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...
Surveillance, with attention to gender and risk factors is advocated. This work provides unique benchmark scores to aid referral decision-making.
Burkholderia cepacia is an aggressive pathogen that colonizes cystic fibrosis (CF) patients, causing greatly increased morbidity and mortality. It is resistant to most antibiotics, but sensitive in vitro to a novel agent, taurolidine. This has not previously been used against B. cepacia, nor given in nebulized form. We assessed the effect of nebulized taurolidine on United Kingdom epidemic (ET12) B. cepacia infection in 20 adult CF patients attending our regional adult cystic fibrosis outpatient clinic using a prospective, randomized, double-blinded placebo-controlled crossover trial. Nebulized taurolidine (4 mL 2% solution) or saline (4 mL 0.9% solution) was given twice daily. Each arm lasted 4 weeks, with a 2-week intervening washout period. Sputum B. cepacia colony counts (primary outcome measure), spirometry, and symptoms (secondary outcome measures) were assessed. Eighteen patients completed the study. There was no change in B. cepacia colony counts or spirometry, nor symptom scores. We conclude that, although taurolidine is well tolerated in nebulized form, in this study it had no in vivo anti-B. cepacia activity.
Although dornase alpha (recombinant human DNase) can thin the viscid pulmonary secretions of cystic fibrosis (CF), clinical trials in groups of unselected patients have shown only modest average improvements in pulmonary function. The product is very expensive, so in conjunction with purchasers we designed selection criteria and a protocol for a 2-week trial to target CF individuals who might gain most benefit. Treatment was to be continued in those showing > 10% improvement in pulmonary function. Those who had a trial of dornase alpha were followed up for 2 years. Of 25 patients who had a 2-week trial of dornase alpha, 17 met the criteria for continuation (average gain in forced expiratory volume 37%). The 11 of these who were still alive at 2 years had a greater initial average FEV1 improvement than those who had died (45% versus 22%), and still had an average improvement of 31% at 2 years. The 8 patients who did not meet the criteria for continuation were older and had required fewer intravenous antibiotic courses. All these were alive at 2 years with unchanged clinical indices. This method of selection for dornase alpha treatment allows targeting to those who gain most benefit without disadvantaging the remaining patients. Furthermore, production of such guidelines in conjunction with purchasers obviates funding difficulties and allows rational prescribing.
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