## 5 In Vitro Antimicrobial Susceptibility Pattern of the _B. burgdorferii_ Complex
### Aminoglycosoides, Glycopeptides, Streptavidins, Fusidic Acid and Nalidixic Acid  
When tested against 11 _B. burgdorferi_ s.l. isolates, typical aminoglycoside derivatives such as tobramycin, amikacin, apramycin and ribostomycin showed no or no significant in vitro activity. Spectinomycin was the anomaly with MIC\({}_{50}\) and MIC\({}_{90}\) of 0.5 and 2 \(\upmu\)g/mL respectively; the MIC\({}_{90}\) of all other compounds was \(\geq\)32 \(\upmu\)g/mL. Similarly, borreliae were fully resistant to fusidic acid and nalidixic acid, with MIC\({}_{90}\) values > 4 and \(>\)256 \(\upmu\)g/mL, respectively [17; 52]. Interestingly, vancomycin (MIC\({}_{90}\): 1 \(\upmu\)g/mL), daptomycin and line-zolid, which usually do not have in vitro activity against common Gram-negative bacteria, displayed a significant antibiotic effect against _B. burgdorferi_ s.l. [42; 65; 99]. The same is true for streptograms such as quinupristin/dalforpistin (MIC\({}_{90}\): 0.125 \(\upmu\)/mL) but not for teicoplanin (MIC\({}_{90}\): \(>\)8 \(\upmu\)g/mL) [17; 52]. Concerning sulphonamides, dapsone, sulfachlor-pyridazine and trimethoprim drugs showed low activity against the stationary phase of _B. burgdorferi_ s.l., and sulfamethoxazole was the least active drug among them in vitro. It is worth noting that trimethoprim did not show synergy in the drug combinations with the three sulfadrugs. However, sulfadrugs and trimethoprim, when combined with other antibiotics such as doxycycline, ciprofloxacin and cefuroxime, were more active than the respective single drugs. Nevertheless, none of the sulfadrug combinations were as efficacious as daptomycin and they were unable to completely eradicate borreliae as stationary phase cells in vitro [100]. Hygromycin A, a known antimicrobial produced by _Streptomyces hygroscopicus_, targets ribosomes and is selectively taken up by _B. burgdorferi_ s.l. Recently, it has also been found that hygromycin A accumulates in _B. burgdorferi_ s.l. and can eradicate LB in mouse models. Moreover, it was less disruptive to the fecal microbiome than other clinically relevant antibiotics because of its selective uptake by borreliae [69].  
Table 2 summarizes the current in vitro data on the susceptibility pattern of _B. burgdorferi_ s.l. with regard to established and more recently introduced antimicrobial agents. The MIC\({}_{90}\) values determined using micro- and macrodilution methods for traditional \(\upbeta\)-lactams, carbapenem, macrolides, tetracyclines, quinolones and glycoptids against borreliae are more or less in agreement with the MIC values provided by other investigators in the current literature [18; 36; 37; 39; 40; 42; 43; 99]. Based on these data, mezlocillin, piperacillin, ceftiaxone, azithromycin, teilithromycin and erythromycin appear to have the greatest in vitro activity on a \(\upmu\)g/mL basis, exhibiting low MIC\({}_{90}\) values \(\leq\) 0.03 \(\upmu\)g/mL and MBC\({}_{90}\) values \(\leq\) 2 \(\upmu\)g/mL. For all of the other antimicrobial agents, the MIC\({}_{90}\) values were found to be \(\geq\)0.06 and \(>\)2 \(\upmu\)g/mL [17; 52]. This is substantiated further by recent findings that azlocillin completely kills late log phase and 7 to 10-day-old spirochetes in the stationary growth phase, and that azlocillin and cefotaxime can efficaciously kill in vitro doxycycline-tolerant _B. burgdorferi_ s.l. Moreover, a combination of azlocillin and cefotaxime completely killed doxycycline-tolerant spirochetes. When tested in vivo, azlocillin has shown good efficacy against _B. burgdorferi_ s.l. in a mouse model [101]. These findings suggest that azlocillin, mezlocillin, and piperacillin may be more efficacious in treating _B. burgdorferi_ s.l. than traditional penicillin. Future research on these penicillin derivatives and evaluation of their potential role in treating LB are warranted.