Medication Summary

The best outcomes in Rocky Mountain spotted fever (RMSF) are achieved when treatment is started within 5 days of symptom onset. Doxycycline is the antibiotic of choice.

Chloramphenicol was previously recommended for the treatment of children younger than 9 years. In national surveillance data, however, patients treated with chloramphenicol were more likely to die than those treated with a tetracycline. Chloramphenicol poses a risk of permanent aplastic anemia and should be avoided if at all possible.

Class Summary

Tetracyclines are the drugs of choice. Although tetracyclines should not be routinely prescribed to children younger than 8 years, the benefits far exceed the risks in RMSF. Doxycycline is the agent of choice because the risk of dental staining is less with this agent than with other tetracyclines.

Doxycycline (Adoxa, Doxy 100, Vibramycin, Monodox)

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Doxycycline is the drug of choice for RMSF. It is a broad-spectrum, synthetically derived bacteriostatic antibiotic in the tetracycline class. When given orally, it is almost completely absorbed.

It concentrates in bile and is excreted in urine and feces as a biologically active metabolite in high concentrations. This agent is the only tetracycline that does not need dosing adjustment in renal failure.

Doxycycline inhibits protein synthesis and, therefore, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. It may block dissociation of peptidyl transfer RNA (tRNA) from ribosomes, arresting RNA-dependent protein synthesis.

Biggs HM , Behravesh CB , Bradley KK , et al. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever and other spotted fever group rickettsioses, ehrlichioses, and anaplasmosis—United States. A practical guide for health care and public health professionals. MMWR Recomm Rep. 2016; 65(RR-2):1–44. Available at: www.cdc.gov/mmwr/volumes/65/rr/rr6502a1.htm.
Buckingham S, Marshall G, Schutze G, et al: Clinical and laboratory features, hospital course, and outcome of Rocky Mountain spotted fever in children. J Pediatr 2007; 150: pp. 180-184.
Kaplan J, and Schonberger L: The sensitivity of various serologic tests in the diagnosis of Rocky Mountain spotted fever. Am J Trop Med Hyg 1986; 35: pp. 840-844.
Kaplowitz L, and Robertson G:. Hyponatremia in Rocky Mountain spotted fever: role of antidiuretic hormone. Ann Intern Med. 1983. 98: pp. 334-335.
Centers for Disease Control and Prevention. Rocky Mountain Spotted Fever - Statistics and Epidemiology. Available at https://www.cdc.gov/rmsf/stats/index.html. Accessed: February 19, 2021.
Holman RC, McQuiston JH, Haberling DL, Cheek JE. Increasing incidence of Rocky Mountain spotted fever among the American Indian population in the United States. Am J Trop Med Hyg. 2009 Apr. 80(4):601-5. [QxMD MEDLINE Link].
Adjemian JZ, Krebs J, Mandel E, McQuiston J. Spatial clustering by disease severity among reported Rocky Mountain spotted fever cases in the United States, 2001-2005. Am J Trop Med Hyg. 2009 Jan. 80(1):72-7. [QxMD MEDLINE Link].
Folkema AM, Holman RC, McQuiston JH, Cheek JE. Trends in clinical diagnoses of Rocky Mountain spotted fever among American Indians, 2001-2008. Am J Trop Med Hyg. 2012 Jan. 86(1):152-8. [QxMD MEDLINE Link]. [Full Text].
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McQuiston JH, Wiedeman C, Singleton J, Carpenter LR, McElroy K, Mosites E, et al. Inadequacy of IgM antibody tests for diagnosis of Rocky Mountain Spotted Fever. Am J Trop Med Hyg. 2014 Oct. 91 (4):767-70. [QxMD MEDLINE Link].
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Todd SR, Dahlgren FS, Traeger MS, Beltrán-Aguilar ED, Marianos DW, Hamilton C, et al. No visible dental staining in children treated with doxycycline for suspected Rocky Mountain Spotted Fever. J Pediatr. 2015 May. 166 (5):1246-51. [QxMD MEDLINE Link].

Media Gallery

Geographic distribution of Rocky Mountain spotted fever incidence in 2010, cases per million: Courtesy of the US Centers for Disease Control and Prevention.
Annual incidence (per million persons) for Spotted Fever Rickettsiosis (SFR) in the United States, 2017. Courtesy of the CDC.
Under a magnification of 98X, this scanning electron microscopic (SEM) image depicts the dorsal view of the head region from an American dog tick, Dermacentor variabilis, magnified 98X. D. variabilis is a known carrier of Rocky Mountain Spotted Fever (RMSF) caused by the bacterium, Rickettsia rickettsii. Courtesy of the Public Health Image Library (PHIL), CDC, photo credit Janice Haney Carr.
Rocky Mountain Spotted Fever (RMSF) rash in a child. It appears day 3-5 of illness, begins in ankles and wrists, and typically involves palms and soles. In early stages it is macular and later it is petechial. Courtesy of the Morbidity and Mortality Weekly Report (MMWR), CDC.
Tick identification. (i) American dog tick (Dermacentor variabilis), ii) Rocky Mountain wood tick (Dermacentor andersoni), and, iii) brown dog tick (Rhipicephalus sanguineus) iv) Lone star tick (Amblyomma americanum). Courtesy of the CDC.

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Table 1. Human Disease Around the World Caused by Spotted Fever Group Rickettsiae.

Organism	Disease or Presentation	Geographic Location
Rickettsia rickettsii	Rocky Mountain spotted fever	North, Central and South America
Rickettsia akari	Rickettsialpox	Worldwide
Rickettsia conorii	Mediterranean spotted fever, boutonneuse fever, Israeli spotted fever, Astrakhan fever, Indian tick typhus	Europe, Asia, Africa, India, Israel, Sicily, Russia
Rickettsia sibirica	Siberian tick typhus, North Asian tick typhus	Siberia, People's Republic of China, Mongolia, Europe
Rickettsia australis	Queensland tick typhus	Australia
Rickettsia honei	Flinders Island spotted fever, Thai tick typhus	Australia, South Eastern Asia
Rickettsia africae	African tick-bite fever	Sub Saharan Africa, Caribbean
Rickettsia japonica	Japanese or Oriental spotted fever	Japan
Rickettsia felis	Cat flea rickettsiosis, flea borne typhus	Worldwide
Rickettsia slovaca	Necrosis, erythema, lymphadenopathy	Europe
Rickettsia heilongjaiangensis	Mild spotted fever	China, Asian region of Russia
Rickettsia parkeri	Mild spotted fever	US

Table 2. Doxycycline Treatment for Rocky Mountain Spotted Fever

Doxycycline is first-line treatment for both adults and children; antibiotics other than doxycycline increase the risk of death^[14]
Dosage for children < 45 kg (100 lb): 2.2 mg/kg body weight given twice a day
Dosage for adults: 100 mg every 12 hours
Treatment is most effective at preventing death if doxycycline is started within the first 5 days of symptoms; if treatment occurs within 5 days, fever generally subsides within 24-72 hours
Patients should be treated for at least 3 days after the fever subsides and until there is evidence of clinical improvement; the standard duration of treatment is 7-14 days - "Fever plus 3, at least a week"

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Author

Asif Noor, MD Assistant Professor of Pediatric Infectious Diseases, NYU Long Island School of Medicine

Asif Noor, MD is a member of the following medical societies: American Academy of Pediatrics, Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Larry I Lutwick, MD, FACP Editor-in-Chief, ID Cases; Moderator, Program for Monitoring Emerging Diseases; Adjunct Professor of Medicine, State University of New York Downstate College of Medicine

Larry I Lutwick, MD, FACP is a member of the following medical societies: American Association for the Advancement of Science, American Association for the Study of Liver Diseases, American College of Physicians, American Federation for Clinical Research, American Society for Microbiology, Infectious Diseases Society of America, Infectious Diseases Society of New York, International Society for Infectious Diseases, New York Academy of Sciences, Veterans Affairs Society of Practitioners in Infectious Diseases

Disclosure: Nothing to disclose.

Chief Editor

Russell W Steele, MD Clinical Professor, Tulane University School of Medicine; Staff Physician, Ochsner Clinic Foundation

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, Southern Medical Association

Disclosure: Nothing to disclose.

Additional Contributors

Joseph Domachowske, MD Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics, Division of Infectious Diseases, State University of New York Upstate Medical University

Joseph Domachowske, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa

Disclosure: Received research grant from: Pfizer;GlaxoSmithKline;AstraZeneca;Merck;American Academy of Pediatrics, Novavax, Regeneron, Diassess, Actelion<br/>Received income in an amount equal to or greater than $250 from: Sanofi Pasteur.

Walid Abuhammour, MD, MBA, CIC, FAAP, FIDSA Professor of Pediatrics, Michigan State University College of Human Medicine; Adjunct Professor, Department of Pediatrics, Hashemite University, Jordan; Head of Pediatric Infectious Diseases, Department of Pediatrics, Al Jalila Children's Hospital, UAE

Walid Abuhammour, MD, MBA, CIC, FAAP, FIDSA is a member of the following medical societies: American Academy of Pediatrics, International Society for Infectious Diseases, International Society for Infectious Diseases, Jordan Medical Association, Jordan Pediatric Society, Michigan Infectious Disease Society, Michigan State Medical Society, National Arab American Medical Association, Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Nicholas John Bennett, MBBCh, PhD, FAAP, MA(Cantab) Assistant Professor of Pediatrics, Co-Director of Antimicrobial Stewardship, Medical Director, Division of Pediatric Infectious Diseases and Immunology, Connecticut Children's Medical Center

Nicholas John Bennett, MBBCh, PhD, FAAP, MA(Cantab) is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics

Disclosure: Received research grant from: Cubist<br/>Received income in an amount equal to or greater than $250 from: Horizon Pharmaceuticals, Shire<br/>Medico legal consulting for: Various.