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Several areas of debate concerning Lyme disease treatment exist and include issues on 1) the efficacy of treating EM with traditional oral antibiotic programs, 2) the benefit of prophylactic antibiotics after a tick bite, 3) the use and choice of long term intravenous antibiotics in those patients with neuroborreliosis, 4) the evaluation and treatment of co-infections caused by Ehrlichiosis, Babesiosis, and Bartonella species, and 5) the purported role of the now FDA withdrawn Lyme vaccine, LYMErix (see An Ounce of Prevention). The first four areas will be discussed in this section.
The traditional recommended treatment, upon finding an engorged tick and making the clinical diagnosis, is a seven to ten day regimen of doxycycline (100mg po BID) for ages > eight, excluding pregnant women (118). This regimen has the advantage of curing the disease Ehrlichiosis, caused by a gram-negative bacterium carried by Ixodes ticks and a frequent coinfection in endemic areas. Second line therapy includes medications such as amoxacillin and cefuroxime. However, Lyme treating physicians are all cognizant of failures with this traditional approach and, in fact, most quoted published series report less than perfect response rates with doxycycline, amoxacillin, and other oral antibiotic programs. Many quote success rates as low as 80%, with 90% being the highest success rate recorded (119). The reasons for this are poorly understood but almost certainly reflect features such as delay in treatment, inoculum and strain effect of Bb…i.e. the quantity of organism introduced to the patient, as well as various subtleties of various strains and the immune response, areas poorly understood in LD (see previous discussion). As stated earlier in this text, we concur with the recommendations of many Lyme treating physicians who provide a course of doxycycline at 200mg twice daily for up to 30 days as the optimal approach to successful treatment of EM/Lyme, specifically with the goal of aborting cases which otherwise might develop late sequelae.
With regard to prophylactic antibiotic use after a tick bite, recent research suggests that a single dose of 200mg doxycycline given within 72 hours after the I. scapularis bite can decrease the chances of developing LD by 87% in a setting where overall transmission rates were around 3.2% (120). It is interesting to note that LD occurred only after the bite of the nymph form of tick, consistent with what our text has proposed (see discussion above). By the author’s reports, infection occurred only if the tick was at least partially engorged and had been estimated to be present > 72 hours. We have previously discussed and disagreed with these timelines for infection (see previous discussion).
Critics of this study point out that a panel of experts of the Infectious Diseases Society of America (IDSA) does not endorse routine antimicrobial use in this setting. They also state that, even in an endemic setting such as upper NY state, approximately 40 people would have to be treated to prevent one case of Lyme disease and that the ratio will be much higher in areas of low endemicity. Moreover, since most cases of LD result from unrecognized tick bites, any benefit from antimicrobial antibiotic use is likely to be reduced significantly. Despite these negative comments, the Jemsek Specialty Clinic is pleased to disagree with the IDSA (to which Dr. Jemsek belongs) and recommends doxycycline prophylaxis for a situation in which an Ixodes scapularis tick has been attached for > 72 hours. Parenthetically, the same ID Society has put forth a formal position on LD treatment which states that the long term use of antibiotics for LD is unnecessary and that persistent LD is rare and overdiagnosed. The panel of nine who claimed this position for the ID Society included few highly experienced LD treating physicians, and included Dr. Allen Steere. The irony here is practically palpable. Steere is a rheumatologist!
For almost two decades, intravenous (IV) therapy, usually with the once daily cephalosporin antibiotic, ceftriaxone (Rocephin), has been an option for various stages of LD. Parenteral or IV therapy is, however, by nature more difficult, sometimes less accessible, potentially more hazardous, and clearly more expensive. The current consensus for the role of IV antibiotics is that it should be reserved for the treatment of patients with prolonged and life altering neurological findings, whether CNS or peripheral. By definition, these conditions reflect advanced neuroborreliosis. In recent years, a more controversial indication for the use of IV therapy has been employed, namely for treatment of the chronic or persistent LD or “post-LD syndrome”, which involves much more subjective ailments such as fatigue, musculoskeletal pain and cognitive difficulties (see earlier discussion). As reported in a summer 2001 article in the New England Journal of Medicine, approximately 125 individuals with “chronic LD” were randomized into two groups, one receiving placebo and the other 30 days of IV Rocephin followed by 60 days of oral doxycycline. In essence, the trial showed no difference in benefit as gauged by Quality of Life (QOL) questionnaires (121). Certain reviewers saw this as an affirmation of their belief that IV therapy was overused and wasteful, whereas others criticize various aspects of the trial, e.g. arbitrary length of IV antibiotics, the inherent faults in QOL reporting, etc. It’s safe to say that the trial has changed few minds and that opposing parties simply reaffirmed their pretrial bias. We regret that this trial did not include, for reasons unexplained, LD patients with documented neurological deficits. On the other hand, the trial was so badly and fatally flawed that this point almost does not matter. Hopefully, better science will follow soon. We deserve it and we need it …… maybe we’ll have to do it.
The Jemsek Specialty Clinic has attempted to integrate various elements of what is known about persistent LD and the biology of the infection. On reflection, it seems reasonable to assume that a chronic CNS infection with a slowly replicative organism like Bb will require prolonged therapy, preferably with an antibiotic with a delivery that allows for the highest drug levels possible in the CNS. For this reason, we treat severe and chronic CNS manifestations of neuroborreliosis with IV antibiotics for as long as 16-32 weeks and have noted repeatedly that clinical improvement may not become apparent until several months into therapy, although we generally see some effect by the third month and certainly the fourth month of therapy (more on concepts of therapy below).
The emerging research on a cystic form of Bb has changed the long-term treatment picture. In theory, biologic and environmental stress promotes conversion or “morphing” of the spirochetal form to a cystic form, apparently within hours, and this form exhibits different surface antigens and therefore a different presentation to the immune system. The converse is documented, i.e. the cystic form can readily convert back to the spirochetal form (122). It is known that antibiotic pressure, utilizing medications effective against the spirochetal form, accelerates cyst formation (123). In vitro, incubation of Bb with ceftriaxone, for example, leads to Bb cyst formation after just four hours, much faster and more completely than doxycycline exposure (123). As expected, neither of these compounds (or any other commonly used antibiotics in LD) have any effect of the cyst. On the other hand, many studies indicate that metronidazole is effective in killing the cystic form, but not the spirochetal form, of the Bb bacteria (124). For that reason, many Lyme aware physicians have begun to see the value of using combination antibiotic therapy with the addition of the agent metronidazole. In our experience, patients with Bb infection routinely develop a Herxheimer reaction (see below) in response to treatment with metronidazole and occasionally these reactions may be severe and limiting. Long term suffering neuroborreliosis patients seem to have the most difficult time with this therapy, suggesting that the cyst load may be higher in this patient group, particularly in the CNS. If this is the case, one might assume that conversion to a cyst form is a natural evolution of the illness for at least some Bb strains.