Are there any evidence for using filgrastim or peg filgrastim to treat ceftrixone associated bone marrow suppression

Comment by InpharmD Researcher

Evidence supporting the use of filgrastim for ceftriaxone-associated bone marrow suppression is limited to anecdotal evidence from scattered case reports; use of peg-filgrastim in this context was not identified. Across reports, management consistently involved prompt discontinuation of ceftriaxone, with filgrastim administered primarily in patients with severe neutropenia, agranulocytosis, pancytopenia, or aplastic anemia (see Tables 1-6). Filgrastim dosing varied between reports, ranging from 75 mcg/day to 300 mcg/day (or approximately 300 mcg as a single dose) administered subcutaneously for 3 to 5 days, with one patient requiring a second course because of recurrent neutropenia. Hematologic recovery generally occurred within days to two weeks after ceftriaxone withdrawal and filgrastim administration, although the relative contribution of filgrastim versus drug discontinuation cannot be determined because of the absence of controlled studies.

PubMed and Google Scholar were searched using combinations of “ceftriaxone,” “bone marrow suppression,” “neutropenia,” “agranulocytosis,” “pancytopenia,” “filgrastim,” “pegfilgrastim,” and “granulocyte colony-stimulating factor.” Six directly relevant case reports were identified and included.

Literature Review

A search of the published medical literature revealed 6 studies investigating the researchable question:

Are there any evidence for using filgrastim or peg filgrastim to treat ceftrixone associated bone marrow suppression

Level of evidence

D - Case reports or unreliable data Read more→

Please see Tables 1-6 for your response.

Ceftriaxone induced aplastic anaemia: A deadfall trap for bone marrow
Design	Case report
Case presentation	An 88-year-old male patient developed aplastic anaemia (AA) temporally associated with ceftriaxone use. The patient, presenting with erythroderma secondary to chronic actinic dermatitis and superimposed bacterial infection, initially had normal baseline hematological parameters. Following culture-directed administration of intravenous ceftriaxone 1 g every 12 hours for three days, a marked decline in hemoglobin, total leukocyte count, platelet count, and red blood cell count was observed within one day. Peripheral blood smear revealed microcytic hypochromic erythrocytes with anisocytosis, severe leukopenia, thrombocytopenia with giant platelets, and reticulocytopenia (0.08%). A bone marrow aspirate showed hypocellularity with marked granulocytic suppression, while extensive infectious workup including viral serologies and bacterial cultures was negative, supporting the diagnosis of drug-induced aplastic anaemia attributed to ceftriaxone. Following cessation of ceftriaxone, treatment with high-dose intravenous methylprednisolone (500 mg daily for 3 days) and subcutaneous filgrastim (300 mcg daily for 5 days; of note, the study states 300 mg but this may potentially be a typo) was initiated. Hematologic parameters began to improve within three days of therapy, with hemoglobin rising to 8.6 g/dL, total leukocyte count increasing to 12,710/μL, platelet count normalizing to 905,000/μL, and red blood cell count improving to 4.39 million/μL. Concurrent topical treatments addressed the skin lesions, which resolved by approximately 70–80%, allowing for patient discharge. The report underscored the rarity but potential severity of cephalosporin-induced aplastic anaemia, emphasizing the importance of prompt recognition and cautious use of ceftriaxone to mitigate life-threatening hematological adverse effects.
Study Author Conclusions	Cephalosporins are widely used antibiotics in the management of skin, soft tissue, respiratory, and urinary tract infections. Although cephalosporins are one of the safest drugs, AA and agranulocytosis have been reported infrequently. Ceftriaxone-induced aplastic anaemia has not been reported in English-language literature to the best of our knowledge. Experience from our case emphasizes on the early identification of ceftriaxone-associated rare life‐threatening adverse effects and the need of cautious use of antibiotics.

Table 1 References:
[1] Rajan M B, Budania A, Bohra GK. Ceftriaxone induced aplastic anaemia: A deadfall trap for bone marrow. Br J Clin Pharmacol. 2019;85(8):1850-1851. doi:10.1111/bcp.13957

Ceftriaxone-Induced Neutropenia Successfully Treated With Alternative β-Lactam Antibiotics: A Case Report and Review of the Literature
Design	Case report
Case presentation	A 37-year-old male patient with prosthetic aortic valve infective endocarditis complicated by central nervous system septic emboli received initial treatment with high-dose ceftriaxone (4 g/day), aligned with EUCAST recommendations for methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia involving central nervous complications. The patient underwent valve replacement surgery on day seven, with adjunctive aminoglycoside and rifampicin therapy. Neutropenia developed on day 28, with a marked drop to 33/μL neutrophils, alongside dermatologic manifestations and mild eosinophilia. Ceftriaxone-induced neutropenia was suspected based on Naranjo criteria scoring and bone marrow analysis revealing myelocyte maturation arrest. Discontinuation of ceftriaxone and initiation of granulocyte colony-stimulating factor (G-CSF; filgrastim 75 mcg/day from day 28 to day 31) resulted in neutrophil recovery within two weeks. Following hematologic recovery, vancomycin was initially used as an alternative but was subsequently replaced by ampicillin sodium on day 40 due to β-lactam antibiotics’ superior efficacy against MSSA and limited availability of nafcillin or oxacillin in Japan. Over the course of ampicillin therapy, mild eosinophilia developed without recurrence of neutropenia. The patient was discharged on oral amoxicillin by day 60. The report further contextualized this outcome by reviewing rare instances of ceftriaxone-induced neutropenia and successful alternative β-lactam rechallenge, highlighting the immunologic hypothesis that neutropenia may be mediated by the R2 side chain of cephalosporins, whereas penicillins with distinct R1 and R2 chains may not provoke cross-reactivity. This case supports the notion that cautious use of alternative β-lactam antibiotics, even after ceftriaxone-induced neutropenia, may be feasible and safe under careful monitoring.
Study Author Conclusions	Our report suggests the possibility that patients who develop ceftriaxone-induced neutropenia can be treated safely with an alternative β-lactam antibiotic, ampicillin sodium, without causing β-lactam cross-reactivity of neutropenia.

Table 2 References:
[2] Satake K, Iijima K. Ceftriaxone-Induced Neutropenia Successfully Treated With Alternative -Lactam Antibiotics: A Case Report and Review of the Literature. Cureus. 2023;15(5):e39176. Published 2023 May 18. doi:10.7759/cureus.39176

Ceftriaxone-Induced Reversible Agranulocytosis: A Case Report and Review of Drug-Induced Agranulocytosis
Design	Case report
Case presentation	A 78-year-old male patient with septic left ankle arthritis complicated by Streptococcus mitis bacteremia initially received empirical vancomycin and piperacillin/tazobactam, followed by de-escalation to ceftriaxone 2 g daily for a planned six-week course based on culture sensitivities. Weekly outpatient monitoring with complete blood count (CBC) and differential revealed a progressive decline in white blood cell counts, culminating in an absolute neutrophil count (ANC) of zero by day 38 of ceftriaxone therapy, despite the patient remaining afebrile and asymptomatic. Upon identification of agranulocytosis with a probable causal relationship to ceftriaxone (Naranjo score of 7), ceftriaxone was promptly discontinued. Antibiotic therapy was switched to oral amoxicillin, and filgrastim (G-CSF; dose not specified) was administered alongside broad-spectrum antibiotics (vancomycin and meropenem) to mitigate infection risk. Extensive infection workup, including blood cultures, urinalysis, respiratory viral panel, and chest imaging, was negative. Rapid hematologic recovery was observed, with ANC rising from zero to 2.74 x10^9/L within one day after filgrastim administration and reaching near baseline by seven days post-treatment modification. Platelet counts and hemoglobin remained stable throughout. The patient was discharged with continued oral antibiotics and had no recurrence of agranulocytosis at one-week follow-up.
Study Author Conclusions	The most common causes of acquired agranulocytosis are drugs including chemotherapy and non-chemotherapy drugs. Agranulocytosis is a serious condition that can contribute to increased mortality. It can be asymptomatic, so frequent monitoring with CBC and differential count should be done in case of prolonged treatment of drugs known to cause agranulocytosis so that it can be recognized in a timely manner. Management includes discontinuation of the offending agent, broad-spectrum antibiotics, sepsis work up, and G-CSF administration. The patient should be kept under observation till the resolution of agranulocytosis. Re-challenge should be avoided unless benefits outweigh risks.

Table 3 References:
[3] Munir F, Javaid HW, Rana MBM, Shaukat F. Ceftriaxone-Induced Reversible Agranulocytosis: A Case Report and Review of Drug-Induced Agranulocytosis. Cureus. 2022;14(3):e23226. Published 2022 Mar 16. doi:10.7759/cureus.23226

Rare but There: Ceftriaxone-Induced Neutropenia in a Patient With a Brain Abscess
Design	Case report
Case presentation	A 70-year-old male patient with Marfan syndrome and hypertension developed ceftriaxone-induced neutropenia during prolonged treatment for a brain abscess. The patient initially presented with tonic-clonic seizures, headache, and neurological deficits, and was diagnosed via MRI with multiple ring-enhancing lesions indicative of cerebral abscesses, with Streptococcus mitis/oralis identified as the causative pathogen from blood cultures. Management involved neurosurgical drainage of the abscesses followed by an eight-week intravenous antibiotic regimen consisting of ceftriaxone 2 g twice daily and metronidazole 500 mg thrice daily. Serial blood counts demonstrated a marked decline in neutrophil count from 7.54 × 10^9/L to 0.87 × 10^9/L after eight weeks of ceftriaxone exposure, consistent with drug-induced neutropenia. Ceftriaxone was discontinued and replaced with meropenem, and granulocyte-colony stimulating factor (G-CSF; 300 mcg once a day subcutaneously for three days) was administered in two courses, resulting in significant recovery of neutrophil levels. Notably, a transient drop in neutrophil count occurred again 10 days after ceftriaxone cessation, necessitating a second G-CSF course, which successfully restored hematologic parameters.
Study Author Conclusions	Ceftriaxone-induced neutropenia, though rare, is a significant clinical challenge, underlining the necessity for heightened awareness among physicians. This case study exemplifies the imperative need for careful monitoring of blood counts in patients undergoing prolonged antibiotic therapy. The prompt recognition and management of neutropenia is essential; discontinuing the offending agent and administering G-CSF can timely reverse the condition, thereby preventing severe outcomes. Moreover, interdisciplinary collaboration is essential in managing complex clinical cases, and it also serves as a reminder of the dynamic nature of patient care, where ongoing education and awareness are vital in improving patient outcomes.

Table 4 References:
[4] Naseem M, Maheen, Ullah S, Alizai Q, Motie A. Rare but There: Ceftriaxone-Induced Neutropenia in a Patient With a Brain Abscess. Cureus. 2024;16(6):e63411. Published 2024 Jun 28. doi:10.7759/cureus.63411

Ceftriaxone-Induced Pancytopenia: A Case Report
Design	Case report
Case presentation	A 72-year-old woman was hospitalized with fever and generalized weakness while receiving intravenous ceftriaxone 2 g/day for a urinary tract infection. She had no evidence of sepsis, with only mildly elevated C-reactive protein (CRP) and procalcitonin (PCT) levels, and no clinical or laboratory findings suggestive of systemic inflammatory response syndrome (SIRS) or organ dysfunction. Her medical history was notable only for a previously diagnosed Baker's cyst, and she reported occasional use of paracetamol for musculoskeletal pain without any chronic medications or known drug allergies. After 5 days of ceftriaxone therapy, she developed pancytopenia with a marked decline in all blood cell lines. Evaluation excluded hemolysis, bleeding, persistent infection, bone marrow infiltration, autoimmune disorders, viral infections, and hematologic malignancy. Bone marrow aspiration, peripheral blood smear, and immunologic and viral investigations were unremarkable. During hospitalization, she received prophylactic subcutaneous fraxiparine for superficial venous thrombosis. Although heparin-induced thrombocytopenia (HIT) was considered because of thrombocytopenia, it was deemed unlikely based on a low 4T score (<5%) and the absence of supporting clinical or laboratory findings. Imaging identified superficial thrombosis of the left great saphenous vein, a Baker's cyst with surrounding subcutaneous edema, a small hepatic hemangioma, and degenerative skeletal changes without evidence of abscess or deep venous thrombosis. Ceftriaxone was discontinued, and the patient received a single subcutaneous dose of filgrastim 30 million units (approximately 300 mcg) on hospital day 5 for suspected ceftriaxone-induced pancytopenia. The extensive diagnostic evaluation excluded alternative causes, supporting ceftriaxone as the most likely cause of the bone marrow suppression.
Study Author Conclusions	This case demonstrates that ceftriaxone, although widely regarded as a safe antibiotic, can induce rare but serious hematologic complications such as pancytopenia. A high index of suspicion is required when patients on antibiotic therapy develop unexplained cytopenias. Detailed medication history, exclusion of other causes, and prompt discontinuation of the suspected drug are essential. The patient’s favorable outcome following drug withdrawal and G-CSF administration supports the likelihood of an idiosyncratic, immune-mediated mechanism. Considering emerging evidence on genetic susceptibility, particularly involving HLA variants, future research should explore pharmacogenomic screening in patients at increased risk for drug-induced hematologic toxicity.

Table 5 References:
[5] Karisik E, Stanojevic-Ristic Z, Jevtic M, Rasic J, Maric M, Popovic M. Ceftriaxone-Induced Pancytopenia: A Case Report. Hematol Rep. 2025;17(3):30. Published 2025 Jun 12. doi:10.3390/hematolrep17030030

Ceftriaxone-induced Agranulocytosis
Design	Case report
Case presentation	A 70-year-old female with a history of hypertension, dyslipidaemia, and obesity presented with fever and new-onset seizure. Initial laboratory evaluation demonstrated leukocytosis (19.33 × 10⁹/L), neutrophilia (18.0 × 10⁹/L), and markedly elevated C-reactive protein (337 mg/L). Brain computed tomography (CT) was normal, while cerebrospinal fluid analysis showed pleocytosis (5,943 cells/mm³; 88% polymorphonuclear cells), hypoglycorrhachia (1.6 mg/dL), and hyperproteinorrhachia (1,217 mg/dL), consistent with bacterial meningitis. Empiric treatment with ceftriaxone 2 g IV twice daily was initiated. The patient required invasive mechanical ventilation because of persistent depressed consciousness, and non-convulsive status epilepticus was diagnosed. After regaining consciousness, she developed left-sided hemiparesis, and brain magnetic resonance imaging (MRI) revealed a right temporal lobe brain abscess measuring 36 × 35 × 24 mm. Cerebrospinal fluid and blood cultures grew Streptococcus pneumoniae, and ceftriaxone therapy was continued with subsequent resolution of neurological deficits. On day 29 of ceftriaxone therapy, the patient developed fever and diffuse folliculitis. Complete blood count revealed severe agranulocytosis (neutrophils 0.1 × 10⁹/L). Ceftriaxone was discontinued because of suspected drug-induced bone marrow toxicity, and filgrastim was initiated for granulocyte stimulation (dose not specified). The patient was diagnosed with neutropenic fever, and empiric antimicrobial therapy with meropenem and vancomycin was started while repeat blood cultures were obtained. After 24 hours, the patient became afebrile, skin lesions resolved, and neutrophil counts began to recover. Following 3 days of filgrastim, neutrophil counts remained >1 × 10⁹/L, blood cultures became sterile, and vancomycin was discontinued. Meropenem was continued for 45 days until brain magnetic resonance imaging (MRI) confirmed resolution of the brain abscess.
Study Author Conclusions	Ceftriaxone-induced agranulocytosis is a rare entity, even though ceftriaxone is a widely used antibiotic. Evidence in the literature shows that it is a dose-dependent adverse reaction and usually occurs after generous cumulative doses.

Table 6 References:
[6] Couto L, Goulart A, Valado I, et al. Ceftriaxone-induced Agranulocytosis. Eur J Case Rep Intern Med. 2021;8(1):002215. Published 2021 Jan 8. doi:10.12890/2021_002215