Resources for Clinicians
Plague should be considered in any patient with clinical signs of plague and a recent history of travel to the western United States or any other plague endemic area. Bubonic plague is the most common primary manifestation, with a bubo usually occurring in the groin, axilla or cervical nodes. Buboes are often so painful that patients are generally guarded and have restricted movement in the affected region. The incubation period for bubonic plague is usually 2 to 6 days.
If bubonic plague is untreated, plague bacteria invade the bloodstream and spread rapidly, causing septicemic plague, and if the lungs are seeded, secondary pneumonic plague. Septicemic and pneumonic plague may also be primary manifestations. A person with pneumonic plague may experience high fever, chills, cough, and breathing difficulty and may expel bloody sputum. If pneumonic plague patients are not given specific antibiotic therapy, the disease can progress rapidly to death.
Although the majority of patients with plague present with a bubo, some may have nonspecific symptoms. For example, septicemic plague can present with prominent gastrointestinal symptoms such as nausea, vomiting, diarrhea, and abdominal pain (MMWR, 2006). Additional rare forms of plague include pharyngeal, meningeal, and cutaneous.
Appropriate diagnostic samples include blood cultures, lymph node aspirates if possible, and/or sputum, if indicated. Drug therapy should begin as soon as possible after the laboratory specimens are taken. If plague is suspected, local and state health departments should be notified immediately. If the patient has pneumonic signs, he/she should also be isolated and placed on droplet precautions.
If plague is suspected, pre-treatment specimens should be taken if possible, but treatment should not be delayed. Specimens should be obtained from appropriate sites for isolating the bacteria, and depend on the clinical presentation:
- Lymph node aspirate: An affected bubo should contain numerous organisms that can be evaluated microscopically and by culture.
- Blood cultures: Organisms may be seen in blood smears if the patient is septicemic. Blood smears taken from suspected bubonic plague patients early in the course of illness are usually negative for bacteria by microscopic examination but may be positive by culture.
- Sputum: Culture is possible from sputum of very ill pneumonic patients; however, blood is usually culture-positive at this time as well.
- Bronchial/tracheal washing may be taken from suspected pneumonic plague patients; throat specimens are not ideal for isolation of plague since they often contain many other bacteria that can mask the presence of plague.
- In cases where live organisms are unculturable (such as postmortem), lymphoid, spleen, lung, and liver tissue or bone marrow samples may yield evidence of plague infection by direct detection methods such as direct fluorescent antibody (DFA) or PCR.
Y. pestis may be identified microscopically by examination of Gram, Wright, Giemsa, or Wayson's stained smears of peripheral blood, sputum, or lymph node specimen. Visualization of bipolar-staining, ovoid, Gram-negative organisms with a "safety pin" appearance permits a rapid presumptive diagnosis of plague.
If cultures yield negative results, and plague is still suspected, serologic testing is possible to confirm the diagnosis. One serum specimen should be taken as early in the illness as possible, followed by a convalescent sample 4-6 weeks or more after disease onset.
Recommended antibiotic treatment for plague
Begin appropriate IV therapy as soon as plague is suspected. 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.
The regimens listed below are guidelines only and may need to be adjusted depending on a patient's age, medical history, underlying health conditions, or allergies. Please use clinical judgment.
- Inglesby TV, Dennis DT, Henderson DA, et al. Plague as a biological weapon: medical and public health management. Working Group on Civilian Biodefense. JAMA. 2000 May 3;283(17):2281-90.
- Koirala J. Plague: disease, management, and recognition of act of terrorism. Infect Dis Clin North Am. 2006 Jun;20(2):273-87, viii.
1Boulanger LL, Ettestad P, Fogarty JD, Dennis DT, Romig D, Mertz G. Gentamicin and tetracyclines for the treatment of human plague: Review of 75 cases in New Mexico, 1985–1999. Clin Infect Dis. 2004 38(5):663-669.
|Adults||Antibiotic||Dose||Route of administration||Notes|
|Streptomycin||1 g twice daily||IM||Not widely available in the US|
|Gentamicin||5 mg/kg once daily, or 2 mg/kg loading dose followed by 1.7 mg/kg every 8 hours||IM or IV||Not FDA approved but considered an effective alternative to streptomycin.1 Due to poor abscess penetration, consider alternative or dual therapy for patients with bubonic disease.|
|Levofloxacin||500 mg once daily||IV or po||Bactericidal. FDA approved based on animal studies but limited clinical experience treating human plague. A higher dose (750 mg) may be used if clinically indicated.|
|Ciprofloxacin||400 mg every 8-12 hours||IV||Bactericidal. FDA approved based on animal studies but limited clinical experience treating human plague.|
|500-750 mg twice daily||po|
|Doxycycline||100 mg twice daily or 200 mg once daily||IV or po||Bacteriostatic, but effective in a randomized trial when compared to gentamicin.2|
|Moxifloxacin||400 mg once daily||IV or po|
|Chloramphenicol||25 mg/kg every 6 hours||IV||Not widely available in the United States.|
|Children3||Streptomycin||15 mg/kg twice daily (maximum 2 g/day)||IM||Not widely available in the United States.|
|Gentamicin||2.5 mg/kg/dose every 8 hours||IM or IV||Not FDA approved but considered an effective alternative to streptomycin.1 Due to poor abscess penetration, consider alternative or dual therapy for patients with bubonic disease.|
|Levofloxacin||10 mg/kg/dose (maximum 500mg/dose)||IM or po||Bactericidal. FDA approved based on animal studies but limited clinical experience treating human plague.|
|Ciprofloxacin||10 mg/kg/dose every 8-12 hours (maximum 400 mg/dose)||IV||Bactericidal. FDA approved based on animal studies but limited clinical experience treating human plague.|
|15 mg/kg/dose every 8-12 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||Bacteriostatic, but FDA approved and effective in a randomized trial when compared to gentamicin.2 No tooth staining after multiple short courses.4|
|Chloramphenicol (for children > 2 years)||25 mg/kg every 6 h (maximum daily dose, 4 g)||IV||Not widely available in the United States|
|Pregnant women3||Gentamicin||Same as adult dose||IM or IV||See notes above|
|Doxycycline||Same as adult dose||IV||See notes above|
|Ciprofloxacin||Same as adult dose||IV||See notes above|
Post-exposure prophylaxis (PEP)
Post-exposure prophylaxis is indicated in persons with known exposure to plague, such as close contact with a pneumonic plague patient or direct contact with infected body fluids or tissues. Duration of post-exposure prophylaxis to prevent plague is 7 days. The recommended antibiotic regimens for PEP are as follows:
Adapted from: Inglesby TV, Dennis DT, Henderson DA, et al. Plague as a biological weapon: medical and public health management Working Group on Civilian Biodefense. JAMA. 2000 May 3;283(17):2281-90.
1Doxycycline and ciprofloxacin are pregnancy categories D and C, respectively. PEP should be given only when the benefits outweigh the risks.
|Preferred agents||Dose||Route of administration|
|Adults||Doxycycline||100 mg twice daily||PO|
|Ciprofloxacin||500 mg twice daily||PO|
|Children||Doxycycline (for children ≥ 8 years)||Weight < 45 kg: 2.2 mg/kg twice daily (maximum daily dose, 200 mg)
Weight ≥ 45 kg: same as adult dose
|Ciprofloxacin||20 mg/kg twice daily (maximum daily dose, 1 g)||PO|
|Pregnant women||Doxycycline1||100 mg twice daily||PO|
|Ciprofloxacin1||500 mg twice daily||PO|
Case Definition and Report Forms
- Plague Surveillance Case Definition (1996)
- Plague Case Report Form [PDF - 3 pages] (for public health officials' use)