Linezolid-Induced Isolated Anemia and Renal Injury Classification
Is This Linezolid Toxicity?
Yes, isolated normocytic anemia with normal WBC and platelets is consistent with linezolid toxicity, though less common than thrombocytopenia. 1
Evidence Supporting Linezolid as the Cause
The FDA label explicitly warns that "myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia) has been reported in patients receiving linezolid," confirming that isolated anemia can occur without affecting other cell lines 1.
Linezolid causes anemia through a chloramphenicol-like suppression of erythropoiesis, producing ringed sideroblasts and vacuolated pronormoblasts in bone marrow—a distinct mechanism from its immune-mediated thrombocytopenia 2.
The patient has received prolonged therapy (duration not specified but implied by "prolonged linezolid"), and the FDA mandates weekly CBC monitoring "particularly in those who receive linezolid for longer than two weeks" because myelosuppression risk increases with duration 1.
Pre-existing anemia is a known risk factor; one guideline notes that "severe anemia may be more common in patients with preexisting anemia prior to the use of linezolid" 3.
Why WBC and Platelets May Be Spared
Research demonstrates two distinct mechanisms for linezolid cytopenias: direct marrow suppression causing anemia (reversible, manageable with transfusions) versus immune-mediated thrombocytopenia 2.
The presence of adequate, normal-appearing megakaryocytes on bone marrow biopsy in linezolid-treated patients with isolated thrombocytopenia confirms that different cell lines can be affected independently 2.
This patient's pattern—isolated anemia with hemoglobin 107 g/L (10.7 g/dL) and normal other counts—fits the erythroid-specific suppression mechanism 2.
Diagnostic Confirmation
Discontinue linezolid immediately; the FDA states "when linezolid was discontinued, the affected hematologic parameters have risen toward pretreatment levels" 1.
Monitor CBC weekly; improvement in hemoglobin after discontinuation strongly supports the diagnosis 1.
Bone marrow biopsy is not routinely necessary unless anemia worsens despite linezolid cessation or other cell lines become involved, which would suggest alternative pathology 4.
Renal Injury Classification: AKI, CKD, or ATIN?
This patient has acute kidney injury (AKI) superimposed on possible early chronic kidney disease, with acute tubulointerstitial nephritis (ATIN) as the most likely histologic pattern given concurrent amikacin and linezolid exposure.
Diagnostic Criteria for Each Entity
Acute Kidney Injury (AKI)
Creatinine increase ≥0.3 mg/dL within 48 hours OR creatinine increase ≥1.5× baseline within 7 days 3.
This patient's creatinine rose from baseline ~0.8–1.0 mg/dL to 1.3 mg/dL, representing a ≥30% increase, meeting AKI criteria 3.
The rise occurred during amikacin therapy, a known nephrotoxin causing acute tubular injury 3.
Chronic Kidney Disease (CKD)
GFR <60 mL/min/1.73 m² for ≥3 months OR kidney damage markers (proteinuria, hematuria, structural abnormalities) present for ≥3 months 5.
A single creatinine of 1.3 mg/dL does not establish CKD; the diagnosis requires duration ≥3 months 5.
If baseline creatinine was truly 0.8–1.0 mg/dL with normal prior function, this is acute-on-chronic at most, not isolated CKD 5.
Acute Tubulointerstitial Nephritis (ATIN)
Histologic diagnosis: lymphocytic infiltrate in the interstitium with tubular injury, sometimes with eosinophils or granulomas 3.
Clinical presentation: AKI with or without fever, rash, eosinophilia, or eosinophiluria (these systemic features are present in <30% of cases) 3.
Drug-induced ATIN is the most common cause; both amikacin (aminoglycoside causing acute tubular injury and occasionally ATIN) 3 and linezolid (documented ATIN in a kidney transplant patient with creatinine rise from 136 to 221 µmol/L [~1.5 to 2.5 mg/dL]) 6 are implicated.
Most Likely Diagnosis: AKI Due to ATIN
Amikacin is the primary culprit: aminoglycosides cause dose-dependent acute tubular injury and occasionally ATIN, with nephrotoxicity documented in guidelines 3.
Linezolid is a secondary contributor: the first reported case of linezolid-induced ATIN showed creatinine elevation, mild hypereosinophilia, anemia, and thrombocytopenia, with biopsy-proven interstitial nephritis that resolved after drug withdrawal 6.
The absence of fever, rash, or eosinophiluria does not exclude ATIN; one case report explicitly noted "no skin rash, arthralgia, eosinophiluria or proteinuria" despite biopsy-confirmed ATIN 6.
Renal biopsy is the gold standard but is not mandatory if creatinine improves after stopping the offending drugs 3, 6.
Management Algorithm
Discontinue amikacin immediately (primary nephrotoxin) 3.
Discontinue linezolid (contributing nephrotoxin and cause of anemia) 1, 6.
Monitor creatinine every 2–3 days; improvement within 1–2 weeks supports drug-induced ATIN 6.
Consider short-course corticosteroids (e.g., prednisone 1 mg/kg/day for 2–4 weeks, then taper) if creatinine does not improve within 7 days after drug cessation, as ATIN may respond to steroids 3.
Perform renal biopsy only if:
Repeat creatinine at 3 months to determine if residual impairment qualifies as CKD 5.
Common Pitfalls
Assuming linezolid cannot cause isolated anemia: The FDA label and case reports confirm anemia can occur without thrombocytopenia or leukopenia 1, 2.
Waiting for systemic signs (fever, rash, eosinophilia) to diagnose ATIN: These are present in <30% of drug-induced ATIN cases 6.
Attributing AKI solely to amikacin and continuing linezolid: Linezolid is nephrotoxic and contributes to both anemia and renal injury; both drugs must be stopped 6.
Performing renal biopsy prematurely: If creatinine improves after drug withdrawal, biopsy is unnecessary 6.
Diagnosing CKD based on a single elevated creatinine: CKD requires ≥3 months of impairment; this is AKI until proven otherwise 5.