The effects of variations in temperature within the physiologic range on minimal inhibitory concentrations (MICs) and on the serum bactericidal activity of 17 different antimicrobial agents for 432 strains of bacteria were studied. Comparison of 3,053 experimental MICs performed at 41.5, 40, 38.5, 37, or 35 C with duplicate standard MICs performed at 35 C showed a progressive increase in antimicrobial activity as the temperature was raised within the experimental range. At the highest temperature (41.5 C), 17.1% of MICs were four or more times lower, 7% were eight or more times lower, and 2% were greater than or equal to 16 times lower than the standard MICs performed at 35 C. Binding to proteins in serum neither accentuated nor diminished the augmenting effect of temperature on antimicrobial activity. Comparison of serum bactericidal activity determined at 35 C and 40 C revealed similar hyperthermic augmentation of antimicrobial activity.
Various commonly used antiseptics were tested against three strains of methicillin-resistant Staphylococcus aureus (MRSA) at stock strength and in serial 10-fold dilutions. The stock solutions of 4% chlorhexidine gluconate-alcohol (Hibiclens), 1% p-chloro-m-xylenol (Acute-Kare), and 3% hexachlorophene (Phisohex) produced 2-log reductions of MRSA after a 15-s exposure, but even after 240 s, these solutions failed to kill all the MRSA. Povidone-iodine (Betadine) solution was maximally effective at the 1:100 dilution, killing all the MRSA within 15 s; other dilutions were less effective, though each killed the MRSA within 120 s. Similar results were obtained with three different strains of methicillin-susceptible S. aureus. Thus, of the four most commonly used antiseptics, povidone-iodine, when diluted 1:100, was the most rapidly bactericidal against both MRSA and methicillin-susceptible S. aureus.
We conclude that AMT has good oral bioavailability and that, when given on a q12 hour x two weekly schedule, the MTD is 2 mg/m2 with delayed LV rescue.
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