Yersinia pestis infection medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Assistant Editors-In-Chief: Esther Lee, M.A.; João André Alves Silva, M.D. [2]; Alison Leibowitz [3]

Overview

When a diagnosis of human plague is suspected upon clinical and epidemiological grounds, appropriate specimens for diagnosis should be obtained immediately and the patient should be started on specific antimicrobial therapy prior to a definitive answer from the laboratory. The drugs of choice are streptomycin or gentamicin, but tetracyclines, fluoroquinolones, and chloramphenicol are also effective. The regimens should be adjusted depending on the patient's age, medical history, underlying health conditions, and allergies. Upon evidence of pneumonia, suspect plague patients should be placed in isolation and managed under respiratory droplet precautions.

Medical Therapy

Shown below is a table summarizing the choices of antibiotics used to treat yersina pestis. Duration of treatment is 10 days, or until 2 days after fever subsides. Oral therapy may be substituted once the patient demonstrates improvement.

▸ Click on the following categories to expand treatment regimens.

Plague Treatment   ▸  Adult Patients   ▸  Children   ▸  Pregnant Patients

Adult Patients Preferred Regimen ▸ Streptomycin 1 g IM q12h OR ▸ Gentamicin 5 mg/Kg q24h, or 2 mg/kg loading dose followed by 1.7 mg/kg q8h, IM or IV Alternative Regimen ▸ Doxycycline 100 mg IV q12h or 200 mg IV q24h OR ▸ Ciprofloxacin 400 mg IV q12h OR ▸ Chloramphenicol 25 mg/Kg IV q6h Children Preferred Regimen ▸ Streptomycin 15 mg/Kg IM q12h (maximum dose, 2 g/day) OR ▸ Gentamicin 2.5 mg/Kg IM or IV q8h Alternative Regimen ▸ Doxycycline (for children ≥8 years) if <45Kg: 2.2 mg/Kg IV q12h (max 200mg/day); if ≥45Kg: 100 mg IV q12h or 200 mg IV q24h OR ▸ Ciprofloxacin 15 mg/Kg IV q12h (maximum dose, 1g) OR ▸ Chloramphenicol (for children >2 years) 25 mg/kg IV q6h (maximum dose, 4g) Pregnant Patients Preferred Regimen ▸ Gentamicin 5 mg/Kg q24h, or 2 mg/kg loading dose followed by 1.7 mg/kg q8h, IM or IV Alternative Regimen ▸ Doxycycline 100 mg IV q12h or 200 mg IV q24h OR ▸ Ciprofloxacin 400 mg IV q12h

Aminoglycosides

Streptomycin, the most effective antibiotic against Yersinia pestis, is the drug of choice for treatment of plague, particularly the pneumonic form. Therapeutic effect is expected with 30 mg/kg/day (maximum of 2 g/day) in divided doses given intramuscularly, and continued for a full course of 10 days or until 3 days following temperature normalization.

Gentamicin, found to be effective in animal studies, is also used to treat human plague patients.

Chloramphenicol

Chloramphenicol, a suitable alternative to aminoglycosides in the treatment of bubonic or septicemic plague, is the drug of choice for patients with a Yersinia pestis invasion of tissue spaces where other drugs travel poorly, such as plague meningitis, pleuritis, or endophthalmitis. Dosage should be 50 mg/kg/day administered in divided doses either parenterally or, if tolerated, orally for 10 days. Chloramphenicol may be used adjunctively with aminoglycosides.

Tetracyclines

Tetracyclines, a group of bacteriostatic antibiotics, are effective in the primary treatment of patients with uncomplicated plague. An oral loading dose of 15 mg/kg tetracycline (maximum of 1g total), should be followed by 25-50 mg/kg/day (maximum of 2 g/day) for 10 days. Tetracyclines may also be used adjunctively with other antibiotics.

Sulfonamides

Although sulfonamides have been used extensively in plague treatment and prevention, some studies have demonstrated higher mortality, increased complications, and longer duration of fever as compared to the use of streptomycin, chloramphenicol or tetracycline antibiotics. Sulfadiazine is given as a loading dose of 2-4 g followed by a dose of 1 g every 4-6 hours for a period of 10 days. In children, the oral loading dose is 75 mg/kg, followed by 150 mg/kg/day orally in six divided doses. The combination drug trimethoprim-sulfamethoxazole has been used both in the treatment and prevention of plague.

Fluoroquinolones

Fluoroquinolones, such as ciprofloxacin, have been effective against Y. pestis in both in vitro and animal studies. Ciprofloxacin is bacteriocidal and has broad spectrum activity against most Gram-negative aerobic bacteria, including Enterobacteriaceae and Pseudomonas aeruginosa, as well as against many Gram-positive bacteria. Although it has been used successfully to treat humans with Francisella tularensis infection, no studies have been published on its use in treating human plague.

Other Classes of Antibiotics

Other cases of antibiotics, such as penicillins, cephalosporins, and macrolides have demonstrated to be ineffective or of variable effect in the treatment of plague and should not be used for this purpose.

Supportive Therapy

Clinicians must prepare for intense supportive management of plague complications, utilizing the latest developments for dealing with Gram-negative sepsis. Aggressive monitoring and management should be instituted for the possibility of:

• Septic shock
• Multiple organ failure
• Adult respiratory distress syndrome (ARDS)
• Disseminated intravascular coagulopathy

Treatment of Plague During Pregnancy and in Children

With prompt and proper therapy, complications of plague in pregnancy can be prevented.

The selection of antibiotics during pregnancy is confounded by the potential adverse effects of three of the most effective drugs:

• Streptomycin may be ototoxic and nephrotoxic to the fetus.
• Tetracycline has an adverse effect on the developing teeth and bones of a fetus.
• Chloramphenicol carries a low risk of "gray baby" syndrome or bone marrow suppression.
• A judiciously administered aminoglycoside is effective and safe for both the mother and fetus, and in children. Because of its intravenous and intramuscular administration and its low risk of adverse effects, gentamicin is the preferred antibiotic for treating plague during pregnancy.