Vancomycin penetration into the fluid lining the epithelial surface of the lower respiratory tract was studied by performing fiberoptic bronchoscopy with bronchoalveolar lavage on 14 critically ill, ventilated patients who had received the drug for at least 5 days. The apparent volume of epithelial lining fluid (ELF) recovered by bronchoalveolar lavage was determined by using urea as an endogenous marker. Vancomycin levels in ELF ranged from 0.4 to 8.1 ,ug/ml (mean, 4.5 ,iglml), while the mean simultaneous level of the drug in plasma was 24 ,ug/ml (range, 9 to 37.4 ,ug/ml). There was a significant relationship (r = 0.64, P < 0.02) between vancomycin levels in plasma and those in ELF, with a correlation whose slope (0.15) indicated that the blood-to-ELF ratio of drug penetration was 6:1. Using the albumin concentration in ELF as a marker of lung inflammation, we found that vancomycin penetration was higher in patients with ELF albumin values of >3.4 mg/ml than in patients with normal values (<3.4 mg/ml) (P < 0.02). These results suggest that the vancomycin distribution includes the ELF of the lower respiratory tract at a concentration that is dependent upon the levels in blood and the alveolar capillary membrane protein permeability. These concentrations were well above the MICs for most staphylococci and enterococci.Vancomycin, a glycopeptide antibiotic, is used worldwide to treat deep-seated gram-positive bacterial infections caused by staphylococci or enterococci resistant to 1-lactams or patients with significant allergy to ,B-lactams (18, 29). These pathogens may be responsible for nosocomial pneumonia, which is a common and life-threatening problem complicating the management of patients receiving mechanical ventilation (24). Successful treatment of bacterial pneumonia will, however, depend upon adequate delivery of the antibiotic to the area of infection. Unfortunately, little is known about the penetration of vancomycin into lung tissue.With the advent of the technique of bronchoalveolar lavage (BAL), it is now possible to directly obtain a sample of the fluid and cells lining the epithelial surface of the human lower respiratory tract (4, 21). Therefore, in an attempt to quantify the penetration of vancomycin into lung alveoli, we obtained both BAL fluid and blood samples from critically ill patients who were receiving this antibiotic as part of their therapy. In addition, we investigated whether vancomycin penetration was modified by the inflammatory status of the lung.( chanically ventilated and, because of the presence of a new pulmonary infiltrate with fever and/or purulent tracheal secretions, underwent flexible fiberoptic bronchoscopy with a protected specimen brush (PSB) and BAL a few days later, after the initiation of treatment with vancomycin. For each patient, the following clinical variables were recorded: age, sex, weight, disease severity score on admission (as assessed by the APACHE II score) (13), creatinine clearance, and lung injury score as previously described by Murray et al. (17). E...

The optimal technique for diagnosing nosocomial bacterial pneumonia in critically ill patients cared for in the intensive care unit remains unclear, especially in the subgroup of patients requiring mechanical ventilation. An important advance has been the development of the protected specimen brush technique. Secretions obtained using this technique and evaluated by quantitative cultures are useful in distinguishing patients with and without pneumonia. However, this procedure has important limitations in that results are not available immediately, and in that a few false negative of false positive results may occur. Bronchoalveolar lavage has been suggested to be of value in establishing the diagnosis of pneumonia, because the cells and liquid recovered can be examined microscopically immediately after the procedure and are also suitable for quantitative culture. Microscopic identification of bacteria within cells recovered by lavage may provide a sensitive and specific means for the early and rapid diagnosis of pneumonia in this setting. The lavage technique can also be conveniently incorporated into a protocol along with quantitative culture of samples obtained using the protected specimen brush. This combination will probably improve the overall accuracy of diagnosis while allowing the administration of prompt empiric antimicrobial therapy in most patients with pneumonia.

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