After infusion of 2 g ampicillin and 1 g sulbactam the concentrations of these two beta-lactams were determined in serum and various compartments of the respiratory tract of 22 patients. About 30 min after the end of the infusion in 15 patients the mean serum concentration of ampicillin was 97 +/- 9.5 mg/l and of sulbactam 37.6 +/- 3.8 mg/l; in the biopsy samples of bronchial mucosa the concentration of ampicillin was 38.6 +/- 7.2 mg/kg and of sulbactam 28.1 +/- 5.2 mg/kg; in bronchial fluid the concentration of ampicillin was 0.6 +/- 0.1 mg/l and of sulbactam 0.3 +/- 0.1 mg/l (n = 15). In a further seven patients serum and pleural empyema samples were analysed and compared. The mean values of Cmax attained 1 to 2 h after the end of the infusion in pleural empyema were 7.6 +/- 3.1 mg/l and 6.2 +/- 1.6 mg/l for ampicillin and sulbactam, respectively. The two beta-lactams were eliminated markedly more slowly from empyema than from serum. These results show that ampicillin and sulbactam rapidly penetrate into various compartments of the respiratory tract and reach therapeutically active concentrations. The ratio of their concentrations (2:1) is largely the same as that in serum. The pharmacokinetic data therefore support the use of ampicillin/sulbactam in the perioperative prophylaxis and the treatment of bacterial infections of the lower respiratory tract.

The question of whether ampicillin and sulbactam are able to penetrate sufficiently into costal cartilage tissue was investigated in 21 children undergoing surgery for funnel chest malformations. The concentrations of both compounds were determined in the core and mantle pieces of samples taken 45 min or 120 min after infusion of ampicillin/sulbactam (33.3/16.7 mg/kg bodyweight) preoperatively for antibiotic prophylaxis. Ampicillin was determined by bioassay and sulbactam was determined by gas-chromatography/mass spectrometry. Mean concentrations of ampicillin were 23.3 mg/kg and 10.4 mg/kg at 45 min and at 27.4 mg/kg and 7.8 mg/kg 120 min in the mantle and core piece, respectively. Mean concentrations of sulbactam were at the same time 21.3 mg/kg and 9.7 mg/kg and 17.5 mg/kg and 11.9 mg/kg, respectively. These values indicate that both compounds achieve high concentrations even in bradytrophic tissue such as cartilage. The concentrations exceed the MIC values of important bacterial pathogens involved in postoperative wound infections. Therefore ampicillin protected by sulbactam appears to be a well-suited agent for perioperative prophylaxis in thoracic surgery.

The pharmacokinetics of ampicillin and sulbactam, a new I-lactamase inhibitor, were investipted in 16 patients undergoing prosthetic cardiac valve insertion. The combination of 2 g of ampidilIn and g of sulbactam was administered as perioperative prophylaxis intravenously over 3 to 6 days. Several serum pharmacokinetic parameters were similar for the two drugs after three intravenous doses were given to p1itents following surgery. The half-lives of eliminatonof ampicillinand sulbactam were 79 4.9 and 88 5.9 min, the volumes of distribution were 15.6 1.4 and 17.7 1.2 liters/70 kg, and the total plasma clearances were 144.4 t 14.5 and 147.2 14.5 m/min, respectively. The peak concentrations of ampiciln and sulbactan in serum were calculated to be 134.3 t 1.3 and 58.3 ± 1.2 pg/ml, respectively. Ampicillin and sulbam rapidly penetrated from the blood into various tissues collected durng heart surgery, such as sternum, pericardium, myocardium, and endocardinm. The concentrations of ampicillin in tissue ranged from 17.8 4 9.9 to 50 *±29.5 ,ug/g, and those of sulbactam in tissue ranged from 8.8 6.2 to 19.6 ± 10.1 gLg/g. The concentrations of ampicillin and sulbactam in serum and tissue also apparently exceded the MICs gainst most B-lactamaseproducing-bacteria usually involved in-postoperative wound infections and prosthetic valve endocarditis. The ratio of the two compounds was approximately 2:1 in serum and in the various tissues affected by the operation. The pharmacokinetics of ampicillin and sulbactam in serum and investigated tissues sugest that the combination of the two ,B-lactams will be effective in the perioperative prophylaxis of patients undergoing heart surgery.Experience in cardiac surgery has demonstrated that such surgery carries a significant risk of infection when antibiotics are not administered perioperatively. Infection of sternal wounds, endocarditis, pneumonia, and bacteremia can all occur postoperatively (4). Prophylaxis with antibiotics, usually of the ,B-lactam group, is therefore almost routine, and this is also the case with the implantation of prosthetic heart valves (2). It has been demonstrated that the efficacy of ampicillin is markedly improved by the addition of sulbactam, a new semisynthetic 3-lactamase inhibitor, and this combination seems particularly indicated for use in perioperative prophylaxis in cardiac surgery, because of its-favorable tolerance and antibacterial spectrum.We have therefore evaluated the pharmacokinetics of ampicillin and sulbactam during the perioperative period in patients undergoing heart surgery. MATERIALS AND METHODSPatients. Sixteen subjects (seven female and nine male) undergoing heart surgery, mainly insertion of prothetic heart valves, were included in the study after informed written consent had been given.

A 45-year-old man with end-stage renal disease underwent a cadaveric kidney transplantation. The allograft had to he removed 10 days after transplantation because of an acute vascular rejection. After explantation, the patient suffered from a life-threatening infection with Staphylococcus epidermidis involving lungs, eyes and liver for 11 months. Despite adequate therapy including vancomycin followed by teicoplanin, he developed spondylodiscitis requiring repeated surgical interventions. The definitive cure was achieved by a sequential therapy with chloramphenicol and quinupristin/dalfopristin.

No abstract