Aim: Evaluation of the delivery of gentamicin and vancomycin from polymethylmethacrylate (PMMA) spacers before and after implantation for the treatment of total hip replacement infections. Methods: Twenty industrially produced spacers containing gentamicin (1.9%) were utilized. Vancomycin (2.5%) mixed with PMMA cement was used to fill holes drilled in the cement of 14 of the 20 spacers immediately before implantation. The spacers were removed from 20 patients 3–6 months after implantation and then immersed in phosphate buffer at 37°C for 10 days. Antibiotic concentrations were determined by fluorescence polarization immunoassay. Results: Gentamicin and vancomycin were still present in all the spacers removed from the patients. The release of gentamicin alone and in combination with vancomycin was in the range 0.05%–0.4% of the initial amount present, whereas the release of vancomycin was in the range 0.8%–3.3%. The release kinetics showed a similar pattern for both drugs. After a high initial release of drug, a reduced, but constant, elution was observed over the next few days. Conclusions: The delivery of gentamicin and vancomycin from PMMA cement was high initially, with sustained release over several months. Incorporation of vancomycin into the surface of the spacers permitted spacers to be prepared with multiple antibiotics present and without adversely affecting the release kinetics of the agents. The gentamicin–vancomycin combination shows potential for the treatment of infection following total hip replacement in specific patients.

The aim of the study was to verify whether antibiotics excreted by the normal pancreas are also excreted in human necrotizing pancreatitis, reaching the tissue sites of the infection. Twelve patients suffering from acute necrotizing pancreatitis were treated with imipenem-cilastatin (0.5 g), mezlocillin (2 g), gentamicin (0.08 g), amikacin (0.5 g), pefloxacin (0.4 g), and metronidazole (0.5 g). Serum and necrotic samples were collected simultaneously at different time intervals after parenteral drug administration by computed tomography-guided needle aspiration, intraoperatively, and from surgical drainages placed during surgery. Drug concentrations were determined by microbiological and high-performance liquid chromatography assays. All antibiotics reached the necrotic tissues, but with varying degrees of penetration, this being low for aminoglycosides (13%) and high in the case of pefloxacin (89%) and metronidazole (99%). The concentrations of pefloxacin (13.0 to 23 micrograms/g) and metronidazole (8.4 micrograms/g) in the necrotic samples were distinctly higher than the MICs for the organisms most commonly isolated in this disease; the concentrations in tissue of imipenem (3.35 micrograms/g) and mezlocillin (8.0 and 15.0 micrograms/g) did not always exceed the MICs for 90% of strains tested, whereas the aminoglycoside concentrations in necrotic tissue (0.5 microgram/g) were inadequate. Repeated administration of drugs (for 3, 7, 17, and 20 days) seems to enhance penetration of pefloxacin, imipenem, and metronidazole into necrotic pancreatic tissue. The choice of antibiotics in preventing infected necrosis during necrotizing pancreatitis should be based on their antimicrobial activity, penetration rate, persistence, and therapeutic concentrations in the necrotic pancreatic area. These requisites are provided by pefloxacin and metronidazole and to a variable extent by imipenem and mezlocillin.

The effects of probiotics on human health are positive and well defined in diarrhoea treatment. There are no clinical results regarding the relationship with dose or duration of treatment. The results from clinical studies have not been conclusive in that the effects of probiotic are dependent on strains, acute or chronic gastrointestinal infection and immunological or inflammatory disease and different dose and duration of treatment. The concentration of probiotics needed to obtain a clinical effect is often quoted as≥10⁶ cfu/ml in the small bowel and≥10⁸ cfu/g in the colon. The dose for treatment of an acute illness by a particular probiotic agent may be lower or higher, in the order of 10-fold or 100-fold or more in terms of colony forming units (cfu). In acute infectious diarrhoea it seems that higher doses of probiotics given for short courses are more effective than lower doses. In chronic or immunological diseases (allergic, inflammatory and/or immune diseases) the effects depend also on the interaction with gut immune system and duration of treatment. To evaluate the efficacy of probiotics it may be essential to identify specific target groups of individuals with more specific higher susceptibilities to the potential effects of probiotics.

Chronic functional constipation is common in infants, and the bacterial composition of stools in this condition is not known. The study aims were to: (i) investigate the composition of the intestinal ecosystem in chronic functional constipation; (ii) establish whether the addition of the water-holding agent calcium polycarbophil to the diet induces an improvement in constipation; and (iii) determine the composition of the intestinal ecosystem after the use of this agent. In total, 42 children (20F, 22M; mean age: 8.6 ± 2.9 y) were studied. Twenty-eight children with functional chronic constipation without anatomical disorders were treated double-blind in random sequence for 1 month with an oral preparation of calcium polycarbophil (0.62 g /twice daily) or placebo. Intestinal flora composition was evaluated by standard microbiological methods and biochemical assays on faecal samples collected before and after treatment. Fourteen healthy children were studied as controls. The results show that (i) the constipated children presented a significant increase in clostridia and bifidobacteria in faeces compared to healthy subjects–different species of clostridia and enterobacteriaceae were frequently isolated; no generalized overgrowth was observed; Clostridia outnumbered bacteroides and E. coli mean counts by 2–3log, while bacteroides and E. coli counts were similar (5-6 log ₁₀/g fresh faeces); these intestinal disturbances could be defined as a dysbiosis, i.e. a quantitative alteration in the relative proportions of certain intestinal bacterial species. (ii) Clinical resolution of constipation was achieved only in 43% of treated children and an improvement in 21% (one bowel movement every 2 d). (iii) Calcium polycarbophil treatment induced no significant changes in the composition of the intestinal ecosystem, nor in blood chemistry parameters.