Antibiotic agents
Class Summary
Patients suspected to have plague should be promptly treated. Prompt treatment with antimicrobials such as aminoglycosides, fluoroquinolones, or doxycycline greatly improves outcome. Streptomycin or gentamicin are preferred. Doxycycline is an effective alternative. Levofloxacin has been approved by the FDA for adults and children aged 6 months or older. New multidrug-resistant strains of Y pestis have been reported in Madagascar.
Streptomycin
Aminoglycoside antibiotic is considered the drug of choice. Disadvantages include an intramuscular route of administration, resistant strains, and high toxicity.
Gentamicin (Garamycin)
Aminoglycoside used as an alternative to streptomycin and is equally effective.
Levofloxacin (Levaquin)
Levofloxacin is the L-isomer of the racemate, ofloxacin, a quinolone antimicrobial agent. The antibacterial activity of ofloxacin resides primarily in the L-isomer. It inhibits bacterial topoisomerase IV and DNA gyrase (topoisomerases type II), enzymes required for DNA replication, transcription, repair, and recombination. It is indicated for treatment and prophylaxis of plague, including pneumonic and septicemic plague, caused by Yersinia pestis in adults and pediatric patients, aged 6 months or older.
Tetracycline (Sumycin)
Frequently used for prophylaxis as well as treatment. Is usually substituted for streptomycin after a few days of therapy to minimize toxicity. Inhibits bacterial protein synthesis by binding with 30S and, possibly, 50S ribosomal subunits.
Doxycycline (Doxy, Vibramycin)
Used as an alternative for tetracycline. Inhibits protein synthesis and thus bacterial growth by binding to 30S and, possibly, 50S ribosomal subunits.
Chloramphenicol (Chloromycetin)
DOC for plague meningitis. The PO form is not available in the United States, but the IV formulation can be obtained. Binds to 50S bacterial-ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis.
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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 |
