Treating Bioterrorism-Related Plague: CDC Issues New Guidelines

Judy Stone, MD

August 03, 2021

The Centers for Disease Control (CDC) has issued the first recommendations for the prevention and treatment of plague since 2000. The new guidelines focus on the possibility of bioterrorism with mass casualty events from an intentional release of Yersinia pestis.

Plague, a deadly infection caused by Y pestis, has been feared throughout history because of large pandemics. The most well-known pandemic was the so-called Black Death in the fourteenth century, during which more than 50 million Europeans died. The biggest concern now is the spread of the bacteria by bioterrorism.

The CDC based their revised guidelines on an extensive systematic review of the literature and multiple sessions with about 90 experts in infectious disease, public health, emergency medicine, ob-gyn, maternal-fetal health, and pediatrics, in addition to representatives from a wide range of federal agencies.

Key Changes

Christina Nelson, a medical officer with the CDC's Division of Vector-Borne Diseases, told Medscape Medical News that now "we have been fortunate to have extended options for treatment." Previously, "streptomycin and gentamicin were the first-line options for adults," she said. Now, on the basis of additional evidence, "[we're] able to…elevate the fluoroquinolones to first-line treatments."

Dr Christina Nelson

On the basis of the Animal Rule, which allows approval of antibiotics without human testing if such testing is not possible, the US Food and Drug Administration has approved several quinolones for both treatment and prophylaxis of plague.

The guidelines offer same-class alternative antibiotics to meet surge capacity. Similarly, trimethoprim-sulfamethoxazole is now an alternative for prophylaxis.

There are additional oral options to conserve IV medications and supplies in a mass casualty event.

Dr Gigi Kwik Gronvall

For the first time, the CDC added specific recommendations for pregnant women. Gigi Kwik Gronvall, PhD, senior scholar at the Johns Hopkins Center for Health Security, Baltimore, Maryland, told Medscape Medical News that she was pleased to see this addition, because "effects on women and during pregnancy are not fully addressed, and it leads to problems down the road, like with COVID," for which "they didn't include pregnant people in their clinical trials for the vaccines" and "don't have enough data to convince pregnant women to actually get the vaccine."

Bubonic Plague

Plague occurs globally, with natural sylvatic (wild animal) outbreaks occurring among rodents and small mammals. It is spread by fleas. When an infected flea bites a human, the person can become infected, most commonly as "bubonic" plague, with swollen lymph nodes, called buboes. Transmission can also occur between people by contact with infected fluids or inhalation of infectious droplets.

Gentamicin or streptomycin remain first-line agents for treating bubonic plague. When used as monotherapy, the survival rate is 91%. They have to be given parenterally and are associated with both nephrotoxicity and ototoxicity; patients require monitoring.

Alternative first-line drugs now include high-dose ciprofloxacin, levofloxacin, moxifloxacin, and doxycycline. Each is administered either intravenously or orally.

Physicians should consider dual therapy and drainage for patients with large buboes. Treatment is for 10 to 14 days.

Pneumonic and Septicemic Plague

The pneumonic and septicemic forms of infection are deadlier than the bubonic. Pneumonic plague can be acquired from inhalation of infected bacteria from animals or people, from lab accidents, or from intentional aerosolization. Without treatment, these forms are almost always fatal. With treatment with aminoglycosides, fluoroquinolones, or tetracyclines, alone or in combination, survival is 82% to 83%. With naturally occurring pneumonic plague, the CDC now recommends levofloxacin or moxifloxacin to cover for community-acquired pneumonia if the source of the infection is uncertain.

Because plague is life threatening, doxycycline is not considered contraindicated in children. It has not been shown to cause tooth staining, unlike other tetracyclines, which should still be avoided if possible.


About 10% of people infected with bubonic plague develop plague meningitis. Symptoms are stiff neck, fever, headache, and coma. The current recommendation for treating plague meningitis is chloramphenicol and moxifloxacin or levofloxacin. However, quinolones can cause seizures, and clinicians should take that into account.

Infection Control

Plague is transmitted between people by droplets, so caretakers should wear a mask in addition to taking standard precautions. They should add eye protection and a face shield if splashing is likely. Airborne precautions are not needed. Plague is not very transmissible from person to person; each infected person on average infects only 1.18 other people. In comparison, someone with chickenpox infects 9 to 10 people on average.


A deliberate attack would likely go undetected until a cluster or unusual pattern of disease became evident. With Y pestis, the infectious dose is low. According to the guidelines, modeling suggests that a "release of 50 kg of Y pestis into the air over a city of 5 million persons could result in 150,000 cases of pneumonic plague and 36,000 deaths."

Because the former Union of the Soviet Socialist Republics (USSR) engineered antibiotic-resistant Y pestis, antibiotics from two different classes should be used empirically until sensitivity tests become available.

Antibiotic prophylaxis would also have to be considered for exposed individuals. Recommendations would be developed at the time by federal and state experts, based in part on the magnitude of the event and the availability of masks and different classes of antibiotics.

Gronvall stressed the need for awareness, saying, "It's important for people to remember that the first sign of the potential attack could be somebody coming into your hospital."

Nelson added, "One of the main take-home that plague still happens, it still happens in the western United States, it still happens around the world.... It's not just a relic of history." She emphasized that clinicians need to be thinking about it, because "it's very important to get antibiotics on board early.... Then patients generally have a good prognosis."

Nelson and Gronvall have disclosed no relevant financial relationships.

Morb Mortal Wkly Rep. Published online July 16, 2021. Full text

Judy Stone, MD, is an infectious disease specialist and author of Resilience: One Familys Story of Hope and Triumph Over Evil and of Conducting Clinical Research, the essential guide to the topic. You can find her at or on Twitter @drjudystone.

For more news, follow Medscape on Facebook, Twitter, Instagram, and YouTube.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.