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Intravenous infusion of carbenicillin was followed by a determination of the concentration of this antibiotic in both the liquor and serum. The examinations, of which the results are reported in this paper, were made on six patients who had undergone surgical operations to the posterior cranial fossa and on whom lumbar punctures were postoperatively performed every day, as well as on seven hydrocephalic patients where a temporary relief of pressure was obtained by draining excess liquor. The level of carbenicillin in the liquor were found to enable even gram-negative problem germs (e.g., Proteus germs) to be controlled.

Bacterial diseases of the central nervous system develop per continuitatem of haematogenically. Each of these two groups can further be subdivided. As an initial therapy when an unknown agent is present chloramphenicol in high doses (200 mg/kg KM) stood the test for adults and older children and ampicillin (200 to 400 mg/kg KM), respectively, for babies and infants. In case of need, this therapy is correlated according to the findings of the culture and the antibiogramme. In secondary meningitides the surgical cure of the focus should be performed only after improvement of the general condition. Recidivating meningitides undergo an operation when liquor fistulae are proved. In an unclarified cause a long-term therapy with oxacillin or lincomycin over 3-6 months is possible. In the meningitis of newborn the combination of ampicillin, carbenicillin or colistin with gentamycin is necessary, intravenously and intrathecally. Hydrocortisone and streptokinase shall prevent the transfer of the liquor spaces. Of great importance is the combat against the cerebral oedema. In mycetogenous meningitis amphotericin B, eventually in combination with 5-fluorocytosine, can be used. There are still no effective remedies against the amoebic meningo-encephalitis.

Addition of antibiotics to bone cement is used more and more in orthopedics and traumatology. Indications are discussed: 1. infection prophylaxis in replacement arthroplasty, 2. therapy and recidive prophylaxis in infected arthroplasty, 3. therapy of chronic osteomyelitis. Our own experiments show release of antibiotics from bone cement Palacos and penetration into cortical bone after experimental osteomyelitis. Carbenicillin and Cephalotin show high level of concentration for 2 weeks, after 3 weeks there is no concentration evident. Lincomycin and Gentamycin in the first days show high tissue levels, after decrease and increase again after second week. Gentamycin was examined during 10 months showing high levels after this time.

After therapeutic doses of carbenicillin (3X10 g/24 h) prolongation of bleeding time, measured according to Ivy, was observed (median time prior to therapy 4 min 08 s-4 min 18 s; 24 h after therapy 15-20 min; 72 h after therapy greater than 30 min) in 5 patients with normal renal function and 2 patients with slight impairment of renal function (Ccr60-70 mlX1.73 m(2)). Prolongation of bleeding time was observed at serum concentrations between 13 and 180 microgram/carbenicillin/ml. After carbenicillin was withdrawn, prolongation of bleeding time was demonstrable for 4 days, i.v. even after the drug had been eliminated completely by urinary excretion. Higher doses of carbenicillin caused more severe disturbances of platelet function. The finding of prolonged bleeding time after carbenicillin may have clinical relevance (e.g. interaction with other anticoagulants, p.o. wound bleeding, gastro-intestinal hemorrhage, thrombopenia).

In investigations into the dosis-activity relationships of bactericidal antibiotics used against E. coli, K. pneumoniae and Staph. aureus four types of activity could be demonstrated. The penicillin type shows almost no improvement in bactericidal activity despite increasing the dosage above a certain level. An increase in concentration of aminoglycoside antibiotics led to a more rapid killing of the bacteria. In cefalotin there was a linear dosis-activity relationship: rising concentrations of antibiotics led to an ever increasing bactericidal effect. The paradoxical bactericidal effect ("Eagle effect'') described for penicillin G with enterococci could not be demonstrated.

In continuance of our investigations from 1968 to 1972, we isolated 32939 microorganisms from urinary tract infections and subjected them to routine sensitivity tests against six antibiotics from 1973 to August 1975. All organisms except enterococci and proteus proved to be sensitive to gentamicin at a level exceeding 90% during the study period of two and a half years. A loss of activity of gentamicin worth mentioning was not detected during the studies. So this antibiotic must further be considered as one of the drugs of first choice in the treatment of urinary tract infections.

Like in other operative disciplines also in orthopedic surgery we can see an icrease of infections with gramnegative bacterial like ps. pyocyanea. Gentamicin is in general very effective against these infections. There are following indications for the use of Gentamicin in orthopedic surgery: 1. Parenteral administration only is indicated if there is no other less toxic antibiotic. If it is used a high dosage is necessary because the bone levels which we investigated were very low. Side effects have to be observed. 2. For local therapy Gentamicin is used in the suction and perfusion system in addition to a systemic therapy with Penicillin, Ampicillin or Cephalosporin. Gentamicin can also be used for the wound perfusion. 3. Added to bone cement Gentamicin should only be taken, when an infected total hip is exchanged or if a hospitalism with ps. pyocyanea is known- The administration of Gentamicin is less indicated : 1. Asthe only antibiotic for parenteral therapy in bone infection. 2. Added to bone cement for a general prophylaxis in all endoprosthetic operations.

Of 60 patients who were suffering from bacterial infections, 30 were treated with mezlocillin and 30 with carbenicillin in a randomized study. The patients received the recommended daily doses of 16 g and 30 g, respectively. Clinical efficacy was found in all patients. Mezlocillin eliminated the strains more reliably than carbenicillin. The bacteriological success rate was 27/30 and 16/30, respectively. We should also take into account the fact that the six patients with cholecystitis who were treated with carbenicillin could not be controlled after treatment.

Bibliographic data on pathophysiology, therapeutic methods and mortality rate of burn disease are compared with own clinical experiences with a standardized therapy. Within a period of 18 month 35 patients with burn disease of special therapeutic problems were treated besides the overall number of patients in the operative intensive care unit of the Klinikum Steglitz. As special devices for patients with burns still do not exist provisional solutions had to be developed. It is referred to the close connexion between prognosis and mortality, on the one hand, and the age of the patients and the degree of burns, on the other hand. Whereas shock treatment, medicamentous therapy and nutrition are largely standardized, there are strongly differing opinions on local treatment and surgical wound care. The routine application of gammaglobulines, antibiotics and heparin controversial, too.

A report is given on the excretion of the renal enzymes alaninaminopeptidasis (AAP), N-acetyl-beta-D-glucosaminidasis (NAG), beta-glucoronidasis (GBC) and alpha-galactosidasis (GAC) in urine after administration of Gentamycin, Cephalotin, Dextran, Carbencillin or combinations of these medicaments. Moreover the effective level of Gentamycin in the urine was measured after isolated administration of Gentamycin. A rhythmic excretion of ciliated-border and lysomal enzymes was observed. Gentamycin was also rhythmically excreted with the urine. It is assumed that this reflects cyclic changes in the cells of the renal tubule. Under long-term administration of Gentamycin or Dextran the excretion of enzymes already reduced during therapy. This was interpreted as an adaptation of the kidney to the medicament. On the other hand there are combinations of medicaments whose effect on the epithelium of the renal tubule is potentiated.

The M.B.C.'s of gentamicin and carbenicillin against Pseudonomas aeruginosa NCTC 10490 were measured under controlled conditions using a Biophotometer. The M.B.C. of gentamicin was 15 mug/ml but even in a concentration of 1,000 mug/ml carbenicillin was not bactericidal. In further experiments, subinhibitory concentrations of gentamicin (1 mug/ml) together with varying concentrations of carbenicillin were added to a log phase culture of the organism. Under these conditions the M.B.C. of carbenicillin was now 6 mug/ml. In tube dilution test the M.B.C. of carbenicillin alone was 15.6 mug/ml and for gentamicin 3.9 mug/ml. The M.B.C.'s of other beta-lactam antibiotics (ampicillin, penicillin G and cephalothin) were four to five times as great as for carbenicillin whereas that for ticarcillin was identical. Parallel to the "multiplication inhibition" test in the Biophotometer we investigated 51 strains of Pseudomonas aeruginosa freshly isolated from clinical material. Their M.B.C.'s were determined in tube dilution tests against doubling dilutions of beta-lactam antibiotics, with and without the addition of 1 mug/ml gentamicin. With this concentration of gentamicin, the M.B.C.'s of carbenicillin and ticarcillin were considerably lower than for these substances alone. In comparison to carbenicillin, ticarcillin was more effective against Pseudomonas aeruginosa. Our findings indicate that for Pseudomonas aeruginosa infections the combination of gentamicin with other beta-lactam antibiotics (ampicillin, penicillin G and cephalothin) is to be avoided. But the combination of gentamicin with either carbenicillin or ticarcillin appeared to be effective.

Minimum inhibitory concentrations (MIC) for penicillin (PEN), ampicillin (AMP), cephalothin (CEF), cefazolin (CEZ), carbenicillin (CAR) and ticarcillin (TIC) were determined against Strep. faecalis, E. coli, K. pneumoniae, Prot. mirabilis and Ps. aeruginosa in Sensitivity Test Broth (STB) and human urine. Marked differences were seen in MIC between these two media, especially against P. mirabilis strains tested. Against E. coli the MIC of AMP, CEF and CEZ were similar or slightly lower in urine than in STB. MIC for CAR against E. coli were higher in urine. Against K. pneumoniae the MIC for CEF and CEZ were 2-4fold higher in urine than in STB. The activity of CAR and TIC against Ps. aeruginosa was lower in urine. Albeit high concentrations of antibiotics (up to 800fold) no inhibition was achieved in urine against P. mirabilis by AMP, CEF or CEZ. Only against Strep. faecalis all tested antibiotics had lower MIC in urine than in STB.

In urosepsis endotoxins usually deriving from gram-negative bacteria can initiate primary disturbances of hemostasis by activation of coagulation up to clinically manifest consumption coagulopathy. The reaction is triggered by an endotoxin induced alteration of granulocytes, endothelial cells, and platelets, thereby releasing procoagulant activities that possibly cause diffuse intravascular coagulation with impairment of vital organs. Additional negative effects on hemostasis can be caused by secondary hyperfibrino(geno)lysis. Secondary disturbances of hemostasis occur in urosepsis as a consequence of an impairment of liver (hypoproduction of coagulation factors, decrease of the clearance of activated coagulation factors) and kidney function (thrombocytopathy by uremic toxins). Disturbances of hemostasis induced by the treatment of urosepsis are the K-hypovitaminosis in parenteral feeding accompanied by antibiotics affecting the intestinal bacterial growth and the alteration of platelet function and fibrin formation by carbenicillin.

The disease occurs without exception in elderly diabetics. Pseudomonas aeruginosa (pyocyaneus) is always found in the secretion. In our reported case of a 71-year old man appeared in addition to a fetid, festering, granulating otitis externa, disturbances of swallowing, hoarseness and severe occipital headaches appear after five months. Neurologically, the N. glossopharyngeus, the N. recurrens and the N. hypoglossus were shown to be paretic. The inflammatory process has pushed forward via the bone of the auditory meatus on to the base of the skull to the jugular foramen and the foramen lacerum. Surgical removal of the inflammatory changes and subsequent treatment with carbenicillin is recommended as the treatment of choice.

Acute pancreatitis is discussed from the viewpoint of a medical intensive care unit, with particular reference to the early and late complications. The measures which must be promptly implemented in order to successfully combat the grave early complications of shock and acute renal failure are stressed. Continuous monitoring ensures that prompt surgical management is undertaken in cases of late complications-abscess formation, sequestration and sepsis. A review of the characteristic clinical and laboratory data of patients with acute pancreatitis treated in our unit is presented in table I.

A synopsis of the present classification of Vibrio fetus is given (tab. 1, 2). Besides the presentation of the importance of these bacteria in veterinary medicine, 97 human infections have been published up to now. The geographic, age and sex distribution of these cases and the material out of which the pathogens were isolated is presented (tab. 3, 4). The clinical picture is summarized. For the culture of Vibrio fetus liver broth as described by TAROZZI incubated for at least 3-4 days was suitable as enrichment medium. The necessity of a prolonged incubation period was shown by results of continous registration of the optical density of growing Vibrio fetus cultures (fig. 1). If specimen is plated out on solid culture media before enrichment, the suitable media are chocolate agar, brain-heart infusion and Bacto-tryptose agar. For subcultures the DST-agar is also useful. Solid media cultures should be incubated microaerobically with 10% CO2 added. The resistance to Cephalothin of Vibrio fetus can be applied for selection on solid culture media. The metabolic activities of different Vibrio fetus biotypes were compared. A hitherto not reported metabolic activity, the hydrolysis of palmitic acid ester, is described (tab. 5). In the tube dilution test Vibrio fetus strains were sensitive to Gentamycin, Streptomycin, Ampicillin, Ciclacillin and Carbenicillin. They were resistent to Penicillin G, Cephalotin and Sulfonamid and showed borderline sensitivities to Tetracyclin, Kanamycin and Chloramphenicol (tab. 6).

The impact of the antibiotics carbenicilin and gentamycin on the aggregation and adhesiveness of thrombocytes and on the rotation thrombelastogramme is investigated in healthy newborns. Thrombocyte aggregation was markedly inhibited by carbenicilline; gentamycine had no influence. Thrombocyte adhesiveness was less influenced by both medicaments. The parameters of TEG, viz. reaction time, clotforming time, thrombus elasticity and index were compared before and after rotation and with and without medicaments. Under carbenicilline a prolongation of the clotforming time and a decrease of thrombus elasticity could be shown to exist after rotation. The impact of medicaments on the rotation thrombelastogramme can only be conceived by comparing the values before and after rotation in each case with and without medicament and not simply evaluating it, so that the rotation thrombelastogramms cannot be recommended to be used for assessing the disturbance of thrombocyte function induced by medicaments.