Effect of vancomycin initial dosing on time to systemic inflammatory response syndrome resolution in patients with methicillin-resistant Staphylococcus aureus bacteremia

Abstract

Current guidelines suggest using vancomycin-loading doses for complicated infections despite a lack of evidence to support this practice. To address this gap, we performed a single-centre cohort study of 124 patients with sepsis due to methicillin-resistant Staphylococcus aureus bacteremia. Patients were allocated into two groups based on initial dose of vancomycin, <20 mg/kg or ≥20 mg/kg, and evaluated for time to resolution of systemic inflammatory response syndrome (SIRS). Among a cohort of 124 patients, 87 received vancomycin initial doses <20 mg/kg and 37 received ≥20 mg/kg. The median time to SIRS resolution was 109 h in the <20 mg/kg group compared to 67 h in the ≥20 mg/kg group. Cox proportional hazard modelling showed a faster resolution of SIRS in the ≥20 mg/kg group (HR = 1.72[1.09-2.73]). Vancomycin initial doses of ≥20 mg/kg led to faster resolution of SIRS although further studies are needed to evaluate the safety and efficacy of this approach.

Relationship Status between Vancomycin Loading Dose and Treatment Failure in Patients with MRSA Bacteremia: It’s Complicated

“…The clinical failure rate of around 40% in each group is consistent with failure rates documented in other studies using trough-based vancomycin dosing for the treatment of MRSA bacteremia [20–22]. Although a few analyses have assessed the impact of PK determined loading doses on day 1 AUC or trough target attainment, only one study has assessed the impact of loading doses on outcomes [23–26]. Wesolek and colleagues [26] performed a retrospective cohort study to evaluate the impact of initial vancomycin doses on resolution of systemic inflammatory response syndrome (SIRS) criteria in patients with sepsis secondary to MRSA bacteremia.…”

“…Although a few analyses have assessed the impact of PK determined loading doses on day 1 AUC or trough target attainment, only one study has assessed the impact of loading doses on outcomes [23–26]. Wesolek and colleagues [26] performed a retrospective cohort study to evaluate the impact of initial vancomycin doses on resolution of systemic inflammatory response syndrome (SIRS) criteria in patients with sepsis secondary to MRSA bacteremia. Patients who received a first dose of vancomycin ≥ 20 mg/kg ( n = 37) experienced resolution of SIRS criteria within 67 h, on average, compared to 109 h in patients receiving first doses of vancomycin < 20 mg/kg ( n = 87) and Cox proportional hazard modeling showed a faster resolution of SIRS in the first dose ≥ 20 mg/kg group [HR = 1.72 (1.09–2.73)].…”

Clinical Practice Guidelines for Therapeutic Drug Monitoring of Vancomycin in the Framework of Model-Informed Precision Dosing: A Consensus Review by the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring

“…Initial regimen It is recommended to use a loading dose of 30 mg/kg (actual body weight) [ 55 , 184 , 185 , 186 , 187 , 188 , 189 , 190 , 191 , 192 , 193 , 194 ] (II). However, there are few safety-related data regarding loading doses of >3 g [ 193 ].…”

The clinical efficacy and safety of vancomycin loading dose

“…[23] However, in several clinical practice guidelines published in Japan and the United States, loading dose is recommended for seriously ill patients with suspected MRSA infection (eg, those with sepsis, meningitis, pneumonia, or infective endocarditis). [4,6] Several studies [16,21] reported better clinical outcomes in patients treated with vancomycin loading dose. However, due to the lack of large size samples and well-controlled design, these studies were not enough to confirm the efficacy and safety of vancomycin loading dose.…”