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Abstract
Emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) strains that also exhibit resistance to tigecycline and colistin have become a major clinical concern, as these two agents are the last-resort antibiotics used for treatment of CRKP infections. A leukemia patient infected with CRKP was subjected to follow-up analysis of variation in phenotypic and genotypic characteristics of CRKP strains isolated from various specimens at different stages of treatment over a period of 3 years. Our data showed that (1) carbapenem treatment led to the emergence of CRKP in the gastrointestinal (GI) tract of the patient, which subsequently caused infections at other body sites as well as septicemia; (2) treatment with tigecycline led to the emergence of tigecycline-resistant CRKP, possibly through induction of the expression of a variant tet(A) gene located in a conjugative plasmid; (3) colistin treatment was effective in clearing CRKP from the bloodstream but led to the emergence of mcr-1-positive Enterobacteriaceae strains as well as colistin-resistant CRKP in the GI tract due to inactivation of the mgrB gene; and (4) tigecycline- and colistin-resistant CRKP could persist in the human GI tract for a prolonged period even without antibiotic selection pressure. In conclusion, clinical CRKP strains carrying a conjugative plasmid that harbors the bla KPC-2 and tet(A) variant genes readily evolve into tigecycline- and colistin-resistant CRKP upon treatment with these two antibiotics and persist in the human GI tract.
Highlights
Multidrug-resistant bacterial pathogens that have emerged in the past decade are characterized by possession of extrachromosomal resistance elements that can undergo cross-species transmission, as well as expression of resistance mechanisms that render last-resort antibiotics, such as the carbapenems, ineffective for clinical applications[1]
The exact molecular mechanism that renders tigecycline effective in treating infections caused by carbapenemresistant Enterobacteriaceae (CRE) is not well-defined, the drug has been widely used in combination with other antibiotics such as carbapenems to treat CRE infections in clinical settings, in China, where colistin was not approved for clinical use and ceftazidime/avibactam was not available
The patient was readmitted for a second round of chemotherapy on September 29 and developed a fever, but was discharged upon treatment with meropenem, isepamicin, and vancomycin for 2 weeks
Summary
Multidrug-resistant bacterial pathogens that have emerged in the past decade are characterized by possession of extrachromosomal resistance elements that can undergo cross-species transmission, as well as expression of resistance mechanisms that render last-resort antibiotics, such as the carbapenems, ineffective for clinical applications[1]. Widespread dissemination of carbapenemresistant Enterobacteriaceae (CRE) in clinical settings threatens to take medicine back to the preantibiotic era, and current efforts to invent and discover new antibiotics apparently have failed to reverse this ominous trend. To address this problem, there has been renewed interest in antibiotics such as the polymyxins, which have not been used clinically due to their relatively high toxicity[2,3]. There has been renewed interest in antibiotics such as the polymyxins, which have not been used clinically due to their relatively high toxicity[2,3] This last hope has been tarnished by the recent discovery of a transmissible element that encodes resistance to polymyxins[4]. The data obtained provide insightful information on the evolution events that lead to the emergence of colistin- and tigecycline-resistant CRKP and the persistence of such strains in the gastrointestinal (GI) tract of the patient
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