## 6 Differences in the Antimicrobial Susceptibility of _Borrelia burgdorferi_ Genospecies  
The heterogeneity of the antibiotic susceptibilities of _B. burgdorferi_ s.l. isolates to antimicrobials has been debated in the scientific literature [17; 103; 102]. In order to demonstrate in vitro the possible differences in the MIC and MBC values for some targeted antimicrobial agents at the genospecies level, a variable number of isolates belonging to different genospecies have been investigated using varied parametric and non-parametric statistical approaches [36; 51; 55; 58; 59; 65; 83; 104]. Several studies used the Kruskall-Wallis test in the genospecies-based statistical analysis of measured MIC values. They found slight but significant differences between the in vitro susceptibilities (MIC values) of the various genospecies to penicillin, amoxicillin, aztreonam and quinupristin/dalfopristin [51; 55; 65]. Similarly, careful evaluation of the MBC values for quinolones revealed that the MBC values of grepafloxacin, clinafloxacin, sitafloxacin and gemifloxacin in _B. burgdorferi_ s.s. isolates were significantly higher than for _B. afzeli_, _B garini_, _B. valaisiana_ and _B. bissettiae_ isolates (\(p<0.05\)) after 72 h of incubation [58]. Other authors, however, found no significant differences in the susceptibilities of strains belonging to the different _Borrelia_ genospecies that are pathogenic for humans [44]. This is most likely due to differences in study designs, the number of isolates used, and the test methodology. Time-kill experiments, however, found lower in vitro activity for some quinolones and ketolides in _B. burgdorferi_ s.s. isolates than in the other _Borrelia_ isolates investigated [52]. These data again point to a somewhat slower killing rate by these antimicrobial agents in some _Borrelia_ isolates and to possible differences in the spirochete drug interactions with regard to the genospecies evaluated [58; 59]. This could be of interest, as _B. burgdorferi_ s.s. and _B. afzeli_ (which represents the most frequently isolated human-pathogenic genospecies in Europe [105]) seem to be significantly less susceptible to some antimicrobial agents in vitro. In contrast, _B. garini_ isolates appear to be more sensitive to many antibiotics than isolates of the genospecies _B. afzeli_, _B. burgdorferi_ s.s., _B. bissettiae_, and _B. valaisiana_[51; 55; 58; 65]. These findings are in close agreement with experimental data published by [PERSON] et al. [75], [PERSON] et al. [104] and [PERSON] et al. [83], demonstrating that _B. garini_ strains are more sensitive to the antimicrobial agents that are used therapeutically. Finally, differences in antibiotic susceptibility also exist within a single species [7; 75]. As demonstrated earlier by [PERSON] et al. [75], individual bacteria within a wild-type population can differ slightly in their susceptibility to various antimicrobial agents. Nevertheless, the observed differences are largely marginal and of questionable clinical relevance for the treatment of LB, as they usually do not exceed the critical serum concentrations for most substances to become inefficiacious [7; 83; 106]. Unfavorable pharmacodynamic and pharmacokinetic conditions in some LB patients infected with \"resistant\" strains may enable the survival of spirochetes at immunologically privileged sites, despite prolonged antibiotic therapy [52]. Moreover, it has been proposed that the more challenging long-term manifestations of LBsuch as ACA and LA, may be associated in part with more-resistant strains [17]. To date, however, the testing of first isolates and strains derived from patients with spirochetal persistence after treatment has been an absolute exception [17]. The recovery and comparison of such isolates is clearly required in order to substantiate these speculations [17; 52; 58].