Penetration of vancomycin into mediastinal and cardiac tissues in humans

Abstract

Vancomycin penetration into heart tissues (valves, myocardium, auricles, and pericardium) and mediastinal tissues (fat and sternal bone) was evaluated after two regimens of vancomycin administration. Ten patients were given 15 mg of vancomycin per kg of body weight before anesthesia. Ten other patients received the same dose and then a second 7.5-mg/kg dose at the time of initiation of cardiopulmonary bypass. Similar and satisfactory vancomycin tissue penetrations were observed in both groups. However, for some patients in the two groups, vancomycin levels in tissue were less than the MICs for potential pathogens (Staphylococcus aureus and Staphylococcus epidermidis).Cardiac surgery is a clean surgery but requires antibiotic prophylaxis to prevent serious postoperative infections of the cardiac valves or the mediastinal tissues (1). Antibiotic prophylaxis is used to protect against pathogens most likely to contaminate the surgical wound, that is, methicillin-resistant or susceptible staphylococci. Cephalosporins (cefazolin, cefamandole) are widely used for that purpose, but vancomycin is an alternative for prophylaxis in allergic patients or when a risk of postoperative infections because of methicillin-resistant staphylococci exists (6,8). Vancomycin is characterized by a slow killing rate of bacteria, and this is particularly true for low levels of the drug (half the MIC) (16). Given this time dependency for bacterial killing, exposure of bacteria to antibiotic concentrations greater than the MIC for long periods of time seems desirable. For prophylaxis for postoperative infections, such adequate antibiotic concentrations should probably be achieved in all potential sites of infection (2, 13).The present study was designed to determine whether two different dose regimens could result in the achievement and maintenance of adequate concentrations in sternal bone, mediastinal fat, and heart tissues. Levels in tissue greater than or equal to the MIC for 90% of methicillin-susceptible or resistant Staphylococcus aureus (1 ,ug/ml) and coagulase-negative staphylococci (2 ,ug/ml) tested (19) were considered adequate.Subject and study design. The study received the approval of the Ethics Committee of our institution (Hopital Nord), and all patients gave informed consent. The study was prospective and randomized and was designed to compare the penetration of vancomycin after either a single (group 1) or two (group 2) intraoperative intravenous doses in patients undergoing mitral or aortic valve replacement. Twenty patients, divided into two groups of 10 patients each, were included in the study. Criteria for inclusion were as follows: 18 years of age or older, absence of prior history of hepatic or renal disease, elective surgery, and no clinical or laboratory signs of infection. Antibiotic administration. Group administered intravenously over a 60-min period. Infusion was started 90 min before the surgical incision. Group 2 patients were given the same dose following the same protocol. A second dose of vancomycin (7....

Using a Vancomycin PBPK Model in Special Populations to Elucidate Case‐Based Clinical PK Observations

“…via passive diffusion 23, 30, 39. In the current study, the lung:plasma partition coefficient of vancomycin was predicted to be 0.62 at steady state.…”

Successful management of discovered pH dependence in vancomycin recovery studies: novel HPLC method for microdialysis and plasma samples

“…However, currently only few pharmacokinetic data about tissue distribution of vancomycin in humans is available (Lamer et al, 1993;Engineer et al, 1981;Matzke et al, 1986;Georges et al, 1997;Farin et al, 1998;Kitzes-Cohen et al, 2000). Present information on tissue penetration of vancomycin is rather limited (Martin et al, 1994;Luzzati et al, 2000), although it is increasingly recognized that effective drug tissue concentrations are fundamental to microbiological and clinical outcome and the prevention of microbiological resistance. For most Gram-positive bacterial infections the site of action is the interstitial space fluid (Joukhadar et al, 2001).…”

The bactericidal effects of anti-MRSA agents with rifampicin and sulfamethoxazole-trimethoprim against intracellular phagocytized MRSA

“…1,2 VCM has poor penetration capacity into the tissue. 3,4 Depending on the patient's immunological condition and lesions of infection, VCM monotherapy against MRSA infections may fail due to its low antibacterial activity against S. aureus.…”