Fluoroquinolones versus doxycycline in the treatment of rickettsial infection: A Tunisian multicenter prospective study

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Published Apr 30, 2026
https://doi.org/10.62438/tunismed.v104i04.6328
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Vol. 104 No. 04 (2026): Tunis Med Apr 2026

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Nadia Ben Lasfar
Infectious Diseases Department, Farhat Hached university Hospital, Faculty of Medecine of Sousse, University of Sousse, 4002, Tunisia
Manel Ben Selma
Infectious Diseases Department, Farhat Hached university Hospital, Faculty of Medecine of Sousse, University of Sousse, 4002, Tunisia
Mariem Ben Ticha
Infectious Diseases Department, Farhat Hached university Hospital, Faculty of Medecine of Sousse, University of Sousse, 4002, Tunisia
Mounir Ben Jemaa
Infectious Diseases Department, Hedi Chaker University Hospital, Faculty of Medecine of Sfax, University of Sfax, 3029, Tunisia
Lamia Ammeri
Infectious Diseases Department, La Rabta University Hospital , Faculty of Medecine of Tunis , University of Tunis , 1007 , Tunisia
Maha Abid
Infectious Diseases Department, Farhat Hached university Hospital, Faculty of Medecine of Sousse, University of Sousse, 4002, Tunisia
Amel Letaief
Infectious Diseases Department, Farhat Hached university Hospital, Faculty of Medecine of Sousse, University of Sousse, 4002, Tunisia
Wissem Hachfi
Infectious Diseases Department, Farhat Hached university Hospital, Faculty of Medecine of Sousse, University of Sousse, 4002, Tunisia

Abstract

Introduction: Doxycycline is considered as the standard treatment of rickettsiosis. Fluoroquinolones used as an alternative therapy, until recent studies have shown that Fluoroquinolones are associated with a deleterious outcome.
Objectives: To compare therapeutic efficacy and safety of fluoroquinolones and doxycycline in the treatment of Rickettsiosis
Methods: we conducted an open-label randomized controlled multicenter study. This study aim to compare the efficacy and safety of oral ciprofloxacin (1000 mg/day) or ofloxacin (400mp/day) in 2 doses with those of oral doxycycline (200mg/day) once daily for 3 to 10 days, according
to the severity of illness, in the treatment of Rickettsioses, We included patients more than 15 year-old who presented the characteristic clinical triad (eschar + rash + fever) and/or microbiological confirmation (positive serology and/or positive qPCR).
Results: Among 112 enrolled patients, 82 retained. Thirty-four patients received fluoroquinolones and 48 received doxycycline. Patients in both groups were comparable with respect to age. Two severe cases were noted with fluoroquinolones (meningitis = one, encephalitis= 1) and three with doxycycline (myocarditis=one, severe sepsis = l and encephalitis =1) .|The defervescence period was 2.6 + 1.04 days in the doxycycline
group and2.31.09 days in the fluoroquinolones group (p20.05). All patients recovered. One patient treated by doxycycline had a digital necrosis, generating amputation.
Conclusions: Both fluoroquinolones and doxycycline were effective for treating patients with rickettsia infections. Even that doxycycline remains the standard of treatment, with the advantage of a single daily dose; fluoroquinolones are an interesting alternative with no deleterious outcome.

Keywords:

Rickettsial infections, fluoroquinolones, doxycycline

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References

  1. Letaïef A. Epidemiology of Rickettsioses in North Africa. Ann N Y Acad Sci. 2006;1078(1):34-41.
  2. Blanton LS. The Rickettsioses: A Practical Update. Infect Dis Clin North Am. 1 mars 2019;33(1):213-29.
  3. Lamloumi M, Berriche A, Zayet S, Mahdi B, Beji I, Abdelmalek R, et al. Epidemiology and clinical characteristics of Mediterranean
  4. spotted fever suspects in a university hospital, Tunisia, 2000–2020. Epidemiol Infect. janv 2025;153:e37.
  5. Rymaszewska A, Piotrowski M. Rickettsia Species: Genetic Variability, Vectors, and Rickettsiosis—A Review. Pathogens. août
  6. ;13(8):661.
  7. Biggs HM. Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever and Other Spotted Fever
  8. Group Rickettsioses, Ehrlichioses, and Anaplasmosis — United States. MMWR Recomm Rep. 2016 . Disponible sur: https://www.
  9. cdc.gov/mmwr/volumes/65/rr/rr6502a1.htm
  10. Premaratna R. Rickettsial illnesses, a leading cause of acute febrile illness. Clin Med. 1 janv 2022;22(1):2-5.
  11. Satjanadumrong J, Robinson MT, Hughes T, Blacksell SD. Distribution and Ecological Drivers of Spotted Fever Group Rickettsia in Asia.
  12. EcoHealth. 1 déc 2019;16(4):611-26.
  13. Rahi M, Gupte MD, Bhargava A, Varghese GM, Arora R. DHR-ICMR Guidelines for Diagnosis & Management of Rickettsial Diseases in
  14. India. Indian J Med Res. 1 juin 2025;141(4):417-22.
  15. Vito AD, Geremia N, Mameli MS, Fiore V, Serra PA, Rocchitta GGM, et al. Epidemiology, Clinical Aspects, Laboratory Diagnosis
  16. And Treatment Of Rickettsial Diseases In The Mediterranean Area During Covid-19 Pandemic: A Review Of The Literature. Mediterr J
  17. Hematol Infect Dis. 17 sept 2020;12(1):e2020056-e2020056.
  18. Raoult D, Drancourt M. Antimicrobial therapy of rickettsial diseases. Antimicrob Agents Chemother. déc 1991;35(12):2457-62.
  19. Blanton LS, Walker DH. Treatment of Tropical and Travel Related Rickettsioses. Curr Treat Options Infect Dis. 1 mars 2016;8(1):42-56.
  20. Keren G, Itzhaki A, Oron C, Keysary A. Evaluation of the Anti-Rickettsial Activity of Fluoroquinolones. Drugs. 1 juin
  21. ;49(2):208-10.
  22. Ruiz Beltrán R, Herrero Herrero JI. Evaluation of ciprofloxacin and doxycycline in the treatment of Mediterranean spotted fever. Eur
  23. J Clin Microbiol Infect Dis Off Publ Eur Soc Clin Microbiol. mai 1992;11(5):427-31.
  24. Botelho-Nevers E, Edouard S, Leroy Q, Raoult D. Deleterious effect of ciprofloxacin on Rickettsia conorii-infected cells is linked to
  25. toxin–antitoxin module up-regulation. J Antimicrob Chemother. 1 juill 2012;67(7):1677-82.
  26. VapC toxins promote the pathogenesis of Rickettsia heilongjiangensis by cleaving essential RNAs from both Rickettsia
  27. and its host | PLOS Pathogens https://journals.plos.org/ plospathogens/article?id=10.1371/journal.ppat.1013380
  28. Lemma AS, Brynildsen MP. Toxin Induction or Inhibition of Transcription or Translation Posttreatment Increases Persistence to
  29. Fluoroquinolones. mBio. 17 août 2021;12(4):10.1128/mbio.01983-21.
  30. Holman RC, Paddock CD, Curns AT, Krebs JW, McQuiston JH, Childs JE. Analysis of risk factors for fatal Rocky Mountain Spotted Fever:
  31. evidence for superiority of tetracyclines for therapy. J Infect Dis. 1 déc 2001;184(11):1437-44.
  32. Rovery C, Raoult D. Mediterranean spotted fever. Infect Dis Clin North Am. sept 2008;22(3):515-30, ix.
  33. Bechah Y, Capo C, Mege JL, Raoult D. Epidemic typhus. Lancet Infect Dis. juill 2008;8(7):417-26.
  34. Botelho-Nevers E, Rovery C, Richet H, Raoult D. Analysis of risk factors for malignant Mediterranean spotted fever indicates that
  35. fluoroquinolone treatment has a deleterious effect. J Antimicrob Chemother. août 2011;66(8):1821-30.