Biomedical subjects
Publications and source records attributed to H Wahlig.
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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.
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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.
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.
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.
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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.
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.
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.
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.
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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.
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.