Medication Summary
Untreated plague can progress to a fulminant illness with a high risk of mortality. Thus, early and appropriate antibiotic treatment is essential.
Historically, streptomycin (15 mg/kg, up to 1 g intramuscularly every 12 h) has been the drug of choice [34] ; however, in the United States, supplies of streptomycin are scarce.
An in vitro comparison [37] and a murine model [38] demonstrated that gentamicin (5 mg/kg intravenously or intramuscularly once daily) is comparable to or superior than streptomycin. Gentamicin has been used successfully in the treatment of human plague, [18] is inexpensive, and can be dosed once daily.
Doxycycline (as dosed for anthrax) is a recommended alternative in patients who cannot take aminoglycosides or in the event of a mass casualty scenario, making parenteral therapy unachievable. [34]
Because chloramphenicol attains high CSF concentrations, [34] it has been used to treat meningeal plague, although no studies have been conducted for substantiation. [39] Chloramphenicol may be challenging to obtain.
Studies in murine models have shown that fluoroquinolones demonstrate efficacy similar to that of the aminoglycosides. [38] Fluoroquinolones are a reasonable alternative therapy. [39]
The FDA has approved levofloxacin and moxifloxacin for the treatment of plague. These have also been approved for use as prophylaxis following exposure to Yersinia pestis.
Trimethoprim-sulfamethoxazole has been used to treat bubonic plague; however, it is not considered first-line therapy.
Beta-lactam antibiotics and macrolides should not be used.
Patients with advanced plague have a presentation of typical gram-negative sepsis and need antibiotic treatment for 10-14 days, along with other supportive measures. [39]
Antibiotics
Class Summary
Therapy must be comprehensive and cover all likely pathogens in the context of this clinical setting. Antibiotic selection should be guided by blood culture sensitivity whenever feasible.
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.
Moxifloxacin (Avelox)
Moxifloxacin is a fluoroquinolone antibiotic that inhibits A subunits of DNA gyrase (topoisomerase type II) and topoisomerase IV, resulting in inhibition of bacterial DNA replication and transcription. It is indicated in adults for treatment and prophylaxis of pneumonic or septicemic plague caused by Yersinia pestis.
Streptomycin
Aminoglycoside antibiotic recommended when less potentially hazardous therapeutic agents are ineffective or contraindicated.
Gentamicin (Garamycin)
Aminoglycoside antibiotic for gram-negative coverage.
Doxycycline (Bio-Tab, Doryx, Doxy, Vibramycin, Vibra-Tabs
Inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.
Chloramphenicol (Chloromycetin)
Binds to 50S bacterial ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. Effective against gram-negative and gram-positive bacteria.
Ciprofloxacin (Cipro, Cipro XR, ProQuin XR)
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1998 world distribution of plague. Image courtesy of the Centers for Disease Control and Prevention (CDC), Atlanta, GA.
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The prairie dog is a burrowing rodent of the genus Cynomys. It can harbor fleas infected with Yersinia pestis, the plague bacillus. Image courtesy of the Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
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Oriental rat flea (Xenopsylla cheopis), the primary vector of plague, engorged with blood. Image courtesy of Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
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Ulcerated flea bite caused by Yersinia pestis bacteria. Image courtesy of Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
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Swollen lymph glands, termed buboes, are a hallmark finding in bubonic plague. Image courtesy of Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
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Wayson stain showing the characteristic "safety pin" appearance of Yersinia pestis, the plague bacillus. Image courtesy of Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
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Fluorescence antibody positivity is observed as bright, intense green staining around the cell wall of Yersinia pestis, the plague bacillus. Image courtesy of Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
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Histopathology of lung in fatal human plague–fibrinopurulent pneumonia. Image courtesy of Marshall Fox, MD, Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
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Histopathology of lung showing pneumonia with many Yersinia pestis organisms (the plague bacillus) on a Giemsa stain. Image courtesy of Marshall Fox, MD, Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
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Histopathology of spleen in fatal human plague. Image courtesy of Marshall Fox, MD, Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
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Histopathology of lymph node showing medullary necrosis and Yersinia pestis, the plague bacillus. Image courtesy of Marshall Fox, MD, Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
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Histopathology of liver in fatal human plague. Image courtesy of Marshall Fox, MD, Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
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Focal hemorrhages in islet of Langerhans in fatal human plague. Image courtesy of Marshall Fox, MD, Centers for Disease Control and Prevention (CDC), Atlanta, Ga.
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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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CDC, Reported Cases of Human Plague - United States, 1970-2018. Image courtesy of the Centers for Disease Control and Prevention (CDC), Atlanta, GA.
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CDC, Reported Plague Cases by Country, 2013-2018. Image courtesy of the Centers for Disease Control and Prevention (CDC), Atlanta, GA.
