Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

pneumonic or septicemic plague: nonpregnant adults and children

1st line – antibiotic monotherapy

Back
ACUTE
|
pneumonic or septicemic plague: nonpregnant adults and children
|
mild to moderate disease and naturally occurring
1st line – 

antibiotic monotherapy

Antibiotic monotherapy is recommended in patients who have mild to moderate disease (i.e., no organ dysfunction), provided that the clinical history suggests that plague is naturally occurring (i.e., close contact with a severely ill and coughing patient with known naturally acquired pneumonic plague, or close or direct contact with an animal with plague).[2] 

First-line options recommended by the Centers for Disease Control and Prevention (CDC) for adults and children include ciprofloxacin, levofloxacin, gentamicin, and streptomycin. Moxifloxacin is not recommended in children as a first-line agent. Alternative options include other fluoroquinolones or aminoglycosides (not detailed here), doxycycline, chloramphenicol, and trimethoprim/sulfamethoxazole.[2]

The World Health Organization (WHO) supports the use of ciprofloxacin, levofloxacin, moxifloxacin, gentamicin, and streptomycin as first-line options for the treatment of pneumonic or septicemic plague.[1]

Clinical judgment should be used to decide whether parenteral or oral (or nasogastric/gastric tube if appropriate) therapy is required. Patients who are started on parenteral therapy can be transitioned to an appropriate oral therapy when there is clinical improvement.[2] Oral antibiotics are more likely to be used in a mass casualty setting. 

Some recommended antibiotics may not be available locally, so you should consult your local guidance. Large-scale distribution and use of these antimicrobials during a bioterrorism response might be under a Food and Drug Administration (FDA)-issued emergency-use authorization (or its equivalent in other countries).

Fluoroquinolones have been associated with serious, disabling, and potentially irreversible adverse effects, including tendonitis, tendon rupture, arthralgia, neuropathies, and other musculoskeletal or nervous system effects.[41]Warnings have also been issued about the increased risk of aortic dissection, significant hypoglycemia, and mental health adverse effects in patients taking fluoroquinolones.[42][52]

Treatment course: 10 to 14 days. Treatment can be extended for patients with ongoing fever or any other concerning clinical signs or symptoms.[2] 

Primary options

ciprofloxacin: children: 15 mg/kg orally every 8-12 hours (maximum 1500 mg/day), or 10 mg/kg intravenously every 8-12 hours (maximum 400 mg/dose); adults: 750 mg orally every 12 hours, or 400 mg intravenously every 8 hours

OR

levofloxacin: children body weight <50 kg: 8 mg/kg orally/intravenously every 12 hours, maximum 250 mg/dose; children body weight ≥50 kg: 500-750 mg orally/intravenously every 24 hours; adults: 750 mg orally/intravenously every 24 hours

OR

moxifloxacin: adults: 400 mg orally/intravenously every 24 hours

OR

gentamicin: children: 4.5 to 7.5 mg/kg intravenously/intramuscularly every 24 hours; adults: 5 mg/kg intravenously/intramuscularly every 24 hours

More

OR

streptomycin: children: 15 mg/kg intravenously/intramuscularly every 12 hours, maximum 1 g/dose; adults: 1 g intravenously/intramuscularly every 12 hours

More

Secondary options

doxycycline: children <45 kg body weight: 4.4 mg/kg orally/intravenously as a loading dose, followed by 2.2 mg/kg every 12 hours, maximum 100 mg/dose; children ≥45 kg body weight and adults: 200 mg orally/intravenously as a loading dose, followed by 100 mg every 12 hours

OR

chloramphenicol: children and adults: 12.5 to 25 mg/kg intravenously every 6 hours, maximum 1 g/dose

More

OR

sulfamethoxazole/trimethoprim: children ≥2 months of age and adults: 5 mg/kg orally/intravenously every 8 hours

More

Plus – infection prevention and control

Back
ACUTE
|
pneumonic or septicemic plague: nonpregnant adults and children
|
mild to moderate disease and naturally occurring
Plus – 

infection prevention and control

Treatment recommended for ALL patients in selected patient group

Follow your local infection prevention and control guidelines. Patients with pneumonic plague require isolation for at least 48 hours and until their clinical condition improves.

Standard and droplet precautions are recommended when providing care to patients with suspected or confirmed pneumonic plague. Droplet precautions may be discontinued once patients have received at least 48 hours of antibiotics and have shown clinical improvement with markedly decreased sputum production.[2] 

During procedures that are likely to generate sprays or splashes, a mask, eye protection, and face shield should be worn. Particulate-filtering facepiece respirators may be considered as an added precaution when performing aerosol-generating procedures.[2] 

1st line – dual antibiotic therapy

Back
ACUTE
|
pneumonic or septicemic plague: nonpregnant adults and children
|
severe disease or suspected intentional release
1st line – 

dual antibiotic therapy

Dual antibiotic therapy with antibiotics from two different classes is recommended in patients with severe pneumonic or septicemic disease (i.e., signs of organ dysfunction), or if there is reason to suspect engineered antimicrobial resistance as part of a bioterrorism attack. After clinical improvement, therapy may be narrowed to a single agent.[2] See antibiotic monotherapy above for a list of suitable antibiotics and their doses.

Plus – infection prevention and control

Back
ACUTE
|
pneumonic or septicemic plague: nonpregnant adults and children
|
severe disease or suspected intentional release
Plus – 

infection prevention and control

Treatment recommended for ALL patients in selected patient group

Follow your local infection prevention and control guidelines. Patients with pneumonic plague require isolation for at least 48 hours and until their clinical condition improves.

Standard and droplet precautions are recommended when providing care to patients with suspected or confirmed pneumonic plague. Droplet precautions may be discontinued once patients have received at least 48 hours of antibiotics and have shown clinical improvement with markedly decreased sputum production.[2] 

During procedures that are likely to generate sprays or splashes, a mask, eye protection, and face shield should be worn. Particulate-filtering facepiece respirators may be considered as an added precaution when performing aerosol-generating procedures.[2] 

Plus – supportive care

Back
ACUTE
|
pneumonic or septicemic plague: nonpregnant adults and children
|
severe disease or suspected intentional release
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Tissue perfusion and oxygenation in septic patients should be maintained by oxygen, fluid resuscitation, and vasopressors if required. Patients with pneumonic plague may require ventilator support.

bubonic or pharyngeal plague: nonpregnant adults and children

1st line – antibiotic monotherapy

Back
ACUTE
|
bubonic or pharyngeal plague: nonpregnant adults and children
|
stable disease and naturally occurring
1st line – 

antibiotic monotherapy

Antibiotic monotherapy is recommended in patients with naturally occurring bubonic or pharyngeal plague who are stable (i.e., absence of disease progression and absence of systemic symptoms).[2] 

First-line options recommended by the CDC for adults and children include ciprofloxacin, levofloxacin, doxycycline, gentamicin, and streptomycin. Moxifloxacin is not recommended in children as a first-line agent. Alternative options include other fluoroquinolones, aminoglycosides, or tetracyclines (not detailed here), chloramphenicol, and trimethoprim/sulfamethoxazole.[2] 

The WHO supports the use of ciprofloxacin, levofloxacin, moxifloxacin, doxycycline, gentamicin, and streptomycin as first-line options for the treatment of bubonic plague.[1]

Clinical judgment should be used to decide whether parenteral or oral (or nasogastric/gastric tube if appropriate) therapy is required. Patients who are started on parenteral therapy can be transitioned to an appropriate oral therapy when there is clinical improvement.[2] Oral antibiotics are more likely to be used in a mass casualty setting. 

Some recommended antibiotics may not be available locally, so you should consult your local guidance. Large-scale distribution and use of these antimicrobials during a bioterrorism response might be under a Food and Drug Administration (FDA)-issued emergency-use authorization (or its equivalent in other countries).

Fluoroquinolones have been associated with serious, disabling, and potentially irreversible adverse effects, including tendonitis, tendon rupture, arthralgia, neuropathies, and other musculoskeletal or nervous system effects.[41] Warnings have also been issued about the increased risk of aortic dissection, significant hypoglycemia, and mental health adverse effects in patients taking fluoroquinolones.[42][52]

Treatment course: 10 to 14 days. Treatment can be extended for patients with ongoing fever or any other concerning clinical signs or symptoms.[2]

Primary options

ciprofloxacin: children: 15 mg/kg orally every 8-12 hours (maximum 1500 mg/day), or 10 mg/kg intravenously every 8-12 hours (maximum 400 mg/dose); adults: 750 mg orally every 12 hours, or 400 mg intravenously every 8 hours

OR

levofloxacin: children body weight <50 kg: 8 mg/kg orally/intravenously every 12 hours, maximum 250 mg/dose; children body weight ≥50 kg: 500-750 mg orally/intravenously every 24 hours; adults: 750 mg orally/intravenously every 24 hours

OR

moxifloxacin: adults: 400 mg orally/intravenously every 24 hours

OR

gentamicin: children: 4.5 to 7.5 mg/kg intravenously/intramuscularly every 24 hours; adults: 5 mg/kg intravenously/intramuscularly every 24 hours

More

OR

streptomycin: children: 15 mg/kg intravenously/intramuscularly every 12 hours, maximum 1 g/dose; adults: 1 g intravenously/intramuscularly every 12 hours

More

OR

doxycycline: children <45 kg body weight: 4.4 mg/kg orally/intravenously as a loading dose, followed by 2.2 mg/kg every 12 hours, maximum 100 mg/dose; children ≥45 kg body weight and adults: 200 mg orally/intravenously as a loading dose, followed by 100 mg every 12 hours

Secondary options

chloramphenicol: children and adults: 12.5 to 25 mg/kg intravenously every 6 hours, maximum 1 g/dose

More

OR

sulfamethoxazole/trimethoprim: children ≥2 months of age and adults: 5 mg/kg orally/intravenously every 8 hours

More

1st line – dual antibiotic therapy

Back
ACUTE
|
bubonic or pharyngeal plague: nonpregnant adults and children
|
unstable disease or suspected intentional release
1st line – 

dual antibiotic therapy

Dual antibiotic therapy with antibiotics from two different classes is recommended in patients with large buboes or unstable disease (e.g., disease progression, systemic symptoms), or if there is reason to suspect engineered antimicrobial resistance as part of a bioterrorism attack. After clinical improvement, therapy may be narrowed to a single agent.[2] See antibiotic monotherapy above for a list of suitable antibiotics and their doses. 

Patients who present with primary bubonic or pharyngeal plague that has progressed to secondary pneumonic or septicemic plague should be treated as per the recommendations for pneumonic and septicemic plague (above).[2] 

Consider – surgical incision and drainage

Back
ACUTE
|
bubonic or pharyngeal plague: nonpregnant adults and children
|
unstable disease or suspected intentional release
Consider – 

surgical incision and drainage

Treatment recommended for SOME patients in selected patient group

Surgical incision and drainage might be necessary if the bubo becomes suppurative.[2]

During procedures that are likely to generate sprays or splashes (e.g., bubo aspiration), a mask, eye protection, and face shield should be worn.[2] Follow your local infection prevention and control guidelines.

pneumonic, septicemic, bubonic, or pharyngeal plague: pregnant

1st line – dual antibiotic therapy

Back
ACUTE
|
pneumonic, septicemic, bubonic, or pharyngeal plague: pregnant
1st line – 

dual antibiotic therapy

Antibiotic therapy is recommended in pregnant women when indicated, even if its use carries some risks for adverse events to the fetus. While available safety data related to use during pregnancy should be considered when selecting an appropriate antibiotic, fetal safety concerns should not prevent access to rapid treatment for pregnant women during a plague outbreak as untreated infection during pregnancy is associated with a high risk of maternal mortality and pregnancy loss, as well as preterm birth and hemorrhage. Efficacy should be the main factor contributing to antibiotic choice in pregnant women.[2] 

Dual antibiotic therapy is recommended in pregnant women with infection caused by either naturally occuring infection or intentional release. Parenteral administration is preferred, when possible, as pregnant women may be less able to tolerate oral medications and there may be decreased gastrointestinal absorption during pregnancy.[2] Oral antibiotics are more likely to be used in a mass casualty setting. 

First-line options recommended by the CDC in pregnant women with pneumonic, septicemic, bubonic, or pharyngeal plague include ciprofloxacin, levofloxacin, or gentamicin. Alternatives include other fluoroquinolones or aminoglycosides, doxycycline, chloramphenicol, or trimethoprim/sulfamethoxazole (not detailed here).[2]

Fluoroquinolones have been associated with serious, disabling, and potentially irreversible adverse effects, including tendonitis, tendon rupture, arthralgia, neuropathies, and other musculoskeletal or nervous system effects.[41] Warnings have also been issued about the increased risk of aortic dissection, significant hypoglycemia, and mental health adverse effects in patients taking fluoroquinolones.[42][52]

Treatment course: 10 to 14 days. Treatment can be extended for patients with ongoing fever or any other concerning clinical signs or symptoms.[2] 

Primary options

gentamicin: 5 mg/kg intravenously/intramuscularly every 24 hours

More

-- AND --

ciprofloxacin: 500 mg orally every 8 hours, or 400 mg intravenously every 8 hours

or

levofloxacin: 750 mg orally/intravenously every 24 hours

Plus – monitoring and supportive care

Back
ACUTE
|
pneumonic, septicemic, bubonic, or pharyngeal plague: pregnant
Plus – 

monitoring and supportive care

Treatment recommended for ALL patients in selected patient group

Consider hospitalization, particularly for those with pneumonic plague or those who are in their second or third trimester, to facilitate parenteral administration of antibiotics and monitoring for preterm labor and maternal hemorrhage. Follow standard guidelines for maternal sepsis and corticosteroid administration for fetal lung maturity.[2]

meningeal plague

1st line – dual antibiotic therapy

Back
ACUTE
|
meningeal plague
1st line – 

dual antibiotic therapy

Dual antibiotic therapy with chloramphenicol plus either levofloxacin or moxifloxacin is recommended by the CDC for the initial treatment of patients with plague who present with signs of meningitis, when possible. Treatment is the same for patients of all ages and pregnant women.[2] 

If chloramphenicol is not available, a nonfluoroquinolone first-line antibiotic (or alternative) for septicemic plague may be used.[2]

For patients who develop secondary meningitis while already receiving antibiotic therapy for plague, chloramphenicol should be added to the existing regimen. Levofloxacin or moxifloxacin may be added instead if chloramphenicol is not available or there is concern over its adverse effects, provided the patient is not already on these agents. The entire combination regimen should be continued for an additional 10 days.[2]

The WHO supports the use of chloramphenicol plus an intravenous fluoroquinolone such as moxifloxacin for the treatment of meningeal plague.[1]

Some recommended antibiotics may not be available locally, so you should consult your local guidance. Large-scale distribution and use of these antimicrobials during a bioterrorism response might be under a Food and Drug Administration (FDA)-issued emergency-use authorization (or its equivalent in other countries).

Fluoroquinolones have been associated with serious, disabling, and potentially irreversible adverse effects, including tendonitis, tendon rupture, arthralgia, neuropathies, and other musculoskeletal or nervous system effects.[41] Warnings have also been issued about the increased risk of aortic dissection, significant hypoglycemia, and mental health adverse effects in patients taking fluoroquinolones.[42][52]

Treatment course: 10 to 14 days. Treatment can be extended for patients with ongoing fever or any other concerning clinical signs or symptoms.[2] 

Primary options

chloramphenicol: children and adults: 25 mg/kg intravenously every 6 hours, maximum 1 g/dose

More

-- AND --

levofloxacin: children body weight <50 kg: 8 mg/kg orally/intravenously every 12 hours, maximum 250 mg/dose; children body weight ≥50 kg: 500-750 mg orally/intravenously every 24 hours; adults: 750 mg orally/intravenously every 24 hours

or

moxifloxacin: children: consult specialist for guidance on dose; adults: 400 mg orally/intravenously every 24 hours

yersiniosis

1st line – rehydration

Back
ACUTE
|
yersiniosis
1st line – 

rehydration

Oral rehydration fluids or intravenous fluids are recommended in patients who are dehydrated.

Consider – antibiotic therapy

Back
ACUTE
|
yersiniosis
Consider – 

antibiotic therapy

Treatment recommended for SOME patients in selected patient group

Antibiotic therapy does not seem to reduce illness severity and is generally not recommended.[49] However, for invasive disease, treatment with antibiotics is usually effective.[50] The Infectious Diseases Society of America recommends trimethoprim/sulfamethoxazole or ciprofloxacin for Yersinia enterocolitica infection.[51] Other options may include third-generation cephalosporins, aminoglycosides, and tetracyclines.[38]​

Fluoroquinolones have been associated with serious, disabling, and potentially irreversible adverse effects, including tendonitis, tendon rupture, arthralgia, neuropathies, and other musculoskeletal or nervous system effects.[41] Warnings have also been issued about the increased risk of aortic dissection, significant hypoglycemia, and mental health adverse effects in patients taking fluoroquinolones.[42][52]

Treatment course depends on the severity of infection.

Primary options

sulfamethoxazole/trimethoprim: children ≥2 months of age: 5 mg/kg orally twice daily, maximum 320 mg/day; adults: 160 mg orally twice daily

More

OR

ciprofloxacin: children: 10-15 mg/kg orally twice daily, maximum 500 mg/dose; adults: 500 mg orally twice daily

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Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

Use of this content is subject to our disclaimer