Pharmacokinetics and bioequivalence in the pig of two ivermectin feed formulations.

Two premix products containing the endectocide ivermectin were compared for pharmacokinetic profiles and bioequivalence in young pigs. Test and reference articles were administered to individual pigs in-feed at 12-h intervals for a total of 14 doses. Plasma concentration-time profiles were compared after provision of the final doses of medicated feed, by which time steady-state concentrations of ivermectin had been achieved. The pharmacokinetic variables monitored were peak concentration (Cmax ), area under the curve (AUC)0-last , elimination half-life of the terminal phase (T1/2 λz) and average steady-state concentration (Css ), determined by noncompartmental analysis. Logarithmic transformation of the variables was carried out when appropriate. Analysis of data by the Classic Method yielded confidence intervals of 80.59-114.47 (for AUC0-last ), 90.38-119.68 (for Cmax ) and 84.70-111.96 (for Css ). It was concluded that the two articles were bioequivalent for ivermectin.

Neutropenic enterocolitis associated with Clostridium tertium.

A 15 year old boy being treated for relapsed acute lymphoblastic leukaemia developed severe diarrhoea and abdominal pain which worsened despite empirical antibiotic treatment. A right hemicolectomy was performed. The caecum and ascending colon showed changes typical of neutropenic enterocolitis. Clostridium tertium was isolated from faeces, blood cultures, and from the resected gut wall, with no evidence of other organisms capable of causing such a condition. As far as is known, this is the first reported case in which neutropenic enterocolitis has been associated with well documented C tertium infection, an organism previously described as a cause of bacteraemia in neutropenic patients.

Do blood cultures need continuous monitoring so that clinical action can be taken outside normal working hours?

Many automated blood culture reading systems monitor bacterial growth 24 hours a day but it is unclear if reacting to prompts indicating bacterial growth outside normal laboratory hours is of clinical benefit. An analysis of 50 blood cultures from 43 patients which had organisms seen on Gram films and had triggered positive out-of-hours showed that examination of the Gram film altered management of seven patients and the results of culture or sensitivity testing altered that of a further four. However, after review, it was felt the clinical outcome would not have been influenced by earlier intervention in any of these patients. We therefore consider that an out-of-hours service for dealing with positive blood cultures is not justified in our hospital. This conclusion may not apply universally, especially in hospitals where potential pathogens show less predictable antimicrobial sensitivity patterns.

Waterbirths: regional audit of infection control practices.

Waterbirths are increasingly being offered as an option, although concerns about associated infection risks have been expressed. We undertook an audit of current practice in our region to help formulate an infection control policy. Questionnaires were sent to the Infection Control Nurses at 16 centres, with a request for completion in conjunction with the Infection Control Doctor. Fourteen (88%) centres responded, 11 of which carried out waterbirthing. Eight had permanent on-site pools, of which five were permanently plumbed in and provided with separate water inlets and outlets. All eight centres had infection control policies for waterbirthing. Six policies included care of the pool using detergent and disinfectant (chlorine-releasing compounds) and two using detergent alone. In none of the centres were the mothers tested for blood-borne viruses. Six centres collected data on infection in mother or child, and two carried out regular microbiological testing of pools. Infection control policies for waterbirths should include instructions for pool maintenance and decontamination, for prevention of legionella, for universal precautions and for use of personal protective equipment. Post-natal surveillance of mothers and babies is required in order to ascertain infection rates.

Clostridium tertium septicemia in patients with neutropenia.

Eighteen adult patients with hematologic malignancy developed bacteremia due to Clostridium tertium while neutropenic. Fifteen had accompanying abdominal pain, colonic bleeding, or diarrhea, and three had perianal cellulitis. Fourteen recovered with antibiotic therapy alone; no patient was treated by surgery. C. tertium is an unusual Clostridium because it is resistant to many beta-lactam antibiotics and to metronidazole but is susceptible to vancomycin, trimethoprim-sulfamethoxazole, and ciprofloxacin. It is possible that use of third-generation cephalosporins (cefotaxime, ceftizoxime, ceftazidime) for treating febrile episodes in the absence of any selective intestinal decontamination with trimethoprim-sulfamethoxazole or ciprofloxacin may have resulted in selection for C. tertium in our patients.

[Rectal absorption of steroids]. / Zur rektalen Resorption von Steroiden.

The investigations were designed to evaluate the systemic absorption of two steroids from suppositories. The suppositories containing either 3H-hydrocortisone (1 mg) or 3H-prednisolone-21-hexanoate (1 mg) were administered to a group of 4 baboons restrained in chairs. The levels of radio-activity in the plasma and urine were measured up to 120 h following rectal administration, and these levels were compared with those of a subsequent intravenous administration (1 mg each). The results show that both hydrocortisone (H) and prednisolone-21-hexanoate (P) are rapidly (tmax = 2-3 h) and significantly (H: 60-78%, P: 47-58%) absorbed from suppositories and thus can also cause systemic effects.

A study of the intestinal absorption of an ester-type prodrug, ME3229, in rats: active efflux transport as a cause of poor bioavailability of the active drug.

The intestinal absorption of a prodrug is affected by a number of factors, such as its membrane permeability, stability in the gut lumen, and conversion to the parent drug in enterocytes. We evaluated the absorption of ME3229, an ester-type prodrug of a hydrophilic glycoprotein IIb/IIIa antagonist. Although the octanol/water distribution coefficient and permeability across a Caco-2 cell monolayer of ME3229 was high enough for us to expect good oral absorption, less than 10% of the dose was absorbed in rats. To clarify this unexpected outcome, we evaluated the rate of its disappearance from the gut lumen (V1), its degradation in the gut lumen (V(deg)), uptake into enterocytes (V(uptake)), and appearance in the mesenteric vein (V2) by using a single-pass perfusion technique in combination with an in vitro metabolism study. Our data suggested that ME3229 crossed the apical membrane and was taken up into enterocytes at a rate compatible with its lipophilicity, but that only a small fraction of the metabolites formed in enterocytes reached the mesenteric vein, primarily attributable to efflux into the intestinal lumen. Transport of the main metabolite across rat intestinal tissue mounted on an Ussing chamber suggested that an active efflux system pumped out any ionic metabolite(s) present.

Paracetamol disposition and metabolite kinetics in patients with chronic renal failure.

The disposition of paracetamol following an oral dose of 1.0 g was compared in 10 healthy volunteers, 7 patients with moderate chronic renal failure and 6 patients with end stage renal failure on maintenance haemodialysis. Paracetamol absorption was normal in the patients with renal failure. The mean plasma half-life of paracetamol from 2 to 8 h was similar in the 3 groups (2.1 to 2.3 h) but from 8 to 24 h it disappeared much more slowly in the renal failure patients (half-life 11.7 compared with 4.9 h in the healthy volunteers). Plasma concentrations of paracetamol glucuronide and sulphate conjugates were greatly increased in the patients with moderate renal failure and the mean plasma half-lives were 30.5 and 21.8 h respectively compared with about 3 h in the healthy volunteers. Plasma concentrations of these metabolites were even higher in the dialysis patients and there was no significant fall over 24 h. The cysteine and mercapturic acid conjugates of paracetamol could only be measured in plasma in the patients with renal failure and concentrations were very low. The fractional urinary recovery of paracetamol and its glucuronide, sulphate, cysteine and mercapturic acid conjugates was similar in healthy volunteers and patients with moderate renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)

An audit of ciprofloxacin use in a district general hospital.

An audit of ciprofloxacin use at Southmead Hospital, Bristol was carried out for forty patients treated in early 1992 employing a modified Delphi technique with six assessors. Most patients assessed (20/40, 50%) had urinary tract infections (UTIs), 5/40 (12.5%) had chest infections, 4/40 (10%) had bacterial gastroenteritis and 3/40 (7.5%) had either bacteraemia or infection following an orthopaedic procedure. A likely bacterial pathogen was isolated from 32/40 (80%) of patients; 14/32 (44%) had Pseudomonas aeruginosa infections and from the remainder Enterobacteriaceae including Salmonella spp. (non-typhoid) were cultured. Oral therapy with ciprofloxacin was used in 37 (93%) of the 40 patients, and the three others received iv treatment. In 21/35 (60%) of patients where an assessment was made by majority scoring, a quinolone was felt to be clinically justified. A quinolone was least likely to be thought justified if the patient had a chest infection. The assessors had few concerns about the effectiveness or toxicity of ciprofloxacin but for 41% (14/34) of patients, where there was a majority opinion, a cheaper alternative was felt to be available; most of these patients had hospital-acquired UTIs caused by Enterobacteriaceae. The duration of therapy was felt to be too long in 35% (10/29) of patients, mainly because of prolonged treatment of UTIs. In some cases of P. aeruginosa infection the assessors would have used higher doses than those prescribed. Ciprofloxacin was the quinolone of choice in 24/32 (75%) of assessable cases. Norfloxacin was chosen to treat UTI due to multi-resistant Enterobacteriaceae in 6.2% (2/32) cases.(ABSTRACT TRUNCATED AT 250 WORDS)