Yonsei Med J.  2016 Jul;57(4):1034-1037. 10.3349/ymj.2016.57.4.1034.

In Vitro Activity of Tigecycline Against Orientia tsutsugamushi

• Lee SM
• Kwon HY
• Im JH
• Baek JH
• Hwang SS
• Kang JS
• Chung MH
• Lee JS

• KMID: 2374140
• DOI: http://doi.org/10.3349/ymj.2016.57.4.1034

Abstract

Scrub typhus is a zoonosis caused by Orientia tsutsugamushi (O. tsutsugamushi) occurring mainly in autumn in Korea. The need of new antibiotics has arisen with a report on strains resistant to antibiotics and chronic infection. This study aims to identify susceptibility of tigecycline in-vitro as a new therapeutic option for O. tsutsugamushi. Antibacterial activity of tigecycline against the O. tsutsugamushi was compared with doxycycline using flow cytometry assay. The inhibitory concentration 50 (IC50) was 3.59×10(-3) µg/mL in doxycycline-treated group. Whereas in 0.71×10(-3) µg/mL tigecycline-treated group. These findings indicate that tigecycline may be a therapeutic option for the treatment of scrub typhus.

Keyword

Orientia tsutsugamushi; scrub typhus; tigecycline; IC50

MeSH Terms

Anti-Bacterial Agents/*pharmacology/therapeutic use
Drug Resistance, Bacterial/drug effects
Humans
Inhibitory Concentration 50
Minocycline/*analogs & derivatives/pharmacology/therapeutic use
Orientia tsutsugamushi/*drug effects/physiology
Scrub Typhus/drug therapy
Anti-Bacterial Agents
Minocycline

Figure

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  Fig. 1 The inhibitory concentration 50 (IC50) of doxycycline (A) and tigecycline (B) against Orientia tsutsugamushi (O. tsutsugamushi). IC50 of doxycycline and tigecycline, in ECV304 cells infected with O. tsutsugamushi. IC50 calculated from mean fluorscence intensity (MFI) at different concentrations of antibiotics using flow cytometry assay. This result shows that tigecycline inhibits the growth of bacteria better than doxycycline.

Reference

1. Smadel JE, Woodward TE, Ley HL, Lewthwaite R. Chloramphenicol (chloromycetin) in the treatment of tsutsugamushi disease (scrub typhus). J Clin Invest. 1949; 28(5 Pt 2):1196–1215.

2. Prezyna AP, Chang TL, Wang TL, Dougherty WJ, Bond HB. Treatment of scrub typhus in the Pescadores Islands with chloramphenicol, aureomycin and terramycin. Am J Trop Med Hyg. 1954; 3:608–614.

3. Watt G, Kantipong P, Jongsakul K, Watcharapichat P, Phulsuksombati D. Azithromycin activities against Orientia tsutsugamushi strains isolated in cases of scrub typhus in Northern Thailand. Antimicrob Agents Chemother. 1999; 43:2817–2818.

4. Watt G, Chouriyagune C, Ruangweerayud R, Watcharapichat P, Phulsuksombati D, Jongsakul K, et al. Scrub typhus infections poorly responsive to antibiotics in northern Thailand. Lancet. 1996; 348:86–89.

5. Corwin A, Soderquist R, Suwanabun N, Sattabongkot J, Martin L, Kelly D, et al. Scrub typhus and military operations in Indochina. Clin Infect Dis. 1999; 29:940–941.

6. Chung MH, Lee JS, Baek JH, Kim M, Kang JS. Persistence of Orientia tsutsugamushi in humans. J Korean Med Sci. 2012; 27:231–235.

7. Chung MH, Han SW, Choi MG, Chang WH, Pai HJ, Shin HS, et al. Comparison of 3-day course of azithromycin with doxycycline for the treatment of scrub typhus. Korean J Infect Dis. 2000; 32:433–438.

8. Olson MW, Ruzin A, Feyfant E, Rush TS 3rd, O'Connell J, Bradford PA. Functional, biophysical, and structural bases for antibacterial activity of tigecycline. Antimicrob Agents Chemother. 2006; 50:2156–2166.

9. Noskin GA. Tigecycline: a new glycylcycline for treatment of serious infections. Clin Infect Dis. 2005; 41:Suppl 5. S303–S314.

10. Spyridaki I, Psaroulaki A, Vranakis I, Tselentis Y, Gikas A. Bacteriostatic and bactericidal activities of tigecycline against Coxiella burnetii and comparison with those of six other antibiotics. Antimicrob Agents Chemother. 2009; 53:2690–2692.

11. Dessus-Babus S, Belloc F, Bébéar CM, Poutiers F, Lacombe F, Bébéar C, et al. Antibiotic susceptibility testing for Chlamydia trachomatis using flow cytometry. Cytometry. 1998; 31:37–44.

12. Kim MJ, Kim MK, Kang JS. Improved antibiotic susceptibility test of Orientia tsutsugamushi by flow cytometry using monoclonal antibody. J Korean Med Sci. 2007; 22:1–6.

13. Kim MJ, Lee SM, Kil SH, Kang JS. Cleavage of p65 Subunit of NF-κB by Orientia tsutsugamushi. J Bacteriol Virol. 2010; 40:151–157.

14. Chung MH, Kang JS. Treatment of tsutsugamushi disease. Korean J Med. 2002; 63:234–238.

15. Maurin M, Benoliel AM, Bongrand P, Raoult D. Phagolysosomal alkalinization and the bactericidal effect of antibiotics: the Coxiella burnetii paradigm. J Infect Dis. 1992; 166:1097–1102.

16. Babinchak T, Ellis-Grosse E, Dartois N, Rose GM, Loh E. Tigecycline 301 Study Group. Tigecycline 306 Study Group. The efficacy and safety of tigecycline for the treatment of complicated intra-abdominal infections: analysis of pooled clinical trial data. Clin Infect Dis. 2005; 41:Suppl 5. S354–S367.

17. Barbour A, Schmidt S, Ma B, Schiefelbein L, Rand KH, Burkhardt O, et al. Clinical pharmacokinetics and pharmacodynamics of tigecycline. Clin Pharmacokinet. 2009; 48:575–584.

18. Edelstein PH, Weiss WJ, Edelstein MA. Activities of tigecycline (GAR-936) against Legionella pneumophila in vitro and in guinea pigs with L. pneumophila pneumonia. Antimicrob Agents Chemother. 2003; 47:533–540.

19. Rose WE, Rybak MJ. Tigecycline: first of a new class of antimicrobial agents. Pharmacotherapy. 2006; 26:1099–1110.

20. Tang HJ, Ko WC, Chen CC, Chen PL, Toh HS, Weng TC, et al. In vitro and in vivo intracellular killing effects of tigecycline against clinical nontyphoid Salmonella isolates using ceftriaxone as a comparator. Antimicrob Agents Chemother. 2011; 55:2755–2759.

21. Conte JE Jr, Golden JA, Kelly MG, Zurlinden E. Steady-state serum and intrapulmonary pharmacokinetics and pharmacodynamics of tigecycline. Int J Antimicrob Agents. 2005; 25:523–529.

22. Ong CT, Babalola CP, Nightingale CH, Nicolau DP. Penetration, efflux and intracellular activity of tigecycline in human polymorphonuclear neutrophils (PMNs). J Antimicrob Chemother. 2005; 56:498–501.

23. Poole K. Efflux-mediated antimicrobial resistance. J Antimicrob Chemother. 2005; 56:20–51.