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Een typerend voorbeeld van een punt dat tot een belangrijke controverse leidde was de aanbeveling niet langdurig antibiotica voor te schrijven zonder aangetoonde persisterende infectie. Dit op grond van onderzoek uit 2001. ( Klempner c.s. N.Eng. J Med 2001; 345(2) 85-92.).
De uitkomsten van diverse latere onderzoeken, waaronder als laatste de PLEASE studie, stemmen goed overeen met de uitkomsten van Klempner.
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https://www.tekenbeetziekten.nl/site/as ... es_dbg.pdfSuccessful antibiotic treatment is possible only if the individual has an effective immune system. With regard to antibiotic treatment, problems also arise with Borrelia due to natural or
acquired resistance. The causative agent of Lyme borreliosis can evade the immune system
by what are known as “escape mechanisms”.(7/74)
In the early stage, i. e. in the first 4 weeks after the start of infection, a failure rate of 10% is
to be expected with antibiotic treatment.[121/135]
In the chronic forms, it is significantly higher at up to 50%.[30/31/52/55/74/99/121]
Even earlier studies referred to the problem area of chronic Lyme borreliosis and the limits of its susceptibility to treatment. [31/55/59/61/62/65/92/94/121/138]
All these studies, the duration of treatment was generally limited to a maximum of four weeks.
Considerable therapeutic failure rates occurred under these conditions, even with repeated courses of treatment. [78/82/90]
The duration of treatment is of decisive importance for the success of antibiotic treatment.
There are now a few studies available which provide evidence of the positive effect and the safety of long-term antibiotic therapy. [25/26/27/30/36/44/46/51/52/81/144]
The limited effect of antibiotic treatment is documented in numerous studies: Pathogens were cultured even after supposedly highly effective antibiotic therapy. [63/74/81/96/119/120/122/139/147]
For example, Borrelia were isolated from the skin after multiple courses of antibiotic treatment [ceftriaxone, doxycycline, cefotaxime]. [40/61/76/81/122/147]
A discrepancy was also found between the antibiotic sensitivity of Borrelia in vitro versus in vivo. [74]
Moreover, additional factors are involved in vivo which lie in the capability of Berrelia to evade the immune system, [60/83/85/86/120] specifically under the influence of various antibiotics. [80]
Hypothetically, the persistence of borrelia is attributed to its residency within the cell and to the development of biologically less actibe permanent forms [sphearoplasts, encystment] among other things. [19/85/86/94/120]
In addition, Borrelia was also shown to develop biofilms with the effect of resisting complement and typical shedding [ casting off antibodies from the surface of the bacterium].[83/85/86]
Other mechanisms, too, e.g. diversification, i.e. changing complement, [85/86/120] promote the " escape mechanism", i.e. the capablility of the pathogen to evade the immune system, that has also been demonstrated in other bacteria.
The ability of the pathogen to down-regulate progteins [pore-forming protein] might also diminish the antibiotic effect [34/74/84]
There are four randomised studies relating to the therapy of chronic lyme borreliosis, [44/78/82/90] in which different antibiotics were compared when used in the antibiotic treatmend of encephalopathy.
It was shown in these studies that the cephalosporins were superior to penicillin. [31/64/92/96]
Doxycycline in its customary dosage resulted in only relatively low serum levels and tussue concentrationss, whereas the concentrations in the case of the cephalosporins were markedly higher, i.e. with regard to the minimun inhibitory concentrations [MC] the values with the cephalosporins were at least ten times higher than with doxycycline. [63]
A wide therapeutic spectrum and a high tissue concentration of antibiotic is necessary in tussue with a poor blood supply [ commective tussue, structures such as the skin, joint capsules, fasciae, tendons], as Borrelis have a particular affinity to these sorts of tissue. [ 42/108]
Of the available antibiotics, tetracyclines, macrolides and betalactams have proved edffective in the treatment of lyme borreliosis. the efficacy if other antibiotics especially the carbapenems, telithromycin and tigecycline is based on in vitro studies [20/74/160] There are no clinical studies except for imipenem, which was given a favourable clinical assessment [64]
The treatment of lyme borreliosis can be conducted either as monotherapy [159] or with a synchronous combined therapy.
The ecciciency of a combined antibiotic therapy has not been scientifically attested to date; this form of treatment is based on microbiological findings and on empirical data that have not so far been systematically investigated.
* only the substances metronidazole and hydroxychloroquine have an effect on encysted forms. [101]
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