Plague Clinical Practice Guidelines (CDC, 2021)

Centers for Disease Control and Prevention (CDC)

These are some of the highlights of the guidelines without analysis or commentary. For more information, go directly to the guidelines by clicking the link in the reference.

August 11, 2021

Clinical practice guidelines on the treatment of plague by the Centers for Disease Control and Prevention (CDC) were published in July 2021 in the Morbidity and Mortality Weekly Report.[1,2]

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 Yersinia 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.

Pregnant women: Because plague has a high case-fatality rate, the CDC recommends antimicrobial treatment and prophylaxis for affected pregnant women even if antimicrobial treatment carries risk to the fetus. Fetal safety concerns should not prevent access to rapid treatment or prophylaxis for pregnant women during a plague outbreak. Antimicrobial safety profiles can help the clinician select the antimicrobial treatment that maximizes benefit to the pregnant woman while minimizing potential risk. In pregnant women with secondary plague meningitis, chloramphenicol should be added to the antimicrobial treatment regimen for all trimesters.

Gentamicin is preferred over streptomycin because streptomycin has been shown to have the greater risk of irreversible fetal ototoxicity. Both ciprofloxacin and levofloxacin are preferred over moxifloxacin because of the lack of safety and efficacy data for moxifloxacin in pregnant women

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.

For more information, see Plague and Pediatric Plague.


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