In vivo application of biodegradable controlled antibiotic release systems for the treatment of implant-related osteomyelitis.

In this study the construction and in vivo testing of antibiotic-loaded polyhydroxyalkanoate rods were planned for use in the treatment of implant-related osteomyelitis. The rods were constructed of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and poly(3-hydroxybutyrate-co-4-hydroxybutyrate), carrying 50% (w/w) Sulperazone or Duocid. They were implanted in rabbit tibia in which implant-related osteomyelitis (IRO) had been induced with Staphylococcus aureus. The effectiveness of the antibiotics in the treatment of IRO was determined. The establishment of IRO with bacterial inoculation was complete after 3 weeks with 100% infection rate in all groups. There was no contamination or super-infection. Both antibiotics were found to be highly effective against the bacteria. Following the application of Sulperazone-P(3-HB-co-4-HB) rods, no infective agents could be isolated from the infection site within the 6-week test period, indicating complete treatment of the infection. Macroscopical evaluation at follow-up revealed no drainage, minimal swelling and increase in local warmth, most probably due to the surgery rather than to a reaction towards the implant. The overall scores for radiological findings by the end of 6 weeks were 0.8/5 for the antibiotic-loaded rod implanted in the right limb, and 1.1/5 for the antibiotic-free rod implanted in the left limb. There was no statistical difference between the antibiotic-loaded and antibiotic-free polymeric rods. In vivo drug release was almost complete within the first week. One interesting observation, however, was that the therapy was still very effective even when the release rate was very high. In the SEM of in vitro tested rods, the polymeric component was unchanged in 2 weeks while the drug leached out, leaving voids behind. In vivo, however, the morphology of the implant was significantly modified within 6 weeks post-implantation. Since a substantial degree of the in vivo drug release was complete within 1 week, we believe that dissolution of the drug must be the predominant mechanism through which the drug release is controlled

Antimicrobial resistance and enterotoxin production among isolates of Escherichia coli in the Far East.

The frequency of association between transferable extrachromosomal D.N.A. (plasmid) mediated antibiotic resistance and enterotoxin productin is unknown. The antimicrobial susceptibility of 176 enterotoxigenic Escherichia coli from 57 children and adults in the Philippines, Korea, Taiwan, and Indonesia has been examined. 126 isolates (72%) were resistant to one or more antibiotic(s); 77 (44%) were resistant to four or more antibiotics. 43 E. coli which produced both heat-labile and heat-stable toxin, 110 isolates which produced only heat-labile toxin, and 23 which produced only heat-stable toxin were frequently resistant to multiple antibiotics. 25 of 31 resistant isolates tested, 80% transferred antibiotic resistance in bacterial mating experiments. In 35% of the matings transferring antibiotic resistance, the ability to produce enterotoxin was also conferred on the recipients. This in-vitro observation suggests that the widespread use of antibiotics could increase the distribution of enterotoxigenic E. coli, as genes coding for antibiotic resistance and enterotoxin production are frequently transferred together

In vivo release of vancomycin from biodegradable beads.

The current delivery system of antibiotics for the treatment of osteomyelitis uses polymethylmethacrylate (PMMA) beads as a local drug-release agent. The nonbiodegradable nature of the PMMA, however, necessitates a second operation to remove the beads. This article explores the alternative of using biodegradable polymers as antibiotic beads for a long-term drug release in vivo. To manufacture an antibiotic bead, lactide-glycolide copolymers were mixed with vancomycin. The mixture was compressed and sintered at 55 degrees C to form beads 8 mm in diameter. An in vivo animal model was proposed to characterize the elution rate of antibiotic over a 55-day period. Biodegradable beads released high concentrations of antibiotic (well above the breakpoint sensitivity concentration) in vivo for the period of time needed to treat bone infection; that is, 4-6 weeks. A bacterial inhibition test was also carried out to determine the relative activity of the released antibiotics. The diameter of the sample inhibition zone ranged from 8 to 18 mm, which is equivalent to 9.1 to 100% of relative activity. In addition, the antibiotic concentration of systemic blood was found to be very low. Antibiotic-impregnated biodegradable beads may have a potential role in the prevention and management of surgical infections. 2002 Wiley Periodicals, Inc

Use of antibiotics is not associated with decreased risk of myocardial infarction among patients with diabetes.

OBJECTIVE: To study the relationship between exposure to antibiotic treatment and risk of subsequent myocardial infarction (MI) in patients with diabetes. RESEARCH DESIGN AND METHODS: A case-control design was used to assess the effect of previous antibiotic exposure in diabetes patients with acute, nonfatal or fatal MI (case subjects) and individually matched control subjects (four control subjects to one case subject, matched on sex, age, and index date). Subjects were sampled from the Northern California Kaiser Permanente Diabetes Registry, a well-characterized, ethnically diverse diabetic population from Kaiser Permanente Medical Care Program, Northern California Region. MI events were ascertained during a 2-year observation period (1998-1999). Separate conditional logistic regression models were specified to assess antibiotic exposure history (cephalosporins only, penicillins only, macrolides only, quinolones only, sulfonamides only, tetracyclines only, as well as more than one, any, or no antibiotic) for three nested windows before the index date (0-6 months, 0-12 months, 0-24 months), facilitating assessment of whether the potential effect was dependent on the timing of the exposure. RESULTS: A total of 1,401 MI case subjects were observed. Odds ratios were calculated in models adjusted for age, sex, race, education attainment, time since diabetes diagnosis, diabetes type and treatment, use of diet and exercise, total cholesterol, HDL cholesterol, triglyceride levels, hypertension, elevated urinary albumin excretion, serum creatinine, BMI, and smoking. We found no evidence of a protective effect of any of these therapeutic classes of antibiotics during any of the three time frames. CONCLUSIONS: Our study does not support the hypothesis that use of antibiotics has a protective effect for prevention of coronary heart disease in diabetic patients

Data lacking to support antibiotics at IUD insertion.

PIP: Despite a lack of clinical evidence to support prophylactic antibiotic use at the time of IUD insertion, many clinicians continue this practice. A 1994 survey of "Contraceptive Technology Update" readers found that 75% of clinicians who provide IUDs supported prophylactic antibiotic use in case the woman had chlamydia or gonorrhea bacteria at the cervix. Two large, independent, controlled studies conducted in Kenya and Nigeria failed to detect significantly lower rates of pelvic inflammatory disease (PID) 3 months after IUD insertion in women treated with antibiotics compared to a placebo. In fact, in the Nigerian study, the rate of PID was 0.6% among the 721 women who received antibiotics and only 0.3% among the 708 women in the placebo group. The Planned Parenthood Federation of America does not endorse the routine prophylactic use of antibiotics at IUD insertion. A Los Angeles (California) Regional Family Planning Council study is underway of 1800 women administered 500 mg of azithromycin ( Zithromax ) before IUD insertion; findings should help to clarify the issue.

Interactions of antibiotics with phagocytes in vitro.

The goal of antimicrobial therapy is to eliminate invading bacteria both in the extracellular and intracellular environment. Thus, recent work has focused on the ability of various antibiotics to enter phagocytic cells and kill intracellular pathogens, since bacteria which survive within phagocytes may often produce prolonged or recurrent infections. In the last ten years the antibiotic modulation of phagocytic cell functions has become the subject of our major investigational activity. Taking into account that entry of antibiotics into phagocytes is necessary for activity against intracellular organisms, we examined the uptake of 11 radiolabelled antibiotics by macrophages. Penicillins and cephalosporins were taken up poorly by phagocytes. Teicoplanin was efficiently concentrated by macrophages, achieving intracellular concentrations higher than those in the surrounding extracellular medium. Roxithromycin was more markedly accumulated within phagocytes than was erythromycin, depending upon an active transport mechanism. Antitubercular drugs were concentrated approximately twofold in the macrophages. Besides, since antibiotics that act on phagocytosed bacteria have clinical advantages, we evaluated the direct action of the above mentioned drugs on the macrophage, by determining their interference with its functions or their potentiation of both phagocytosis and killing of bacteria

Cellular viability and ultrastructure of stented, antibiotic sterilized and cryopreserved sheep biological valves implanted for one year in tricuspid position.

The aim of the study was an evaluation of viability and damage of biological cells sterilized with antibiotics and cryopreserved a year after the implantation. Sheep antibiotic sterilised and cryopreserved biological valves were implanted in tricuspid position in young sheeps for one-year period. After this time the valves removed and studied morphologically. The control group consisted of 7 intact valves, the comparative group, so called group of valves after the processing antibiotic sterilization and cryopreservation consisted of 7 valves after mentioned procedures. Histologic investigations were based on paraffin sections of formalin-fixed valve cusps, stained with H&E and Masson trichrome. Valve viability was assessed using intravital staining with fluoresceine diacetate, whereas damaged cells were visualized by intravital staining with neutral red. Additionally, the ultrastructural studies were performed. The viability and ultrastructural results were compared with the pathologic process in the valve. Conclusions: 1. preliminary preparation with antibiotic sterilisation and cryopresrevation induces valve leaflet oedema and degenerative ultrastructural processes, colliquative cell necrosis and apoptotic morphology of a part of valve cells; 2. cryopreserved and antibiotic sterilised pulmonary valve after one-year implantation behaves lining cells, but ultrastructural changes indicates many degenerative phenomena in smaller degree than after preparation, sterilization and cryopreservation. Histopathologically the degenerative changes were prevalent

The use of first- and second-line outpatient antibiotics under the Saskatchewan Drug Plan.

The Saskatchewan Drug Plan proposed de-listing several second-line antibiotics from its formulary for reasons of potential overuse and expense. This study evaluated the use of second-line antibiotics as initial and secondary courses of therapy depending on the patient's prior use of other antibiotics and other factors. A total of 637,607 courses of therapy dispensed to Plan members for selected antibiotics between July 1989 and June 1990 were evaluated. Second-line antibiotics were used in 5.0% of all initial courses of therapy. This use was correlated with patient characteristics that may warrant use of second-line antibiotics as initial therapy: age, rural residence, the use of bronchodilators or inhaled steroids, and the number of prior courses of antibiotic therapy. The potential savings from de-listing second-line antibiotics from the formulary are limited because of their use in only 5% of all initial courses of therapy. Savings would be further reduced by administrative costs and physician time required to process prior authorisation requests, and the costs of treating any additional antibiotic treatment failures that may result from reduced access

The impact of fusafungine on the prescription of antibiotics in the treatment of rhinopharyngitis

OBJECTIVE: The analysis in France, during the period 01/12/99 to 30/11/2000, of the prescription of systemic antibiotics in patients with rhinopharyngitis and of the variables statistically related to such prescriptions and the potential role of fusafungine in the form of a rhinopharyngeal spray. METHODS: A retrospective study, based on a panel of 1,010 general practitioners, in a cohort of 30,568 patients presenting with rhinopharyngitis. The fusafungine group consisted of 16,076 patients who had rhinopharyngitis and in whom fusafungine was prescribed. The control group consisted of 14,492 patients with rhinopharyngitis without prescription of fusafungine. The overall rate of antibiotic prescription was documented. A stepwise statistical analysis was conducted to specify the variables statistically associated with the prescription of a systemic antibiotic. The rate of prescription of a systemic antibiotic and the cost of the treatment were also compared within both groups. RESULTS: The overall rate of systemic antibiotic prescription was 52.9%, falling from 60.4% in the group without fusafungine down to 46.2% in the group with fusafungine (p<0.01) whichever the systemic antibiotic prescribed. The stepwise analysis documented various variables that appear to be related to the systemic antibiotic prescription. A saving of 0.7 euros per prescription was noted in the fusafungine group. CONCLUSION: Although various variables appear to influence systemic antibiotic prescription in patients with rhinopharyngitis, our study shows that prescription of fusafungine in spray from led to statistically significant reduction in systemic antibiotic prescription

No association between Helicobacter pylori genotypes and antibiotic resistance phenotypes within families.

BACKGROUND: Triple therapy combining a proton pump inhibitor with two antibiotics, e.g. clarythromycin (CLR), metronidazole (MTZ) or amoxicillin (AMX), represents the standard in Helicobacter pylori eradication regimens. Resistance to antimicrobial agents, particularly MTZ (up to 56% in Western countries) and CLR (up to 15% in southern Europe), is frequently observed and may be associated with treatment failure [1]. Recently, several studies indicated that individual H. pylori colonies from a single anatomic site may not always yield identical genotypes, or the identical patterns of susceptibility to antibiotics [2-5]. Representative for every single patient we analyzed 27 H. pylori antrum isolates for susceptibility to antimicrobial agents in order to test whether identical H. pylori genotypes exhibit a similar pattern of susceptibility to antibiotics. METHODS: PCR, RELP, PFGE, antibiotic susceptibility testing. RESULTS: H. pylori genotype and antibiotic susceptibility pattern in families do not segregrate. CONCLUSION: Molecular typing of H. pylori from family members does not predict antibiotic susceptibility pattern