Masaad Saeed Almutairi

Background: Linezolid is used for Gram-positive bacterial infections. Thrombocytopenia is one of its main adverse effects resulting from myelosuppression. Several studies have assessed risk factors that may increase the risk of this adverse effect. However, most studies included patients with hemato-oncologic diseases, which may confound such assessments. This study aimed to investigate risk factors for linezolid-associated thrombocytopenia in patients without hemato-oncologic diseases. Methods: This was a multicenter retrospective case-control study of adult patients treated with linezolid twice daily for ≥3 days. Patients with hemato-oncologic diseases, active dengue fever, active COVID-19, baseline platelet count <100 × 103/mm3, concurrent therapy with trimethoprim/sulfamethoxazole or valproic acid, and a recent platelet transfusion within 7 days were excluded. Thrombocytopenia was defined as a drop in platelet count below 100 × 103/mm3. Results: Out of 158 evaluated patients, 33 developed thrombocytopenia, indicating an incidence rate of 20.9%. Of all the risk factors assessed, creatinine clearance of <60 mL/min and bacteremia/infective endocarditis were significantly associated with linezolid-associated thrombocytopenia (adjusted odds ratios, 3.25 and 5.95; 95% CI 1.12–9.45 and 1.23–28.66; p = 0.031 and 0.026, respectively). End of therapy platelet counts were significantly lower in the cases than in the controls (79 vs. 243 × 103/mm3; p < 0.001). Similarly, the percentage of platelet count change was significantly different (−55.1% vs. −10.2%; p < 0.001). Conclusions: In our study, the incidence rate of linezolid-associated thrombocytopenia was 20.9%, and we found that patients with renal impairment and bacteremia may need close monitoring of platelet counts. Prospective studies are warranted to evaluate the potential need for renal dose adjustment.

Antibiotic use is becoming increasingly challenging with the emergence of multidrug-resistant organisms. Pharmacokinetic (PK) alterations result from complex pathophysiologic changes in some patient populations, particularly those with critical illness. Therefore, antibiotic dose individualization in such populations is warranted. Recently, there have been advances in dose optimization strategies to improve the utilization of existing antibiotics. Bayesian-based dosing is one of the novel approaches that could help clinicians achieve target concentrations in a greater percentage of their patients earlier during therapy. This review summarizes the advantages and disadvantages of current approaches to antibiotic dosing, with a focus on critically ill patients, and discusses the use of Bayesian methods to optimize vancomycin dosing. The Bayesian method of antibiotic dosing was developed to provide more precise predictions of drug concentrations and target achievement early in therapy. It has benefits such as the incorporation of personalized PK/PD parameters, improved predictive abilities, and improved patient outcomes. Recent vancomycin dosing guidelines emphasize the importance of using the Bayesian method. The Bayesian method is able to achieve appropriate antibiotic dosing prior to the patient reaching the steady state, allowing the patient to receive the right drug at the right dose earlier in therapy.