Piperacillin–tazobactam induced bicytopenia in low cumulative treatment doses

Chen, Chien‐Chou; Lin, Hsin‐An; Hung, Yi‐Jen; Chen, Jui‐Hung

doi:10.1136/bcr-2019-232944

Cited by 6 publications

(10 citation statements)

References 6 publications

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“…1,3 Piperacillin, a member of the ureidopenicillin subclass, has been implicated in β-lactam-induced neutropenia more often than any other agent, with 246 cases. 2,3,5,29,31,[39][40][41][42][43][44][45][46][47][48][49][50][51][52][53] Cases involving piperacillin or piperacillin-tazobactam were included in this count. Notably, a systematic review of piperacillin or piperacillin-tazobactam-induced neutropenia identified 183 cases using the Food and Drug Administration Adverse Event Reporting System.…”

Section: Incidence and Characteristicsmentioning

confidence: 99%

A Review of β-Lactam–Associated Neutropenia and Implications for Cross-reactivity

2020

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Objective: To review the incidence, management, and current understanding of the pathophysiology of β-lactam–induced neutropenia and to critically evaluate the practicality and safety of direct substitution to an alternative β-lactam in the setting of this reaction. Data Sources: A literature analysis using the PubMed and Ovid search engines (July 1968 to October 2020) was performed using the search terms neutropenia, leukopenia, β-lactam, nonchemotherapy, agranulocytosis, and G-CSF (granulocyte colony-stimulating factor). Study Selection and Data Extraction: The included English-language studies evaluated the incidence, mechanism, and/or management of β-lactam–induced neutropenia in pediatric or adult patients. Data Synthesis: Drug-induced neutropenia is a well-documented adverse reaction of β-lactam antibiotics, with an incidence of approximately 10% following at least 2 weeks of intravenous therapy. However, multiple gaps in knowledge remain in the mechanism of pathophysiology and optimal management of this reaction. Both direct toxic and immune-mediated mechanisms have been implicated. Although the cornerstone of management includes cessation of the offending agent, controversy exists on the appropriateness of direct substitution or future use of an alternative β-lactam. Relevance to Patient Care and Clinical Practice: Given the frequency of use and superiority of β-lactams over alternative therapy for several infectious disease states, practical recommendations are needed on the management and safe use of β-lactams following β-lactam–induced neutropenia. Conclusion: Future use of β-lactams with differing R1 side chains, particularly those from a separate class, should not be deemed contraindicated following β-lactam–induced neutropenia and may be considered when indicated, with close laboratory monitoring.

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Section: Incidence and Characteristicsmentioning

confidence: 99%

A Review of β-Lactam–Associated Neutropenia and Implications for Cross-reactivity

2020

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“…3 Two of the prior studies reported bicytopenia with neutropenia and thrombocytopenia. 1,4 The other study reported a fall in only one cell line. All the patients reported a successful recovery in cell lines on the discontinuation of the medication.…”

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confidence: 96%

“…Ihtisham Qayum, MBBS 1 Awais Naeem, MBBS 1 Uzma Ikhtiar Khan, MBBS 1 Sohail Anwar, MBBS 1 Hafez M. Abdullah, MD 2 1 Internal Medicine Khyber Teaching Hospital Peshawar, Pakistan 2 Internal Medicine University of South Dakota Sanford School of Medicine Sioux Falls, SD…”

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confidence: 99%

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Tazobactam–Piperacillin Associated Transient Neutropenia and Thrombocytopenia

Qayum

Naeem

Khan

et al. 2020

American Journal of Therapeutics

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Piperacillin/tazobactam

2018

Reactions Weekly

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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.

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Piperacillin–tazobactam induced bicytopenia in low cumulative treatment doses

Cited by 6 publications

References 6 publications

A Review of β-Lactam–Associated Neutropenia and Implications for Cross-reactivity

A Review of β-Lactam–Associated Neutropenia and Implications for Cross-reactivity

Tazobactam–Piperacillin Associated Transient Neutropenia and Thrombocytopenia

Piperacillin/tazobactam

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