Re: Persister cells, dormancy andinfectious disease.

[Guest guest]

Yes, I saw this too and I am trying to work out what regimen might be best and most obtainable from doctors and best tolerated etc

Nelly

Re: [infections] Persister cells, dormancy andinfectious disease.

An interesting quote from that article: A disarmingly simple approach to sterilize an infec-tion was first proposed by Bigger in 1944 (REF. 1). Theproposal is to kill bacterial cells with a high dose of anantibiotic, then allow the antibiotic concentration todecrease, which will enable persisters to resuscitate andstart to grow. If a second dose of antibiotic is adminis-tered shortly after persisters start to grow, a completesterilization might be achieved. This approach is success-ful in vitro, and a P. aeruginosa biofilm can essentiallybe sterilized with 2 consecutive applications of a fluo-roquinolone (K. L., unpublished observations). Perhapsunderstandably, this approach has not been received withenthusiasm by specialists in clinical microbiology. Thegoal of established therapies is to maintain the plasmalevel of an antibiotic at a maximum concentration, inorder to discourage the development of resistance. Mostimportantly, an optimal pulse-dosing regimen wouldprobably vary from patient to patient. However, it seemsthat some patients might have inadvertently taken solv-ing the problem of intractable persistent infections intotheir own hands. Individuals who suffer from persistentinfections that require a lengthy therapy are often cured,but why a year-long regimen is better than a month-longone is unclear. An efficacious fluctuating dose of antibi-otics administered serendipitously by the patient mightbe responsible for persister eradication in these cases.The patients might adjust drug dosing simply throughbeing absent-minded, which sooner or later could pro-duce the perfect drug-administration regimen. Curingpersistent infections might therefore result from patientnon-compliance. Analysing how persistent infections arecured might shed light on the likelihood of developinga rational regimen for the pulse-dosing sterilization ofinfection.On Sat, Mar 24, 2007 at 07:28:43PM +0100, Nelly Pointis wrote:>Full text at:>>http://www.biology.neu.edu/pdf/KL2007Pers.pdf>>Nat Rev Microbiol. 2007 Jan;5(1):48-56. Epub 2006 Dec 4.>>> Persister cells, dormancy and infectious disease.>> K.>> Antimicrobial Discovery Center, Department of Biology, Northeastern >University, 360 Huntington Avenue, Boston, Massachusetts 02115, USA. >k.lewis@...>> Several well-recognized puzzles in microbiology have remained unsolved >for decades. These include latent bacterial infections, unculturable >microorganisms, persister cells and biofilm multidrug tolerance. >Accumulating evidence suggests that these seemingly disparate phenomena >result from the ability of bacteria to enter into a dormant (non-dividing) >state. The molecular mechanisms that underlie the formation of dormant >persister cells are now being unravelled and are the focus of this Review.>> Publication Types:>> * Research Support, N.I.H., Extramural> * Review>>> PMID: 17143318 [PubMed - indexed for MEDLINE]

[Guest guest]

Yes, I saw this too and I am trying to work out what regimen might be best and most obtainable from doctors and best tolerated etc

Nelly

Re: [infections] Persister cells, dormancy andinfectious disease.

An interesting quote from that article: A disarmingly simple approach to sterilize an infec-tion was first proposed by Bigger in 1944 (REF. 1). Theproposal is to kill bacterial cells with a high dose of anantibiotic, then allow the antibiotic concentration todecrease, which will enable persisters to resuscitate andstart to grow. If a second dose of antibiotic is adminis-tered shortly after persisters start to grow, a completesterilization might be achieved. This approach is success-ful in vitro, and a P. aeruginosa biofilm can essentiallybe sterilized with 2 consecutive applications of a fluo-roquinolone (K. L., unpublished observations). Perhapsunderstandably, this approach has not been received withenthusiasm by specialists in clinical microbiology. Thegoal of established therapies is to maintain the plasmalevel of an antibiotic at a maximum concentration, inorder to discourage the development of resistance. Mostimportantly, an optimal pulse-dosing regimen wouldprobably vary from patient to patient. However, it seemsthat some patients might have inadvertently taken solv-ing the problem of intractable persistent infections intotheir own hands. Individuals who suffer from persistentinfections that require a lengthy therapy are often cured,but why a year-long regimen is better than a month-longone is unclear. An efficacious fluctuating dose of antibi-otics administered serendipitously by the patient mightbe responsible for persister eradication in these cases.The patients might adjust drug dosing simply throughbeing absent-minded, which sooner or later could pro-duce the perfect drug-administration regimen. Curingpersistent infections might therefore result from patientnon-compliance. Analysing how persistent infections arecured might shed light on the likelihood of developinga rational regimen for the pulse-dosing sterilization ofinfection.On Sat, Mar 24, 2007 at 07:28:43PM +0100, Nelly Pointis wrote:>Full text at:>>http://www.biology.neu.edu/pdf/KL2007Pers.pdf>>Nat Rev Microbiol. 2007 Jan;5(1):48-56. Epub 2006 Dec 4.>>> Persister cells, dormancy and infectious disease.>> K.>> Antimicrobial Discovery Center, Department of Biology, Northeastern >University, 360 Huntington Avenue, Boston, Massachusetts 02115, USA. >k.lewis@...>> Several well-recognized puzzles in microbiology have remained unsolved >for decades. These include latent bacterial infections, unculturable >microorganisms, persister cells and biofilm multidrug tolerance. >Accumulating evidence suggests that these seemingly disparate phenomena >result from the ability of bacteria to enter into a dormant (non-dividing) >state. The molecular mechanisms that underlie the formation of dormant >persister cells are now being unravelled and are the focus of this Review.>> Publication Types:>> * Research Support, N.I.H., Extramural> * Review>>> PMID: 17143318 [PubMed - indexed for MEDLINE]