Evaluating Oral Ciprofloxacin for Treatment of Plague

Plague is a zoonotic disease caused by the bacterium Yersinia pestis. Although the disease naturally occurs on most continents, it remains a significant public health threat, in particular, in regions such as sub-Saharan Africa.

There are three forms of plague. Bubonic plague, the most common form, is characterized by the presence of swollen and painful lymph nodes, known as “buboes,” that typically arise in the groin, neck, and armpits. If untreated, the disease can spread into the bloodstream, causing septicemic plague; or it can spread into the lungs, causing pneumonic plague—the most serious form.

Without appropriate antibiotic therapy, plague can be life-threatening. Streptomycin and doxycycline are two antibiotics approved by the US Food and Drug Administration (FDA) for treatment of plague. However, although streptomycin is considered the gold standard treatment for plague, this antibiotic is not widely available in the United States and is also associated with significant adverse effects. And, although doxycycline is an acceptable and low-cost treatment alternative, it is bacteriostatic and may have limited efficacy for serious infections.

“Fluoroquinolones, including ciprofloxacin, have recently been approved by the FDA for treatment of plague, based on animal and in vitro studies,” write Titus Apangu, MD, from the Uganda Virus Research Institute, Entebbe, and colleagues from the Centers for Disease Control and Prevention (CDC), Atlanta, Georgia in a research letter, recently published in the journal, Emerging Infectious Diseases.

“Clinical experience with these agents, however, is limited,” they add.

With this in mind, Dr. Apangu and colleagues conducted a study in the West Nile region of Uganda, using ciprofloxacin to treat five patients with plague. Between 2011 and 2014, the investigators offered patients with suspected plague the chance to enroll in an open-label study to examine the safety and effectiveness of ciprofloxacin for treating this disease.

The study enrolled five patients, ranging in age from 10 to 52 years. Four of these individuals had bubonic plague, and one had pneumonic plague. In all patients, the disease was confirmed by using microbial culture.

Three patients were hospitalized for treatment, while the remaining two were treated as outpatients. They received oral ciprofloxacin for 10 days, at a dosage of approximately 15 mg/kg twice daily (with a maximum dose for adults of 750 mg twice daily). In addition, they all received acetaminophen, and two of the patients also received fluid therapy. All patients were monitored daily during treatment.

According to the authors, all five patients recovered from their fevers within just two days of treatment. And, by 14 days, all had been discharged and returned to their normal activities.

Fluoroquinolones have properties that make them particularly suitable for treatment of plague, the authors state, “including bactericidal activity, good oral bioavailability, excellent tissue penetration, and an established safety record.”

Laboratory studies and animal studies have also suggested that, with respect to the ability to kill Yersinia pestis, ciprofloxacin is as effective as streptomycin and more effective than doxycycline.

“These results add to the growing body of evidence supporting broader use of oral ciprofloxacin for treating plague in people, especially in resource-poor areas where intravenous treatment is limited,” Dr. Apangu and colleagues conclude.

Despite previous warnings from the FDA on the use of fluoroquinolones, in certain situations, “the benefits of fluoroquinolones outweigh the risks, and it is appropriate for them to remain available as a therapeutic option.”

Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals, and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.