Antibiotic Treatment

Is long term antibiotic treatment a taboo?

It is accepted that patients with tuberculosis undergo long term therapy over 6 months and up to 2 years, using tuberculosis medicine (tuberculostatics), because the mycobacterium tuberculosis is a bacterium with generation cycles, i.e. a slowly growing bacterium. Borrelias are bacteria with a long generation cycle, too. Even though, long term therapy is not prescribed. The strategy of a long-term antibiotic treatment appears to be successful for chlamydia-infections too as recent studies showed (1). You can also find older studies therefor (10). The long-term antibiotic treatment is also used in case of erysipelas and forms of acne.

A long lasting bacterial bronchitis in children is believed to be origin of chronic cough. Here again, biofilm-producing pathogens are suspected to play a role in this chronic form of bronchitis; a long term antibiotic treatment is recommended in this case (5).

Further research in Basel shows that slower growing bacteria and slower growing fractions of bacteria can be particularly problematic for antibiotic treatments (6); again, longer antibiotic treatments are advised. Borrelias are slower growing bacteria, too. We don’t know, why it is not recommended for this bacteria.

 

A combination of antibiotics?

In other infections, such as legionella, TBC and HIV (AIDS), the success of the therapy can be enhanced by a combination of at least two antibiotics. Also for malaria there is now a recommendation for a combination therapy to prevent further resistances. However, it is not recommended for Borrelias.

Now (2015) also the first study published, which indicates that even in Lyme disease a combination antibiotic therapy might not entirely outlandish (12) and the next in 2016 (13).

In the case of a possible chlamydia infections, the treatment with a combination of antibiotics is also promising (1), (10). Many Lyme patients are also diagnosed with co-infections such as chlamydia (of course also with Chlamydia pneum.). We also find infections with mycoplasma (2), (11) and/or yersinia and/or ehrlichia, Epstein-Barr-virus (EBV), etc.

The International Lyme and Associated Diseases Society (ILADS) and the German Borreliosis Society (DBG) both recommend long term and combined antibiotic therapies since a long time.

 

What about Ceftriaxon?

We can also support Klempner’s study in 2013 (7) thanks to our own experience. A mono-therapy with ceftriaxon does not bring significant improvements of the patient’s symptoms, not even in the long term. It is effective against the native spiral form of borrelia. But it is also important to simultaneously tackle the persister forms of borrelia and other pathogens. Some of these can also build persister forms (see: General Information, (2), the study mentioned above (1) and the Comments and Professional Opinion (1)-(15)) and biofilms. As a result, a combination of antibiotics should be used as long as there is not one antibiotic that is capable of treating all the persistent forms of borrelias and other pathogens, and co-infections and biofilms. We have been using a combination of antibiotics for some time. In our experience, we use ceftriaxon rather rarely and even doxycycline in a mono-therapy (not in combination with other antibiotics) has shown no significant success for a longer time.

It might be worth reconsidering the treatment with ceftriaxon as it does not tackle persister forms of borrelias (or other pathogens), nor does it help with possible co-infections and biofilms. It is indeed possible to combine other antibiotic substances that are better processed and that show fewer risks and side effects as ceftriaxon. These substances definitely improve the risk/success relation for the patients during the therapy. There are even hints that ceftriaxon and doxycyclin may favor the formation of persistent forms of borrelias (4).

 

Risks and side effects of long term antibiotic treatment

A long term treatment with antibiotics or a combination-therapy does not come without any risks; this is clear to any therapist. This is why we insist on regular control tests (symptoms, laboratory, ECG, ultrasound) and the administration of supportive substances (e.g. probiotics, CoEnzym Q10) before, during and after the long term treatment in order to reduce risks. Possible risks are, for instance, diarrhea or pseudomembranous enterocolitis associated to antibiotic treatments. Naturally, if problems arise during the treatment (diarrhea, allergies, etc.) or if the laboratory values and other tests show a risk, it has to be stopped and alternatives must be found. It is crucial that the patient is medically assisted and watched.

However, if no side effects occur, if none of the control tests show pathological findings, if the pain is reduced and other improvements are constantly seen, then what argument is there against long term treatment? For other conditions and infections, it is also accepted to continue with the therapy until the symptoms have improved or completely resolved.

 

Which dosage?

When treating infections, all therapists face two questions: what is the appropriate dose of antibiotics and how long should it be prescribed for? This will depend on the individual condition the age and the gender of the patient. It will also depend on how well the patient will metabolise the medication (cytochrom-P450-system, gender medicine, etc.)  Another influential factor is the immune system of the patient, i.e. how much support does it need in order to ‘fight’ the infection?

We develop multi resistant bacteria from frequent, untargeted and changing administration of antibiotics in the breeding of animal. A combination of antibiotics can reduce this risk (8). In general, even the general medical community agrees that developing antibiotic-resistances with borrelias is practically unknown or extremely rare or it needs several steps. A new study recommends using aggressive antibiotic strategies against bacteria that develop very slowly or in several steps antibiotic-resistances (9). Borrelia develope no antibiotic-resistances.

As mentioned at the beginning in the explanation of possible influential factors, supporting measures can also have effects on the length and intensity of the antibiotic treatment. A change of diet, anti-inflammatory therapy, naturopathic procedures to strengthen the immune system and well adjusted exercising and physiotherapy are one these possible measures

A long term antibiotic treatment or even a simple antibiotic therapy is not recommended if the immune system manages the infection on its own, whether because the strain is not sufficiently aggressive (virulent) or because the immune system is strong enough. In this case, the affected person has positive antibody titers, but no symptoms (i.e. s/he is not ill). These patients will not need any therapy.

The practical background, that no patient should return to and being evaluated by the therapist after a three-week therapy because s/he is considered sufficiently treated by the general medical opinion and only needs to wait for the remaining symptoms to fade away, is questionable. Tough, if those remaining symptoms do not fade away, then a symptomatic (not antibiotic) therapy is usually applied, even if it is unsuccessful. We believe that there are still remaining active pathogens; however this opinion is not shared by the medical community.

The studies of Prof. Zeidler (refer to (1)) and Prof. Saviola (refer to (3)) might be an indication that there are indeed some pathogens that trigger chronic ailments, that antibiotic treatments are successful and that there are not only autoimmune or inflammtion processes at stake. Maybe it is worth to consider a two-ways strategy (3).

It is important to mention that a Herxheimer reaction may occur during the antibiotic treatment. This is often not recognized and mistaken for intolerance or an allergic reaction to the antibiotic which leads to an interruption of the treatment.

With an antibiotic treatment, we can only reduce the amount of the germs. For overcoming of the infection and/or eradication of all pathogens, we need the immune system. But sometimes it is also enough, if the immune system can control the germ. Then, the patient is symptom-free. Some antibiotics (e.g. azithromycin and doxycycline) and even some naturopathic products have immunomodulatory and anti-inflammatory effects that can be used, especially when other anti-inflammatory substances do not show any effect.

 

Alternatives

Because the aim is always to improve the immune system, there are, of course, certain naturopathic therapies and method that can be helpful, especially in patients who cannot tolerate, for whatever reasons, an antibiotic treatment.

Both infections and autoimmune illnesses often lead to inflammations. Therefore, an anti-inflammatory therapy is always helpful to start with as it will reduce the intensity of the symptoms, which are triggered by the inflammation. For this purpose, there are synthetic and natural substances.

Regarding dosages in the case of doxycycline, you will find information in the section General Information on how to measure the doxycycline levels in the blood in order to adapt the dosage according to the patient’s needs. This is fundamental for us because there are patients who are not in the therapeutic range with 200mg of doxycycline. This could explain and identify certain treatment failures.

 


(1)   Prof. Henning Zeidler: „New insights into Chlamydia and arthritis. Promise of a cure?“, Ann Rheum Dis 2014;73:637-644.

Comment: This study showed that both, Chlamydia trachomatis and Chlamydia pneumomiae, can cause chronical recurrent arthritis!

 

 (2)   Prof. Garth L. Nicolsen et. al.: „Mycoplasma Infections in Chronic Illnesses“, z.B. bei Fibromyalgie, CFS, RA; Medical Sentinel Vol. 4, Oct. 1999; 172-175,191,

Comment: A patient can be infected with several or all strains from one species of bacteria at the same time!

 

(3)   Saviola G et. al. „Clarithromycin in rheumatoid arthritis: the addition to methotrexate and low-dose methylprednisolone induce a significant additive value-a 24 month single-blind pilot studie“, Rheumatol Int. 2013 July 18

(4)   Kersten A., Poitschek S., Aberer E. (1995): Effects of penicillin, ceftriaxone and doxycycline on morphology of Borrelia burgdorferi“, Antimicrob Agents Chemother. 39, 1127-1133

(5)   A. Irnstätter et.al. “Chronischer Husten im Kindesalter“, Kinder- und Jugendmedizin 05/2013, Schattauer 2013, S 336 ff

(6)   Beatrice Claudi et.al. „Variation of Salmonella in Host Tissues Delays Eradication by Antimicrobial Chemotherapy”. Cell, published 14. August 2014, doi: 10.1016/j.cell. 2014.06.045

(7)   Mark S. Klempner et al : Treatment Trials for Post-Lyme Disease Symptoms Revisited. The American Journal of Medicine (2013) 126, 665-669

(8)   Hof H, Dörries Rüdiger: “Medizinische Mikrobiologie”, 5. Auflage, 2014, Georg Thiema Verlag KG, S. 309 (oben), ISNB  978-3-13-125315-6

(9)   Roger D.Kouyos et. al.:„ The path of least resistance: aggressive or moderate treatment?”, Proc.R.Soc. B 2014 281, 20140566, published 24 September 2014

(10) Rihl M, Kuipers JG  et.al. “Combination Antibiotics for Chlamydia-Induced Arthritis: Breakthrough to a Cure?”, Arthritis & Rheumatism, Vol. 62, No. 5, May 2010, pp 1203-1207, American College of Rheumatology

(11) Nicolson GL, Gan R, Haier J.: “Multiple co-infections (Mycoplasma, Chlamydia, human herpes virus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms.”,  APMIS 2003;111:557–66.

(12) Feng J, Auwaerter PG, Zhang Y (2015):”Drug Combinations against Borrelia burgdorferi Persisters In Vitro: Eradication Achieved by Using Daptomycin, Cefoperazone and Doxycycline”, PLoS ONE 10(3): e0117207. doi:10.1371/journal. pone.0117207

(13) Jie Feng, Megan Weitner, Wanliang Shi, Shuo Zhang and Ying Zhang: Eradication of Biofilm-Like Microcolony Structures of Borrelia burgdorferi  by Daunomycin and Daptomycin but not Mitomycin C in Combination with Doxycycline and Cefuroxime, 2016, Microbiol. 7:62. doi: 10.3389/fmicb.2016.00062


 

More studies:

 

  • Bayer ME, Zhang L, Bayer MH. Borrelia burgdorferi DNA in the urine of treated patients with chronic Lyme disease symptoms. A PCR study of 97 cases. Infection 1996; 24 No.5.

 

  • Cameron, DJ. Lyme Disease Clinical Trial – Effectiveness of Retreatment on Health-Related Quality of Life. Abstract, Lyme & Other TBDs: Emerging Tick Borne Diseases, Fri Oct 28th, 2005, Philadelphia, PA.

 

  • Cimmino MA, Accardo S. Long term treatment of chronic Lyme arthritis with Benzathine penicillin. Ann Rheum Dis 1992 Aug; 51(8):1007-8.

 

  • Cimmino MA, Moggiana GI, Parisi M, Accardo S. Treatment of Lyme arthritis. Infection 1996 Jan-Feb; 24(1):91-3.

 

  • Cimperman J, Maraspin V, Lotric-Furlan S, Ruzic-Sabljic E, Strle F. Lyme meningitis: a one-year follow up controlled study. Wien Klin Wochenschr 1999; 111(22-23):961-3.

 

  • Cimmino MA, Moggiana GI, Parisi M, Accardo S. Treatment of Lyme arthritis. Infection 1996 Jan-Feb; 24(1):91-3.

 

  • Dattwyler RJ, Volkman DJ, Luft BJ, Halperin JJ, Thomas J, Golightly MG. Seronegative Lyme disease. Dissociation of specific T- and B-lymphocyte responses to Borrelia burgdorferi. N Engl J Med 1988 Dec 1; 319(22):1441-6.

 

  • Donta ST. Tetracycline therapy for chronic Lyme disease. Clin Infect Dis 1997; 25 Suppl 1:pS52-6.

 

  • Fallon BA et al. Repeated antibiotic treatment in chronic Lyme disease. J Spirochet Tick Borne Dis, 1999 Fall/Winter:p94-101.

 

  • Fallon BA et al. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology, 2007.

 

  • Gasser R, Reisinger E, Eber B, Pokan R, Seinost G, Bergloff J, Horwarth R, Sedaj B, Klein W. Cases of Lyme borreliosis resistant to conventional treatment: improved symptoms with cephalosporin plus specific beta-lactamase inhibition. Microb Drug Resist 1995 Winter; 1(4):341-4.

 

  • Georgilis K, Peacocke M, Klempner MS. Fibroblasts protect the Lyme disease spirochete, Borrelia burgdorferi, from ceftriaxone in vitro. J Infect Dis 1992 Aug; 166(2):440-4.

 

  • Goldings AS, Taylor JP, Rawlings J. Lyme borreliosis in Texas. Tex Med 1991 Sep; 87(9):62-6.

 

  • Hold DA, Pattani NJ, Sinnott JT 4th, Bradley E. Lyme borreliosis. Infect Control Hosp Epidemiol. 1991 Aug; 12(8):493-6.

 

  • Hoffmann H. Lyme borreliosis – problems of serological diagnosis. Infection 1996. Nov-Dec; 24(6):470-2.

 

  • Hudson BJ, Steward M, Lennox VA, Fukunaga M, Yabuki M, et al. Culture-positive Lyme borreliosis. Med J Aust 1998 May 18; 168(10):500-2.

 

  • Klempner MS, Hu LT, Evans J, Schmid CH, Johnson GM, Trevino RP, Norton D, Levy L, Wall D, McCall J, Kosinski M, Weinstein A. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med 2001. Jul 12; 345(2):85-92.

 

  • Krupp, LB et al. Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial. Neurology, 2003. 60(12):p.1923-30.

 

  • Kufko IT, Mel’nikov VG, Andreeva EA, Sokolova ZI, Lesniak OM, Beikin laB. Comparative study of results of serological diagnosis of Lyme borreliosis by indirect immunofluorescence and immunoenzyme analysis. Klin Lab Diagn 1999; 3:34-7.

 

  • Lawrence C, Lipton RB, Lowy FD, Coyle PK. Seronegative chronic relapsing neuroborreliosis. Eur Neurol 1995; 35(2):113-7.

 

  • Luft BJ, Dattwyler RJ, Johnson RC, Luger SW, Bosler EM, Rahn DW, Masters EJ, Grunwaldt E, Gadgil SD. Azithromycin compared with amoxicillin in the treatment of erythema migrans. A double-blind, randomised, controlled trial. Ann Intern Med 1996 May 1; 124(9):785-91.

 

  • Luft BJ, Volkman DJ, Halperin JJ, Dattwyler RJ. New chemotherapeutic approaches in the treatment of Lyme borreliosis. Ann N Y Acad Sci 1988; 539:352-61.

 

  • MacDonald AB, Berger BW, Schwan TG. Clinical implications of delayed growth of the Lyme borreliosis spirochete, Borrelia burgdorferi. Acta Trop 1990. Dec; 48(2):89-94.

 

  • Mursic VP, Wanner G, reinhardt S, Wilske B, Busch U, Marget W. Formation and cultivation of Borrelia burgdorferi spheroplast L-form variants. Infection 1996; 24(3):218-26.

 

  • Oksi, J et al. Borrelia burgdorferi detected by culture and PCR in clinical relapse of disseminated Lyme borreliosis. Ann med, 1999. 31)3):p225-32.

 

  • Oksi J, Kalimo H, Marttila RJ, Marjamaki M, Sonninen P, Nikoskelainen J, Vilijanen MK. Inflammatory brain changes in Lyme borreliosis. A report on three patients and review of literature. Brain 1996. Dec; 119 (Pt6):2143-54.

 

  • Oksi, J et al. Comparison of oral cefixime and intravenous ceftriaxone followed by oral amoxicillin in disseminated Lyme borreliosis. Eur J Clin Microbiol Infect Dis, 1998. 17(10):p715-9.

 

  • Petrovic M, Vogelaers D, Van Renterghem, Carton D, De Reuck J, Afschrift M. Lyme borreliosis – a review of the late stages and treatment of four cases. Acta Clin Belg 1998. Jun 53(3):178-83.

 

  • Preac-Mursic V, Weber K, Pfister HW, Wilske B, Gross B, Baumann A, Prokop J. Survival of Borrelia burgdorferi in antibiotically treated patients with Lyme borreliosis. Infection 1989 Nov-Dec; 17(6):355-9.

 

  • Schoen RT. Treatment of Lyme disease. Conn Med 1989. Jun; 53(6):335-7.

 

  • Steere AC. Lyme disease. N Engl J Med 1989. Aug 31; 321(9):586-96.

 

  • Straubinger RK. PCR-based quantification of Borrelia burgdorferi organisms in canine tissues over a 500-day postinfection period. J Clinical Microbiology 2000; 38(6):2191-2199.

 

  • Straubinger RK, Straubinger AF, Summers BA, Jacobson RH. Status of Borrelia burgdorferi infection after antibiotic treatment and the effects of corticosteroids: an experimental study. J Infectious Diseases 2000; 181(3):1069-1081.

 

  • Straubinger RK, Straubinger AF, Summers BA, Jacobson RH, Erb HN. Clinical and serologic follow-up in patients with neuroborreliosis. Neurology 1998 Nov; 51(5):1489-91.

 

  • Treib J, Fernandez A, Haass A, Grauer MT, Holzer G, Woessner R. Clinical and serologic follow-up in patients with neuroborreliosis. Neurology 1998 Nov; 51(5):1489-91.

 

  • Valesova H, Mailer J, Havlik J, Hulinska D, Hercogova J. Long-term results in patients with Lyme arthritis following treatment with ceftriaxone. Infection 1996; 24(1)98-102.

 

  • Weber K. Treatment failure in erythema migrans: a review. Infection 1996; 24:73-5.

 

  • Wolfe D, Fries C, Reynolds K, Hathcock L. The epidemiology of Lyme disease in Delaware 1989-1992. Del Med J 1994 Nov; 66(11):603-6, 609-13.

 

  • Wahlberg, P et al. Treatment of late Lyme borreliosis. J Infect, 1994. 29(3):p255-61.

 

  • Warner G, O’Connell S, Lawton N. Atypical features in three patients with florid neurological Lyme disease. J Neurol Neurosurg Psychiatry 1999; 67(2):275.

 

  • Waniek C, Prohovnik I, Kaufman MA, Dwork AJ. Rapidly progressive frontal-type dementia associated with Lyme disease. J Neuropsychiatry Clin Neurosci 1995. Summer, 7(3):345-7.

 

  • Zamponi N, Cardinali C, Tavoni, MA, Porfiri L, Rossi R, Manca A. Chronic neuroborreliosis in infancy. Ital J Neurol Sci 1999 Oct; 20(5):303-7.

 

  • Ziska MH, Donta ST, Demarest FC. Physician preferences in the diagnosis and treatment of Lyme disease in the United States. Infection 1996. Mar-Apr; 24(2):182-6.

 

Relapses and failures with short-term antibiotic therapy in Lyme Disease:

 

  • Logigian (1990): After 6 mo’s of therapy, 10/27 patients treated with IV AB’s relapsed or had treatment failure.

 

  • Pfister (1991): 33 patients with neuroborreliosis were treated with IV AB’s. After a mean of 8.1 months 10/27 were symptomatic and borrelia persisted in the CSF in 1 pt

 

  • Shadick (1994): 10/38 pts relapsed (5 with IV) within 1 year of treatment, and had repeated AB treatment

 

  • Asch (1994): 28% relapsed w/ major organ involvement 3.2 years after initial treatment

 

  • Aalesova (1996):10/26 relapsed or progressed at 36 mo

 

  • Trieb (1998): >50% pts symptomatic after 4.2/+/- 1.2 yrs

 

  • Shadick (1999): 69/184 (37%) report a previous relapse

 

Benefits of longer antibiotic therapy in disseminated Lyme Disease:

 

  • Wahlberg,P. et al, Treatment of late Lyme borreliosis. J Infect, 1994. 29(3): p255-61

 

  • Donta, ST., Tetracycline therapy for chronic Lyme disease. Clin Infect Dis, 1997. 25 Suppl 1: p.S52-6.

 

  • Oksi, J et al., Comparison of oral cefixime and intravenous ceftriaxone followed by oral amoxicillin in disseminated Lyme borreliosis. Eur J Clin Microbiol Infect Dis,1998.17(10):p715-19

 

  • Oksi, J., et al. Borrelia burgdorferi detected by culture and PCR in clinical relapse of disseminated Lyme borreliosis. Ann Med, 1999. 31(3):p.225-32

 

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