Antimicrobial Treatment Patterns and Illness Outcome Among United States Patients With Plague, 1942–2018

Abstract

Background Plague is a rare and severe zoonotic illness with limited empiric evidence to support treatment recommendations. We summarize treatment information for all patients with plague in the United States (US) as collected under the auspices of public health surveillance. Methods We reviewed use of specific antimicrobials and illness outcome among cases of plague reported from 1942–2018. Antimicrobials were a priori classified into high-efficacy (aminoglycosides, tetracyclines, fluoroquinolones, sulfonamides, and chloramphenicol) and limited-efficacy classes (all others). Logistic regression models were created to describe associations between use of specific antimicrobial classes and illness outcome while controlling for potential confounding factors. Results Among 533 total reported plague cases during 1942–2018, 426 (80%) received high-efficacy antimicrobial therapy. Mortality differed significantly among those receiving high-efficacy therapy (9%) and only limited-efficacy therapy (51%). Aminoglycosides and tetracyclines were used more commonly than other classes, and their use was associated with increased odds of survival of plague. Gentamicin use was associated with higher mortality than streptomycin, and aminoglycoside use was linked to higher mortality than for tetracyclines. Fluoroquinolones have been used in treatment of >30% of patients in recent years and limited data suggest clinical effectiveness. Conclusions Most US patients with plague have received effective antimicrobials. Aminoglycosides and tetracyclines substantially improve survival of plague, and fluoroquinolones may be equally as effective, yet lack sufficient data. Early recognition and early treatment with any of these antimicrobial classes remain the most important steps to improving survival of plague.

Antibiotic Therapy of Plague: A Review

“…Bubonic plague, septicemic plague and pneumonic plague are the three main clinical forms of this disease. Bubonic plague accounts for 70% to 90% of human cases, whereas the septicemic and pneumonic forms respectively account for around 30% and less than 5% [ 17 , 18 , 19 , 20 , 21 , 22 ]. It is noteworthy that the septicemic form is mainly diagnosed in USA because of the increasing standardized blood culture programs implemented in the country’s hospital laboratories [ 23 ].…”

“…It is undeniable that the advent of antibiotics has greatly reduced the death rate for plague patients [ 22 , 26 , 45 , 46 ]. However, early administration remains essential.…”

“…However, early administration remains essential. Even when antibiotics known to be effective are given, patients who develop the bubonic form of plague are most likely to survive: after treatment with antibiotics, around 10% of patients with bubonic plague and 30% to 50% of patients with pneumonic or septicemic plague will nevertheless die [ 22 , 23 , 45 , 47 ]. However, a recent meta-analysis of deaths associated with pneumonic plaque and data from the large outbreak of pneumonic plague in Madagascar in 2017 indicated that the death rate in patients with confirmed or probable pneumonic plague was between 8–25% [ 48 , 49 ].…”

“…The clinical data indicate that many classes of antibiotics (i.e., aminoglycosides, tetracyclines, fluoroquinolones, sulfonamides, phenicols, and β-lactams) have been administered to patients with the different forms of plague [ 22 , 75 , 121 , 122 , 123 ]. A review of published case reports found that aminoglycosides, tetracyclines, and fluoroquinolones (but not sulfonamides) were most consistently effective in the treatment of pneumonic plague.…”

“…A review of published case reports found that aminoglycosides, tetracyclines, and fluoroquinolones (but not sulfonamides) were most consistently effective in the treatment of pneumonic plague. However, the higher case fatality rate of pneumonic plague associated with sulfonamides drugs might be due to bias since ancillary care was less effective when the drug was introduced in the 1930s [ 22 , 75 ].…”