Aztreonam concentrations in human tissues obtained during thoracic and gynecologic surgery

Abstract

The concentrations of aztreonam in human tissues obtained during surgery were measured after a single 2-g intravenous dose. The average concentration in the skeletal muscle, atrial appendage, lung, sternum, pericardial fluid, endometrium, myometrium, fallopian tube, and ovary varied from 3 to 33 ,ug/g (or ,ug/mI). These concentrations significantly exceed the MIC for 90% of strains for most members of the family Enterobacteriaceae.Single parenteral doses of aztreonam produce significant concentrations in serum (14), cerebrospinal fluid (3, 5), bile (9), blister fluid (17), peritoneal fluid (16) Aztreonam assays. Skeletal muscle, atrial appendage, sternum, and lung tissue samples were minced into very small pieces and weighed. The sternum samples were pulverized with a Spex 6700 Freezer/Mill (Spex Industries, Metuchen, N.J.). The tissues were then diluted with 1 ml of 0.1 M phosphate buffer (pH 6.0) per g of sample. After dilution, the samples were homogenized for 1 min by using a Tekmar homogenizer (Tekmar, Cincinnati, Ohio). The homogenates were diluted with 3 ml of 50% methanol (in pH 6.0 phosphate * Corresponding author. buffer) per g of homogenate. The diluted homogenates were then centrifuged, and the supernatant was decanted and saved.The pellet was extracted twice with 5 ml of 30% methanol (in pH 6 phosphate buffer) per g of pellet. Filtered (Millex, 0.45-[im pore size; Millipore Corp., Bedford, Mass.) extracts were assayed by high-pressure liquid chromatography equipment that was previously described (11). Serum obtained simultaneously with thoracic tissues and fluids was assayed by a previously described high-pressure liquid chromatography method (11), and a similar method was used to assay pericardial and pleural fluid.Commercially obtained samples of tissue or body fluid (Agrilab Inc., Bridgewater, N.J.) were mixed with known amounts of aztreonam at the time the specimens were obtained from study patients. These spiked samples were assayed for aztreonam, and the results were used to correct clinical specimen assay results for losses during storage.The limit of detection, assay coefficient of variability, and recovery from spiked samples for each type of high-pressure liquid chromatography assay ranged from 0.5 to 1.3 ,ig/g (or jLg/ml), 5.3 to 14.7%, and 80.4 to 101%, respectively.Gynecologic tissue and simultaneous serum were assayed by microbiologic methods. The method for serum was previously described (14).Frozen tissue samples were thawed and cut into small pieces, and 0.2-g samples were weighed into a labeled test tube. These samples were refrozen at -78°C until assayed. On the day of assay, the samples were extracted by a procedure similar to that used for the high-pressure liquid chromatography assay of thoracic tissues.

Plasma vs heart tissue concentration in humans – literature data analysis of drugs distribution

“…Other antibiotics reported to penetrate the heart, to achieve concentrations well above the respective MICs, but not to exceed the plasma concentrations are as follows: aztreonam [90], fusidic acid [85] and vancomycin [89]. There are three case reports on the daptomycin level in pericardial fluid [91] or in aortic and mitral valves [92].…”

Clinical Pharmacokinetics of Aztreonam

“…Tissue to plasma concentration ratios in 22 samples for sternal bone increased from 0.03 at 0.46 to 0.78 hours after intravenous administration to 0.07 or 0.08 after 4 hours (Beam et al 1986). More recently, diffusion rate constants were estimated in bone after an intravenous bolus injection of aztreonam to 6 patients undergoing dental surgery (Fracas so et al 1989).…”

“…In lung tissue, plasma to tissue concentration ratios of between 0.35 and 0.46 were found (Beam et al 1986). …”

Evaluation of the novel culture-based FAST-T system allowing selection of optimal antibiotics for critically ill patients within 4 h (for other than bloodstream infectious).

“…AST was limited to antibiotics used for the treatment of respiratory infections, which were selected according to the American Thoracic Society/Infectious Disease Society of America guidelines (43-45). Antibiotics were added to FASM-T medium at respective maximal concentrations that could be achieved at the site of infection according to literature data: amikacin, 9 μg/mL (46); azithromycin 8 μg/mL (46, 47); aztreonam 22 μg/mL (48, 49); cefepime 24 μg/mL (46, 49, 50); gentamicin 5 μg/mL (56, 51); levofloxacin 12 μg/mL (46, 52); linezolid 25 μg/mL (53, 54); meropenem 10 μg/mL (55); piperacillin-tazobactam (25 for piperacillin and 3.5 for tazobactam) μg/mL (56); vancomycin 12 μg/mL (46, 57) (all from Sigma-Aldrich, St. Louis, MO). Probes were incubated at 37 °C, for 4, 8, and 24 h.…”