Linezolid‐induced rare triad of hypoglycaemia, bone marrow suppression and hyponatraemia in elderly

Abstract

What is known and objective Linezolid, a member of the oxazolidinone class of antibacterial drugs, is approved by the US Food and Drug Administration (FDA) for the treatment of vancomycin‐resistant Enterococcus faecium infections, nosocomial and community‐acquired pneumonia, as a part of anti tubercular regimen and complicated and uncomplicated skin and soft tissue infections, including diabetic foot infections. Linezolid has potential adverse effects like bone marrow suppression, peripheral neuropathy and hyponatremia. One of the extremely rare reported adverse effects of the drug is hypoglycaemia. We present a case of Linezolid toxicity presenting as resistant hypoglycemia, bone marrow suppression and severe hyponatremia all together in a single patient. Case description We present a case of an 82 years old gentleman with no known chronic co‐morbidities. He was started on Linezolid 600 mg twice a day for 10 days by a local doctor possibly for some minor infection post hip surgery. He was in respiratory distress on arrival. Blood sugars showed severe hypoglycemia of 36 mg/dL (2.0 mmol/L). He was admitted in intensive care unit and started on injectable antibiotics and 5% dextrose infusion and sugars were strictly monitored. His blood tests revealed severe hyponatremia with sodium level of 119 mEq/L and haemoglobin (Hb) of 8.8 gm/dL, leucocytes of 6500/µL, platelets of 82 000/µL. The infection markers were normal throughout. The platelet count went progressively down from 82 000/µL on admission to 20 000/µL 2 days later; before it started rising back. Similarly there was drop in Hemoglobin and white cell counts. He required vasopressors to maintain mean arterial pressures. The blood sugar levels stabilized after the same. However patient had suffered acute lung injury secondary to aspiration and became NIV dependent and eventually passed away. What is new and conclusion Our case was unique in a way that our patient had adverse effects of linezolid like myelosuppression as well as the rare side effects of hypoglycemia at the same time. This combination of adverse events has never been described in the past to our knowledge. All the adverse effects responded to antibiotic de‐challenge in our case. We had ruled out the possibility of other causes of Hypoglycemia such as sepsis, insulinoma, alcohol excess, malnutrition or hypoadrenalism. We searched the PubMed database and found four case reports out of which two were diabetics and other two were non diabetics. Out of 15 cases described by Vishwanathan et al only three cases were non diabetics. Our patient was non diabetic as well. Therefore our case is only the sixth reported case of hypoglycemia in non diabetic receiving Linezolid to our knowledge.

A retrospective test for a possible relationship between linezolid‐induced thrombocytopenia and hyponatraemia

“…On the other hand, ALB level but not Ccr was identified as an independent variable affecting the development of hyponatraemia, suggesting that the risk of hyponatraemia increases when ALB level is low (Table 4). Four cases of hyponatraemia while receiving LZD therapy have been reported 14‐17 . In two of the four cases, a contributing factor for hyponatremia has signalled strongly a syndrome of inappropriate antidiuretic hormone secretion (SIADH) 15,16 .…”

“…Hyponatraemia can cause a wide range of clinical symptoms, from minor symptoms such as headaches, nausea and anorexia to severe and even life‐threatening conditions 13 . Thus far, four cases of severe hyponatraemia occurring while receiving LZD have been reported 14‐17 …”

“…Moreover, we have encountered several patients with hyponatraemia whose platelet (PLT) levels decreased concomitantly. Singhania et al 17 reported a case of concurrent hyponatraemia, bone marrow suppression and thrombocytopenia while receiving LZD. Many previous studies have suggested a relationship between LZD‐induced thrombocytopenia and trough LZD concentration, and between trough concentration and creatinine clearance 19‐22 .…”

Linezolid-Induced Pancytopenia in Patients Using Dapagliflozin: A Case Series

“…Correlation and Difference Compared with this Case Series [11] An 82-year-old gentleman was administered with linezolid 600 mg twice a day for 10 days, possibly for a minor infection post hip surgery, and developed myelosuppression and hypoglycemia. The patient finally passed away.…”

“…[5][6][7][8][9][10] Risk factors include prolonged dosing beyond two weeks, [5][6][7] higher doses per body weight, 9,10 renal insufficiency, [3][4][5][6][7] and hypoalbuminemia. 9 Neutropenia is a rare adverse effect of linezolid that has been reported once, 11 and pancytopenia is a rare adverse effect of linezolid, which usually manifests as a sudden decrease in leukocytes and hemoglobin and is reversible. Most reports regarding pancytopenia are seen in pediatrics and long-term use.…”