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The assay described is an agar diffusion test using Bacillus stearothermophilus as test organism. Incubation is at 62° C; results can be obtained rapidly within 2 to 3 hours. The test was developed for the determination of gentamicin concentrations in serum and other body fluids. Because of its high sensitivity the test strain is also suitable for the determination of other antibiotics. The test is designed primarily for the determination of concentrations in individual samples and thus for monitoring during therapy. The ease with which the test can be carried out is thus an important feature of it. On comparison with a standard method (agar diffusion test) using both serum samples from patients and samples with known gentamicin concentrations a highly significant correlation (r=0.95) was seen between the two methods.

Bone cement, used to fix prostheses into the bone, must be sterilized prior to implantation. Two sterilization techniques, gamma and beta radiation, were investigated, examining the influence upon molecular weight, static and dynamic mechanical characteristics and rheological properties. A number of experimental cements were studied prepared from methylmethacrylate (MMA) co-polymers, either single powders or powder blends, mixed with MMA monomer. It was found that with both gamma and beta radiation, there was a decrease in molecular weight of all powders, including a MMA/styrene co-polymer, in relation to the radiation dose. This fall in molecular weight resulted in a drop in tensile strength, Young's modulus and strain to failure of all cements tested. However, the deterioration in mechanical strength was highlighted by the dynamic testing. Fatigue lives of cements after testing in tension-tension, at 2 Hz under load control and irradiated with 25 kGy gamma radiation, displayed significant decreases. This result indicated the utmost importance of conducting such tests upon experimental bone cements prior to in vivo use. The rheological time profiles of curing cements were also found to be influenced by 25 kGy gamma radiation, with a reduction of complex viscosity after sterilization.

Nach einmaliger intramuskularer Applikation von 80 mg (41 Patienten) oder 120 mg Gentamicin (23 Patienten) kommt es, nach Ausscheidung der Hauptmenge des Antibiotikums in den ersten 24 Stunden nach Injektion, dosisabhangig zu einer viele Tage anhaltenden Urinausscheidung niedriger Wirkstoffkonzentrationen. So konnte nach Gabe von 120 mg bei 2 Patienten noch nach 20 Tagen Gentamicin im Harn nachgewiesen werden. Die Serumkonzentrationen lagen 1 Stunde nach Injektion von 120 mg im Maximum bei 8,2 µg/ml, im Mittel bei 5,76 µg/ml. Die Halbwertzeit betrug 2 Stunden. Wie Tierversuche und die Untersuchung menschlicher Gewebeproben beweisen, wird Gentamicin praktisch ausschlieslich in der Niere, vorzugsweise im Rindenparenchym, gespeichert.

A randomised, double-blind study was performed in two groups of 15 patients undergoing total hip replacements, using antibiotic-loaded acrylic cement containing 0.5 g and 1.0 g gentamicin base respectively per 40 g pack of powdered polymer. Postoperatively, the gentamicin levels in the blood, in the urine and in the wound drainage fluid were measured. In both groups of patients, the serum gentamicin concentrations were low whereas the wound drainage fluid contained highly effective antibacterial concentrations. Serum, urine and wound secretion levels showed approximately two-fold higher concentrations in the group of patients receiving the higher gentamicin load.

Die Zusammenhange zwischen Properdin-System und Antikorperbildung wurden an Kaninchen im Verlaufe von Immunisierungsprozessen untersucht. Dabei wurden die Veranderungen des Serum-Properdin-Spiegels mit Hilfe einer von McNall (1957) angegebenen, in einigen Punkten modifizierten properdin-Nachweismethode verfolgt, und gleichzeitig spezifische Antikorperbestimmungen und papierelektrophoretische Analysen der Immunsera durchgefuhrt. 1. Wahrend des Immunisierungsprozesses kommt es zu einer deutlichen, kurz andauernden Zunahme des Serum-Properdin-Gehaltes. Nach einem zweiten, geringeren Anstieg nahern sich die Properdin-Werte den Ausgangsgrosen. 2. Die Antikorperbildung setzt sofort nach Immunisierungsbeginn ein, und die Titer der Immunsera steigen wahrend langerer Zeit mehr oder weniger stark an. 3. Im Verlaufe der Immunisierung kommt es nach charakteristischen Veranderungen aller Serumproteinkomponenten zu einem fur die Antikorperbildung typischen γ-Globulin-Anstieg. Die Proteinvermehrung im γ-Globulin ist papierelektrophoretisch erst spater nachweisbar als die im Hamagglutinationstest erfasbare Antikorperbildung. 4. Die zur Immunisierung verwendeten Tuberkelbakterien verbinden sich, ahnlich wie das Zymosan, in vitro mit dem Properdin normaler Kaninchensera. Der Keim-Properdin-Komplex hat wie der Zymosan-Properdin-Komplex die Eigenschaft, Komplement zu inaktivieren.

Minimum inhibitory concentrations (MIC) of (6R,7R)-7-(2-[3,5-dichloro-4-oxo-1(4H)-pyridyl-a1-acetamido)-3-([(5-methyl-1,3,4-thiadiazol-2-yl)-thio]methyl)-8-oxo-5-thia-1-azabicyclo[4,2,0]oct-2-ene-2-carboxylic acid (cefazedone, Refosporen)), a new semisynthetic cephalosporin derivative were determined by a broth dilution technique. In comparison with cefazolin 130 gram-positive and gram-negative bacteria, recent clinical isolates, were tested. In parallel, inhibition zones for the same organisms were determined by a standardized disc technique using 30-micrograms discs. According to the calculated regression lines a good correlation was found for cefazedone and cefazolin between the MIC values and the diameters of the inhibition zones (correlation coefficients r = --0.90 and --0.92, respectively). Taking into account the dosages recommended for cefazedone and the mean serum concentrations to which they give rise, appropriate categories of sensitivity (break points) for susceptibility testing are recommended.

Authors describe a new method of treatment for bone and soft tissue infections using polymethyl methacrylate balls containing Gentamycin. Advantages of this method can be summarized in 3 points: 1. From the patients point of view saving the rinsing-sucking drainage, early mobilisation etc. 2. From nursing point of view a significant facilitation of the patient's care. 3. From the hospital management's point of view: improved hygienic conditions by eliminating the possible infections related to a rinsing-sucking wet system. Cutting down hospital expences both by abbreviation of the time of hospitalization and saving on expensive antibiotics.

Das von Buchholz u. Engelbrecht [2] vor uber 15 Jahren entwickelte Konzept der Beladung von Knochenzementen mit Antibiotika fur den praventiven und therapeutischen Einsatz bei totalen Huftendoprothesenoperationen eroffnete eine neue Dimension fur die antibakterielle Therapie bei schwer erreichbaren Infekt-lokalisationen. Ganz im Sinne des bis dahin fast vollig vergessenen Postulats von Paul Ehrlich (1909) nach einer gezielten Therapie, stand die Buchholzsche Idee am Anfang einer bedeutsamen Entwicklung lokaler Therapieformen unter Verwendung besonderer Trager-Wirkstoff-Kombinationen.

Comparing several antibiotics and different bone cements, the mixture of Palacos R (polymethylmethacrylate, PMMA) with gentamicin proved to be the most suitable one as far as a high and sustained release of the antibiotic from the artificial resin is concerned. A continuous leaching of gentamicin was observed for more than 5 years. Gentamicin proved to be stable in Palacos R for the whole period of time. The release of 12 antibiotics from Palacos R was evaluated in vitro. Four other bone cements were included in this study as well, in order to evaluate the leaching of gentamicin from these materials. The combination Gentamicin-Palacos R (GP) showed a 2--3 fold higher and much more prolonged release than did the other mixtures. From this investigation, which also included studies of commercially available antibiotic bone cement mixtures, it is quite obvious that there exist distinct differences in the various bone cements as well as in the various antibiotics as regards their qualification for use in alloarthroplasty. Pharmacokinetic studies in patients after implantation of GP showed low gentamicin concentrations in serum (on average 1.8 microgram/ml) and urine. However, in wound exudate, derived directly from the vicinity of the implanted cement, gentamicin concentrations up to 150 micrograms/ml were observed. Also in tissue samples from the vicinity of the implant, high concentrations were measurable for a long period of time (up to 5 1/2 years).

Applying a single i.m. dose of 80 mg (41 patients) and 120 mg (23 patients) of gentamicin, respectively, investigations in females have shown that, although the bulk of the antibiotic is excreted with the urine within the first 24 hours after injection, slow excretion is maintained at a very low level. According to the dose administered gentamicin remains detectable in the urine for many days. Thus, after injection of 120 mg in two patients gentamicin was detectable in the urine for a period of up to 20 days. Peak serum levels one hour after i.m. injection of 120 mg did not exceed 8.2 mug/ml, the mean concentration was 5.76 mug/ml. Serum half life was 2 hours. Studies of distribution in animal and human tissues have shown that gentamicin is accumulated almost exclusively in the kidneys, mainly in the cortex.

In mice, dogs, and rabbits blood and serum levels were evaluated after parenteral application of (6R,7R)-7-(2-[3,5-dichloro-4-oxo-1(4H)-pyridyl]acetamido)-3-([(5-methyl-1,3,4-thiadiazol-2-yl)-thio]methyl)-8-oxo-5-thia-1-aza-bicyclo[4,2,0]oct-2-ene-2-carboxylic acid (cefazedone, Refosporen), cephalothin and cefazolin. In all three animal species cefazedone produced higher and more prolonged serum levels than did cefazolin. Evaluation of serum protein binding in mouse, dog and rabbit serum revealed marked differences between the species. Cefazedone and cefazolin tissue concentrations were evaluated in rabbits. Both antibiotics did not penetrate the CSF or brain tissue. In all other tissues examined (except bone marrow) higher and more prolonged tissue levels were attained with cefazedone than with cefazolin.

Micrococcin M, micrococcin M1 and eight micrococcin M derivatives, and two peptide antibiotics produced by micrococci and staphylococci were investigated for their antibacterial activity and therapeutic value. These antibiotics appeared to act solely on Gram-positive bacteria, especially on staphylococci and streptococci, in quite low concentrations in vitro and exerting both bacteriostatic and bactericidal effects. Gram-negative bacteria were virtually not susceptible. Resistance to micrococcins developed very rapidly, due to existence of numerous primarily resistant cells in sensitive populations. Complete cross-resistance resulted from acquiring resistance to one of the micrococcin antibiotics. Therapeutic effects are poor, as micrococcins are not absorbed from the injection site or from the intestinal tract after peroral administration. Importance of micrococcins in nature may be high, especially when ecology of normal bacterial flora and carriage of staphylococci and streptococci are concerned.

Operations of long duration, organ-transplants, and those where heterogenic material is implanted, all entail a particularly high risk of infection and consequent severe complications. The prophylactic use of antibiotics is therefore indicated in these situations.

Gentamicin incorporated in beads of polymethylmethacrylate has been shown capable of being released over a period of several months in concentrations sufficiently high to control most pathogens. The therapeutic efficacy of such beads has been demonstrated in a model of osteomyelitis of the femur in the dog. Good tolerance has been shown, both in the animal model and in tissue cultures. In forty-one patients with infection of either bone or soft tissue, mainly of the lower limb, the findings were similar. The concentrations in serum and urine were low, which excludes side-effects. The insertion of gentamicin-PMMA beads may prove to be a valuable new form of local antibiotic therapy.

Gentamicin PMMA beads (PMMA = polymethylmethacrylate) represent a new form of local antibiotic therapy for treating chronic bone and soft tissue infections. Gentamicin is released in high concentrations from PMMA. The therapeutic efficacy of the beads was demonstrated in a model of bone infection in dogs. Sufficiently high tissue concentrations of gentamicin were measurable for a period of 4 months. A very good tolerance of the beads was demonstrated in dogs as well as in cell cultures. High gentamicin concentrations exceeding the MBC values of relevant pathogens were measurable in patients at the site of infection. Serum and urine concentrations were low and therefore toxic side effects are excluded.

The assay described is an agar diffusion test using Bacillus stearothermophilus as test organism. Incubation is at 62 degrees C; results can be obtained rapidly within 2 to 3 hours. The test was developed for the determination of gentamicin concentrations in serum and other body fluids. Because of its high sensitivity the test strain is also suitable for the determination of other antibiotics. The test is designed primarily for the determination of concentrations in individual samples and thus for monitoring during therapy. The ease with which the test can be carried out is thus an important feature of it. On comparison with a standard method (agar diffusion test) using both serum samples from patients and samples with known gentamicin concentrations a highly significant correlation (r = 0.95) was seen between the two methods.

Spontaneous osteosarcoma is a comparatively common tumor in the long bones of large dogs. The morphological and biological characteristics are similar to those of human osteosarcoma. In six dogs, the primary bone tumor was deliberately excised marginally or intralesionally and the osseous defect was refilled with bone cement containing 125, 250, and 375 mg methotrexate (MTX). Systemic adverse reactions were mild, not dose-dependent, and inconstant but always reversible with low doses of citrovorum factor. The serum concentrations did not exceed 2 × 10-7 mol/1 on the 1st day and then decreased continuously. Local tumor recurrence occurred with 1–6 months postoperatively. The histological evaluation showed total cell necrosis surrounding the MTX cement plug, up to 10.8 mm across dependent on the MTX dose, and a varying area of partial necrosis more peripherally. MTX had no effect on the articular cartilage.

Radical surgery in malignant bone tumors can either be limited by anatomical structures or seems inadequate in the palliative stabilization of bone metastases. Incomplete removal of the tumor and stabilization by compound osteosynthesis or endoprosthesis contains two problems: 1) the wide spread of malignant cells by manipulation in the tumor bearing area; 2) progressive destruction of bone due to remaining tumor. To overcome these problems we developed methotrexate bone cement (MTX-Palacos) with the aim to obtain high local concentrations of methotrexate in order to destroy remaining tumor cells and avoid systemic side effects. In vitro studies showed that methotrexate is released continuously from this cement without relevant changes of its biomechanical properties. Animal studies with transplanted osteosarcomas and mamma carcinomas in mice showed a considerable decrease of tumor growth when a plug of MTX-Palacos was inserted in the center of the tumor. Histological findings showed that in the surroundings of the plug the tumor was destroyed considerably contrary to normal bone cement which had no effect on the tumor at all. The results are discussed with regard to clinical application of MTX-Palacos.

The chemotherapeutic efficacy of (6R,7R)-7-(2-[3,5-dichloro-4-oxo-1(4H)-pyridyl]-acetamido)-3-([(5-methyl-1,3,4-thiadiazol-2-yl)-thio)-8-oxo-5-thia-1-azabicyclo[4,2,0]oct-2-ene-2-carboxylic acid (cefazedone, Refosporen) was assayed in comparison to cefazolin and cephalothin in experimental bacterial murine infections with 6 gram-positive and 8 gram-negative strains of the genera Staphylococcus, Streptococcus, Pneumococcus, Escherichia, Klebsiella, Proteus, Pasteurella and Salmonella. In 5 out of 14 strains (Staphylococci, Streptococci, E. coli, Klebsiella) cefazedone was markedly superior to cefazolin, whereas both compounds were of similar activity against the remaining 9 isolates. As compared to cephalothin, cefazedone exhibited highly superior effectiveness in all organisms tested.

The indecation and the efficacy of antibiotic prophylaxis in endoprosthetic operations are discussed with reference to prospective studies. After parenteral administration of 80 mg gentamicin the antibiotic concentrations in the serum and in the wound exudate were studied for 2 to 6 hrs after administration. During this observation period the gentamicin concentrations in the wound exudate were about equal to those in the serum. A comparison of the concentrations after parenteral and after local administration of gentamicin showed much higher concentrations in the wound exudate when gentamicin was administered with the bone cement.