Vancomycin concentrations in infected and noninfected human bone

Abstract

Concentrations of vancomycin in bones of 14 patients undergoing total hip arthroplasty (group 1) and 5 patients with osteomyelitis (group 2) were studied. Group 1 received vancomycin, 15 mg/kg intravenously, 1 h prior to anesthesia. Group 2 received doses adjusted to achieve peak levels in serum of 20 to 30 ,ug/ml and trough levels of <12 ,Ig/ml; bone specimens were collected during surgical debridement. The specimens were pulverized and eluted into phosphate buffer, and the supernatants were analyzed for vancomycin content by fluorescence polarization immunoassay. In group 1, vancomycin was detectable in all cancellous specimens with a mean concentration of 2.3 ± 4.0 ,ug/g (range, 0.5 to 16 ,ug/g); 10 of 14 cortical specimens had detectable vancomycin; the mean cortical concentration was 1.1 ± 0.8 ,ug/g (range, not detectable to 2.6 ,ug/g). In group 2, vancomycin was detectable in only two of five cortical bone specimens (mean concentration, 5.9 ± 3.5 ,ug/ g). Cancellous bone was obtained in one patient; the vancomycin concentration was 3.6 ,ug/g. In most patients the vancomycin levels in bones were higher than the MIC for susceptible staphylococci following single prophylactic doses. In the few infected patients studied, penetration was variable and deserves further study.Vancomycin is often recommended for the treatment of osteomyelitis caused by methicillin-resistant staphylococcal species, as well as for all forms of gram-positive staphylococcal and streptococcal osteomyelitis in patients with allergies to beta-lactam antibiotics. Nonetheless, no studies of vancomycin penetration into human bone have been reported. Therefore, we measured concentrations in noninfected bone specimens from humans following a single preoperative intravenous dose of vancomycin and in infected bone specimens following multiple-dose therapy for osteomyelitis. MATERIALS AND METHODSStudy groups. Nineteen adult patients were studied. Group 1 consisted of 14 patients undergoing total hip arthroplasty for osteoarthritis. Group 2 consisted of five patients with osteomyelitis undergoing surgical bone debridement.(i) Group 1. Vancomycin (15 mg/kg of total body weight, to a maximum dose of 1 g) was administered intravenously over 60 min beginning approximately 1 h prior to induction of anesthesia. A 2-to 3-g sample of cortical and cancellous bone was obtained from the femoral neck intraoperatively.Blood was collected for vancomycin assay 15 min after the end of the infusion and at the time of bone sampling.(ii) Group 2. Patients in group 2 had been receiving vancomycin for at least 48 h for treatment of sternal (four patients) or tibial (one patient) osteomyelitis. Doses were adjusted to achieve peak levels of 20 to 40 jig/ml of serum and trough levels of -12 ,ug/ml. Peak levels were obtained 15 min after the end of a 60-min infusion. Bone debrided intraoperatively was collected for analysis. On the day of bone sampling, blood was obtained simultaneously and at the nadir of the dosing interval. * Corresponding author. Specimen analysis. Se...

The microbiology of chronic osteomyelitis in a developing world setting

“…Vancomycin penetrates bone relatively poorly, with the ratio of bone to serum concentration being only approximately 20% in infected bone. 13 Cefazolin outperformed vancomycin in one series, despite its bone penetration being inferior to that of vancomycin (approximately 15%).…”

Microbiological and pharmacological tests on new antibiotic‐loaded PMMA‐based composites for the treatment of osteomyelitis

“…V has a high molecular weight, a longer half-life and a higher ability to bind to bone than G; the high levels of V in bone confirm these pharmacokinetic properties. 8,26,27 This interaction should be different in case of G. In fact, G showed a high ability to diffuse from the nail as well as the bone, with more rapid kinetics, as indicated by the results obtained after 3 and 7 days. Even if V and G concentrations in bone exhibited very high variability as shown by SE drug concentrations, they were very different in P-TCP and P-BaSO 4 groups, without reaching statistical significance.…”

Determination of Vancomycin in Human Plasma, Bone and Fat by Liquid Chromatography/Tandem Mass Spectrometry

“…For the analysis of vancomycin concentration in bone and fat: Based on the method previously described by Graziani et al [16], phosphate buffered saline pH 7.3 (PBS) was selected as the extraction solvent to extract vancomycin from bone and fat tissue. The bone samples were crushed with pliers, finely cut further with a scalpel, then weighed and immersed in the extraction solvent PBS (the ratio of bone/ PBS was around 1:5, w/v) at 4°C overnight to extract vancomycin from the bone.…”

“…Various analytical methods have been developed for measuring vancomycin in liquid samples only, such as plasma/serum, urine, human drainage tissue fluid and bronchoalveolar lavage fluid, including HPLC methods [8][9][10] and LC-MS/MS methods [11][12][13][14][15]. A few methods have been reported for the determination of vancomycin in both liquid and solid samples, such as immunoassays for plasma/serum and bone [16,17], HPLC method for plasma, bone and atrial appendage tissue [18], and LC-MS/MS for serum, perivascular fat and atrial wall samples [19]. It appears that no method has been reported for the determination of vancomycin in human plasma, bone and fat tissues using LC-MS/MS.…”