[Frequency of severe abdominal wall hemorrhage with subcutaneous anticoagulation using calcium-heparin]. / Häufung schwerer Bauchwandblutungen unter subkutaner Antikoagulation mit Calcium-Heparin.

Four cases of severe bleeding among 50 elderly patients undergoing subcutaneous calcium heparin treatment are reported. In three patients the bleeding was localized in the abdominal wall and the fourth in the retroperitoneum; 2 patients died. Heparin doses ranged between 2x12,500 and 2x20,000 I.U/day. The thrombin times, measured before the next administration, were in the subtherapeutic range in all patients. We conclude that in elderly patients subcutaneous heparin treatment in therapeutic doses should be reserved for exceptional cases.

[Bolus injection, short infusion or intravenous drip of aminoglycoside antibiotics? In vivo study with netilmicin and Pseudomonas aeruginosa]. / Bolusinjektion, Kurzinfusion oder Dauer-infusion von Aminoglykosid-Antibiotika? In-vivo-Studie mit Netilmicin und Pseudomonas aeruginosa.

The efficacy of various dosage schedules of netilmicin against Pseudomonas aeruginosa has been compared using an in vivo model (normal and granulocytopenic mice). Bolus injections were at least as effective as simulated short infusions or simulated continuous infusions of identical total amounts of netilmicin.

Antibiotic therapy of infections due to Pseudomonas aeruginosa in normal and granulocytopenic mice: comparison of murine and human pharmacokinetics.

An effort was made to elucidate the limits of drug-activity tests in small animals. Human plasma kinetics of gentamicin, netilmicin, ticarcillin, ceftazidime, and ceftriaxone were approximated in normal and in granulocytopenic mice infected with various strains of Pseudomonas aeruginosa in the thigh muscle or intraperitoneally. The effect of such dosing on bacterial time-kill curves and on survival was compared with the effect of identical amounts of drug given as a single-bolus injection. With beta-lactams, a highly significant superiority of fractionated dosing (simulated human kinetics) over bolus injections (murine plasma kinetics) was demonstrated, whereas with aminoglycosides it was a single-bolus injection that tended to be more active. Thus, when tested in conventional small-animal models, aminoglycoside activity may be overestimated, whereas beta-lactam activity may be underestimated in respect to humans. These differences found in vivo most probably reflect the different pharmacodynamics between aminoglycosides and beta-lactam drugs (time-kill curves, dose-response curves, and postantibiotic effect) similar to those previously observed in vitro.

Impact of dosing intervals on activity of gentamicin and ticarcillin against Pseudomonas aeruginosa in granulocytopenic mice.

The influence of dosing intervals on the activity of gentamicin and ticarcillin against Pseudomonas aeruginosa was studied in vivo. Granulocytopenic mice infected with P. aeruginosa in the thigh muscle were treated with 1-hr or 3-hr injections of gentamicin, ticarcillin, or gentamicin-ticarcillin. Plasma pharmacokinetics of the drugs were correlated with antibacterial activity. Gentamicin injected every 1 hr tended to be less active than gentamicin injected at longer intervals. In contrast, ticarcillin given every 1 hr was significantly more efficacious than equivalent total doses injected every 3 hr. The dosing schedule of gentamicin-ticarcillin was again important for ticarcillin but did not appreciably affect the antibacterial activity of gentamicin. Thus, antimicrobial chemotherapy of P. aeruginosa infections in the granulocytopenic host might be improved by administering ticarcillin rather than gentamicin as a constant infusion.