Posted 10/4/2011 7:24 PM (GMT 0)
http://mpkb.org/home/pathogenesis/microbiota/biofilm
Penetration of biofilm
Some researchers claim that antibiotics cannot penetrate the matrix that surrounds a biofilm. But research by Dr. Kim Lewis of Tulane University and other scientists has confirmed that the inability of antibiotics to penetrate the biofilm matrix is much more of an exception than a rule. According to Lewis, “In most cases involving small antimicrobial molecules, the barrier of the polysaccharide matrix should only postpone the death of cells rather than afford useful protection.”
In a paper entitled “The Riddle of Biofilm Resistance,” 37 Lewis discusses her laboratory-based observations of how pulsed, low dose antibiotics are able to break up biofilm, while antibiotics administered in a standard manner (high, constant doses) cannot. According to Lewis, the use of pulsed, low-dose antibiotics to target biofilm bacteria is supported by observations she and her colleagues have made in the laboratory.
Using computer modeling software, another team of researchers have modeled the action of antibiotics on bacterial biofilms and found that pulsing antibiotics can be a superior way of targeting treatment resistant biofilm bacteria. According to Cogan et al, “Exposing a biofilm to low concentration doses of an antimicrobial agent for longer time is more effective than short time dosing with high antimicrobial agent concentration.” 38
Persisters
After antibiotics penetrate a biofilm, a number of cells called “persisters” are left behind. Persisters are simply cells that are able to survive the first onslaught of antibiotics, and if left unchecked, gradually allow the biofilm to form again. According to Lewis, persister cells form with particular ease in immunocompromised patients because the immune system is unable to help the antibiotic “mop up” all the biofilm cells it has targeted. Paradoxically, dosing an antibiotic in a constant, high-dose manner (in which the antibiotic is always present) helps persisters persevere.39
Conversely, in the case of low, pulsed dosing, the survival of persisters is not enhanced. Pulsed low dosing causes the persister cells to lose their phenotype (their shape and biochemical properties), meaning that they are unable to switch back into biofilm mode. A second application of the antibiotic should then completely eliminate the persister cells, which are still in planktonic or free-floating mode. This method has been characterized by one research team as an example of “resonant activation”:
We proposed a novel strategy to “kill” persister cells by triggering them to switch, in a fast and synchronized way, into normally growing cells that are susceptible to antibiotics.
Fu et al.40
Lewis states: “It is entirely possible that successful cases of antimicrobial therapy of biofilm infections result from a fortuitous optimal cycling [pulsed dosing] of an antibiotic concentration that eliminated first the bulk of the biofilm and then the progeny of the persisters that began to divide.”