Guidelines Summary
In 2021, the Centers for Disease Control and Prevention (CDC) published clinical practice guidelines on the treatment of plague. [23, 25] These are some of the highlights of the guidelines.
Plague is treatable with antimicrobials and supportive care. Early recognition and administration of effective antimicrobials are key to saving lives. Persons exposed to Yersinia pestis can avoid illness if given effective antimicrobial prophylaxis.
Aminoglycosides and fluoroquinolones are the mainstays of treatment for plague. Tetracyclines, chloramphenicol, and trimethoprim-sulfamethoxazole might also be suitable treatment, depending on the type of disease and the age and pregnancy status of the patient. Dual therapy with distinct classes of antimicrobials is recommended in the case of a bioterrorist attack with Y pestis engineered for resistance to treatment.
FDA-approved antimicrobials for plague include streptomycin, ciprofloxacin, levofloxacin, moxifloxacin, and doxycycline. Although not approved for plague, gentamicin, chloramphenicol, and trimethoprim-sulfamethoxazole are considered effective.
Bubonic and pharyngeal plague
Gentamicin or streptomycin is a first-line agent for bubonic plague; they must be given parenterally and are associated with nephrotoxicity and ototoxicity. Alternative first-line agents include high-dose ciprofloxacin, levofloxacin, moxifloxacin, and doxycycline, administered intravenously or orally. Consider dual therapy and drainage for patients with large buboes. Treatment is for 10-14 days.
Pneumonic and septicemic plague
For naturally occurring pneumonic plague, the CDC recommends levofloxacin or moxifloxacin. Because plague is life threatening, doxycycline is not considered contraindicated in children and has not been shown to cause tooth staining, unlike other tetracyclines, which should be avoided if possible. For children aged 3 mo to 17 yr, moxifloxacin is recommended as an alternative antimicrobial, rather than a first-line agent, because of lack of FDA approval for use in children and because of higher reported rates of prolonged QTc interval than seen with other fluoroquinolones.
Plazomicin is not recommended as an alternative antimicrobial for children 1 mo to 17 yr because there are no published data on use and dosage in pediatric patients.
Plague meningitis
Moxifloxacin and levofloxacin should be effective for plague meningitis because they have been shown to have robust activity against Y pestis and excellent CNS penetration. Quinolones, however, can cause seizures. When possible, dual therapy with chloramphenicol and moxifloxacin or levofloxacin should be used as initial treatment in patients with plague and signs of meningitis, such as nuchal rigidity. If chloramphenicol is not available, a non-fluoroquinolone first-line antimicrobial or an alternative antimicrobial for septicemic plague can be used.
For patients who develop secondary plague meningitis while already receiving antimicrobial therapy, chloramphenicol should be added to the existing antimicrobial treatment regimen for plague. Moxifloxacin or levofloxacin can be added to the treatment regimen instead of chloramphenicol if it is not available or if the clinician prefers not to use chloramphenicol in young children because of potential adverse effects. After chloramphenicol, moxifloxacin, or levofloxacin is added, the entire regimen of antimicrobials should be continued for an additional 10 days.
Treatment of plague in neonates
The CDC recommends that treatment should be started without delay for symptomatic neonates who have been infected with Y pestis. First-line antimicrobial options for neonates with pneumonic or septicemic plague are gentamicin, ciprofloxacin, levofloxacin, and streptomycin. For neonates with bubonic or pharyngeal plague, first-line options are gentamicin, ciprofloxacin, levofloxacin, streptomycin, and doxycycline. Administration via the intravenous route is recommended to ensure that the full dose is successfully given.
All neonates who are exposed postnatally to Y pestis should receive postexposure prophylaxis. Prophylaxis also should be considered for asymptomatic neonates whose mothers had untreated Y pestis infection during the last 7 days of pregnancy.
Infection control
Caretakers should wear a mask in addition to taking standard precautions, as well as wear eye protection and a face shield if splashing is likely.
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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).
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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.
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Inguinal bubo on upper thigh of a person with bubonic plague. Image courtesy of the Centers for Disease Control and Prevention (CDC).
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Yersinia pestis bacteria on fluorescent antibody test. Image courtesy of the Centers for Disease Control and Prevention (CDC).
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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.
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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.
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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.
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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.
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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.
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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.
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Reported cases of human plague in US 1970-2012. Courtesy of the CDC.
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Worldwide distribution of plague cases 2000-2009. Courtesy of the CDC.
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Human plague cases and deaths in US 2004-2014. Courtesy of the CDC.
Tables
| 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 |
| 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 |
| 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 |
| 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 |
