VIENNA—On many doctors’ wish lists: a device that directly measures interstitial antimicrobial concentrations in the lungs of patients with respiratory infections. Such a device would make dosing adjustments for these patients far easier by allowing more accurate assessment of antimicrobial delivery to the lungs than is currently possible.

Fortunately, such a technology could be ready for routine use in a few years, reports Markus Müller, MD, a Professor of Internal Medicine and Clinical Pharmacology at Vienna University in Austria. Dr. Müller helped to test the technology—closed-chest microdialysis—in five patients without recent lung infections who were undergoing elective surgery for lung tumors.[1]

“We were able to measure the concentration of a standard antibiotic, cefpirome, in lung tissue and saw that it compared favorably to the bloodstream concentration,” Dr. Müller said. Blood levels of a drug do not necessarily reflect the tissue concentrations, he pointed out. Importantly, no microdialysis-related complications were observed. The study therefore provides the first evidence that microdialysis is a safe and feasible method of measuring antimicrobial concentrations in human lung tissue.

“The beauty of this technique is that you get the drug concentration profile over time, not just at a single point in time,” Dr. Müller stressed. “You really see the pharmacokinetic behavior of the drug in the tissue.”

The investigators initiated microdialysis at the end of lung surgery, just before closing the chest. A flexible, 50-cm microdialysis catheter was fed into the thoracic cavity through a venous cannula, and a probe at the end of the catheter was inserted into the lung. After baseline microdialysis measurements were taken, the patients received 2 g of cefpirome, a fourth-generation cephalosporin, intravenously for five minutes. The probe was left in place for four hours.

The drug’s lung interstitial fluid concentration reached 66% of the plasma concentration within the four-hour observation period. This finding supports the view that cefpirome has a favorable tissue-penetration profile, especially because about 10% of the drug is bound to plasma proteins after administration.[2]

The cefpirome level in the interstitial lung fluid exceeded the minimum inhibitory concentration needed to suppress at least 90% of isolates (MIC90) for most relevant bacteria—Klebsiella species, Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa. It would have surpassed the MIC90 for S aureus and P aeruginosa for more than nine hours and the MIC90 for Klebsiella and S pneumoniae for more than 12 hours, the investigators estimated.

Complications probably did not occur because the microdialysis catheter is so thin, suggested Dr. Müller; its diameter is about half that of a biopsy needle. The technology is routinely used in Europe to monitor brain biochemistry, he noted.

—Timothy Begany

References
1. Herkner H, Müller MR, Kreischitz N, et al. Closed-chest microdialysis to measure antibiotic penetration into human lung tissue. Am J Respir Crit Care Med. 2002;165:273-276.
2. Mayer BX, Hollenstein U, Brunner M, et al. Micellar electrokinetic chromatography for the analysis of cefpirome in microdialysis and plasma samples obtained in vivo from human volunteers. Electrophoresis. 2000;21:1558-1564.

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