Penetration of vancomycin into human lung tissue

Abstract

Vancomycin penetration into lung tissue was evaluated in thirty patients following the administration of 1 g of vancomycin as a 1 h i.v. infusion. Mean concentrations (range) of vancomycin in lung tissue were 9.6 (6.3-12.1) mg/kg at 1h, 5.7 (4.7-7.4) mg/kg at 2 h, 4.2 (0.8-6.5) mg/kg at 3-4 h, 2.4 (1.4-4.7) mg/kg at 6 h, and 2.8 (0.9-7.8) mg/kg at 12 h after the end of infusion. Ratios of lung tissue to serum concentration ranged 0.24 to 0.41 at 1 and 12 h, respectively. One of six patients observed at 6 h, and 3 of 7 patients at 12 h did not have detectable levels of vancomycin in lung tissue. A 1 h iv infusion of a 1 g dose of vancomycin does not achieve sustained lung concentrations above the MIC for susceptible staphylococci over a dosing interval of 12 h. Therefore, a more appropriate modality of administration, such as continuous infusion, should be considered.

Pharmacodynamics of Vancomycin at Simulated Epithelial Lining Fluid Concentrations against Methicillin-Resistant Staphylococcus aureus (MRSA): Implications for Dosing in MRSA Pneumonia

“…Despite more than 50 years of clinical use of vancomycin, knowledge regarding the degree of penetration into ELF has been lacking, with only two studies, limited by a small number of patients and single-time-point pharmacokinetic comparisons, addressing this issue (5,19,35). Recently published guidelines (1,28,38) support the notion of poor vancomycin penetration into ELF, citing that vancomycin is to be dosed to achieve high trough levels of 15 to 20 mg/liter for MRSA pneumonia, which has been adopted by some clinicians for all infection sources, with some institutions utilizing vancomycin doses of Ͼ4 g/day (22,25).…”

Continuous versus Intermittent Infusion of Vancomycin in Severe Staphylococcal Infections: Prospective Multicenter Randomized Study

“…In addition, less vancomycin might be required, hence reducing the cost of treatment. However, in endocarditis, therapeutic failures have been reported with minimal concentrations below 10 mg/liter (20) and concentrations above 10 mg/liter may be required to inhibit bacterial growth at the site of infection (7,17). At the time the study was designed, all of the participating centers considered that targeted trough concentrations of 5 to 10 mg/ liter were insufficient in critically ill patients with severe infections.…”

Rifampin Combination Therapy for Nonmycobacterial Infections

“…Another concern with the rifampin-vancomycin combination is that each drug penetrates tissue differently based on kinetics. For example, vancomycin penetration into lung tissue is not sustained, and the same was seen for the meninges and infected bone, whereas rifampin easily penetrates these tissues (61,109,120). The rifampin-vancomycin in vitro interaction appears to range from antagonistic to indifferent, with very few synergistic studies (25,26,112,119,158,218,246,251,258,261).…”