Four years' experience of intravenous colomycin in an adult cystic fibrosis unit

Abstract

aa Most adult patients with cystic fibrosis (CF) are colonized with Pseudomonas aeruginosa [1] and usually require i.v. antibiotic therapy to treat pulmonary exacerbations with this organism. Strains of P. aeruginosa are showing increasing resistance to conventional antipseudomonal antibiotics [2, 3], yet despite this 98.8% are still sensitive to colomycin sulphomethate, an antibiotic which is easy to administer intravenously. Colomycin is a cationic cyclic polypeptide (sometimes known as polymixin E) isolated from the soil organism Bacillus colistinus [4]. The i.v. preparation is colomycin sulphomethate, formulated by treating the colistin base with sodium bisulphite in the presence of a formaldehyde [5]. It is bactericidal to many Gram-negative pathogens and works by disrupting the protein and phospholipid layers of the bacterial cell wall [6, 7], causing it to become porous with subsequent cell death [8]. This predominantly physiochemical action may account for the low levels of bacterial resistance seen to this antibiotic [9, 10]. Following parenteral administration , it penetrates most tissues but does not readily cross the blood-brain barrier. Excretion is mainly renal (65-75%) [11]. Despite the apparent suitability of this antibiotic as an antipseudomonal agent, i.v. colomycin sulphomethate is not now commonly used, since studies in the 1970s using large doses (up to 26 megaunits (MU)·day-1) demonstrated significant renal and neurotoxic side-effects [12, 13]. Thus, there have been few recent studies reviewing the use of this antibiotic. Often in combination with other antibiotics, i.v. colo-mycin sulphomethate has been used in more moderate doses to treat pseudomonal chest disease in our adult CF patients for the last 4 yrs. The efficacy and side-effects of this therapy have been reviewed in these patients over this period. Patients and methods Fifty-nine CF patients attending the Liverpool adult centre (72% of the clinic) are colonized by P. aeruginosa, and 52 of these (88%) have received i.v. antibiotics (28 male, 24 female; mean age 26 yrs, range 17-39 yrs, body mass index (BMI) mean 21.8, range 16.4-26.7) for pulmonary exacerbations with the organism. The notes of all 52 patients were reviewed and the number and length of i.v. colomycin courses, dose prescribed, other i.v. antibiotics concurrently used, use of nebulized colomycin, organisms cultured from sputum and their sensitivities, pre-and post-i.v. treatment spirometry and pre-and post-i.v. treatment renal function and any side-effects were noted. Results Over the study period 135 courses of i.v. colomycin at a dose of 2 MU t.d.s. were administered to these 52 adult CF patients. Every patient had received at least one course of i.v. colomycin (mean two courses each, range 1-7, median length 14 days, longest continuous course 210 days in a severely ill patient). In total, 2,414 patient days of i.v. Four years' experience of intravenous colomycin in an adult cystic fibrosis unit. M.J. Ledson, M.J. Gallagher, C. Cowperthwaite, R.P. Convery, M.J. Wal...

Pharmacokinetics and Pharmacodynamics of Aerosolized Antibacterial Agents in Chronically Infected Cystic Fibrosis Patients

“…for 12 days resulted in an improvement of FEV 1 values by 9.2%, and therapy of patients with colistin plus another antipseudomonal agent improved lung function by 18.5% (323); in another study performed by this group, an improvement of lung function of 6.9% due to combination therapy was reported (324).…”

Polymyxins Revisited

“…Virtually all patients received other antimicrobial agents, and their impact on outcomes at- (35,40,119), with particularly high success rates (ϳ85% to 95%) in treating urinary tract infections. In the late 1990s, colistimethate used in the treatment of respiratory exacerbations in patients with cystic fibrosis was reported (33,34,95). In those reports, patients with chronic bronchopulmonary infection with P. aeruginosa were given a ϳ2-week trial, with modest clinical and spirometric improvement.…”

“…Approximately 2% of patients will develop allergic manifestations including fever, eosinophilia, and macular and urticarial rashes (85,95). However, the more prominent side effects involve neurotoxicity and nephrotoxicity, perhaps attributed to high binding to brain and renal tissue (91).…”

Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus

“…Efficiency has been shown at doses ranging from 1 million units twice daily [43] to 2 million units three times daily [72]. Colistin has been used with efficiency by the parenteral route in patients with multiresistant P. aeruginosa infection [73,74].…”

“…However, two studies reported a low frequency of nephrotoxicity [73,74]. The UK is the only known European country where colistin is given intravenously in CF patients.…”