Usefulness of a hub and spoke TDM-guided expert clinical pharmacological advice program of dalbavancin for optimizing very long-term curative or suppressive treatment of chronic staphylococcal infections

A hub and spoke model for optimizing long-term treatment of chronic staphylococcal infections with dalbavancin based on therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) was implemented. This multicentric retrospective cohort study included patients receiving dalbavancin monotherapy lasting >6 weeks at different spoke hospitals having treatment optimized by means of a TDM-guided ECPA program at a hub hospital. Optimal pharmacokinetic/pharmacodynamic target against staphylococci with an MIC up to 0.125 mg/L was defined as dalbavancin concentrations >8.04 mg/L. Patients received dalbavancin therapy for curative (curative group) or suppressive (suppressive group) purposes. Clinical outcome was assessed by means of repeated ambulatory visits. A total of 12 spoke hospitals applied for 414 TDM-based ECPA for 101 patients, of whom 64.4% (65/101) were treated for curative and 35.6% (36/101) were for suppressive purposes. In the curative and suppressive groups, TDM-based ECPA optimized treatment for up to 14 and 28 months, respectively, and ensured median optimal exposure of 95.7% and 100%, respectively. In the curative group, having <70% of treatment time with concentrations above the optimal target increased failure risk [odds ratio (OR), 6.71; confidence interval (CI), 0.97–43.3; P = 0.05]. In the suppressive group, infective endocarditis was associated with an increased risk of ineffective treatment (OR, 8.65; CI, 1.29–57.62; P = 0.046). Mild adverse events were reported in 4.5% (5/101) of cases. A hub and spoke TDM-guided ECPA program of dalbavancin may be cost-effective for optimizing long-term treatment of chronic staphylococcal infections and for patients admitted to hospitals lacking in-house MD clinical pharmacologists

Daptomycin underexposure in a young intravenous drug user who was affected by life-threatening Staphylococcus aureus-complicated skin and soft tissue infection associated with bacteraemia

We describe the case of an intravenous drug user affected by life-threatening Staphylococcus aureus-complicated skin and soft tissue infection with associated bacteraemia who, while on replacement therapy with methadone, required 11 mg/kg/day daptomycin to achieve trough (Cmin) and peak (Cmax) plasma levels similar to those observed with the standard dosage of 6 mg/kg in healthy volunteers (mean \ub1 standard deviation: Cmin 12.35 \ub1 0.80 mg/L, C max 63.90 \ub1 8.71 mg/L). Clinical pharmacological advice based on real time therapeutic drug monitoring may be helpful for optimizing daptomycin exposure in these patients. Physicians should take into account that dosages much higher than the standard ones may be needed, probably as a consequence of augmented drug clearanc

Daptomycin underexposure in a young intravenous drug user who was affected by life-threatening Staphylococcus aureus-complicated skin and soft tissue infection associated with bacteraemia

We describe the case of an intravenous drug user affected by life-threatening Staphylococcus aureus-complicated skin and soft tissue infection with associated bacteraemia who, while on replacement therapy with methadone, required 11 mg/kg/day daptomycin to achieve trough (Cmin) and peak (Cmax) plasma levels similar to those observed with the standard dosage of 6 mg/kg in healthy volunteers (mean \ub1 standard deviation: Cmin 12.35 \ub1 0.80 mg/L, C max 63.90 \ub1 8.71 mg/L). Clinical pharmacological advice based on real time therapeutic drug monitoring may be helpful for optimizing daptomycin exposure in these patients. Physicians should take into account that dosages much higher than the standard ones may be needed, probably as a consequence of augmented drug clearanc

Might real-time pharmacokinetic/pharmacodynamic optimisation of high-dose continuous-infusion meropenem improve clinical cure in infections caused by KPC-producing Klebsiella pneumoniae?

The effect of real-time pharmacokinetic/pharmacodynamic (PK/PD) optimisation of high-dose continuous-infusion meropenem on the clinical outcome of patients receiving combination antimicrobial therapy for treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp) infections was retrospectively assessed. Data for all patients with KPC-Kp-related infections who received antimicrobial combination therapy containing high-dose continuous-infusion meropenem optimised by means of therapeutic drug monitoring (TDM) were retrieved. Optimal PK/PD exposure was considered a steady-state concentration to minimum inhibitory concentration ratio (Css/MIC) of 1\u20134. Univariate binary logistic regression analysis was performed to identify independent predictors of clinical outcome. Among the 30 eligible patients, 53.3% had infections caused by meropenem-resistant KPC-Kp (MIC\u2009 65\u200916\u2009mg/L). Tigecycline and colistin were the two antimicrobials most frequently combined with meropenem. Mean doses of continuous-infusion meropenem ranged from 1.7 to 13.2\u2009g/daily. The Css/MIC ratio was 651 in 73.3% of cases and 654 in 50.0%. Clinical outcome was successful in 73.3% of cases after a median treatment length of 14.0 days. In univariate analysis, a significant correlation with successful clinical outcome was found for a Css/MIC ratio 651 (OR\u2009=\u200910.556, 95% CI 1.612\u201369.122; P\u2009=\u20090.014), a Css/MIC ratio 654 (OR\u2009=\u200912.250, 95% CI 1.268\u2013118.361; P\u2009=\u20090.030) and a Charlson co-morbidity index of 654 (OR\u2009=\u20090.158, 95% CI 0.025\u20130.999; P\u2009=\u20090.05). High-dose continuous-infusion meropenem optimised by means of real-time TDM may represent a valuable tool in improving clinical outcome when dealing with the treatment of infections caused by KPC-Kp with a meropenem MIC\u2009 64\u200964\u2009mg/L

Development and Validation of the Acute PNeumonia Early Assessment Score for Safely Discharging Low-Risk SARS-CoV-2-Infected Patients from the Emergency Department

A continuous demand for assistance and an overcrowded emergency department (ED) require early and safe discharge of low-risk severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients. We developed (n = 128) and validated (n = 330) the acute PNeumonia early assessment (aPNea) score in a tertiary hospital and preliminarily tested the score on an external secondary hospital (n = 97). The score’s performance was compared to that of the National Early Warning Score 2 (NEWS2). The composite outcome of either death or oral intubation within 30 days from admission occurred in 101 and 28 patients in the two hospitals, respectively. The area under the receiver operating characteristic (AUROC) curve of the aPNea model was 0.86 (95% confidence interval (CI), 0.78–0.93) and 0.79 (95% CI, 0.73–0.89) for the development and validation cohorts, respectively. The aPNea score discriminated low-risk patients better than NEWS2 at a 10% outcome probability, corresponding to five cut-off points and one cut-off point, respectively. aPNea’s cut-off reduced the number of unnecessary hospitalizations without missing outcomes by 27% (95% CI, 9–41) in the validation cohort. NEWS2 was not significant. In the external cohort, aPNea’s cut-off had 93% sensitivity (95% CI, 83–102) and a 94% negative predictive value (95% CI, 87–102). In conclusion, the aPNea score appears to be appropriate for discharging low-risk SARS-CoV-2-infected patients from the ED