A Perilous Combination: Coinfection with Human Plague-Report of Two Cases and Review of the Literature, 1937-2022.

Plague in humans and animals is caused by , a zoonotic gram-negative bacterium endemic in certain regions of Asia, Africa, and the United States. Coinfection with both and Streptococci species has been anecdotally reported in humans and associated with severe and rapidly fatal disease. This report presents two cases of patients who died following and coinfection. Additional cases of previously published coinfection were identified and reviewed using a search of electronic databases. The first case patient developed cough and dyspnea following 4 days of fever, malaise, and back pain and died before receiving medical care. Postmortem blood cultures were positive for , , and . The second case patient was hospitalized with fever, vomiting, diarrhea, and dyspnea and died of sepsis and respiratory failure on the day of admission. and were isolated from blood cultures drawn on admission. Seven additional cases of and coinfection were identified, dating between 1948 and 2009. These patients were healthy overall before their illness, with ages ranging from 9 to 60 years. The majority of patients had primary bubonic plague with associated pneumonia or septicemia. None of the patients who died received timely antimicrobial therapy directed against gram-negative pathogens. In every case but one, an occupational or environmental risk factor for plague was later identified. infection begins with a pre-inflammatory phase, during which and other pathogens can rapidly proliferate. Streptococci, which are frequently asymptomatic colonizers, may become invasive in this environment, leading to coinfection. The challenges of diagnosing in the context of coinfection may delay effective treatment. This case series and literature review illustrate the importance of clinicians remaining alert to environmental and occupational exposures in patients presenting with an infectious syndrome, especially in those who have an unexpectedly severe clinical presentation.