Medical Care

Plague is a treatable disease, but clinicians must have a high index of suspicion and initiate appropriate antibiotics at the earliest possible time.^[21]Initial evaluation of patients with plague may begin on an emergent outpatient basis. However, hospitalization is generally required to initiate therapy. Isolation of hospitalized patients varies based on the type of disease. Standard precautions are indicated for cases of bubonic plague. Droplet precautions are indicated for patients with pneumonic plague and for all patients until pneumonia has been excluded and treatment initiated. In patients with pneumonic plague, isolation should be continued until 48 hours of appropriate antibiotic treatment has been administered. Aggressive supportive medical care as necessary to stabilize and maintain the patient's hemodynamic and respiratory status.

Currently recommended antibiotic treatment for plague is summarized in the tables below. Gentamicin and fluoroquinolones are typically first-line treatments in the United States. Duration of treatment is 10 to 14 days, or until 2 days after fever subsides. Oral therapy may be substituted once the patient improves.

Recommended antibiotic treatment for plague in adults (Source: CDC, Atlanta, GA)^[22]

Table. (Open Table in a new window)

Antibiotic	Dose	Route of Administration
Streptomycin	1 g twice daily	IM
Gentamicin	5 mg/kg once daily, or 2 mg/kg loading dose followed by 1.7 mg/kg every 8 hours	IM or IV
Levofloxacin	500 mg once daily	IV or po
Ciprofloxacin	400 mg every 8-12 hours	IV
Ciprofloxacin	500-750 mg twice daily	po
Doxycycline	100 mg twice daily or 200 mg once daily	IV or po
Moxifloxacin	400 mg once daily	IV or po
Chloramphenicol	25 mg/kg every 6 hours	IV

Recommended antibiotic treatment for plague in Children* (Source: CDC, Atlanta, GA)^[22]

Table. (Open Table in a new window)

Antibiotic	Dose	Route of Administration
Streptomycin	15 mg/kg twice daily (maximum 2 g/day)	IM
Gentamicin	2.5 mg/kg/dose every 8 hours	IM or IV
Levofloxacin	10 mg/kg/dose (maximum 500 mg/dose)	IV or po
Ciprofloxacin	15 mg/kg/dose every 12 hours (maximum 400 mg/dose)	IV
Ciprofloxacin	20 mg/kg/dose every 12 hours (maximum 500 mg/dose)	po
Doxycycline	Weight < 45 kg: 2.2 mg/kg twice daily (maximum 100 mg/dose) Weight ≥ 45 kg: same as adult dose	IV or po
Chloramphenicol (for children > 2 years)	25 mg/kg every 6 h (maximum daily dose, 4 g)	IV

* All recommended antibiotics for plague have relative contraindications for use in children and; however, use is justified in life-threatening situations.

In 2021, the CDC updated its Antimicrobial Treatment and Prophylaxis of Plague: Recommendations for Naturally Acquired Infections and Bioterrorism Response.^[23]See Guidelines for a brief summary of the recommendations.

Additionally, updated guidelines on the diagnosis and treatment of bubonic plague have been published by the Infectious Diseases Society of America (IDSA) (see Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America).^[24]

Provide supportive medical care as necessary to stabilize and maintain the patient's hemodynamic and respiratory status.

Updated (2014) guidelines on the diagnosis and treatment of bubonic plague have been published by the Infectious Diseases Society of America (IDSA) (see Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America).^[24]

Surgical Care

Incision and drainage of buboes may be indicated. Material drained from the buboes is infectious until patient is appropriately treated.

Consultations

Consultations may include the following:

Infectious disease specialist
Intensive care specialist, if hemodynamic or respiratory instability is present

Diet

No special diet is required.

Activity

No specific activity restrictions are required.

Prevention

Persons engaging in outdoor activities in areas where plague is endemic should wear long pants when possible and use insect repellent on clothing and skin. Persons also should avoid direct contact with ill or dead animals and never feed squirrels, chipmunks, or other rodents. In addition, pet owners should regularly use flea control products on their pets and consult a veterinarian if their pet is ill. Rodent habitat can be reduced around the home by removing brush, clutter, and potential rodent food sources such as garbage or pet food.

Guidelines

Butler T. Plague into the 21st century. Clin Infect Dis. 2009 Sep 1. 49(5):736-42. [Medline].
Williamson ED. Plague. Vaccine. 2009 Nov 5. 27 Suppl 4:D56-60. [Medline].
Prentice MB, Rahalison L. Plague. Lancet. 2007 Apr 7. 369(9568):1196-207. [Medline].
Rocca P. The modern plague. Del Med J. 2007 May. 79(5):189-90. [Medline].
Piarroux R, Abedi AA, Shako JC, Kebela B, Karhemere S, Diatta G, et al. Plague epidemics and lice, Democratic Republic of the Congo. Emerg Infect Dis. 2013 Mar. 19(3):505-6. [Medline]. [Full Text].
Runfola JK, House J, Miller L, Colton L, Hite D, Hawley A, et al. Outbreak of Human Pneumonic Plague with Dog-to-Human and Possible Human-to-Human Transmission--Colorado, June-July 2014. MMWR Morb Mortal Wkly Rep. 2015 May 1. 64 (16):429-34. [Medline].
Ben Ari T, Gershunov A, Gage KL, et al. Human plague in the USA: the importance of regional and local climate. Biol Lett. 2008 Dec 23. 4(6):737-40. [Medline]. [Full Text].
Thiagarajan B, Bai Y, Gage KL, Cully JF Jr. Prevalence of Yersinia pestis in rodents and fleas associated with black-tailed prairie dogs (Cynomys ludovicianus) at Thunder Basin National Grassland, Wyoming. J Wildl Dis. 2008 Jul. 44(3):731-6. [Medline].
Adams DA, Jajosky RA, Ajani U, Kriseman J, Sharp P, Onwen DH, et al. Summary of notifiable diseases--United States, 2012. MMWR Morb Mortal Wkly Rep. 2014 Sep 19. 61 (53):1-121. [Medline].
Kugeler KJ, Staples JE, Hinckley AF, Gage KL, Mead PS. Epidemiology of human plague in the United States, 1900-2012. Emerg Infect Dis. 2015 Jan. 21 (1):16-22. [Medline].
Kwit N, Nelson C, Kugeler K, Petersen J, Plante L, Yaglom H, et al. Human Plague - United States, 2015. MMWR Morb Mortal Wkly Rep. 2015 Aug 28. 64 (33):918-9. [Medline].
Cleri DJ, Vernaleo JR, Lombardi LJ, et al. Plague pneumonia disease caused by Yersinia pestis. Semin Respir Infect. 1997 Mar. 12(1):12-23. [Medline].
World Health Organization. Human plague in 2002 and 2003. Wkly Epidemiol Rec. 2004 Aug 13. 79(33):301-6. [Medline].
Gupta ML, Sharma A. Pneumonic plague, northern India, 2002. Emerg Infect Dis. 2007 Apr. 13(4):664-6. [Medline].
Josko D. Yersinia pestis: still a plague in the 21st century. Clin Lab Sci. 2004 Winter. 17(1):25-9. [Medline].
Neerinckx S, Bertherat E, Leirs H. Human plague occurrences in Africa: an overview from 1877 to 2008. Trans R Soc Trop Med Hyg. 2010 Feb. 104(2):97-103. [Medline].
Human plague: review of regional morbidity and mortality, 2004-2009. Wkly Epidemiol Rec. 2009 Feb 5. 85(6):40-5. [Medline].
Mittal V, Bhattacharya D, Rana UV, Rai A, Pasha ST, Kumar A, et al. Prompt laboratory diagnosis in timely containment of a plague outbreak in India. J Commun Dis. 2006 Dec. 38(4):317-24. [Medline].
Russell P, Nelson M, Whittington D, et al. Laboratory diagnosis of plague. Br J Biomed Sci. 1997 Dec. 54(4):231-6. [Medline].
Tomaso H, Jacob D, Eickhoff M, et al. Preliminary validation of real-time PCR assays for the identification of Yersinia pestis. Clin Chem Lab Med. 2008. 46(9):1239-44. [Medline].
Crook LD, Tempest B. Plague. A clinical review of 27 cases. Arch Intern Med. 1992 Jun. 152(6):1253-6. [Medline].
Plague: Resources for Clinicians. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/plague/healthcare/clinicians.html. October 5, 2015; Accessed: March 30, 2016.
[Guideline] Nelson CA, Meaney-Delman D, Fleck-Derderian S, Cooley KM, Yu PA, Mead PS. Antimicrobial treatment and prophylaxis of plague: recommendations for naturally acquired infections and bioterrorism response. MMWR Recomm Rep. 2021 Jul 16. 70 (3):1-27. [Medline]. [Full Text].
Stevens DL, Bisno AL, Chambers HF, Dellinger EP, Goldstein EJ, Gorbach SL, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014 Jul 15. 59 (2):e10-52. [Medline].
Stone J. Treating bioterrorism-related plague: CDC issues new guidelines. Medscape Medical News. August 3, 2021. Available at https://www.medscape.com/viewarticle/955928#vp_1.
Weir E. Plague: a continuing threat. CMAJ. 2005 Jun 7. 172(12):1555. [Medline].
Wang X, Zhang X, Zhou D, Yang R. Live-attenuated Yersinia pestis vaccines. Expert Rev Vaccines. 2013 Jun. 12(6):677-86. [Medline].

Media Gallery

Male Xenopsylla cheopis (oriental rat flea) engorged with blood. This flea is the primary vector of plague in most large plague epidemics in Asia, Africa, and South America. Both male and female fleas can transmit the infection. Image courtesy of the Centers for Disease Control and Prevention (CDC).
Wright stain peripheral blood smear of patient with septicemic plague demonstrating bipolar, safety pin staining of Yersinia pestis. Although Wright stain often demonstrates this characteristic appearance, Giemsa and Wayson stains most consistently highlight this pattern. Courtesy of Jack Poland, PhD, Centers for Disease Control and Prevention (CDC), Fort Collins, CO.
Inguinal bubo on upper thigh of a person with bubonic plague. Image courtesy of the Centers for Disease Control and Prevention (CDC).
Yersinia pestis bacteria on fluorescent antibody test. Image courtesy of the Centers for Disease Control and Prevention (CDC).
Pictured is a flea with a blocked proventriculus, which is equivalent to the gastroesophageal region in a human. In nature, this flea would develop a ravenous hunger because of its inability to digest the fibrinoid mass of blood and bacteria. If this flea were to bite a mammal, the proventriculus would be cleared, and thousands of bacteria would be regurgitated into the bite wound. Courtesy of the United States Army Environmental Hygiene Agency.
After the femoral lymph nodes, the next most commonly involved regions in plague are the inguinal, axillary, and cervical areas. This child has an erythematous, eroded, crusting, necrotic ulcer at the presumed primary inoculation site in the left upper quadrant. This type of lesion is uncommon in patients with plague. The location of the bubo is primarily a function of the region of the body in which an infected flea inoculates plague bacilli. Courtesy of Jack Poland, PhD, Centers for Disease Control and Prevention (CDC), Fort Collins, Colo.
Ecchymoses at the base of the neck in a girl with plague. The bandage is over the site of a prior bubo aspirate. These lesions are probably the source of the line from the children's nursery rhyme, "ring around the rosy." Courtesy of Jack Poland, PhD, Centers for Disease Control and Prevention (CDC), Fort Collins, Colo.
Acral necrosis of the nose, the lips, and the fingers and residual ecchymoses over both forearms in a patient recovering from bubonic plague that disseminated to the blood and the lungs. At one time, the patient's entire body was ecchymotic. Reprinted from Textbook of Military Medicine. Washington, DC, US Department of the Army, Office of the Surgeon General, and Borden Institute. 1997:493. Government publication, no copyright on photos.
Acral necrosis of the toes and residual ecchymoses over both forearms in a patient recovering from bubonic plague that disseminated to the blood and the lungs. At one time, the patient's entire body was ecchymotic. Reprinted from Textbook of Military Medicine. Washington, DC: US Department of the Army, Office of the Surgeon General, and Borden Institute. 1997:493. Government publication, no copyright on photos.
Rock squirrel in extremis coughing blood-streaked sputum related to pneumonic plague. Courtesy of Ken Gage, PhD, Centers for Disease Control and Prevention (CDC), Fort Collins, Colo.
Reported cases of human plague in US 1970-2012. Courtesy of the CDC.
Worldwide distribution of plague cases 2000-2009. Courtesy of the CDC.
Human plague cases and deaths in US 2004-2014. Courtesy of the CDC.

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Table.

Antibiotic	Dose	Route of Administration
Streptomycin	1 g twice daily	IM
Gentamicin	5 mg/kg once daily, or 2 mg/kg loading dose followed by 1.7 mg/kg every 8 hours	IM or IV
Levofloxacin	500 mg once daily	IV or po
Ciprofloxacin	400 mg every 8-12 hours	IV
Ciprofloxacin	500-750 mg twice daily	po
Doxycycline	100 mg twice daily or 200 mg once daily	IV or po
Moxifloxacin	400 mg once daily	IV or po
Chloramphenicol	25 mg/kg every 6 hours	IV

Table.

Antibiotic	Dose	Route of Administration
Streptomycin	15 mg/kg twice daily (maximum 2 g/day)	IM
Gentamicin	2.5 mg/kg/dose every 8 hours	IM or IV
Levofloxacin	10 mg/kg/dose (maximum 500 mg/dose)	IV or po
Ciprofloxacin	15 mg/kg/dose every 12 hours (maximum 400 mg/dose)	IV
Ciprofloxacin	20 mg/kg/dose every 12 hours (maximum 500 mg/dose)	po
Doxycycline	Weight < 45 kg: 2.2 mg/kg twice daily (maximum 100 mg/dose) Weight ≥ 45 kg: same as adult dose	IV or po
Chloramphenicol (for children > 2 years)	25 mg/kg every 6 h (maximum daily dose, 4 g)	IV

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Author

Vinod K Dhawan, MD, FACP, FRCPC, FIDSA Professor, Department of Clinical Medicine, University of California, Los Angeles, David Geffen School of Medicine; Chief, Division of Infectious Diseases, Rancho Los Amigos National Rehabilitation Center

Vinod K Dhawan, MD, FACP, FRCPC, FIDSA is a member of the following medical societies: American College of Physicians, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Coauthor(s)

Robert D Schremmer, MD Associate Professor, Department of Pediatrics, University of Missouri-Kansas City School of Medicine; Attending Physician, Division of Emergency Medical Services, Children's Mercy Hospital and Clinics

Robert D Schremmer, MD is a member of the following medical societies: Academic Pediatric Association, American Academy of Pediatrics

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.

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

José Rafael Romero, MD Director of Pediatric Infectious Diseases Fellowship Program, Associate Professor, Department of Pediatrics, Combined Division of Pediatric Infectious Diseases, Creighton University/University of Nebraska Medical Center

José Rafael Romero, MD is a member of the following medical societies: American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, New York Academy of Sciences, Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Acknowledgements

Leslie L Barton, MD Professor Emerita of Pediatrics, University of Arizona College of Medicine

Leslie L Barton, MD is a member of the following medical societies: American Academy of Pediatrics, Association of Pediatric Program Directors, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.