Rate of aggregate heat production. (ΔQ/Δt). In preliminary studies (data not shown) we have found that in general the aggregate heat Q at any time t is related to the number of bacteria present, and thus that the change ΔQ/Δt for a given portion of the Q vs. t data is roughly

proportional to the rate of bacterial growth during the time Δt. A clear example of an antibiotic producing change in ΔQ/Δt alone as a function of antibiotic concentration is the effect of Chloramphenicol on S. aureus at PF-4708671 times up to ~900 minutes (Fig. 5B). Antibiotics which change ΔQ/Δt as a function of their concentration could be called “”growth rate inhibitors.”" Maximum aggregate heat Q at time t. (Q max ) Fig. 5B (S. aureus, Chloramphenicol) also provides a clear example of this key feature. In this case differences in Q max as a function of concentration

are clearly related to differences in growth rate as measured by ΔQ/Δt. However, our IMC method employs sealed ampoules which thus have fixed initial amounts and types of liquid medium and gas mix in the headspace, fixed total volume, and no means of removing products of bacterial activity. Thus there is a limit to the amount of heatproducing bacterial activity (including selleck chemicals llc growth) which can take place. Therefore if sufficient time elapses, the P max values tend back toward baseline and the related Q max values tend to reach the same maximum value for all subinhibitory antibiotic selleckchem concentrations of a given antibiotic. This is clearly seen for S. aureus and Cefazolin (Fig. 1, Column B). Looking at the data in Fig. 5 for S. aureus alone (i.e., 0 mg l-1 Choramphenicol) one can see that at about 900 minutes, aggregate heat production Q is slowing and starting to approach a maximum. Therefore, we conclude that the value VAV2 of Q at any time t depends on whether the bacteria are still active or whether activity is either becoming increasingly limited by the sealed-system environment or has finally ceased. In fact, our results suggest that the ultimate value of Q max is strictly related

to the closed system used and is not different for different antibiotics. Figs 1, 2 and 3 show data for 7 different antibiotics for E. coli. All exhibit maximum values of Q, and the values were all approximately 9–10 J, regardless of which antibiotic was employed. Thus it does not appear that Q max provides much information regarding antibiotic effects – except as another way to express the information contained in ΔQ/Δt at a given place in the time history. Using IMC data to compare modes of action. By using the above key features of all heatflow and aggregate heat curves of the antibiotics for a single bacterium, it is possible to quite an extent to group the antibiotics by their modes of action. This is best illustrated by examining the results for S. aureus (Fig. 4, 5 and 6).