|Year : 2016 | Volume
| Issue : 1 | Page : 21-23
Linezolid induced pancytopenia in a patient of extensively drug-resistant pulmonary tuberculosis: An unusual outcome
Rajiv Garg, Ashwini Kumar Mishra, RamAwadh Singh Kushwaha, Anubhuti Singh
Department of Pulmonary Medicine, KGMU, Lucknow, Uttar Pradesh, India
|Date of Web Publication||23-Dec-2015|
Department of Pulmonary Medicine, KGMU, Lucknow, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Linezolid (Lnz) is the first oxazolidinones to be developed and introduced in clinical use. Its use is growing by day and day in the treatment of resistant pulmonary tuberculosis (TB). Lnz has been associated with adverse hematological effects, primarily thrombocytopenia. But pancytopenia is a very rare complication. Myelosuppression is a rare and a serious side effect of Lnz. Here, we present a case of extensively drug-resistant pulmonary TB, which was started on Lnz. Patient returned 1-month back with clinical presentation suggestive of pancytopenia which was confirmed on bone marrow aspiration and was attributed to the use of Lnz. Patient improved on stopping the Lnz and adding steroid for a short course. This case report emphasizes the importance of both the use of Lnz for well-defined indications and appropriate hematological monitoring during the course of treatment.
Keywords: Linezolid, myelosuppression, tuberculosis
|How to cite this article:|
Garg R, Mishra AK, Kushwaha RS, Singh A. Linezolid induced pancytopenia in a patient of extensively drug-resistant pulmonary tuberculosis: An unusual outcome. J Assoc Chest Physicians 2016;4:21-3
|How to cite this URL:|
Garg R, Mishra AK, Kushwaha RS, Singh A. Linezolid induced pancytopenia in a patient of extensively drug-resistant pulmonary tuberculosis: An unusual outcome. J Assoc Chest Physicians [serial online] 2016 [cited 2019 Dec 16];4:21-3. Available from: http://www.jacpjournal.org/text.asp?2016/4/1/21/159874
| Introduction|| |
Due to little clinical experience with the use of linezolid (Lnz) in the management of mycobacterial infections little is known about its adverse effect. Lnz has been associated with adverse hematological effects, primarily thrombocytopenia. But pancytopenia is a very rare complication. Myelosuppression is a rare and a serious side effect of Lnz. This case report emphasizes the importance of the use of Lnz for well-defined indications and appropriate hematological monitoring during the course of treatment.
| Case Report|| |
A 20-year-old female, previously treated case of tuberculosis (TB) was prescribed capreomycin, moxifloxacin, amoxicillin clavulanic acid, and Lnz 600 mg for extensively drug-resistant (XDR) pulmonary TB. Initial pretreatment baseline and 7th day blood parameters were within normal limits. 1 month later, patient was admitted in our department with complaints of hemoptysis, severe epistaxis, bleeding from oral ulcers, melena, abdominal pain and increased bleeding from wound sites, ecchymotic patches over lower limb from last 3 days. The patient's hematology results were consistent with pancytopenia, and Lnz was the suspected as the offending cause. With the initiation of intravenous hydration and blood transfusion and the discontinuation of Lnz, the patient's condition and blood counts improved by the following week. Steroid was given for refractory drug-induced myelosuppression. [Table 1] summarizes the patient's hematological parameters at baseline, at the time of admission, 1-week post-Lnz discontinuation and after giving steroids. The bone marrow aspirate [Figure 1] revealed cellular marrow with evidence of dysmorphic changes in all lineages (drug induced).
|Table 1: Hematological parameters corresponding to day from the start of Lnz therapy|
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|Figure 1: Bone marrow aspirate revealed cellular marrow with evidence of dysmorphic changes in all lineages (drug induced)|
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| Discussion|| |
The minimum inhibitory concentration of Lnz to inhibit the growth of 90% of organisms for Mycobacteriumtuberculosis is in the range of 1–2 mgL-1. Because of limited experience with the use of Lnz as an antitubercular drug, its adverse effects are not fully known. Lnz has been associated with adverse hematological effects, primarily thrombocytopenia. But myelosuppression is a rarely reported complication. Multidrug-resistant (MDR) and (XDR) TB is a growing clinical and public health concern. To treat these forms of TB is very difficult and clinical outcome is usually not satisfactory.,, Acquired drug resistance is a very serious and difficult problem nowadays in the treatment of TB. Since the first report of XDR-TB strains in 2007 in India, the problem is continuously increasing. Use of Lnz is increasing as newer (Group V) drug for the treatment of MDR and XDR pulmonary TB. Although previous studies have suggested that Lnz (1200 mg/day) may be effective for treating MDR-TB and XDR-TB ,,,, potential toxicity (e.g. myelosuppression and neurotoxicity) could limit its prolonged use. The use of Lnz is especially relevant in a country like India, which bears the burden of a third of the world's MDR-TB patients. Lnz is indicated for the treatment of Gram-positive bacterial infections, including bacterial pneumonia, skin and soft tissue infections, and vancomycin-resistant enterococcal infections, MDR, and XDR pulmonary TB. The most common adverse effects include diarrhea, nausea, and headache; less common side effects include hypertension, lactic acidosis, and elevated liver enzymes. The most severe adverse effects, seen with prolonged use of Lnz are irreversible peripheral neuropathy, optic neuropathy, and reversible myelosuppression.
Time- and dose-dependent reversible myelosuppression was observed in preclinical studies with Lnz. The mechanism of Lnz-induced hematological adverse events remains uncertain at present. Controversy exists as to whether Lnz myelotoxicity resembles that of chloramphenicol., Reversible chloramphenicol bone marrow suppression is dose-dependent and is thought to occur by the inhibition of mitochondrial protein synthesis. The reversibility of Lnz's hematological effects ,,,,, suggests that a similar mechanism may be involved.,, Laboratory evidence  has suggested that Lnz-induced thrombocytopenia may be an immune-mediated phenomenon of platelet destruction. Preliminary evidence indicated a high toxicity profile for its long-term use at the dose of 600 mg b.i.d., as up to 25–45% of cases reported severe anemia and/or thrombocytopenia and peripheral and optic neuropathy.,,, A daily 300 mg dose of Lnz may be useful for increasing the chances of culture conversion in the treatment of patients with intractable MDR/XDR-TB and might have fewer side effects, especially neurotoxicity, compared with a daily 600 mg dose of Lnz therapy. Reversible myelosuppression is manageable and common with antibiotics ,, [Table 2]. A summary  of the hematological effects observed during clinical trials reported thrombocytopenia in 2.4% of Lnz patients versus 1.5% for controls while pancytopenia was not observed. Hence, we thought of reporting this unusual outcome. Current recommendations suggest monitoring of complete blood counts in predisposed patients. Given Lnz's efficacy for treating resistant mycobacteria, the benefits of Lnz treatment may outweigh the potential risk of reversible myelosuppression. Complete blood counts should be monitored weekly, particularly for those patients who receive Lnz for longer than 14 days, those with preexisting myelosuppression, those with a chronic infection who have received previous or concomitant antibiotic therapy, and those receiving concomitant drugs that produce bone marrow suppression. Our patient possessed the first of these specified risk factors and, unfortunately, failed to return to the clinic for scheduled blood work. The severity of this adverse event documented in this case report emphasizes the importance of hematological monitoring during Lnz therapy.
| Conclusion|| |
Keeping in mind the severity of adverse events that long-term Lnz treatment can have it should be used only for well-documented and well-defined indications. Continuous monitoring of blood parameters of patients undergoing long-term Lnz therapy on regular intervals should be ensured. Regular frequent visits should be advised for patients on long-term Lnz therapy. Before starting Lnz treatment complete routine baseline hematological evaluation must be done.
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[Table 1], [Table 2]