Abstract
Plague—a deadly disease caused by the bacterium Yersinia pestis—is still an international public health concern. There are three main clinical forms: bubonic plague, septicemic plague, and pulmonary plague. In all three forms, the symptoms appear suddenly and progress very rapidly. Early antibiotic therapy is essential for countering the disease. Several classes of antibiotics (e.g., tetracyclines, fluoroquinolones, aminoglycosides, sulfonamides, chloramphenicol, rifamycin, and β-lactams) are active in vitro against the majority of Y. pestis strains and have demonstrated efficacy in various animal models. However, some discrepancies have been reported. Hence, health authorities have approved and recommended several drugs for prophylactic or curative use. Only monotherapy is currently recommended; combination therapy has not shown any benefits in preclinical studies or case reports. Concerns about the emergence of multidrug-resistant strains of Y. pestis have led to the development of new classes of antibiotics and other therapeutics (e.g., LpxC inhibitors, cationic peptides, antivirulence drugs, predatory bacteria, phages, immunotherapy, host-directed therapy, and nutritional immunity). It is difficult to know which of the currently available treatments or therapeutics in development will be most effective for a given form of plague. This is due to the lack of standardization in preclinical studies, conflicting data from case reports, and the small number of clinical trials performed to date.
Highlights
Accepted: 7 May 2021Plague is one of the most infamous and most feared diseases because it has caused three pandemics, with consequential disruption of the political, social, economic, cultural and religious orders [1,2,3,4,5,6,7,8]
Measurement of the minimum inhibitory concentration (MIC) in a microdilution assay that complied with the Clinical and Laboratory Standards Institute’s guidelines for the Enterobacteriaceae revealed that tetracyclines, fluoroquinolones, aminoglycosides, sulfonamides, and most of β-lactams are active against Y. pestis; the MIC90 ranged from below 0.125 mg/L to 4 mg/L (Table 1) [50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71]
Another alternative to antibiotics would be the use of predatory bacteria, i.e., bacteria whose survival necessarily depends on predation of Y. pestis [194,195,196]
Summary
Plague is one of the most infamous and most feared diseases because it has caused three pandemics, with consequential disruption of the political, social, economic, cultural and religious orders [1,2,3,4,5,6,7,8]. The animal surveillance data and the occurrence of human cases in previously disease-free areas suggest that the territories occupied by plague are growing. The threat of plague is compounded by the emergence of strains resistant to the antibiotics of choice for disease control or the potential use with harmful intent of strains that have deliberately been rendered resistant to our entire therapeutic arsenal [15,16]. For this reason, several research groups are developing antiplague strategies. We will first briefly describe the main clinical forms of plague
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