Next Article in Journal
Bacteriophages and Lysins as Possible Alternatives to Treat Antibiotic-Resistant Urinary Tract Infections
Previous Article in Journal
Biofilm Control Strategies: Engaging with the Public
Previous Article in Special Issue
Antimicrobial Susceptibility and Characterization of Resistance Mechanisms of Corynebacterium urealyticum Clinical Isolates
Open AccessCommunication

Bacteriostatic and Bactericidal Effect of Tigecycline on Leptospira spp.

Department of Veterinary Sciences, University of Pisa, Viale delle Piagge 2, 56124 Pisa, Italy
*
Author to whom correspondence should be addressed.
Antibiotics 2020, 9(8), 467; https://doi.org/10.3390/antibiotics9080467
Received: 30 June 2020 / Revised: 28 July 2020 / Accepted: 30 July 2020 / Published: 30 July 2020

Abstract

Tigecycline is a relatively new antimicrobial, belonging to glycylcyclines with antimicrobial activity against a large spectrum of bacteria. Very few data are available on its effect on Leptospira spp., which consist in a bacteriostatic mechanism. The aim of this investigation was to evaluate the bacteriostatic and bactericidal effect of tigecycline on reference Leptospira strains belonging to 16 serovars. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined through the microdilutions method, and tetracycline was used as the control. Results showed that tigecycline had higher MIC and MBC values than tetracycline. Obtained MIC values were between 4 and 32 µg/mL, while MBC values between 16 and >128 µg/mL. Patoc (MIC: 4 µg/mL; MBC: 16 µg/mL) resulted in the most susceptible serovar, while the most resistant were Bataviae (MIC: 32 µg/mL; MBC: 64 µg/mL), Bratislava (MIC: 8 µg/mL; MBC 128 µg/mL), and Tarassovi (MIC: 8 µg/mL; MBC: >128 µg/mL). This is the first investigation focused on the effect of tigecycline against Leptospira spp. reference strains. Since tigecycline is used as a treatment for bacteremia and urinary tract disease, and these symptoms could be linked to Leptospira infection, the possibility of using this antibiotic as a treatment for leptospirosis should be evaluated. Further studies are needed to explore the possibility to use tigecycline for in vivo application against Leptospira.
Keywords: Leptospira; minimum inhibitory concentration (MIC); microdilutions method; tigecycline; antibiotic susceptibility; leptospirosis Leptospira; minimum inhibitory concentration (MIC); microdilutions method; tigecycline; antibiotic susceptibility; leptospirosis

1. Introduction

Leptospirosis is a zoonotic re-emerging disease caused by spirochetal Gram-negative bacteria belonging to genus Leptospira [1]. Recently, more than 260 antigenically distinct serovars of Leptospira spp. were isolated and identified, and the genus Leptospira was sub-grouped, based on it DNA relatedness to pathogenic, intermediate, and saprophytic species on the basis of the different levels of virulence exhibited for animals and humans. In detail, pathogenic Leptospira causes mild to severe infection, intermediate Leptospira may potentially be a pathogen and is responsible for mild infections, while saprophytic Leptospira spreads in environments and is a nonpathogen [2,3,4]. Recent studies highlighted the important role of intermediate and saprophytic Leptospira in the epidemiology of leptospirosis, because these can share habitats and could give rise to recombination events with pathogenic serovars [5,6,7].
Leptospirosis is diffused worldwide and occurs in tropical, subtropical, and temperate zones, representing public health problems, since its epidemiology involves humans and domestic and wild animals, which can be maintenance or accidental hosts [1,8,9]. Maintenance hosts, generally do not develop symptoms referable to disease and they represent important renal carriers, contributing to maintaining and sharing the infection, shedding Leptospira with urine in the environment. The accidental contact with Leptospira colonized urine represents the primary cause of incidental infection, producing clinical diseases [1,4]. For these reasons, Leptospira epidemiology is strictly connected to maintenance host species [10]. Therefore, specific Leptospira serovars are related to specific animal species, which involves specific maintenance hosts. Generally, for example, rodents are associated with Icterohaemorrhagiae and Ballum serogroups [11,12,13], swine with Pomona and Tarassovi serogroups [14,15,16,17,18], horse with Bratislava serogroups [19,20], and bovine and ovine with Sejroe serogroups [21,22].
Leptospirosis by pathogenic serovars can cause mild to severe infections in both humans and animals. Most cases are mild and they resolve spontaneously. [23]. Conventionally, the treatment for acute and severe leptospirosis consists of strong antimicrobial therapy with tetracycline, penicillin, or doxycycline [1,23]. Generally, molecules belonging to the tetracycline class are those mainly used in veterinary and human practices [1,23,24,25].
Tigecycline is a relatively new antimicrobial, belonging to glycylcyclines, which derive from tetracyclines [26].
Tigecycline showed antimicrobial effects in vitro against many Gram-positive and Gram-negative bacteria, including multi-drug resistant strains (methicillin resistant Staphylococcus aureus, extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, multi-drug resistant Acinetobacter baumanii, and vancomycin-resistant Enterococcus spp.) [27,28]. The action of tigecycline consists of a bacteriostatic mechanism, which relies on the binding of 30 s ribosomal subunits of bacteria and blocking the entry of transfer of RNA [26].
Studies on the antimicrobial effects on Leptospira isolates or reference cultures are scarce, probably due to problems in the determination of antibiotic susceptibility [1,23]. A standardized microdilution method has been developed to accurately investigate the Leptospira antibiotic susceptibility, resolving the difficulties related to preventing the contamination of the medium, evaluating the bacterial growth, and reproducibility of the assay [29,30,31].
The aim of this investigation was to evaluate, through the microdilutions method, the bacteriostatic and bactericidal effects of tigecycline on reference Leptospira strains belonging to 16 serovars.

2. Results

Table 1 shows the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of tetracycline and tigecycline for different strains of Leptospira spp.
For tetracycline, MIC values were between 0.5 and 2.0 µg/mL, while MBC values were between 16 and 64 µg/mL. Canicola, Autumnalis, and Hebdomadis resulted in the most susceptible serovars, with MIC values of 0.5 µg/mL, while MBC values were between 16 and 32 µg/mL. On the other hand, Tarassovi and Ballum resulted in the most resistant serovars with MIC and MBC values of 2 and 64 µg/mL, respectively.
Concerning tigecycline, obtained MIC values were between 4 and 32 µg/mL, while MBC values between 16 and >128 µg/mL. Patoc resulted in the most susceptible serovar, with MIC and MBC values of 4 and 16 µg/mL, respectively. Additionally, the most resistant serovars were Bataviae (32 µg/mL for MIC and 64 µg/mL for MBC), Bratislava (8 µg/mL and 128 µg/mL), and Tarassovi (8 µg/mL and >128 µg/mL).

3. Discussion

Treatments for Leptospira infections are based on the use of antibiotics belonging to a few specific molecules, generally tetracyclines. These antibiotics are conventionally used in medicine, thanks to no antimicrobial resistant events highlighted for Leptospira. The knowledge of antibiotic treatments against leptospirosis is strictly connected to in vivo clinical evaluation, usually in patients with severe and acute Leptospira infections [1,4,23]. Very few studies explored the efficacy and mechanisms of the action of new chemotherapeutic molecules [29,30,31]. This is the first investigation showing the in vitro effect of tigecycline against Leptospira spp.
The obtained results were consistent with other data available in literature, according to which tetracycline MIC values for Leptospira reference strains or isolates are, on average, between 0.25 and 6.25 µg/mL [29,30,31,32,33,34]. Considering that the results obtained for tetracycline were very similar to those reported in literature, it is correct to suppose that the results for MIC and MBC for tigecycline were also similar, not under- or overestimated. Since tetracycline and tigecycline belong to the same antibiotic class, it is reasonable to exclude any causes of strain attenuation due to the passages for culture maintenance, mutation, or acquisition of genes for antibiotic resistance.
Results showed that tigecycline had higher MIC and MBC values than tetracycline, used as the control. To the best of the authors’ knowledge, no studies have focused on the tigecycline effect on Leptospira, excluding one in vivo assay. An administration of 5 mg/kg/day of tigecycline for 5 days was useful to reduce the presence of spirochetes in the blood of hamsters experimentally infected with 105 Leptospira interrogans serovar Canicola [35].
Considering spirochetes sensu latu, tigecycline showed inhibitory effects on Borrelia spp. Borrelia burgdorferi was susceptible to tigecycline at concentrations between 0.006 and 6 µg/mL [36,37,38,39]. Additionally, for Borrelia bavariensis, B. garinii, B. afzelii, B. spielmanii, B. valaisiana, and B. lusitaniae, MIC values between 0.012 and 0.5 µg/mL have been reported [38,39]. Moreover, tigecycline MBC values for Borrelia spp. were between 4 and 16 µg/mL [39]. Results on the Borrelia spp. tigecycline effect were similar to those obtained in this investigation against Leptospira.
Although the tigecycline effect was investigated only in one in vivo study on Leptospira and in other studies on different spirochetes species, this investigation highlighted the bacteriostatic and bactericidal effect on Leptospira spp. strains of this antimicrobial molecule. Since this is the first investigation, further studies should be carried out to understand the antimicrobial effects against Leptospira, using reference strains and isolates, and to determine its potential employment for leptospirosis treatment or antimicrobial resistance. Moreover, further genomic studies are required to elucidate the molecular mechanisms responsible to elucidate the Leptospira antimicrobial susceptibility or resistance. Leptospira species don’t have the ability to acquire genes for antimicrobial resistance during horizontal transfer and, if present, it is probably limited [24,31]. In humans, leptospirosis is a dead-end infection, where human-to-human transmission is very rare, considering that the infection is also usually monomicrobial, horizontal resistance gene acquisition from other bacterial species, as well as in the environment, very difficult [24]. Finally, the major causes of Leptospira antibiotic resistance seem to be related to spontaneous target gene mutations, as was in vitro evaluated for spontaneous mutation of the target gene 16S rRNA and rpsL for the development of spectinomycin and streptomycin resistance, respectively [40,41].

4. Materials and Methods

4.1. Leptospira spp. Strains

In this investigation, the following references of Leptospira strains were employed: Leptospira interrogans serovar Icterohaemorrhagiae (serogroup Icterohaemorrhagiae, strain Bianchi); L. interrogans serovar Canicola (serogroup Canicola, strain Alarik); L. interrogans serovar Pomona (serogroup Pomona, strain Mezzano); L. kirschneri serovar Grippotyphosa (serogroup Grippotyphosa, strain Moskva V); L. borgpetersenii serovar Tarassovi (serogroup Tarassovi, strain Mitis Johnson); L. interrogans serovar Bratislava (serogroup Australis, strain Riccio 2); L. interrogans serovar Hardjo (serogroup Sejroe, serovar Hardjoprajitno); L. borgpetersenii serovar Ballum (serogroup Ballum, strain Mus 127); L. interrogans serovar Copenhageni (serogroup Icterohaemorrhagiae, strain Wijmberg); L. interrogans serovar Bataviae (serogroup Bataviae, strain Pavia); L. interrogans serovar Zanoni (serogroup Pyrogenes, strain Zanoni); L. borgpetersenii serovar Poi (serogroup Javanica, strain Poi); L. interrogans serovar Lora (serogroup Australis, strain Riccio 37); L. interrogans serovar Autumnalis (serogroup Autumnalis, strain Akiyami A); L. interrogans serovar Hebdomadis (serogroup Hebdomadis, strain Hebdomadis); and Leptospira biflexa serovar Patoc (serogroup Semaranga, strain Patoc I).
Each strain was maintained in pure culture in the Ellinghausen–McCullough–Johnson–Harris (EMJH) medium, sub-cultured, and checked weekly for purity and viability.

4.2. Antibiotics

Tigecycline was purchased from Sigma–Aldrich (St. Louis, MO, USA), while tetracycline was purchased from Carlo Erba (Cornaredo, MI, Italy). Tetracycline was employed as the control to compare the results of tigecycline effects.

4.3. Minimal Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC)

The MIC determination was performed by the broth microdilution method, described by Liegeon et al. [31]. Leptospira cultures were quantified with spectrophotometry using optical density at 420 nm (Multiskan™ FC Microplate Photometer; Thermo Fisher Scientific, Haverhill, MA, USA) to reach a turbidity of 0.5 of the McFarland standard, which corresponds to approximately 1.5 × 108 cfu/mL [42,43]. In each well of 96-well plates, two-fold serial dilutions were performed in EMJH media, ranging from 128 to 0.25 μg/mL and from 64 to 0.125 μg/mL for tigecycline and tetracycline, respectively. The final volume in each well was 100 μL, including 5 μL of standardized strain. Two microplates were prepared for each strain: one to determine the MIC and the other for the MBC. They were incubated for 3 days at 30 °C, then 20 μL of resazurin sodium salt (Alfa Aesar, Thermo Fisher Scientific, Haverhill, MA, USA), diluted 1:30 in EMJH medium, was added to each well. The plates were incubated at 30 °C for another 2 days. A change in color from blue to pink indicated Leptospira growth. The MIC value was reported as the lowest concentration able to prevent a color change.
MBC was determined by plating 10 μL from each well (starting from the MIC value to higher antibiotic concentrations) in 1.5% EMJH agar. Plates were incubated at 30 °C for 4 days. The MBC value was reported as the lowest concentration able to prevent bacterial growth.
All tests were performed in triplicate and the results were expressed as the mode.

5. Conclusions

Tigecycline administration is usually employed in human patients for treatment of bacteria that causes pneumoniae and diabetic foot infections, but also for urinary tract infections and bacteremia [44,45]. Considering that bacteremia and urinary tract diseases could be symptoms compatible with Leptospira infection, the possibility of using this antibiotic as a treatment for leptospirosis should be evaluated. Data obtained in this in vitro investigation seem to be encouraging, and further studies are auspicial to explore the possibility of using tigecycline for in vivo application against Leptospira.

Author Contributions

Conceptualization, F.B. and G.C.; investigation, F.B. and G.C.; data curation, F.B., G.C., and F.F.; writing—original draft preparation, F.B., G.C., and F.F.; writing—review and editing, F.B., G.C., and F.F.; supervision, F.F.; funding acquisition, F.B. and F.F. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by University of Pisa, grant “Fondi di Ateneo”.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Adler, B.; de la Peña Moctezuma, A. Leptospira and leptospirosis. Vet. Microbiol. 2010, 140, 287–296. [Google Scholar] [CrossRef] [PubMed]
  2. Vincent, A.T.; Schiettekatte, O.; Goarant, C.; Neela, V.K.; Bernet, E.; Thibeaux, R.; Ismail, N.; Mohd Khalid, M.K.N.; Amran, F.; Masuzawa, T.; et al. Revisiting the taxonomy and evolution of pathogenicity of the genus Leptospira through the prism of genomics. PLoS Negl. Trop. Dis. 2019, 13, e0007270. [Google Scholar] [CrossRef] [PubMed]
  3. Guglielmini, J.; Bourhy, P.; Schiettekatte, O.; Zinini, F.; Brisse, S.; Picardeau, M. Genus-wide Leptospira core genome multilocus sequence typing for strain taxonomy and global surveillance. PLoS Negl. Trop. Dis. 2019, 13, e0007374. [Google Scholar] [CrossRef] [PubMed]
  4. Levett, P.N. Leptospirosis. Clin. Microbiol. Rev. 2001, 14, 296–326. [Google Scholar] [CrossRef] [PubMed]
  5. Cilia, G.; Bertelloni, F.; Mignone, W.; Spina, S.; Berio, E.; Razzuoli, E.; Vencia, W.; Franco, V.; Cecchi, F.; Bogi, S.; et al. Molecular detection of Leptospira spp. in wild boar (Sus scrofa) hunted in Liguria region (Italy). Comp. Immunol. Microbiol. Infect. Dis. 2020, 68, 101410. [Google Scholar] [CrossRef]
  6. Balamurugan, V.; Gangadhar, N.L.; Mohandoss, N.; Thirumalesh, S.R.A.; Dhar, M.; Shome, R.; Krishnamoorthy, P.; Prabhudas, K.; Rahman, H. Characterization of leptospira isolates from animals and humans: Phylogenetic analysis identifies the prevalence of intermediate species in India. Springerplus 2013, 2, 362. [Google Scholar] [CrossRef]
  7. Chiriboga, J.; Barragan, V.; Arroyo, G.; Sosa, A.; Birdsell, D.N.; España, K.; Mora, A.; Espín, E.; Mejía, M.E.; Morales, M.; et al. High Prevalence of Intermediate Leptospira spp. DNA in Febrile Humans from Urban and Rural Ecuador. Emerg. Infect. Dis. 2015, 21, 2141–2147. [Google Scholar] [CrossRef]
  8. Bertelloni, F.; Cilia, G.; Turchi, B.; Pinzauti, P.; Cerri, D.; Fratini, F. Epidemiology of leptospirosis in North-Central Italy: Fifteen years of serological data (2002–2016). Comp. Immunol. Microbiol. Infect. Dis. 2019, 65, 14–22. [Google Scholar] [CrossRef]
  9. Picardeau, M. Virulence of the zoonotic agent of leptospirosis: Still terra incognita? Nat. Rev. Microbiol. 2017, 15, 297–307. [Google Scholar] [CrossRef]
  10. Tagliabue, S.; Figarolli, B.M.; D’Incau, M.; Foschi, G.; Gennero, M.S.; Giordani, R.; Giordani, R.; Natale, A.; Papa, P.; Ponti, N.; et al. Serological surveillance of Leptospirosis in Italy: Two-year national data (2010–2011). Vet. Ital. 2016, 52, 129–138. [Google Scholar] [CrossRef]
  11. Blasdell, K.R.; Morand, S.; Perera, D.; Firth, C. Association of rodent-borne Leptospira spp. with urban environments in Malaysian Borneo. PLoS Negl. Trop. Dis. 2019, 13, e0007141. [Google Scholar] [CrossRef] [PubMed]
  12. Mori, M.; Bourhy, P.; Le Guyader, M.; Van Esbroeck, M.; Djelouadji, Z.; Septfons, A.; Kodjo, A.; Picardeau, M. Pet rodents as possible risk for leptospirosis, Belgium and France, 2009 to 2016. Eurosurveillance 2017, 22. [Google Scholar] [CrossRef] [PubMed]
  13. Coppola, F.; Cilia, G.; Bertelloni, F.; Casini, L.; D’Addio, E.; Fratini, F.; Cerri, D.; Felicioli, A. Crested porcupine (Hystrix cristata L.): A new potential host for pathogenic Leptospira among semi-fossorial mammals. Comp. Immunol. Microbiol. Infect. Dis. 2020. [Google Scholar] [CrossRef] [PubMed]
  14. Bertelloni, F.; Mazzei, M.; Cilia, G.; Forzan, M.; Felicioli, A.; Sagona, S.; Bandecchi, P.; Turchi, B.; Cerri, D.; Fratini, F. Serological Survey on Bacterial and Viral Pathogens in Wild Boars Hunted in Tuscany. Ecohealth 2020, 17, 85–93. [Google Scholar] [CrossRef]
  15. Cilia, G.; Bertelloni, F.; Angelini, M.; Cerri, D.; Fratini, F. Leptospira Survey in Wild Boar (Sus scrofa) Hunted in Tuscany, Central Italy. Pathogens 2020, 9, 377. [Google Scholar] [CrossRef]
  16. Vale-Goncalves, H.M.; Cabral, J.A.; Faria, M.C.; Nunes-Pereira, M.; Faria, A.S.; Veloso, O.; Vieira, M.L.; Paiva-Cardoso, M.N. Prevalence of Leptospira antibodies in wild boars (Sus scrofa) from Northern Portugal: Risk factor analysis. Epidemiol. Infect. 2015, 143, 2126–2130. [Google Scholar] [CrossRef]
  17. Vengust, G.; Lindtner-Knific, R.; Zele, D.; Bidovec, A. Leptospira antibodies in wild boars (Sus scrofa) in Slovenia. Eur. J. Wildl. Res. 2008, 54, 749–752. [Google Scholar] [CrossRef]
  18. Boqvist, S.; Bergström, K.; Magnusson, U. Prevalence of Antibody to Six Leptospira Servovars in Swedish Wild Boars. J. Wildl. Dis. 2012, 48, 492–496. [Google Scholar] [CrossRef]
  19. Arent, Z.; Frizzell, C.; Gilmore, C.; Allen, A.; Ellis, W.A. Leptospira interrogans serovars Bratislava and Muenchen animal infections: Implications for epidemiology and control. Vet. Microbiol. 2016, 190, 19–26. [Google Scholar] [CrossRef]
  20. Rocha, T.; Ellis, W.A.; Montgomery, J.; Gilmore, C.; Regalla, J.; Brem, S. Microbiological and serological study of leptospirosis in horses at slaughter: First isolations. Res. Vet. Sci. 2004, 76, 199–202. [Google Scholar] [CrossRef]
  21. Farina, R.; Cerri, D.; Renzoni, G.; Andreani, E.; Mani, P.; Ebani, V.; Pedrini, A.; Nuvoloni, R. Leptospira interrogans in the genital tract of sheep. Research on ewes and rams experimentally infected with serovar hardjo (hardjobovis). New Microbiol. 1996, 19, 235–242. [Google Scholar] [PubMed]
  22. Cerri, D.; Ebani, V.V.; Fratini, F.; Pinzauti, P.; Andreani, E. Epidemiology of leptospirosis: Observations on serological data obtained by a diagnostic laboratory for leptospirosis from 1995 to 2001. New Microbiol. 2003, 26, 383–389. [Google Scholar] [PubMed]
  23. Haake, D.A.; Levett, P.N. Leptospirosis in humans. Curr. Top. Microbiol. Immunol. 2015, 387, 65–97. [Google Scholar] [CrossRef] [PubMed]
  24. Trott, D.J.; Abraham, S.; Adler, B. Antimicrobial Resistance in Leptospira, Brucella, and Other Rarely Investigated Veterinary and Zoonotic Pathogens. Microbiol. Spectr. 2018, 6. [Google Scholar] [CrossRef]
  25. Kim, D.; Kordick, D.; Divers, T.; Chang, Y.F. In vitro susceptibilities of Leptospira spp. and Borrelia burgdorferi isolates to amoxicillin, tilmicosin, and enrofloxacin. J. Vet. Sci. 2006, 7, 355–359. [Google Scholar] [CrossRef] [PubMed]
  26. Greer, N.D. Tigecycline (Tygacil): The First in the Glycylcycline Class of Antibiotics. Baylor Univ. Med. Cent. Proc. 2006, 19, 155–161. [Google Scholar] [CrossRef]
  27. Jamal, W.Y.; Al Hashem, G.; Khodakhast, F.; Rotimi, V.O. Comparative in vitro activity of tigecycline and nine other antibiotics against gram-negative bacterial isolates, including ESBL-producing strains. J. Chemother. 2009, 21, 261–266. [Google Scholar] [CrossRef]
  28. Zhanel, G.G.; Homenuik, K.; Nichol, K.; Noreddin, A.; Vercaigne, L.; Embil, J.; Gin, A.; Karlowsky, J.A.; Hoban, D.J. The glycylcyclines: A comparative review with the tetracyclines. Drugs 2004, 64, 63–88. [Google Scholar] [CrossRef]
  29. Ressner, R.A.; Griffith, M.E.; Beckius, M.L.; Pimentel, G.; Miller, R.S.; Mende, K.; Fraser, S.L.; Galloway, R.L.; Hospenthal, D.R.; Murray, C.K. Antimicrobial susceptibilities of geographically diverse clinical human isolates of Leptospira. Antimicrob. Agents Chemother. 2008, 52, 2750–2754. [Google Scholar] [CrossRef]
  30. Murray, C.K.; Hospenthal, D.R. Determination of susceptibilities of 26 Leptospira sp. serovars to 24 antimicrobial agents by a broth microdilution technique. Antimicrob. Agents Chemother. 2004, 48, 4002–4005. [Google Scholar] [CrossRef]
  31. Liegeon, G.; Delory, T.; Picardeau, M. Antibiotic susceptibilities of livestock isolates of leptospira. Int. J. Antimicrob. Agents 2018, 51, 693–699. [Google Scholar] [CrossRef] [PubMed]
  32. Hospenthal, D.R.; Murray, C.K. In vitro susceptibilities of seven Leptospira species to traditional and newer antibiotics. Antimicrob. Agents Chemother. 2003, 47, 2646–2648. [Google Scholar] [CrossRef] [PubMed]
  33. Murray, C.K.; Hospenthal, D.R. Broth Microdilution Susceptibility Testing for Leptospira spp. Antimicrob. Agents Chemother. 2004, 48, 1548–1552. [Google Scholar] [CrossRef] [PubMed]
  34. Correia, L.; Loureiro, A.P.; Lilenbaum, W. Reduced susceptibility in leptospiral strains of bovine origin might impair antibiotic therapy. Epidemiol. Infect. 2019, 147. [Google Scholar] [CrossRef]
  35. Tully, C.C.; Hinkle, M.K.; McCall, S.; Griffith, M.E.; Murray, C.K.; Hospenthal, D.R. Efficacy of minocycline and tigecycline in a hamster model of leptospirosis. Diagn. Microbiol. Infect. Dis. 2011, 71, 366–369. [Google Scholar] [CrossRef]
  36. Sapi, E.; Kaur, N.; Anyanwu, S.; Luecke, D.F.; Datar, A.; Patel, S.; Rossi, M.; Stricker, R.B. Evaluation of in-vitro antibiotic susceptibility of different morphological forms of Borrelia burgdorferi. Infect. Drug Resist. 2011, 4, 97–113. [Google Scholar] [CrossRef]
  37. Barthold, S.W.; Hodzic, E.; Imai, D.M.; Feng, S.; Yang, X.; Luft, B.J. Ineffectiveness of tigecycline against persistent Borrelia burgdorferi. Antimicrob. Agents Chemother. 2010, 54, 643–651. [Google Scholar] [CrossRef]
  38. Yang, X.; Nguyen, A.; Qiu, D.; Luft, B.J. In vitro activity of tigecycline against multiple strains of Borrelia burgdorferi. J. Antimicrob. Chemother. 2009, 63, 709–712. [Google Scholar] [CrossRef]
  39. Ates, L.; Hanssen-Hübner, C.; Norris, D.E.; Richter, D.; Kraiczy, P.; Hunfeld, K.P. Comparison of in vitro activities of tigecycline, doxycycline, and tetracycline against the spirochete Borrelia burgdorferi. Ticks Tick. Borne. Dis. 2010, 1, 30–34. [Google Scholar] [CrossRef]
  40. Poggi, D.; De Giuseppe, P.O.; Picardeau, M. Antibiotic resistance markers for genetic manipulations of Leptospira spp. Appl. Environ. Microbiol. 2010, 76, 4882–4885. [Google Scholar] [CrossRef]
  41. Fukunaga, M.; Mifughi, I. Mechanism of Streptomycin Resistance in Leptospira Biflexa Strain Urawa. Microbiol. Immunol. 1988, 32, 641–644. [Google Scholar] [CrossRef] [PubMed]
  42. Lambert, A.; Wong Ng, J.; Picardeau, M. Gene inactivation of a chemotaxis operon in the pathogen Leptospira interrogans. FEMS Microbiol. Lett. 2015, 362, 1–8. [Google Scholar] [CrossRef]
  43. Lambert, A.; Takahashi, N.; Charon, N.W.; Picardeau, M. Chemotactic behavior of pathogenic and nonpathogenic Leptospira species. Appl. Environ. Microbiol. 2012, 78, 8467–8469. [Google Scholar] [CrossRef] [PubMed]
  44. Stein, G.E.; Babinchak, T. Tigecycline: An update. Diagn. Microbiol. Infect. Dis. 2013, 75, 331–336. [Google Scholar] [CrossRef] [PubMed]
  45. Grossman, T.H. Tetracycline antibiotics and resistance. Cold Spring Harb. Perspect. Med. 2016, 6. [Google Scholar] [CrossRef] [PubMed]
Table 1. Determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for tetracycline and tigecycline among the 16 investigated Leptospira spp. strains. Results are expressed as mode and values reported in µg/mL.
Table 1. Determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for tetracycline and tigecycline among the 16 investigated Leptospira spp. strains. Results are expressed as mode and values reported in µg/mL.
Leptospira SerovarTetracyclineTigecycline
MICMBCMICMBC
Icterohaemorrhagiae216864
Canicola0.532432
Pomona116832
Tarassovi2648>128
Grippotyphosa116864
Bratislava1328128
Ballum264864
Hardjo132832
Copenhageni232832
Bataviae2323264
Zanoni132432
Poi216832
Lora2321632
Autumnalis0.516832
Hebdomadis0.516864
Patoc28416
Back to TopTop