Non-chemotherapy drug-induced neutropenia - an update

Abstract

To date, non-chemotherapy drug-induced severe neutropenia (neutrophil count of ≤0.5 x 10/L) also called idiosyncratic drug-induced agranulocytosis is little discussed in the literature. In the present paper, we report and discuss the clinical data and management of this rare disorder. Areas covered: To do this, we carried out a review of the literature using PubMed database of the US National Library of Medicine. We also used data from the American Society of Hematology educational books, textbooks of Hematology and Internal medicine, and information gleaned from international meetings. Expert opinion: Idiosyncratic agranulocytosis remains a potentially serious adverse event due to the frequency of severe sepsis with severe deep tissue infections (e.g., pneumonia), septicemia, and septic shock in approximately two-thirds of all hospitalized patients. In this context, several prognostic factors have been identified that may be helpful when identifying 'susceptible' patients. Old age (>65 years), septicemia or shock, renal failure, and a neutrophil count ≤0.1 × 10/L have been consensually accepted as poor prognostic factors. In our experience, modern management with pre-established procedures, intravenous broad-spectrum antibiotics and hematopoietic growth factors (particularly G-CSF) is likely to improve the prognosis. Thus with appropriate management, the mortality rate is currently between 5 to 10%.

Comparison of Neutropenia Associated with Ceftaroline or Ceftriaxone in Patients Receiving at Least 7 Days of Therapy for Severe Infections

“…In most scenarios, ceftaroline was used empirically in culture‐negative infections, which may be suggestive of using a single antibiotic agent to facilitate transitions of care in scenarios where MRSA and Enterobacteriales are suspected. Although clinical outcomes data for non–chemotherapy drug–induced neutropenia are extremely limited, neutropenia is associated with significant morbidity and mortality in immunocompromised populations . Our findings are consistent with limited evidence that has identified ceftaroline use with neutropenia and reemphasizes the need for consistent neutrophil monitoring when ceftaroline is prescribed for prolonged durations.…”

“…Although neutropenia is a known adverse effect of β‐lactam antibiotics, the number of reports suggesting ceftaroline‐associated neutropenia is concerning . Whereas the causal relationship of this association remains unclear when comparing ceftaroline to other β‐lactams, the potential effects of non–chemotherapy‐associated neutropenia could lead to an increased propensity for severe infection, hospital readmission, prolonged hospitalization length of stay (LOS), increased cost, and increased patient mortality …”

Agranulocytosis Induced by Vancomycin. Case Report and Literature Review

“…Drug-induced agranulocytosis is a serious entity that implies an increased risk of infections [ 3 ]. Agranulocytosis or severe neutropenia is defined by an absolute neutrophil count <500/mm 3 [ 1 , 2 ]. In Europe, the annual incidence of drug-induced agranulocytosis ranges from 1.6 to 9.2 cases per million population [ 2 ].…”

“…Agranulocytosis or severe neutropenia is defined by an absolute neutrophil count <500/mm 3 [ 1 , 2 ]. In Europe, the annual incidence of drug-induced agranulocytosis ranges from 1.6 to 9.2 cases per million population [ 2 ]. Mortality rates of agranulocytosis induced by non-chemotherapeutic drugs were reported up to 16% in a retrospective review.…”

“…Agranulocytosis means the absence of granulocytes, although this term is often used to indicate severe degrees of neutropenia [ 1 , 2 ]. It can be linked to several causes and drug-induced agranulocytosis is a serious adverse event [ 2 ]. Among noncytostatic drugs, some antibiotics can cause agranulocytosis, with a mortality of 5–10% [ 1 , 3 ].…”