Abstract

The excretion of tetracycline HCl in sputum was studied in 42 hospital patients suffering from various respiratory disorders who were receiving oral tetracycline therapy of 1·0 gram daily in divided doses.

The tetracycline levels were estimated biologically by a cup-plate agar diffusion method using B. cereus. Two separate methods of sputum homogenization are described: enzymic liquefaction with pronase, a powerful proteolytic enzyme, and ultracentrifugation at 103,000 g for three hours which sediments the viscous mucoids leaving 80-90% as a clear, non-viscous supernatant. The two methods allowed duplicate assays on sputum samples and generally showed close agreement. The ultracentrifugation technique is favoured for normal purposes because of its simplicity and the avoidance of any biochemical interference.

A close correlation was shown between the tetracycline levels in sputum samples and the average serum level for each patient. Over the serum tetracycline range 1·0-5·0 μg/ml, the mean sputum tetracycline levels after centrifugation were 23-18%, and the average level was 0·50 μg/ml.

The levels found in sputum were compared with the minimum inhibitory concentration of tetracycline for strains of H. influenzae and Strep. pneumoniae. Eighty-six percent of 29 H. influenzae strains tested and all Strep. pneumoniae strains tested were sensitive to 0·5 μg/ml tetracycline. The remaining H. influenzae strains had a minimum inhibitory concentration of 1·0 μg/ml or higher, a tetracycline level in sputum which appeared to be outside the mean range at the oral dosage of 1·0 gram daily.

Hence it is suggested that a small proportion of patients with lower respiratory tract infections due to H. influenzae would be unresponsive, or only partially responsive, to this usual therapeutic range of tetracycline.