Bullets and Bugs

Physicians should consider the bacterial load when dosing their antibiotics.

The inoculum effect is a phenomenon that has been described for many different antibiotics and how they affect several different organisms.  A general observation is that a higher concentration of organisms requires a higher concentration of antibiotic to achieve the same degree of bacterial killing.  Simplistically, it would make sense that the more organisms there are to kill, the more antibiotic molecules are needed to do so.  If 1,ooo soldiers invade your land, your supply of 1,000,000 should be adequate defense.  However, if 100,000,000 soldiers invade, you’re going to need more bullets.  However, the mechanisms for the inoculum effect appears to be complex, depending upon the number of antibiotic molecules necessary to kill a single organism, the various resistance mechanisms employed by bacteria, the quantity of inactivating enzymes produced by the organisms, the growth cycle characteristics of the organisms, and so forth.  Regardless of the mechanism, it appears that in most cases, a higher concentration of bacteria — that is,  a greater number of bacteria in any given volume of fluid or tissue — will decrease the effectiveness of antibiotics. 

Unfortunately, the implications of this phenomenon have not yet translated into clinical practice, even though it was first recognized in 1945.  For one thing, the actual concentration of bacteria in the infected tissue is usually unknown.  Such a determination is not a part of standard clinical practice.  While most laboratories can perform a quantitative bacterial culture, clinicians rarely ask for it to be done. 

It is not clear what the clinical response should be to a higher bacterial concentration.  Should we throw more bullets into the fray?  That is, would a higher dose of antibiotics be necessary?  In some cases, this could be the solution.  In the era when many of our more popular antibiotics — such as the aminoglycosides — had a significant dose-related toxicity, such a solution was unfeasible.  However, now with our large number of safer antibiotics, it is not such a farfetched possibility.  In other cases, higher antibiotic doses may not work, as in those situations where the concentration of bacteria affects their growth phase, thereby inactivating those antibiotics dependent on a particular growth phase.  In such situations, a switch to a different antibiotic class would likely be appropriate or. potentially, debridement of the infected tissue to thin their numbers and give our side a fighting chance.  The paradigm shift in medicine would take advantage of these observations and improve clinical practice.