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Ceftaroline-Associated Neutropenia: Case Series and Literature Review of Incidence, Risk Factors, and Outcomes.

ABSTRACT: Ceftaroline is increasingly prescribed for "off-label" indications involving longer durations and higher doses. There have been postmarketing case reports of neutropenia among patients who have received extended durations of ceftaroline, but limited published data currently exist on its incidence and risk factors. We review a total of 37 published cases of ceftaroline-associated neutropenia including cases (n = 4) identified in our health care system. The median time from ceftaroline initiation to development of neutropenia (range) was 25 (8-125) days, with a median duration of neutropenia (range) of 4 (1-16) days. Agranulocytosis (absolute neutrophil count [ANC] nadir < 100 cells/mm³) developed in 49% of cases (n = 18), and there was an ANC nadir of 0 in 27% (n = 10). The overall incidence of neutropenia among cases receiving ceftaroline for ≥7-14 days (range) was 12% (7%-18% per individual study), higher than for comparator antibiotics in the literature. Risk factors for ceftaroline-associated neutropenia varied among studies and remain poorly defined.

SUBMITTER: Sullivan EL

PROVIDER: S-EPMC6524829 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Ceftaroline-Associated Neutropenia: Case Series and Literature Review of Incidence, Risk Factors, and Outcomes.

Sullivan Eva L EL Turner R Brigg RB O'Neal Hollis R HR Crum-Cianflone Nancy F NF

Open forum infectious diseases 20190328 5

Ceftaroline is increasingly prescribed for "off-label" indications involving longer durations and higher doses. There have been postmarketing case reports of neutropenia among patients who have received extended durations of ceftaroline, but limited published data currently exist on its incidence and risk factors. We review a total of 37 published cases of ceftaroline-associated neutropenia including cases (n = 4) identified in our health care system. The median time from ceftaroline initiation ...[more]

PMID: 31123688

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Project description:ImportanceIntra-arterial chemotherapy (IAC) has quickly gained popularity as a mainstay of treatment for retinoblastoma. Intra-arterial chemotherapy has been described as having several advantages over systemic chemotherapy, including reducing systemic toxicity and neutropenia; however, studies on the risk of neutropenia after IAC remain limited.ObjectiveTo estimate the incidence of neutropenia after IAC, as well as identify risk factors associated with the development of neutropenia.Design, setting, and participantsThis case series included pediatric patients with unilateral or bilateral retinoblastoma who were treated with IAC at a single quaternary care center from July 13, 2013, to January 6, 2023.ExposureAll patients were treated with IAC and underwent multiple IAC cycles depending on treatment response. The primary chemotherapy agent used was melphalan, but topotecan or carboplatin could be used along with melphalan. Melphalan doses were kept to 0.4 mg/kg or less per cycle. After each IAC cycle, complete blood cell counts were obtained within 10 to 12 days and repeated until the absolute neutrophil count (ANC) was greater than or equal to 1000/μL.Main outcomes and measuresThe primary outcome was the minimum ANC after each IAC cycle. The secondary outcome was the development of severe (grade 3 or 4) neutropenia (ANC <1000/μL). Regression analyses were used to identify associations between variables and outcomes. Receiver operating characteristic curves were used to calculate threshold dose for each chemotherapy agent potentially associated with the development of severe neutropenia.ResultsA total of 64 eyes of 49 patients (mean [SD] age, 1.7 [1.2] years; 25 females [51.0%]) with retinoblastoma were treated with 171 cycles of IAC. The mean (SD) nadir ANC was 1325.3 (890.7)/μL and occurred a median (IQR) of 10 (10-14) days (range, 6-28 days) after IAC administration. The frequency distribution of post-IAC neutropenia grades 0, 1, 2, 3, 4, and missing was 31 (18.1% of cycles), 25 (14.6%), 40 (23.4%), 37 (21.6%), 26 (15.2%), and 12 (7.0%), respectively. Factors weakly correlated with a lower ANC were higher melphalan dose (β = -2356 [95% CI, -4120.6 to -611.2]; adjusted R2 = 0.251; P = .01) and higher topotecan dose (β = -4056 [95% CI, -7003.6 to -1344.5]; adjusted R2 = 0.251; P = .006).Conclusions and relevanceIn this case series of patients with retinoblastoma, the incidence of severe neutropenia after IAC was nearly 40%, which is higher than previously reported. Extended laboratory monitoring may aid in capturing previously overlooked cases of neutropenia. Topotecan may be associated with the development of neutropenia; limiting topotecan doses, especially in the setting of a high melphalan dose, may be beneficial in reducing the risk of neutropenia.

Dataset Information

Ceftaroline-Associated Neutropenia: Case Series and Literature Review of Incidence, Risk Factors, and Outcomes.

Publications

Ceftaroline-Associated Neutropenia: Case Series and Literature Review of Incidence, Risk Factors, and Outcomes.

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