LInezolid Monitoring to MInimise Toxicity (LIMMIT1): A multicentre retrospective review of patients receiving linezolid therapy and the impact of therapeutic drug monitoring.

BACKGROUND: Linezolid is a broad-spectrum antimicrobial with limited use due to toxicity. This study aimed to evaluate linezolid toxicity in a large multicentre cohort. Secondary objectives were to identify factors contributing to toxicity, including the impact of therapeutic drug monitoring (TDM). METHODS: Patients administered linezolid between January 2017 and December 2019 were retrospectively reviewed. Data were collected on patient characteristics, linezolid therapy and outcomes. Descriptive statistics were performed on all patients, and statistical comparisons were undertaken between those who did and did not experience linezolid toxicity. A multivariable logistic regression model was constructed to identify any covariates that correlated with toxicity. RESULTS: Linezolid was administered to 1050 patients; of these, 381 did not meet the inclusion criteria and 47 were excluded as therapy ceased for non-toxicity reasons. There were 105 of 622 (16.9%) patients assessed to have linezolid toxicity. Patients who experienced toxicity displayed a higher baseline creatinine (96.5 µmol/L vs. 79 µmol/L; P = 0.025), lower baseline platelet count (225 × 109/L vs. 278.5 × 109/L; P = 0.002) and received a longer course (median 21 vs. 14 days; P < 0.001) than those who did not. Linezolid TDM was performed in 144 patients (23%). Multivariable logistic regression demonstrated that TDM-guided appropriate dose adjustment significantly reduced the odds of linezolid toxicity (aOR = 0.45; 95% CI 0.21-0.96; P = 0.038) and a treatment duration > 28 days was no longer significantly associated with toxicity. CONCLUSIONS: This study confirmed that linezolid treatment-limiting toxicity remains a problem and suggests that TDM-guided dose optimisation may reduce the risk of toxicity and facilitate prolonged courses beyond 28 days.

"Antibiotic hardstop" on electronic prescribing: impact on antimicrobial stewardship initiatives in patients with community acquired pneumonia (CAP) and infective exacerbations of chronic obstructive pulmonary disease (IECOPD).

BACKGROUND: Antimicrobial resistance (AMR) remains a major public health threat and the exploration of interventions which may reduce inappropriate antimicrobial use are of particular interest. An Antibiotic Hardstop (AH) was included within the eMeds system introduced to the Central Coast Local Health District (CCLHD) in 2018. The function allows prescribers to set a predetermined time at which antibiotic orders would cease. By default, the function set prescribed length to 5 days with a view to encourage prescribers to review existing antimicrobial orders and reduce inappropriate use. METHODS: Records of adult inpatients prescribed broad spectrum antimicrobials with a registered indication of community acquired pneumonia (CAP) or an infective exacerbation of chronic obstructive pulmonary disease (IECOPD) between the 1st of March 2017 and 31st May 2017 for the pre eMeds cohort and 1st March 2019 and 31st May 2019 for the post eMeds cohort were randomly selected from our local health network's Guidance MS® system. Baseline demographics, antimicrobial prescribing records and documented adverse events related to the AH function were collated/analysed. The days of therapy (DOT) and length of therapy (LOT) for each encounter were calculated manually and results analysed using a two-tailed t-test or Mann-Whitney U test. RESULTS: Of patients eligible to have the AH function activated during their admission, 34% (n = 34) had the function deployed at least once. Following the introduction of eMeds mean DOT for the pooled indications cohort was reduced by 3.02 days (CI 95% 0.41-5.63, p < 0.05) and mean LOT by 1.97 days (CI 95% 0.39-3.55, p < 0.05). The hardstop function resulted in 2 cases of delayed or unintentionally ceased therapies. CONCLUSIONS: Following the introduction of electronic prescribing and AH, a significant reduction was observed in the DOT and LOT for antimicrobial use for inpatients with CAP and IECOPD without a significant increase in adverse events. Further research is required to determine the extent to which the AH functionality directly contributed to this effect and if the effect is present across a broader range of indications.