Use of parenteral colistin for the treatment of serious infection due to antimicrobial-resistant Pseudomonas aeruginosa.
(33/414)
Serious infection due to strains of Pseudomonas aeruginosa that exhibit resistance to all common antipseudomonal antimicrobials increasingly is a serious problem. Colistin was used as salvage therapy for 23 critically ill patients with multidrug-resistant P. aeruginosa infection. Twenty-two patients who had septic shock (n=14) and/or renal failure (n=21) received mechanical ventilatory support at baseline. The most common types of infection were pneumonia (n=18) and intra-abdominal infection (n=5). Colistin was administered for a median of 17 days (range, 7-36 days). Seven patients died during therapy, at a median of 17 days (range, 4-26 days) after initiation of treatment. A favorable clinical response was observed in 14 patients (61%); only 3 patients experienced relapse. Bacteremia was the only significant factor associated with treatment failure (P=.02). One patient manifested diffuse weakness that resolved after temporary cessation of colistin therapy. Colistin provides an important salvage therapeutic option for patients with otherwise untreatable serious P. aeruginosa infection. (+info)
Colistin interactions with the mammalian urothelium.
(34/414)
Here we describe the effect of colistin on the barrier function of the mammalian urinary bladder epithelium. Addition of colistin to the mucosal solution of the rabbit urinary bladder epithelium (urothelium) resulted in an increase in the transepithelial conductance. The magnitude of the increase in transepithelial conductance was dependent on the membrane voltage, concentration of colistin, and presence of divalent cations in the bath solution. The initial site of action of colistin was at the apical membrane. Colistin increased the membrane conductance only when the apical membrane potential was cell interior negative. The more negative the membrane potential, the larger the conductance increase. The concentration dependence of the conductance increase saturated, suggesting a membrane binding site. Divalent cations decreased the magnitude of the conductance increase. This divalent cation action occurred at two sites: one in competition with colistin for a membrane binding site, and the other by rapidly blocking the induced conductance. At short exposure times, the increase in conductance was reversed by either removing colistin from the bath or changing the voltage so that the apical membrane was cell interior positive. At long exposure times, the increase was only partially reversible by voltage or removal from the bath. This finding suggests that at long exposure times, there is a toxic effect of colistin on the urothelium. (+info)
Colistin for Klebsiella pneumoniae-associated sepsis.
(35/414)
Klebsiella pneumoniae that was resistant to all available antibiotics (minimum inhibitory concentration of imipenem, 32 microg/mL), including carbapenems, was isolated from blood samples obtained from a 48-year-old patient in the intensive care unit. The patient developed septic shock, which was successfully treated with colistin, the only antibiotic with activity against this multidrug-resistant strain. (+info)
Pharmacokinetics of colistin methanesulphonate and colistin in rats following an intravenous dose of colistin methanesulphonate.
(36/414)
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. (+info)
Effect of antimicrobial agents on the production and release of shiga toxin by enterotoxaemic Escherichia coli isolates from pigs.
(37/414)
Edema disease (ED) of pigs is an enterotoxaemic disease caused by enterotoxaemic Escherichia coli (ETEEC) infection. Antimicrobial therapy for pigs with ED is controversial because it may induce death of sickish piglets. In this study, we investigated the effects in vitro of 7 antimicrobial agents, ampicillin, gentamicin, colistin, bicozamycin, fosfomycin, sulfamethoxazole-trimethoprim and enrofloxacin, on the release and production of shiga toxin (Stx) 2e by ETEEC strains. We found that more Stx 2e accumulated in the bacterial cells than was released into supernatant. Associated with inhibition of cell wall synthesis, the exposure to ampicillin or fosfomycin increased the release of Stx 2e. The production levels of Stx 2e in all antimicrobial-treated cultures were equal to the level in the control or less than in the control. These results suggest that cell wall synthesis inhibitors, such as ampicillin and fosfomycin, may change for the worse in the signs in ETEEC infectious pigs. On the other hand, gentamicin, colistin, bicozamycin and enrofloxacin may be useful for the treatment of pigs with ED. (+info)
New clinical evidence from the European tobramycin trial in cystic fibrosis.
(38/414)
The major cause of morbidity and mortality in patients with cystic fibrosis (CF) is respiratory disease (Penketh et al., Thorax 1987; 42: 526-532). Recent studies in the USA have shown that intermittent administration of inhaled tobramycin is beneficial to patients with CF who are chronically infected with Pseudomonas aeruginosa (Ramsey et al., N Engl J Med 1999; 340: 23-30; Ramsey et al., Proceedings of the 12th Annual North American Cystic Fibrosis Conference, 1998, Montreal, Canada; Ramsey et al., Abstract from 23rd European Cystic Fibrosis Conference, 1999, the Hague, Netherlands). In Europe, the use of nebulised colistin in patients chronically infected with P. aeruginosa is widespread. A recently published study compared the efficacy and safety of tobramycin nebuliser solution (TNS) and nebulised colistin in CF patients . One hundred and fifteen patients were randomised to receive either TNS or colistin in a multi-centre open-labelled study that assessed change from baseline in FEV(1) and sputum P. aeruginosa density. TNS produced a mean 6.7% improvement in lung function (P=0.006), whilst there was no significant improvement in the colistin-treated patients. The TNS-treated patients had a significantly greater improvement in lung function than those treated with colistin (P=0.008). The safety profile of both treatments was good. We conclude that patients treated with TNS for 1 month experience improved lung function compared with patients treated with colistin. (+info)
Insights into cystic fibrosis microbiology from the European tobramycin trial in cystic fibrosis.
(39/414)
The infection of the airways of cystic fibrosis patients by Pseudomonas aeruginosa is a complex, multistaged process that is associated with a deterioration of lung function. The complexity of the formation of biofilms and their interaction with the immune system means that treatment with antibiotics has been an uncertain science. Tobramycin nebuliser solution (TNS) is a novel formulation of the antibiotic tobramycin developed specifically for inhalation. A recent large trial comparing TNS with inhaled colistin provided an opportunity to define further the effect of antibiotic treatment on microbial infection. In the TNS group, the percentage of patients with a tobramycin minimal inhibitory concentration (MIC) > or = 4 mg l(-1) increased from 38 to 49%, and the percentage of patients with a colistin MIC > or = 4 mg l(-1) remained at 55%. In the colistin group, the percentage of patients with a colistin MIC > or = 4 mg l(-1) remained at 34%, whereas the percentage of patients with a tobramycin MIC > or = 4 mg l(-1) decreased from 27 to 16%. Furthermore, clinical and bacterial response to TNS and colistin was independent of the MIC at baseline. Neither antimicrobial therapy was associated with infection by Burkholderia cepacia or other inherently resistant pathogens. We conclude that conventional measures of antimicrobial resistance may underestimate the effectiveness of tobramycin and colistin when delivered at the high concentrations achieved with the TNS formulation. (+info)
Effect of nebulized colistin sulphate and colistin sulphomethate on lung function in patients with cystic fibrosis: a pilot study.
(40/414)
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. (+info)