Seeing The Light?
Hopkins?
New Theory on Lyme Disease Treatment?
July 2014- This is an article from Johns- how many times have we been sued over Lyme disease- Hopkins. Paul Auwaerter is a co-author on the study and also the editor of the infamous 2006 IDSA Lyme Guidelines.
The study indicates Doxycycline and Amoxicillin are NOT the best treatment for Lyme "persisters" (165 others had better results), that biofilms do exist, and the study names some of the more effective FDA medications.
I am still scratching my head and wondering if Auwaerter is being held captive in an underground cave somewhere, but no, I'm sorry, I won't volunteer to participate in the search and rescue efforts if he is.
UPDATE- September 2014- Patients continue to run from Auwaerter and Hopkins after their appointments. He has not changed, is seemingly ignoring the facts, and continues to risk the health, well-being and lives of those with Lyme disease.
Identification of novel activity against Borrelia burgdorferi persisters using an FDA approved drug library
Jie Feng1, Ting Wang1, Wanliang Shi1, Shuo Zhang1, David Sullivan1, Paul G Auwaerter2 and Ying Zhang1
- 1Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
- 2Fisher Center for Environmental Infectious Diseases, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA
Correspondence: Y Zhang, E-mail: yzhang@jhsph.edu
Received 17 April 2014; Revised 30 May 2014; Accepted 3 June 2014
Article Located Here
http://www.nature.com/emi/journal/v3/n7/full/emi201453a.html
Below are some highlighted quotes I picked through for those too sick or unable to read straight through the entire study.
"The actual numbers of PTLDS cases is unknown, but recruitment of these patients for clinical trials has been difficult." [Got to start out with a laugh.]
"Although animals do not experience symptoms that might be judged to be PTLDS, in various animal models (mice, dogs and rhesus macaque monkeys), antibiotic therapy with doxycycline, ceftriaxone or tigecycline has not fully eradicated B. burgdorferi, as determined by methods including xenodiagnosis, although viable organisms have not been able to be cultured in conventional culture media."
"These morphological variants have altered antibiotic susceptibilities." [Talking about cyst and L-forms, etc.]
"Frontline drugs such as doxycycline and amoxicillin kill the replicating spirochetal form of B. burgdorferi quite effectively, but they exhibit little activity against non-replicating persisters that are enriched in the stationary phase or in biofilm-like aggregates of B. burgdorferi."
"In our preliminary studies, we determined that stationary-phase B. burgdorferi were refractory to killing by the frontline drugs, doxycycline or amoxicillin (Figure 2) and could thus serve as a persister model for drug screens."
"We observed that B. burgdorferi cultures were primarily in the spirochetal form during the log phase (Figure 1B, left panel), but variant forms such as coccoid or round-body forms and micro-colonies were significantly more abundant in stationary-phase cultures (Figure 1B, right panel)."
"These antibiotics [high doses of doxycycline and amoxicillin used for Lyme disease treatment] do not kill the cystic or round-body forms of B. burgdorferi, but metronidazole does have activity against the cystic form of B. burgdorferi."
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"The results demonstrated that the current antibiotics, doxycycline and amoxicillin, were highly active against log-phase B. burgdorferi but had little activity against stationary-phase B. burgdorferi (Figure 2).
Metronidazole had some activity against log-phase B. burgdorferi but had little activity against stationary-phase B. burgdorferi (Figure 2).
These findings suggest that the current antibiotics used to treat Lyme disease would have little or no activity on B. burgdorferi persisters, if existing, in vivo."
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***** "Of the 1524 drugs in the FDA-approved drug library tested, 165 had higher activity against B. burgdorferi persisters than doxycycline and amoxicillin." ******
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"The anti-persister activities of some drugs were significantly higher than the frontline antibiotics, doxycycline and amoxicillin (Table 1).
For example, daptomycin, clofazimine, carbomycin and some cephalosporin antibiotics (such as cefoperazone, cephalothin, cefotiam and cefuroxime) had among the highest activities against stationary-phase B. burgdorferi persisters.
Antimalarial antibiotics(amodiaquine and quinine), aminoglycoside streptomycin, bismuth, tetracycline, and sulfa drugs also had relatively high activity against B. burgdorferi persisters (Table 1).
We also included the currently used Lyme disease treatment antibiotics for comparison with the new active hits.
It is interesting to note that cephalosporin antibiotics, ceftriaxone and cefuroxime, and tigecycline had some activity against persisters, but their anti-persister activities were not as strong as cefoperazone, daptomycin, clofazimine or carbomycin (Table 1).
Doxycycline, amoxicillin, penicillin G, macrolide antibiotics, azithromycin and clarithromycin had relatively poor activity against B. burgdorferi persisters (Table 1)."
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"Using this rapid method, we screened the FDA approved drug library for activity against non-replicating persisters of B. burgdorferi and identified a number of interesting drug candidates that have excellent anti-persister activity (Table 1).
These include daptomycin, clofazimine, carbomycin, certain cephalosporins, and some sulfa drugs. Most of the candidate drugs are used for treatment of infections other than Lyme disease and would represent a novel use of old drugs for anti-persister activity."
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"We determined that daptomycin had the highest activity against B. burgdorferi persisters among all the active hits (Table 1, Figure 3D) but had a high MIC (12.5–25 µg/mL) against log-phase organisms (Table 2). ...
Microscope examination revealed spirochetal shaped remnants after daptomycin treatment (Figure 3A), suggesting that the cells were dead and did not change form to coccoid shape, which occurred following cefoperazone and tetracycline treatment (Figures 3E and 3I)."
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"Here, we observed that carbomycin (Table 1, Figure 3G), a 16-membered macrolide, had higher bactericidal activity against stationary-phase B. burgdorferi than the classic macrolides such as azithromycin, clarithromycin, and erythromycin.
The MIC data (Table 2) demonstrated that carbomycin was also effective against multiplying B. burgdorferi. Macrolides that can penetrate B. burgdorferi cells may have greater activity than penicillin or ceftriaxone. Carbomycin may be a candidate for further investigation to enhance monotherapy treatment of Lyme disease."
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"Cefoperazone (a third generation cephalosporin) appears to be the best β-lactam antibiotic against stationary-phase B. burgdorferi, followed by some second generation cephalosporins such as cefotiam (Figure 3H), cefmetazole and cefonicid."
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"Doxycycline is used clinically as a frontline drug for treating Lyme disease. Doxycycline has low MIC values24 and good activity on multiplying B. burgdorferi. Interestingly, we observed that tetracycline had higher activity against stationary-phase B. burgdorferi persisters than doxycycline (Table 1).
This result is consistent with a previous study, which determined that tetracycline is more active than doxycycline in a minimum bactericidal concentration test."
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"Here, we observed that clofazimine was highly active against stationary-phase B. burgdorferi persisters (Figure 3F), although the MIC of clofazimine was relatively high (6.25 µg/mL).
The preferential activity of clofazimine against B. burgdorferi persisters may be due to its high lipophilicity and its effects on the membrane. It is of interest to note that clofazimine is known to accumulate in host tissues,37 and this property may allow clofazimine to accumulate to high concentrations and act preferentially against B. burgdorferi persisters if they occur in human tissues."
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"In addition, some sulfa drugs such as sulfameter and sulfisoxazole were observed to be effective against stationary-phase B. burgdorferi, while sulfamethoxazole exhibited low MIC values (≤0.2 µg/mL). "
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"While concern remains whether PTLDS is due to persisting organisms, identification of antibiotics that have activity against B. burgdorferi persisters we feel should prompt testing of some antibiotic combinations that could impact either persisters if they exist or presence of antigenic debris, and by whatever mechanisms, study whether such an approach may lead to improved clinical outcomes in Lyme disease including Lyme arthritis or patients with PTLDS."
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[And here comes Auwaerter's contribution- with the Hopkins standard line wedging its way in there...]
"In summary, this study represents the first high throughput screen against B. burgdorferi in vitro persisters and identified a number of interesting FDA-approved drugs that have excellent anti-persister activity.
Further studies are needed to evaluate these drug candidates in animal models of B. burgdorferi persistence and determine whether they can break the persistence phenomenon the current Lyme disease antibiotics failed to eliminate.
Although the question of B. burgdorferi persistence in humans has been raised, there is no high-quality evidence to support this concept or the idea that additional antibiotic therapy is helpful for patients for PTLDS.
Whether earlier resolution of B. burgdorferi infection, either alone or in combination with current Lyme disease antibiotics, will decrease long term symptoms of fatigue or PTLDS is unknown and will require further study."
The End
BTW- I still do NOT recommend going to Hopkins for diagnosis or treatment of Lyme disease.
Lucy Barnes
July 6, 2014