Cefamandole Bone Diffusion in Patients Undergoing Total Hip Replacement

The pharmacokinetics and tissue penetration of ceftiaxone after a single intravenous injection of 1,000 mg to 17 patients for antibiotic prophylaxis in thoracic surgery were studied. The patients were scheduled for elective noncardiac thoracic surgery. Adequate levels in serum (higher than Noncardiac thoracic surgery is "contaminated-aseptic surgery" in most cases (4,6,7,11). Antibiotic prophylaxis is used against pathogens most likely to contaminate the surgical wound: Escherichia coli, various members of the family Enterobacteriaceae, Streptococcus spp., Haemophilus influenzae, Staphylococcus aureus, and Pseudomonas spp. (4,6,7,11 Ceftriaxone concentrations were determined by high-performance liquid chromatography (HPLC) (19), with a normal-phase technique and an NH-bonded-phase column (Spherisorb C18 Waters; 100 mm; 5-pm internal diameter).The mobile phase was a combination of acetonitrile (50 ml)

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics and tissue penetration of a single dose of ceftriaxone (1,000 milligrams intravenously) for antibiotic prophylaxis in thoracic surgery

Martin

Ragni

Lokiec

et al. 1992

“…Aztreonam concentrations in cancellous bone (mean, 20% of that in concomitant serum) are similar to those of moxalactam (18%) (21), cefazolin (18%) (21), cefadroxil (23%) (23), cephalothin (5 to 33%) (7,9,26), cefamandole (5 to 20%) (18,24,26), cefuroxime (10 to 70%) (7), clindamycin (10 to 50%) (1,28), ceftazidime (54%) (1), and amoxicillin (16.4%) (2). However, the ranges for all these antibiotics were very wide (25,28), with some specimens showing no detectable concentrations.…”

mentioning

confidence: 64%

“…In general, single-dose (versus multiple-dose) studies (8,21) and studies that corrected for blood contamination (1,21,24) detected lower penetration values. In dogs, cefazolin, penicillin, and cefamandole in serum rapidly equilibrate with the interstitial fluid of bone (5,11,16).…”

mentioning

confidence: 97%

Aztreonam penetration into synovial fluid and bone

MacLeod¹,

Bartley²,

Jo³

et al. 1986

Eighteen patients with uncomplicated degenerative joint disease requiring joint replacement (hip or knee) were given a single 2-g intravenous dose of aztreonam over a 5-min period preoperatively. The mean concentration in synovial fluid of 83.0 9.2 >g/ml averaged 0.99 times the concomitant levels in serum. The mean concentration in cancellous bone of 16.0 4.3 Lg/g averaged 0.20 times the concomitant levels in serum.The increasing incidence of gram-negative bone and joint infections (14,19), particularly in patients with underlying diseases (13), combined with a higher incidence of poor therapeutic outcome in patients with such infections treated with available antimicrobial agents (10,29) (17), except that the samples were pulverized with a Spex freezer-mill prior to assay. The limit of detection of the assay was 0.1 ,ug/g of bone. The coefficient of variation and mean recovery from standards were 8.0 and 79.0%, respectively.Bone samples were prepared for high-pressure liquid chromatography by a procedure identical to that used for the bioassay and then filtered (Millex; 0.45 pum [pore size]; Millipore Corp., Bedford, Mass.). They were then analyzed with a high-pressure liquid chromatography system consisting of an Altex model 11OA pump set for 2 ml/min, a 37-to 50-,um silica gel precolumn, a 30-to 38-,um C18 guard column, a Waters Associates, Inc., 10-,um ,Bondpak analytical column (150 by 3.9 mm), and a UV detector set for 290 nm. The mobile phase was 85 parts 5 mM tetrabutylammonium sulfate, adjusted to pH 2.85 with 1 M KH2PO4, and 15 parts acetonitrile. Samples were introduced via a 20-,u precision loop injector. The limit of detection was 1 ,ug/g, the coefficient of variation was 8.1%, and the mean recovery from standards was 87.0%.The method used for microbiological assay of synovial fluid was identical to that previously reported for urine (20), except that samples were diluted 1:20 in 0.1 M phosphate buffer (pH 6) prior to assay. The limit of detection was 0.4 ,g/ml. The coefficient of variation and mean recovery were 3.5 and 98%, respectively. The high-pressure liquid chromatographic assay of synovial fluid was done by a method identical to that previously reported for serum (20). The limit of detection was 0.5 ,ug/ml. The coefficient of variation and recovery from standards were 8.5 and 98%, respectively.Assays of hemoglobin in blood, bone, and synovial fluid and correction of aztreonam concentrations for blood contamination were performed by previously described methods (17). Samples whose blood contents were 51% or more were excluded from analysis. No specimens suitable for assay could be obtained from patient 6.Results of the aztreonam assays are listed in Table 1. The mean concentration in serum at the time of bone and synovial fluid removal was 78 ,ug/ml. The mean concentration in bone was 16 ,ug/g. Concentrations of aztreonam in individual bone specimens were variable but showed a 710

“…The interference of blood contamination was evaluated by measuring the hemoglobin concentration in the cortical and medullary tissue suspensions. Corrections of the antibiotic concentrations measured in tissue, expressed as the percentage of the simultaneous level in serum, were done by using the formula of Roncoroni et al (14). The supernatant was passed through a microconcentrator (Amicon; Millipore).…”

Section: Methodsmentioning

confidence: 99%

Cefixime penetration in human renal parenchyma

Leroy

Oser

et al. 1995

The diffusion of cefixime, a new orally active expanded-spectrum cephalosporin, was studied in 12 patients undergoing nephrectomy after receiving 200-mg oral doses every 12 h for 2 days. The patients were divided into two groups according to the time of perioperative sampling after the last dose: 4 h (group 1) and 12 h (group 2). Preoperative blood samples were taken just before administration of the last dose of cefixime. Simultaneous blood and tissue samples were collected perioperatively at 4 h (time to peak level) and 12 h (residual level). The intrarenal concentrations of cefixime were measured by an isocratic reversed-phase high-pressure liquid chromatographic (HPLC) assay. Concentrations in serum were determined by both microbiological and HPLC assays. The mean peak levels in serum were 3.41 ؎ 0.43 g/ml (group 1), and the residual levels averaged 1.54 ؎ 1.17 g/ml (group 2). The diffusion in renal parenchyma was not significantly different in the cortexes and medullas of both groups of patients: 5.7 to 6.4 g/g in group 1 and 4.6 to 4.7 g/g in group 2. The decrease in cefixime concentrations was slower in tissue than in serum; the ratios of concentrations in tissue to those in serum were 3.5 to 3.6 and 1.7 to 1.9 at 4 and 12 h, respectively. The intrarenal concentrations of cefixime remained higher than the MIC for the most susceptible gram-negative bacteria during the time interval between the administration of two doses.