The pharmacokinetics of minocycline have been studied after single intravenous infusions and repeated oral doses to human subjects with varying degrees of renal impairment. There was no evidence of reduced drug clearance with reduced renal function after intravenous doses although there appeared to be an increase in the tissue distribution of antibiotic in the body in uremia. After identical multiple oral dosage regimens serum levels of antibiotic were comparable in normal and mildly uremic subjects. There was no evidence of renal toxicity in normal or uremic subjects with the repeated dosage regimen used.
A cluster of three cases of staphylococcal septic endarteritis originating from percutaneously inserted brachial artery catheters for regional cancer chemotherapy prompted an epidemiologic and clinical study of bacteremic infections associated with this therapeutic modality. Nine cases were identified over a 3 1/2-year period (1.6% of all catheterizations), all caused by Staphylococcus aureus. The cluster followed discontinuation of hexachlorophene for scrub of the extremity prior to cannulation; phage-typing suggested the three cases were caused by the patients' own strains of Staphylococcus. These infections produced a distinctive clinical syndrome which facilitates implicating the catheter in the genesis of fever occurring in a patient receiving intra-arterial chemotherapy: early localized pain (89%) and hemorrhage (78%), and Osler's nodes distally (44%), later followed by local inflammation (78%), purulence (56%) and signs of systemic sepsis (100%) (each factor, p less than or equal to .005). Duration of cannulation did not influence susceptibility to infection. However, difficult cannulations or need for repositioning the catheter (p = .0096), prior radiation therapy (p = .033), leukopenia (p less than .05) and hypoalbuminemia (p less than .05) were all associated with septicemia. In the 25 months since implementation of specific control measures, there have been no further catheter-related septicemia in 310 catheterization (p less than .001). Guide-lines for prevention and management of these infections are provided.
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