Oral ciprofloxacin monotherapy effective against bubonic plague: NEJM

A new study published in The New England Journal of Medicine revealed that for the treatment of bubonic plague, a 10-day oral ciprofloxacin monotherapy was not less effective than a sequential aminoglycoside–ciprofloxacin combination.

The plague is a potentially pandemic infectious illness with serious consequences. Weak evidence supports the current therapy recommendations. This study was designed to evaluate the 2 treatment alternatives because of the dearth of higher-quality information supporting treatment regimens and the drawbacks of aminoglycosides (like injectable administration, undesirable side effects, and inadequate intracellular penetration).

People with clinically diagnosed bubonic plague in Madagascar between 2020 and 2024 were recruited for this study (pregnant women excluded). This research examined injectable aminoglycoside for 3 days followed by oral ciprofloxacin for 7 days (aminoglycoside–ciprofloxacin) or oral ciprofloxacin for 10 days (ciprofloxacin monotherapy).

Therapy failure, which was characterized as death, fever, subsequent pneumonic plague, or alternative or longer plague therapy, was the main end goal on day 11. The upper limit of the 95% CI around the risk difference had to be less than 15 percentage points in order to demonstrate that ciprofloxacin monotherapy was not inferior in patients with laboratory-confirmed or likely infections.

A total of 933 individuals in all were screened, and 450 patients who were thought to have bubonic plague were recruited and randomly assigned. 2 patients (one each group) had suspected infection, and 220 patients (110 per group) had confirmed infection. The median age of the randomly assigned patients was 14 years (range: 2 to 72), and 53.2% of them were male.

Treatment failure occurred in 9.0% (10 of 111) of patients with confirmed or probable infection in the ciprofloxacin monotherapy group and 8.1% (9 of 111) of patients in the aminoglycoside–ciprofloxacin group (difference, 0.9 percentage points; 95% CI: -6.0 to 7.8). Ciprofloxacin monotherapy was not inferior to aminoglycoside–ciprofloxacin therapy. Almost, 3 patients in each group had secondary pneumonic plague, and 5 patients in the ciprofloxacin monotherapy group and 4 in the aminoglycoside–ciprofloxacin group died overall.

The patients with confirmed or likely infections saw similar rates of adverse events in both groups: 18.0% experienced adverse events in the ciprofloxacin monotherapy group and 18.9% in the aminoglycoside–ciprofloxacin group, with 7.2% and 5.4%, respectively, experiencing severe adverse events. Overall, 10 days of oral ciprofloxacin was a successful substitute for an injection of an aminoglycoside in individuals with confirmed or suspected bubonic plague.

Source:

Randremanana, R. V., Raberahona, M., Bourner, J., Rajerison, M., Edwards, T., Randriamparany, R., Fehizoro Razafindratsinana, T., Razananaivo, L. H., Zadonirina, G., Mayouya-Gamana, T., Salam, A. P. A., Mangahasimbola, R. T., Andrianaivoarimanana, V., Pesonel, E., Rakotoarivelo, R. A., Randria, M. J. de D., Horby, P., Olliaro, P., & IMASOY Study Group. (2025). Ciprofloxacin versus aminoglycoside-ciprofloxacin for bubonic plague. The New England Journal of Medicine, 393(6), 544–555. https://doi.org/10.1056/NEJMoa2413772