Case Presentation: A 72-year-old female was referred to the emergency department after being found to be neutropenic with an absolute neutrophil count (ANC) of 165/mm^3 on outpatient laboratory analysis. She had been admitted one month earlier for septic arthritis of the left knee and was discharged on ceftriaxone 2g daily via peripheral indwelling catheter. Her ANC several days prior to discharge, and one day prior to starting ceftriaxone, was 7221/mm^3. She continued taking ceftriaxone for the next three weeks and was then found to be neutropenic. Her only symptoms on admission were pain in the left knee, dysgeusia, and diarrhea. Physical exam was unremarkable. A complete blood count showed ANC 0/mm^3. A complete infectious work up was negative. The etiology of the agranulocytosis was suspected to be drug induced from ceftriaxone. The medication was stopped and she was started on granulocyte colony stimulating factor (G-CSF). Her ANC subsequently increased to 4131/mm^3 and she was discharged home with outpatient follow up.
Discussion: Agranulocytosis, classically defined as a neutrophil count below 0.5 x 10^9/L, is a life threatening condition with a mortality rate of 5%. Drug induced agranulocytosis is a rare idiosyncratic reaction that can occur with a variety of drugs, including antithyroid drugs, beta-lactam antibiotics, clozapine, and ticlopidine. Agranulocytosis from ceftriaxone is very rare, with one review of case reports involving 980 patients only being able to identify six cases where there was a probable relationship between the agranulocytosis and ceftriaxone. Data from clinical trials show that neutropenia from ceftriaxone occurred in 3% of patients, but only in those receiving 2g for four weeks; this timeline is similar to our patient. Thus, it appears that higher doses and/or prolonged treatment with ceftriaxone is a risk factor for the development of agranulocytosis.
The treatment of drug induced agranulocytosis includes identification and cessation of the offending agent, performing an infectious work up, and starting broad spectrum antibiotics if necessary. Although neutrophil counts should improve once the offending agent is stopped, G-CSF can be administered to decrease the time to resolution. The usefulness of G-CSF in drug induced agranulocytosis has been investigated in the past, but with mixed results depending on the severity of the agranulocytosis. In our patient who had severe agranulocytosis and was given G-CSF, the ANC improved within several days, although the dose had to be increased as there was no improvement in ANC with the initial dose.
Conclusions: Ceftriaxone is a commonly used antibiotic. However, serious side effects, such as agranulocytosis, need to be monitored for, especially in patients who are on prolonged therapy or receiving high doses. G-CSF should be administered once agranulocytosis is detected and if there is no improvement in ANC counts within 1-2 days, consideration should be given to increasing the dose in order to allow for more rapid improvement in ANC.