engleski

Hematologic Effects of Linezolid in Febrile Neutropenic Patients

Introduction: Linezolid (LZD) is an oxazolidinone antibacterial effective for the treatment of infections caused by Gram-positive pathogens including methicillin resistant Staph spp., glycopeptide resistant Enterococcus spp., and multi-drug resistant Strep pneumoniae. Hematopoietic suppression is a side effect associated with several classes of antibiotics. Linezolid has been associated with reversible thrombocytopenia and anemia, predominately in patients with serious infections treated beyond the recommended 28 days. In patients receiving myelosuppressive chemotherapy, additional bone marrow suppression may have clinical significance. The effect of LZD on platelet (PLT) and white blood cell (WBC) recovery and on hemoglobin (HGB) levels was assessed compared to vancomycin (VAN) in febrile neutropenic oncology patients. Methods: LZD was compared to VAN in a randomized, double- blind, multi-center trial. Oncology patients with febrile neutropenia (absolute neutrophil count <500/mm3) and a proven or suspected Gram-positive infection received LZD (600 mg) or VAN (1 g) IV q12h for 10-28 days. Laboratory values were checked at defined times, including end-of-therapy (EOT) and follow-up (FU), 7 days posttherapy. Results: 605 patients were treated (304 LZD, 301 VAN) ; treatment groups were similar with respect to demographics, comorbidities, severity and type of illness, and duration of neutropenia. Hematologic/lymphatic cancers were the most common in both groups (95.4% LZD, 93.7% VAN). Average duration of treatment was similar between groups (LZD 11.4 days ; VAN 11.5 days). Overall mortality rate at 16 days posttherapy was 5.6% for LZD vs 7.6% for VAN (p=0.31). Overall clinical success rates at FU were comparable between LZD and VAN (57.0% vs 52.9%, p=0.32). Mean ( SD) values for HGB, PLT, WBC, and ANC at baseline (BL), EOT, and FU were as follows: BL EOT* FU* HGB LZD 8.8 ( 1.6) 9.4 ( 1.5) 10.0 ( 1.6) g/dL VAN 8.8 ( 1.6) 9.3 ( 1.5) 10.0 ( 1.7) PLT LZD 28 ( 31) 75 ( 116) 141 ( 148) K/mm3 VAN 32 ( 54) 75 ( 99) 150 ( 165) WBC LZD 0.77 ( 2.4) 3.85 ( 5.2) 4.79 ( 5.2) K/mm3 VAN 1.18 ( 9.0) 4.39 ( 5.5) 5.12 ( 6.5) ANC LZD 0.12 ( 0.34) 2.48 ( 4.14) 2.99 ( 4.41) K/mm3 VAN 0.11 ( 0.29) 2.79 ( 4.36) 2.93 ( 3.59) * Statistical significance not observed between groups for mean change from baseline Incidence of complications related to bleeding was similar in the groups (34 reports for LZD and 38 for VAN) and were reported for <1% of patients in either group with the exception of epistaxis (3.3% LZD, 5.0% VAN) and petechiae (1.7% LZD, 1.0% VAN). Conclusion: LZD did not suppress recovery of PLT counts when compared with VAN and did not have an effect on HGB or WBCs. Treatment did not result in increased incidence of events related to bleeding. LZD is a reasonable therapeutic option for the treatment of febrile neutropenic oncology patients with proven or suspected Gram-positive infections.

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