Delayed-type of hypersensitivity reaction due to piperacillin/tazobactam causing severe thrombocytopenia

Background: High-level expression of AmpC b-lactamase genes is associated with increased resistance to b-lactam antibiotics. bla CMY-2 is the most prevalent plasmid-encoded AmpC gene found in Escherichia coli worldwide, and the gene is often found on plasmids of the IncI1 replicon type. Replication of IncI1 plasmids is controlled by antisense RNA transcribed from the gene inc, and nucleotide changes in the hairpin loop region of inc have been associated with increased plasmid copy number of IncI1 mini-plasmid constructs. The objective of this study was to determine the mechanism(s) responsible for increased bla CMY-2 expression in three piperacillin/tazobactam-selected E. coli mutant strains with bla CMY-2 encoded on a 100 kb IncI1 plasmid.Methods: Mutants were selected from a clinical E. coli strain by exposure to superinhibitory concentrations of piperacillin/tazobactam. b-Lactam susceptibilities were measured by agar dilution. Relative bla CMY-2 transcript levels, gene copy number and IncI1 plasmid copy number were measured by real-time PCR. The inc gene of all strains was sequenced.Results: Piperacillin/tazobactam MICs were 16-to 128-fold higher for mutant strains than for their parent strain. This increase in MICs correlated with 3-to 13-fold increases in bla CMY-2 gene expression, bla CMY-2 copy number and IncI1 plasmid copy number. Two mutants with 8-and 13-fold increases in IncI1 copy number had single point mutations located within the hairpin loop region of inc.Conclusions: These findings demonstrate that inc point mutations can be associated with increased copy number of a 100 kb IncI1 plasmid, and lead to increased bla CMY-2 expression and piperacillin/tazobactam resistance.

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Delayed-type of hypersensitivity reaction due to piperacillin/tazobactam causing severe thrombocytopenia

Cited by 2 publications

References 0 publications

Hematologic adverse effects induced by piperacillin–tazobactam: a systematic review of case reports

Hematologic adverse effects induced by piperacillin–tazobactam: a systematic review of case reports

Piperacillin/tazobactam

Contact Info

Product

Resources

About