Safety of linezolid in patients with decreased renal function and trough monitoring: a systematic review and meta-analysis

Abstract

Background Linezolid causes hematological toxicity, mostly thrombocytopenia, which leads to treatment discontinuation and failure. Recent studies revealed that during linezolid therapy, the incidence of treatment-related hematological toxicity is significantly higher in patients with decreased renal function (DRF) than in those with normal renal function. Linezolid monitoring is necessary due to the high frequency of hematological toxicity in patients with DRF and the relationship between blood concentration and safety. We performed a systematic review and meta-analysis to evaluate the safety correlation between DRF and trough monitoring. Methods Articles published before June 24, 2022, on MEDLINE, Web of Sciences, Cochrane Register of Controlled Trials, and ClinicalTrials.gov were systematically analyzed. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the Mantel–Haenszel method and the variable effects model. Results The incidence of hematological toxicity was significantly higher in patients with DRF than in those without DRF (OR = 2.37; p < 0.001). Subgroup analysis, performed according to hematotoxicity classification, including thrombocytopenia, anemia, and pancytopenia, revealed a significantly higher incidence of thrombocytopenia (OR = 2.45; p < 0.001) and anemia (OR = 2.31; p = 0.006) in patients with DRF than in those without; pancytopenia (OR = 1.41; p = 0.80) incidences were not significantly higher. Based on a systematic review, linezolid trough concentrations > 6–7 μg/mL may be associated with an increased incidence of thrombocytopenia. However, no confidential threshold values for the development of thrombocytopenia were found in the area under the concentration curve values for children or adults. Conclusion We observed a high frequency of hematological toxicity during linezolid therapy in patients with DRF. To ensure safety, linezolid trough concentrations should be ≤6–7 μg/mL.

Towards a better detection of patients at-risk of linezolid toxicity in clinical practice: a prospective study in three Belgian hospital centers

“…Previous vancomycin treatment, age, and impaired renal function (GFR <60 mL/min/1.73 m 2 ), also identified in the univariate analysis, are the most probable causes of overdosing, since vancomycin is nephrotoxic, and age is associated with progressive reduction of renal function. These findings are consistent with earlier studies, although threshold values might slightly vary (10-14 days of treatment (Takahashi, Takesue et al, 2011;Chen, Guo et al, 2012;Hirano, Sakamoto et al, 2014), GFR <30-60 mL/min or creatinine clearance <50 mL/min (Takahashi, Takesue et al, 2011;Chen, Guo et al, 2012;Hirano, Sakamoto et al, 2014;Liu, Aoki et al, 2022), C min < 12-13 mg/L (Huang, Yang et al, 2023)). These differences could be ascribed to differences in the enrolled population (most previous studies performed in Asian populations) or in the definition of thrombocytopenia (variable threshold values for numbers of platelets or their percentage of reduction).…”

Evaluation of the Effectiveness and Use of Anti-Methicillin-Resistant Staphylococcus aureus Agents for Aspiration Pneumonia in Older Patients Using a Nationwide Japanese Administrative Database

“…The use of anti-MRSA antibiotics can result in adverse drug events. For example, vancomycin has been associated with nephrotoxicity in numerous studies, with rates ranging from 5 to 43% [ 15 , 16 ], and linezolid causes hematological toxicity, mostly thrombocytopenia, which occurs in 28.9–78.6% and 10.5–42.9% of patients with and without decreased renal function (DRF), respectively [ 17 ]. And as low Creatinine Clearance (C-Cre) is a risk for developing linezolid-induced thrombocytopenia [ 18 ], it may be more likely to occur in Japanese individuals with lower C-Cre due to lower body weight.…”

Oral Antibiotics for Bacteremia and Infective Endocarditis: Current Evidence and Future Perspectives

“…For that reason, linezolid TDM is suggested in critically ill patients and a Chinese expert consensus statement for linezolid dose optimization has been published in 2022 [111,112]. Data from a meta-analysis including 3580 patients who were prescribed linezolid revealed that eGFR ≤ 50 mL/min raised the risk for thrombocytopenia more than two-fold, and the risk become even higher as kidney function worsened or hemodialysis was needed; renal impairment was a risk factor for linezolid-induced anemia, too [113,114]. In addition, a smaller retrospective study has showed that as eGFR declines, the incidence of linezolid discontinuation due to thrombocytopenia increases and, in many cases, it may start within the first week of treatment [115].…”