## 9 Evidence from Isolates from Patients and Primates with Spirochetal Persistence
Consequently, despite persistence there was no evidence for acquired antimicrobial resistance in these clinical _B. burgdorferi_ s.l. isolates re-cultured after antimicrobial chemotherapy [7]. These observations corroborate those of [PERSON] et al., who used xenodiagnosis to demonstrate persistence of borreliae for up to 3 months in 4 out of 10 animals after prolonged therapy with doxycycline and ceftaxone in a mouse models [153]. The results for EM patients treated with antibiotics suggest that the population of spirochetes detected after chemotherapy may differ genetically from the bacterial population that had initiated the infection. This is further supported by observations that the plasmid pattern can differ in isolates belonging to the same genospecies cultured from the patient's EM site before and after chemotherapy [7]. These differences are likely to result from the selection of clones that are capable of persisting with the selection pressure rapidly resulting in the selection of clonal subtypes of the same or co-infecting genospecies [7]. Similarly, the persistence of group A streptococci and _Chlamydia_ spp. after chemotherapy treatment of an infection has been observed but is not necessarily equivalen \begin{table}
\begin{tabular}{c c c c c c} \hline \hline  & & \multicolumn{4}{c}{**EM Patients**} \\ \hline
**Clinical information** & 1 & 2 & 3 & 4 & 5 \\ \hline Sex & F & F & F & F & M \\ Age (yrs.) & 43 & 38 & 53 & 68 & 36 \\ Symptoms at first visit a & MEM & EM & EM & EM, L, PFP & EM, L \\ Recognition of tick bite & Yes & Yes & No & No & Yes \\ Size of EM (cm) & \(7\times 2\); \(6\times 8\) & \(10\times 16\) & \(7\times 11\) & \(9\times 12\) & \(7\times 12\) \\ Systemic complaints b & None & None & Yes & None & None \\ Initial treatment & \multicolumn{2}{c}{Cefriaxone \(1\times 2\)} & \multicolumn{2}{c}{Amoxicillin \(3\times\)} & \multicolumn{2}{c}{Cefuroxime \(2\times\)} & \multicolumn{2}{c}{Azithromycin 2} \\  & g i.v. & \(500\) mg p.o. & \(500\) mg p.o. & \(500\) mg p.o. & \(\times\) 500 mg p.o. \\ Duration (d) & 14 & 14 & 14 & 14 & 1 \(\times\) 500 mg p.o. \\ \hline IgM-IFT (titre) c & 256 & 128 & Neg. & Neg. & Neg. \\ IgG-IFT (titre) c & 128 & 128 & Neg. & Neg. & Neg. \\ Initial culture & _B. afzelli_ & _B. garini_ & _B. afzelli_ & _B. afzelli_ & _B. afzelli_ \\ MIC/MBC d & 0.0156/0.25 & 0.0312/0.5 & 0.0625/8 & 0.0625/8 & 0.0039/0.125 \\ Follow-up culture & _B. afzelli_ & _B. garini_ & _B. afzelli_ & _B. afzelli_ & _B. garini_ \\ MIC/MBC d & 0.0312/0.5 & 0.0625/1 & 0.125/16 & 0.0625/8 & 0.0019/0.125 \\ \hline \hline \end{tabular}  
* EM: erythema migrans, MEM: multiple erythema migrans, PFP: peripheral facial palsy, L: lymphocyte.
* Systemic complaints: fever, headache, myalgia, c No significant titer change at second biopsy, d MIC/MBC (ng/mL) of antimicrobial used for specific therapy in the individual patients.  
\end{table} 
Table 4: Clinical information and laboratory data on five patients with EM and a culture-confirmed persistent _B. burgdorferi_ s.l infection after antimicrobial chemotherapy (modified from [152]). failure or a relapse of symptoms [154; 155]. These findings are in concordance with animal experiments, demonstrating the survival of infectious _Borrelia_ isolates in antibiotically treated mice. Survival was correlated with genetic recombination and diminished levels or complete loss of lp25 and lp28-1, linear plasmids that are known to carry genes that are important for the infectiousness of borreliae. Such attenuated residual spirochetes were well adapted to persist in their hosts, but were no longer transmissible to new mammalian hosts [153]. In one patient, however, the plasmid pattern of the two subsequent _B. garini_ isolates did not change at all despite antibiotic treatment. Therefore, in some individuals, survival of small numbers of bacteria may result in persistent complaints [7; 60].