Foscarnet prophylaxis of cytomegalovirus infections in patients undergoing allogeneic bone marrow transplantation (BMT): a dose-finding study.

This is a dose-finding study using foscarnet for CMV prophylaxis after allogeneic bone marrow transplantation (BMT) in 20 high risk patients (unrelated donors, or T cell depleted, and/or advanced disease). Foscarnet was started on day +1 after BMT and continued until day +100. We explored four different dose levels, patients being entered at the lowest dose level until one patient experiences CMV-reactivation, identified as two consecutive positive CMV antigenemias (CMVAg-emia). The four dose levels expressed as mg/kg/day between days 1 and 30 (induction) and between days 31 and 100 (maintenance) were respectively: dose level I = 60/30 (n = 5); dose level II = 120/60 (n = 4); dose level III = 120/90 (n = 5) and dose level IV = 120/120 (n = 6). All patients showed engraftment: PMN > or =0.5 x 109/l at a median interval of 16, 21, 17, 15 days after BMT, and Plt > or =30x10(9)/l on days 19, 16, 17, 17 respectively. CMVAg-emia was seen in 10 patients at a median interval of 53 days post-BMT (range 33-89) with a median of 10 CMV antigen+ cells (range 1-16). There was a dose effect of foscarnet on CMVAg-emia: respectively 4/5 patients (80%), 2/4 (50%), 3/5 (60%) and 1/6 (18%) at dose levels I, II, III, IV (P = 0.1). CMV disease was seen in 3/9 (33%) at dose levels I, II and 0/11 at dose levels III, IV (P = 0. 07). The median number of CMV antigen-positive cells at diagnosis of CMV infection was different: 13 in dose levels I-II and two in dose levels III-IV (P = 0.01). Increased creatininine was seen in 15 patients with a mean of 1.8 mg% (range 1.5-5.7) and was the cause of discontinuation in nine patients (45%). Renal toxicity was reversible in all nine patients. Overall actuarial TRM at 2 years was 31%: 47% for patients at dose levels I-II and 19% for patients at dose levels III-IV. In conclusion, foscarnet exhibits a dose-dependent prophylactic effect on CMVAg-emia, CMV disease and transplant-related mortality with acceptable and reversible renal toxicity.

Amoxycillin/clavulanate versus amoxycillin in recurrent otitis media and therapeutic failure in children.

A total of 102 children with recurrent otitis media or therapeutic failure after treatment with phenoxymethyl penicillin were entered into a double-blind study with parallel groups, comparing treatment with amoxycillin/clavulanate suspension (Spektramox) for 7 days with amoxycillin suspension (Imacillin) for 10 days. Bacterial and clinical investigations were performed. A total of 91 patients were evaluated for efficacy at the first follow-up visit (10-12 days after start of treatment). Amoxycillin/clavulanate and amoxycillin showed equally high, satisfactory treatment results, i.e. more than a 90% response. Similarly, there was no statistically significant difference between the treatment groups at the second follow-up visit (about 30 days after start of treatment). Bacteriological cultures from the nasopharynx showed equal distribution of Haemophilus influenzae, Branhamella catarrhalis and Streptococcus pneumoniae between the study groups. Elimination of the initially occurring pathogens was equal in the two study groups with the exception of B. catarrhalis which was eliminated to a significantly higher extent with amoxycillin/clavulanate. Both drugs were well tolerated. In patients with recurrent otitis media or therapeutic failure, treatment with amoxycillin/clavulanate for 7 days results in high, satisfactory clinical effects and is comparable to treatment with amoxycillin for 10 days.

Analgesic efficacy of paracetamol/codeine and paracetamol/dextropropoxyphene in pain after episiotomy and ruptures in connection with childbirth.

Pain after episiotomy and/or perineal/vaginal rupture in childbirth is severe in many patients and in most cases it can be treated with oral analgesics. In this trial the efficacy and side-effect profile of two combination analgesics, paracetamol/codeine and paracetamol/dextropropoxyphene hydrochloride, were compared in post-partum pain after episiotomy and/or rupture of the perineum. Eighty-five patients were analysed for efficacy and 96 were included in an analysis of side-effects. Paracetamol/codeine was shown to give faster and more efficient pain relief while not causing constipation or other troublesome side-effects.

Clinical evaluation of rectally administered ampicillin in acute otitis media.

An ampicillin suppository was compared with amoxycillin suspension in the treatment of acute otitis media in children. Both antibiotics were given three times daily for 5 days in a daily dose of 25-50 mg/kg body weight. Safety was evaluated in 454 patients in the group given suppository and in 229 given the suspension, and 421 and 229 patients, respectively, were evaluable for efficacy. Ampicillin was rapidly absorbed and produced plasma concentrations well above the minimum inhibitory concentration for common respiratory pathogens. The overall clinical outcome was satisfactory (cured plus improved) in 89% of the patients given the suppository and in 86% given the suspension. Gastro-intestinal disturbances occurred in 28.4% of the patients given the suppository compared with 14.4% of those given the suspension. Perianal irritation was recorded in 12.1% of the patients given the suppository and in 5.2% of those given the suspension. Treatment was interrupted in 9.8% of patients given the suppository and in 0.9% of those given the suspension. In spite of these discomforts rectally administered ampicillin is considered to be a good alternative in children when oral medication is not feasible.

Analgesic efficacy and side-effect profile of paracetamol/codeine and paracetamol/dextropropoxyphene after surgical removal of a lower wisdom tooth.

A double-blind randomized analgesic trial was carried out on 180 patients undergoing surgical removal of an impacted lower wisdom tooth. The patients took their first dose of either 1000 mg paracetamol plus 60 mg codeine or 650 mg paracetamol plus 65 mg dextropropoxyphene when pain appeared after the decline of the local anaesthesia. If needed, another two doses were available during the observation period (less than or equal to 10 h). The analgesic efficacy of paracetamol/codeine was overall superior to paracetamol/dextropropoxyphene in all variables. Sufficient pain relief was obtained in most patients. The pain reduction after the first dose was 64% in the group receiving paracetamol/codeine compared with 53% in the group receiving paracetamol/dextropropoxyphene and the mean durations of effect of the first dose were 6.6 and 5.8 h, respectively. Side-effects appeared in all patient groups but were most frequent in women taking paracetamol/codeine.