Antimicrobial Treatment and Prophylaxis of Plague: Recommendations for Naturally Acquired Infections and Bioterrorism Response

Abstract

This report provides CDC recommendations to U.S. health care providers regarding treatment, pre-exposure prophylaxis, and postexposure prophylaxis of plague. Yersinia pestis, the bacterium that causes plague, leads to naturally occurring disease in the United States and other regions worldwide and is recognized as a potential bioterrorism weapon. A bioweapon attack with Y. pestis could potentially infect thousands, requiring rapid and informed decision making by clinicians and public health agencies. The U.S. government stockpiles a variety of medical countermeasures to mitigate the effects of a bioterrorism attack (e.g., antimicrobials, antitoxins, and vaccines) for which the 21st Century Cures Act mandates the development of evidence-based guidelines on appropriate use. Guidelines for treatment and postexposure prophylaxis of plague were published in 2000 by a nongovernmental work group; since then, new human clinical data, animal study data, and U.S. Food and Drug Administration approvals of additional countermeasures have become available. To develop a comprehensive set of updated guidelines, CDC conducted a series of systematic literature reviews on human treatment of plague and other relevant topics to collect a broad evidence base for the recommendations in this report. Evidence from CDC reviews and additional sources were presented to subject matter experts during a series of forums. CDC considered individual expert input while developing these guidelines, which provide recommended best practices for treatment and prophylaxis of human plague for both naturally occurring disease and following a bioterrorism attack. The guidelines do not include information on diagnostic testing, triage decisions, or logistics involved in dispensing medical countermeasures. Clinicians and public health officials can use these guidelines to prepare their organizations, hospitals, and communities to respond to a plague mass-casualty event and as a guide for treating patients affected by plague.

Yersinia pestis antibiotic resistance: a systematic review

“…Although plague, especially the pneumonic form, can cause high and rapid mortality, the disease can be treated with early antimicrobial treatment [37]. Based on a systematic review of 762 published clinical cases from 1937 to 2019, aminoglycosides, tetracyclines, fluoroquinolones, and sulfonamides proved to be effective against plague.…”

“…Fluoroquinolones have been exclusively administered since the 1980s, when they were developed [38]. According to the latest recommendations on antimicrobial treatment for plague from the Centers for Disease Control and Prevention (CDC), aminoglycosides and fluoroquinolones are the mainstays of antimicrobial treatment for plague, while tetracyclines, chloramphenicol, and trimethoprimsulfamethoxazole (TMP-SMX) could also be options for treatment depending on the age and pregnancy status of the patient [37]. Nevertheless, a study of plague in Vietnam revealed that patients treated with TMP-SMX had a longer duration of fever and some developed complications [38].…”

“…Tetracyclines have few major adverse events, but they are contraindicated for pregnant women and infants [39]. Table 1 displays the first choices of treatment protocols for plague from the CDC [37]. Apart from doxycycline (for bubonic and pharyngeal plague), the other antibiotics in the table can be used to treat all forms of plague.…”

“…Close contacts ( < 2 m) of patients infected with pneumonic plague and individuals exposed to airborne droplets are at high risk of infection [34]. Therefore, they are suggested to receive orally administered ciprofloxacin, levofloxacin, doxycycline, and moxifloxacin as the first options for 7 days according to the CDC recommendations [37]. However, in a mass casualty setting, doxycycline, ciprofloxacin, and tetracycline are suggested as the preferred choice for postexposure prophylaxis based on the suggestions of Working Group on Civilian Biodefense.…”

Notes from the Field: Delays in Identification and Treatment of a Case of Septicemic Plague — Navajo County, Arizona, 2020

“…With rare pathogens, particularly in the context of the COVID-19 pandemic, timely laboratory identification is crucial for accurate clinical diagnosis and treatment; reeducation was conducted with the laboratories regarding the reporting requirements. This patient did not receive high-efficacy antibiotic treatment, a tetracycline, until approximately 30 days after symptom onset; he recovered, possibly in part because he received antibiotics with some demonstrated efficacy against Y. pestis , including trimethoprim/sulfamethoxazole, early in the illness course ( 3 ).…”