may help clinicians in choosing the best drugs combination.

Accidents, Traffic↗

[Elimination of polypeptide antibiotics (colistin and bacitracin) in the milk after intramuscular or intramammary administration].

The elimination in cow's milk of polypeptidic antibiotic residues (colistin sulfate, colistin methanesulfonate and bacitracin) was investigated following intramuscular and intramammary administrations of eight drugs marketed in France. The quantitative analysis was performed according to the microbiological method of agar diffusion. The mean elimination periods lasted between three and six milkings for injected preparations, between four and six milkings for intramammary ones. These results were used as a basis to determine the withdrawal times required on these drugs. The problem of the diffusion of the residues into milk from a quarter treated by the intramammary route, to the untreated quarters was also addressed.

Animals↗

The international standard for colistin.

An International Standard for Colistin has been established and the International Unit defined as the activity contained in 0.00004878 mg of this preparation. The unit was defined on the basis of a collaborative assay in which nine laboratories from six different countries participated. The material used to prepare the international standard had been manufactured in Japan; it was shown to have a composition similar to that of material produced in Europe and to be suitable for the assay of colistin from the existing sources of manufacture.

Colistin↗

[Bioavailability of erythromycin and colistin in calves (author's transl)].

Bioavailability of erythromycin and colistin was studied in plasma, ruminal liquid and nasal mucus after simultaneous injection by intraruminal or intramuscular route. After intramuscular injection, erythromycin was found in plasma and respiratory tract, colistin in plasma. After oral administration, only erythromycin was found in nasal cavity secretions but nitrogen metabolism and volatile fatty acid production were modified in rumen.

Animals↗

[In vitro effect of cephacetril and colistin combinations on Klebsiella pneumoniae and Proteus Strains (author's transl)].

In 14 out of 43 Klebsiella pneumoniae strains (33%) the combination cephacetril-colistin showed a synergistic, in 11 strains (25%) an additive effect. In Proteus strains no synergistic action was found. The combination was more likely to be synergistic or additive in strains requiring higher minimal inhibitory concentrations of cephacetril and colistin. Most highly resistant Klebsiella pneumoniae strains were synergistically inhibited by concentrations of both drugs, which can easily be obtained in serum by usual clinical doses.

Cephacetrile↗

[Polyacrylic bone cement with added erythromycin and colistin. In vitro studies on bacteriologic activity and diffusion properties].

Erythromycin and colistin are not antagonists and have the property of inhibiting the growth of a large number of aerobic and anaerobic organisms. When they were worked into Chirurgischen Knochenzement Simplex P Radiopaque, the growth of 98% of all anaerobic and aerobic test organisms was inhibited. Separately conducted investigations have shown that each antibiotic can diffuse out of polymerized cement and that the concentration of each antibiotic is far above the minimal inhibitory concentration (MIC) of 96% of the organisms. Consequently, in our opinion it would be of benefit to test the Chirurgische Knochenzement Simplex P Radiopaque with erythromycin and colistin clinically.

Acrylates↗

Combined effect of ampicillin, colistin and dexamethasone administered intramuscularly to dairy cows on the clinico-pathological course of E. coli-endotoxin mastitis.

The effects of a single intramuscular injection of a drug product containing ampicillin, colistin and dexamethasone, as a suspension in a diester of propylene glycol of medium-chain fatty acids, on the clinico-pathological course of experimental Escherichia coli-endotoxin mastitis was examined in 30 dairy cows. Cows were divided into five groups, six cows per group, and 24 of them were infused with E. coli endotoxin into two quarters of their udders. The drug product was injected at 25,000 IU colistin sulphate, 10.0 mg ampicillin anhydrate and 0.025 mg dexamethasone acetate.kg-1 body weight as follows: Group 2 cows, immediately post-endotoxin infusion (PEI); Group 3 cows, 2 h PEI and, Group 4 cows, 4 h PEI. Group 1 cows were not treated with the product and served as a positive (endotoxin only) control while Group 5 cows were not challenged with endotoxin and were not treated with the product. A clinical mastitis score (CMS) was developed to quantitatively assess the degree of inflammation. Blood biochemistry and hematological parameters were used to monitor the immediate effects of treatment on several conventional inflammatory markers. Milk somatic cell counts (MSCC), milk electrical conductivity and daily milk production were among the parameters used to monitor systemic and local inflammatory reactions. Administration of the drug product immediately PEI and 2 h PEI clearly nullified some of the most severe early systemic reactions to inflammation but the effect of therapy on the local inflammatory markers was not as obvious. Notewhorthy, however, were the effects of the treatment on reducing the duration of elevated quarter MSCC and the increase in the speed of return to pre-endotoxin challenge daily milk production levels.

Ampicillin↗

The susceptibility of gram-negative rods and their adaptive forms resistant to colistine to the bactericidal action of sera.

The susceptibility of Escherichia coli K1, Salmonella enteritidis, Salmonella typhimurium strains and their adaptative forms resistant to colistine (Colr forms) was compared with respect to their sensitivity to the bactericidal action of normal cord serum and normal bovine serum. It has been shown that the Colr forms are more susceptible to sera as compared to initial strains. The increase of sensitivity of the Colr forms is connected with structural changes within bacterial cell wall which is the target for complement as well as for colistine.

Animals↗

Combination of pipemidic acid, colistin sodium methanesulfonate and nystatin may be less effective than nystatin alone for prevention of infection during chemotherapy-induced granulocytopenia in acute leukemia.

Pipemidic acid (PPA) and colistin sodium methanesulfonate (CLM) may selectively suppress aerobic gram-negative bacilli. Twenty-nine patients with acute leukemia were randomized after each course of consolidation chemotherapy to receive a single agent of nystatin (NYS) (34 courses) versus a combination of NYS, PPA and CLM (36 courses). The duration of fever over 39 degrees C was longer with the three drug combination (4.6 +/- 5.1 days) than with NYS alone (1.8 +/- 1.8 days) (P less than 0.01). Four cases of pneumonia occurred and four patients including one having pneumonia died of infection with the three drug combination, while no pneumonia or death occurred with NYS alone (P = 0.06 and P = 0.06, respectively). The combination of NYS, PPA and CLM may be less effective than NYS alone for the prevention of infection in acute leukemia patients with chemotherapy-associated granulocytopenia.

Acute Disease↗

In vitro inhibition of the classical pathway of human complement by a natural microbial product, colistin sulphate.

Colistin sulphate was found to be an inhibitor of the classical pathway of the complement system. The main sites of inhibition were the interaction of EAC14 with C2 and EAC142 with C3. It also inhibited EAC14 formation from EA and C2-deficient serum, EAC1-7 formation from EAC1-3, C5, C6 and C7 and the interaction of EAC1-7 with C8 and C9, though less efficiently. It did not inhibit formation of C3/C5 convertase of the alternative pathway. The inhibition of the classical pathway was reversible since hemolytic activity was completely restored after dialysis.

Animals↗

Pefloxacin and vancomycin vs. gentamicin, colistin sulphate and vancomycin for prevention of infections in granulocytopenic patients: a randomised double-blind study.

To test the value of pefloxacin for the prevention of infections in patients with chemotherapy-induced neutropenia, oral pefloxacin plus vancomycin (PV) (n = 76) or gentamicin, colistin sulphate and vancomycin (GCV) (n = 74) were administered in a randomised double-blind study. Infections were significantly less severe in the PV than in the GCV group. Patients receiving PV had significantly fewer episodes of bacteraemia and central venous line infections than patients treated with GCV. Gram-positive and gram-negative infections were significantly less frequent in patients receiving PV, because of fewer infections with Staphylococcus species and enterobacteriaceae. Stool culture detected significantly more gram-positive organisms in the PV group and more gram-negative organisms in the GCV group. Thus, PV was more efficacious than GCV for the prevention of gram-positive and gram-negative infections in the neutropenic patients, despite lower efficacy in eradicating gram-positive organisms from the lower intestinal tract.

Adult↗

Open follow-up study of tobramycin nebuliser solution and colistin in patients with cystic fibrosis.

A previous study of tobramycin nebuliser solution (TNS) compared with colistin [C] in cystic fibrosis (CF) patients, chronically infected with pseudomonas, showed benefit for the TNS treated patients over one treatment cycle only. The current report is of an extension of that study. An open randomised cross-over study of TNS compared with C was conducted on 21 patients who had previously been on the 1 cycle study. They continued for a further 5 months and then crossed over to the alternate treatment. There was an advantage for TNS over C in FEV(1) % predicted change over time. The C slope was -0.88% per month and the TNS slope 0.35% per month (p=0.0002). This suggests advantages of TNS over C in a study with a small number of patients. Larger studies are required.

Administration, Inhalation↗

Amikacin and colistin for treatment of Acinetobacter baumannii meningitis.

We report a case of a 52-year-old man with post-surgical meningitis due to a multi-drug resistant Acinetobacter baumannii. Despite therapy with intravenous amikacin and imipenem the meningitis progressed. Upon institution of combination therapy with amikacin by the intravenous and intrathecal (IT) routes, and intravenous colistin the patient experienced successful clinical and microbiological outcomes.

Acinetobacter Infections↗