[Tissue diffusion of amoxicillin-clavulanic acid for antibiotic prophylaxis in colorectal surgery]. / Diffusion tissulaire de l'amoxicilline-acide clavulanique pour une antibioprophylaxie en chirurgie colorectale.

Tissue penetration of amoxicillin and clavulanic acid given for antibiotic prophylaxis was studied in 15 patients. On induction of anesthesia patients were given 2 g amoxicillin and 200 mg clavulanic acid. The same dose was given two hours later. At time of surgical incision amoxicillin and clavulanate levels were 15.9 +/- 7.7 micrograms/g and 2.23 +/- 2.69 micrograms/g in abdominal wall fat and 16.6 +/- 10.5 and 1.72 +/- 1.35 micrograms/g in epiploic fat, respectively. Similar levels were measured at time of closure of the abdomen. In colonic wall, amoxicillin et clavulanate levels were 22.7 +/- 13.4 micrograms/g and 2.65 +/- 2.35 micrograms/g. By comparison with blood levels, tissue penetration of both drugs was 20 to 30 p. cent into fatty tissues and 60 to 70 p. cent into colonic wall.

[Pharmacokinetics and tissue penetration of single-dose netilmicin used for antibiotic prophylaxis during colo-rectal surgery]. / Pharmacocinétique et diffusion tissulaire de la nétilmicine utilisée en dose unique pour l'antibioprophylaxie en chirurgie colo-rectale.

Pharmacokinetics and tissue penetration of netilmicin were studied after the use of a single dose (6 mg/kg) given for antibioprophylaxis in colo-rectal surgery. Thirteen patients, scheduled for elective surgery, were given 6 mg/kg IV netilmicin over 30 min, together with 1000 mg IV ornidazole. Netilmicin peak serum concentration (10 min after end of infusion) was 24.4 +/- 3.4 mg/l and trough level (24 h) was 0.9 +/- 0.5 mg/l. Plasma elimination half-life was 409 +/- 70 min, le volume apparent volume of distribution was 38 +/- 101 and total body clearance was 0.07 +/- 0.02 ml/min. Adequate netilmicin levels (5 greater than or equal to CMI 90 of involved pathogens Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus) were obtained in 100 per cent of patients in abdominal wall and epiploid fat, at time of opening, and in colonic wall at time of anastomosis. Adequate levels were obtained at time of closure in abdominal wall and epiploid fat in 92 to 100 per cent of patients. In situation of allergy to beta-lactam antibiotics, the use of netilmicin in combination with ornidazole may be recommended.

[Drug-induced agranulocytosis. Discussion of the responsibility of metronidazole]. / Agranulocytose d'origine médicamenteuse. Discussion de la responsabilité du métronidazole.

A case of severe agranulocytosis is reported in a 43 year old white male with Guillain-Barré syndrome. This patient was treated for an acute aspiration pneumonia and received several antibiotic regimens. An acute agranulocytosis occurred during the stay in the intensive care unit and was followed by a severe septic shock. Bone marrow aplasia was confirmed by needle aspiration. Metronidazole was withdrawn and agranulocytosis improved within three days. None of the other drugs given to the patient were withdrawn. Another bone marrow examination performed several days later revealed a markedly improved granulopoiesis. The patient died with multiple organ failure. The role of metronidazole is discussed in this case as this drug seemed highly responsible for the observed agranulocytosis.