[Clavulanic acid. Its effect on Staphylococcus aureus other than its inhibitory effect on beta-lactamases]. / L'acide clavulanique. Son effet sur le staphylocoque doré outre l'effet inhibiteur sur les bêtalactamases.

The influence of clavulanic acid (CA) on growth kinetics of Staph. aureus strains with MIC values (minimal inhibitory concentration) of penicillin (Pc) between 0,06 and 1 024 IU/ml was examined. Furthermore, it was tried to select mutants of the parent strains with increased resistance to CA and, in the affirmative case, to find out a relationship between Pc and CA resistance. The experiments showed that CA in subinhibitory concentrations induced a considerable increase of the latent phase of Pc sensitive strains but less of the Pc resistant ones. CA delayed also the generation time but this effect was apparently independent of Pc resistance. Successive subculturing of strains in gradually increasing CA concentrations resulted in an increase of CA resistance by a factor of 4 to 8 compared with that of the parent strains. In parallel, the Pc resistance increased by a factor of 16 to 64, however only in case of strains originally sensitive to Pc. A synergistic or additive effect of CA and Pc evaluated by the index of the fractional inhibitory concentration (IFIC) was not only shown in Pc resistant but also in Pc sensitive strains. This effect was equally demonstrable in strains with increased CA resistance. In this case, however, the MIC of Pc in the presence of CA was increased by a factor of 32 to 64 in originally Pc sensitive strains and by a factor of 2 to 4 in the originally Pc resistant ones. These results indicate a possible selection of CA resistant strains with an increased Pc resistance.

Amikacin concentrations in serum following intraoperative irrigation of the pleura and peritoneum.

Serum concentrations of amikacin following operative wound irrigation were studied in 17 patients having laporatomy and in eight patients having thoracotomy. Irrigation was done with 500 mg of amikacin in 200 ml of saline. The irrigant was reaspirated after 3 minutes. Measurement of amikacin in the irrigant allowed calculation of the retained dose. Serum levels were measured before surgery, and at 30 minutes, 60 minutes, 6 hours, and 12 hours following irrigation. Amikacin was assayed by a microbiological technique. The retained dose after peritoneal irrigation was 350 +/- 128 mg, and after pleural irrigation was 100 +/- 79 mg. The average maximum serum level in the peritoneal irrigation group was 9.4 +/- 6.7 gm/ml; in the thoracotomy group it was 3.5 +/- 1.7. Fourteen of the 17 laparotomy patients but only one of the eight thoracotomy patients had measurable plasma levels at 6 hours. Plasma half-life in the laparotomy group was 2.81 +/- 1.34 hours, and in the thoracotomy group 1.53 +/- 0.83 hours. Interoperative amikacin irrigation, even with immediate aspiration, results in significant absorption in both thoracotomy and laporatomy patients. There was less absorption and a shorter serum half-life in the thoracotomy patients.