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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 13  |  Issue : 1  |  Page : 57-59

Linezolid-induced pancytopenia and hyponatremia


Department of Internal Medicine, Armed Forces Medical College, Pune, Maharashtra, India

Date of Submission16-Mar-2021
Date of Decision18-May-2021
Date of Acceptance05-Jun-2021
Date of Web Publication28-Apr-2022

Correspondence Address:
Dr. Vishal Mangal
Department of Internal Medicine, Armed Forces Medical College, Pune - 411 040, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/joah.joah_29_21

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  Abstract 


Linezolid (LnZ) is an antibiotic that is effective against Gram-positive bacteria and vancomycin-resistant enterococcus. LnZ is notorious to cause adverse hematological effects, primarily thrombocytopenia; however, pancytopenia is an infrequent complication. Euvolemic hyponatremia is a very rare adverse effect in patients receiving LnZ for more than 2 weeks. Early identification of pancytopenia and hyponatremia due to LnZ can result in avoidance of unnecessary investigations with improved patient outcome. An 80-year-old male with no previous comorbidities was admitted with a fracture neck of the left femur. He was empirically prescribed tablet LnZ 600 mg twice daily by the orthopedics team for soft-tissue infection over the sacral area. He underwent surgery for the left femur's fracture neck and was continued on LnZ in the postoperative period. Two weeks after the surgery, he was noticed to have pancytopenia and hyponatremia. After a thorough evaluation, LnZ was suspected to be the cause of pancytopenia and euvolemic hyponatremia. After 2 weeks of withholding LnZ, his pancytopenia and hyponatremia resolved. Physicians should be aware of the rare adverse effects of LnZ and should identify the patients at risk before administrating the drug. Regular monitoring of hematological and biochemical parameters is mandatory if intended to continue the drug for a more extended period.

Keywords: Case report, hyponatremia, linezolid, pancytopenia


How to cite this article:
Kumar S, Dhakal N, Mangal V, Menon A. Linezolid-induced pancytopenia and hyponatremia. J Appl Hematol 2022;13:57-9

How to cite this URL:
Kumar S, Dhakal N, Mangal V, Menon A. Linezolid-induced pancytopenia and hyponatremia. J Appl Hematol [serial online] 2022 [cited 2022 May 17];13:57-9. Available from: https://www.jahjournal.org/text.asp?2022/13/1/57/344263




  Introduction Top


Linezolid (LnZ) belongs to the oxazolidinone group of antibiotics.[1] LnZ is a bacteriostatic antibiotic with a unique mechanism of action. It binds to bacterial 23S ribosomal RNA of 50S subunit and prevents the formation of 70S ribosome, thus inhibiting the protein synthesis.[2] It is mainly effective against glycopeptide-resistant Enterococci and methicillin-resistant Staphylococcus aureus (MRSA). LnZ is mainly indicated for the treatment of Gram-positive bacterial infections, bacterial pneumonia, skin and soft-tissue infections, and multidrug-resistant (MDR) and extreme drug-resistant (XDR) pulmonary tuberculosis.[3],[4] LnZ is notorious to cause adverse hematological effects, primarily thrombocytopenia; however, pancytopenia is an infrequent complication.[5],[6] Euvolemic hyponatremia is not a labeled adverse drug reaction of LnZ; however, a few case reports have reported the incidence of euvolemic hyponatremia in patients receiving LnZ for more than 2 weeks.[7],[8],[9] In this case report, we present an 80-year-old male who developed pancytopenia and hyponatremia secondary to 3 weeks of Lnz treatment for skin infection over the sacral area and fracture neck of the left femur. Pancytopenia and hyponatremia resolution was evident within 2 weeks of stopping LnZ. To the best of our knowledge this is the first case of simultaneous occurrence of pancytopenia and hyponatremia in the same patient following LnZ treatment.


  Case Report Top


An 80-year-old male, with no previous comorbidities, sustained a fracture neck of left femur following a trivial fall. He was admitted on the 3rd day of the incident to an orthopedic center. On the 5th day of the illness, he was empirically started on tablet LnZ 600 mg twice a day for skin infection over the sacral area. The patient underwent left bipolar hip resurfacing arthroplasty on day 11 of incidence. He was continued on tablet LnZ 600 mg twice a day in the postoperative period. On the 6th postoperative day, the patient was shifted to a step-down center for convalescence. The patient continued to take tablet LnZ. During the hospital stay, on the 10th postoperative day, he was found to have anemia with a hemoglobin level of 6.7 g/dL [Table 1]. However, his anemia worsened over the next few days, and the patient became symptomatic. He was transferred to our center for anemia workup and further management. At presentation, the patient was symptomatic with easy fatigability. On examination, he was conscious, oriented, and afebrile, with a pulse rate of 96 beats/min, blood pressure of 132/80 mm Hg, respiratory rate of 20/min, and oxygen saturation of 95% at room air. On general physical examination, he had pallor; however, the systemic examination was within normal limits. Because of symptomatic anemia, the patient was transfused two units of packed red blood cells. He was evaluated for the cause of anemia. His peripheral blood smear was suggestive of normocytic normochromic anemia, with a mean corpuscular volume of 86 fl (reference range: 80–98 fL). The stool for occult blood was negative with no evidence of active bleed. The postoperative wound was healthy with no hematoma. His serum iron studies, folic acid level, and Vitamin B-12 levels were within normal limits. A detailed review of past reports revealed pancytopenia [Table 1]. The patient's hematology results were consistent with pancytopenia, and LnZ administration in a dosage of 600 mg BD for 21 days was suspected as the cause. Tablet LnZ was immediately discontinued, and the patients' condition and blood count improved over the next 10 days. [Table 1] summarizes the trend of patients' hematological parameters.
Table 1: Hematological profile of the patient

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During the evaluation, the patient was also found to have asymptomatic hyponatremia. The patient's sodium levels dropped gradually to 120 mEq/L (reference range: 136–145 mEq/L) on day 20 of LnZ treatment, from a level of 136 mEq/L before initiating LnZ. The trend of patient's sodium levels is shown in [Table 2]. He was evaluated extensively for the cause of hyponatremia. There was no clinical evidence of volume depletion, and a clinical diagnosis of euvolemic hyponatremia was made. His serum osmolality was 251 mOsm/kg (reference range: 275–295 mOsm/kg), spot urine sodium was 78 mEq/L (Reference range : 20 - 40 mEq/L) urine osmolality was >100 mOsm/kg (reference range: 38–1400 mOsm/kg). Other causes of hyponatremia such as adrenal insufficiency, hypothyroidism, cardiac failure, and the hepatic disease were ruled out. The patient was diagnosed with a syndrome of inappropriate antidiuretic hormone secretion (SIADH) as per Schwartz and Bartter criteria. After ruling out other possible causes of SIADH, hyponatremia was attributed to LnZ-induced SIADH. On day 22, LnZ was discontinued, and levels returned to normal after 12 days of discontinuing LnZ. The patient was discharged and follow-up after 1 week revealed normal cell counts and serum sodium levels. The patient was ambulant and satisfied as discontinuation of LnZ saved him from undergoing invasive procedures such as bone marrow aspiration and biopsy as part of pancytopenia evaluation.
Table 2: Serial serum sodium levels

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Causality assessment

Using the Naranjo Adverse Drug Reaction Scale, LnZ had a score of 7, suggesting that LnZ as a cause of SIADH is probable.[10]


  Discussion Top


LnZ is indicated to treat Gram-positive bacterial infections, bacterial pneumonia, skin and soft tissue infections, and MDR and XDR pulmonary tuberculosis.[1],[2] LnZ has been associated with adverse hematological effects, mainly thrombocytopenia.[3] However, LnZ-induced myelosuppression is a rarely reported complication. There are a few case reports which have reported myelosuppression associated with LnZ. Time and dose-dependent reversible myelosuppression were observed in preclinical studies with LnZ.[4],[5] The mechanism of LnZ-induced myelosuppression is dose-dependent and is thought to occur by the inhibition of mitochondrial protein synthesis, which resembles chloramphenicol myelotoxicity.[6],[11]

LnZ was started empirically in our patient for skin infection over the sacral area and was continued in the postoperative period to provide antimicrobial cover after surgery because of its effectiveness against methicillin-susceptible Staphylococcus aureus/MRSA and its use in complicated/uncomplicated skin and soft-tissue infections. A dose of 600 mg twice a day was given. In our patient, pancytopenia developed in the 3rd week. LnZ was discontinued considering that pancytopenia may be caused by LnZ. On follow-up, the patient was given supportive treatment, and his pancytopenia recovered after 2 weeks of withholding the drug.

In our case, in the 3rd week of hospital stay, the patient also developed asymptomatic euvolemic hyponatremia with a sodium value of 120 mEq/L. Other causes of euvolemic hyponatremia such as hypothyroidism, pituitary, and adrenal insufficiency were excluded, and the blood and urine chemistry were highly suggestive of SIADH, and a workup toward an underlying etiology of SIADH did not reveal any cause. His medications were reviewed, and LnZ was suspected to be the cause of SIADH.[7],[8] LnZ was withheld, and his hyponatremia resolved within 2 weeks of withdrawing LnZ.

Hyponatremia is not a common adverse effect of LnZ. We could find only a few case reports[7],[8] and one retrospective cohort study[9] that reported euvolemic hyponatremia in patients who received LnZ for more than 2 weeks and resolution of hyponatremia after the withdrawal of LnZ.[7],[8],[9] To the best of our knowledge this is the first case of cooccurrence of pancytopenia and hyponatremia due to LnZ in an elderly male.


  Conclusion Top


Physicians need to be aware of the common and atypical adverse effects including pancytopenia and hyponatremia associated with LnZ. Before considering LnZ, it is advisable to identify patients at risk, especially elderly patients and those with renal insufficiency. Limiting the use of LnZ to patients with well-defined indications will minimize the number of patients likely to experience serious adverse events.

Informed consent

Written informed consent was obtained from the patient.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Zyvoxam Product Monograph. Compendium of Pharmaceutical Specialties. Ottawa: Canadian Pharmacists Association; 2004. p. 2341-4.  Back to cited text no. 1
    
2.
Moellering RC. Linezolid: The first oxazolidinone antimicrobial. Ann Intern Med 2003;138:135-42.  Back to cited text no. 2
    
3.
Parlak E, Tan H. Pancytopenia due to linezolid treatment. Turk Pediatri Ars 2015;50:185-8.  Back to cited text no. 3
    
4.
Lakhani N, Thompson W, Bombassaro AM. Probable linezolid-induced pancytopenia. Can J Infect Dis Med Microbiol 2005;16:286-8.  Back to cited text no. 4
    
5.
Nimeiri HS, Nemiary DS. Challenges with linezolid therapy and reversible pancytopenia. Ann Hematol 2003;82:533.  Back to cited text no. 5
    
6.
Green SL, Maddox JC, Huttenbach ED. Linezolid and reversible myelosuppression. JAMA 2001;285:1291.  Back to cited text no. 6
    
7.
AlMolaiki MA, Abu Esba LC. A case of linezolid-associated hyponatremia in a Saudi patient. Biomed J Sci Tech Res 2019;13:103-05.  Back to cited text no. 7
    
8.
Ioannou P, Stavroulaki M, Mavrikaki V, Papakitsou I, Panagiotakis S. A case of severe hyponatremia due to linezolid-induced SIADH. J Clin Pharm Ther 2018;43:434-6.  Back to cited text no. 8
    
9.
Tanaka R, Suzuki Y, Takumi Y, Iwao M, Sato Y, Hashinaga K, et al. A retrospective analysis of risk factors for linezolid-associated hyponatremia in Japanese patients. Biol Pharm Bull 2016;39:1968-73.  Back to cited text no. 9
    
10.
Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-45.  Back to cited text no. 10
    
11.
Bernstein WB, Trotta RF, Rector JT, Tjaden JA, Barile AJ. Mechanisms for linezolid-induced anemia and thrombocytopenia. Ann Pharmacother 2003;37:517-20.  Back to cited text no. 11
    



 
 
    Tables

  [Table 1], [Table 2]



 

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