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The treatment options for vancomycin-resistant Enterococcus (VRE) are limited. A combination of daptomycin (DAP) and β-lactam (BL) has been suggested; however clinical studies supporting this are lacking. Patients with VR E. faecium bacteremia who received ≥ 8 mg/kg daptomycin for ≥ 72 h and initiated ≤ 5 days of culture collection between 2010 and 2021 were included. DAP+BL was defined as receiving BL for ≥ 24 h and within 24 h of DAP initiation. The primary endpoint was a composite clinical success (neither 14-day mortality, microbiological failure, nor change in the anti-VRE regimen). Outcomes were analyzed using multivariable logistic regression and augmented inverse probability weighting (AIPW). A total of 430 patients were enrolled (DAP, n = 45; DAP+BL, n = 385). Clinical success was achieved in 19 (42.2%) patients in the DAP group and 244 (63.4%) in the DAP+BL group [adjusted odds ratio, 3.19; 95% confidence interval (CI) 1.61–6.33; P = 0.001]. Marginal analysis showed that the efficacy of DAP+BL was particularly significant with DAP dose ≥ 9 mg/kg and DAP minimum inhibitory concentration (MIC) ≥ 2 mg/L. With the balance of AIPW, standardized mean clinical success rates for DAP and DAP+BL 37.3% and 63.5%, respectively. The difference between DAP+BL and DAP was of 26.2% in favor of DAP+BL (95% CI, 10.0–42.3%; P = 0.001). DAP+BL was associated with a significantly higher rate of compositive clinical success than DAP for treatment of VR E. faecium bacteremia. The study suggested BL in combination with high-dose DAP for VR E. faecium bacteremia treatment, especially when VRE showed a high DAP MIC. [ABSTRACT FROM AUTHOR]

• More than 50% of people living with human immunodeficiency virus (PLWH) in Taiwan had at least one non-communicable disease. • The prevalence of polypharmacy was 18.7%, and this increased with age. • The prevalence of potential drug–drug interactions was 16.5%, which was lower than noted previously. • Older PLW; those with polypharmacy; and those who are taking booster-containing antiretroviral therapy, medications in the alimentary tract and metabolism category, or anti-neoplastic and immunomodulating agents were at higher risk of drug–drug interactions. To investigate the prevalence of polypharmacy and potential drug–drug interactions (DDIs), and the factors associated with DDIs among people living with human immunodeficiency virus (HIV; PLWH) in the modern era of antiretroviral therapy (ART). This cross-sectional study included PLWH who had been on ART for ≥3 months at two designated HIV hospitals in Taiwan. All ART and non-ART prescriptions were collected from the NHI-MediCloud System and screened for DDIs using the University of Liverpool HIV drug interactions database. A case–control analysis was conducted to investigate the factors associated with DDIs. In total, 1007 PLWH were included in this study from June 2021 to August 2022. The median age was 40 (interquartile range 33–49) years, and 96.2% were taking integrase strand transfer inhibitor (INSTI)-based ART. The proportions of PLWH with at least one non-communicable disease and polypharmacy were 50.0% and 18.7%, respectively. Seven (0.7%) PLWH had red-flagged DDIs, and 159 (15.8%) had amber-flagged DDIs. In multi-variable models, the prevalence of DDIs was associated with older age [adjusted odds ratio (aOR) per 1-year increase 1.022), number of co-medications (aOR 1.097), use of boosted INSTI-based ART (vs unboosted INSTI, aOR 8.653), and concomitant medications in the alimentary tract and metabolism category (aOR 11.058) and anti-neoplastic and immunomodulating agents (aOR 14.733). In the INSTI era, the prevalence of potential DDIs is lower than noted previously, but remains substantial. Clinicians should monitor DDIs routinely, especially in older PLWH, those taking a higher number of co-medications, and those who are taking booster-containing ART or medications from specific categories. [ABSTRACT FROM AUTHOR]

• Linezolid mean daily dose and body height were associated with mortality in vancomycin-resistant Enterococcus bloodstream infection. • Increasing the mean linezolid daily dose was protective in shorter patients. • A trough concentration >12.2 mg/l was a risk factor for thrombocytopenia. We analyzed the risk factors affecting linezolid treatment outcome in vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI). We conducted a multicenter observational study of patients who received linezolid 600 mg every 12 hours for VRE BSI. The primary outcome was 28-day mortality. The estimated area under the concentration-time curve and trough concentration were calculated. Multivariable logistic regression was used for the outcome analysis. A total of 170 patients were included: 114 (67.1%) survived and 56 (32.9%) did not. A total of 26 (18.2%) isolates showed a linezolid minimum inhibitory concentration (MIC) of ≤1 mg/l, 113 (79.0%) of 2 mg/l, and 4 (2.8%) of 4 mg/l. The univariable analysis showed that the linezolid MIC and concentration-time curve/MIC were not associated with mortality (P = 0.95 and P = 0.42, respectively). After adjusting for underlying comorbidity and disease severity, the linezolid dose per body weight (LDBW), body height, and interaction between them were independent risks for mortality. Marginal analysis showed that increasing the LDBW was protective in patients with a body height <160 cm. A trough concentration of >12.2 mg/l was a risk factor for thrombocytopenia. The LDBW and body height were interactively associated with clinical outcomes of linezolid treatment for VRE BSI. [ABSTRACT FROM AUTHOR]

• The risks of VLLV or LLV are similar for PLWH receiving DTG- vs PI-based regimens. • PLWH with shorter durations of suppressive ART had a higher risk of VLLV or LLV. • VLLV or LLV does not increase the risk of subsequent virologic failure in our study. The impact of very low-level viremia (VLLV) and low-level viremia (LLV) are rarely investigated among people living with HIV (PLWH) receiving dolutegravir- vs protease inhibitor (PI)-based antiretroviral therapy (ART). Virally suppressed PLWH receiving long-term PI-containing ART were included in this study. The incidences of developing VLLV (plasma HIV RNA load (PVL) 20–49 copies/ml), LLV (PVL 50–999 copies/ml), and virological failure (any PVL ≥ 1000 copies/ml) were compared between those switched to dolutegravir-based ART and those remaining on PI-containing ART. A total of 183 PLWH were switched to dolutegravir-based regimens and 309 remained on PI-containing regimens. The incidences of VLLV and LLV were 26.5 and 13.2 per 100 person-years of follow-up in the dolutegravir group, respectively, and 17.1 and 7.0 per 100 person-years of follow-up in the PI group; there were no statistically significant differences after adjusting for confounders. The rate of virological failure was 1.3 per 100 person-years of follow-up in the dolutegravir group and 1.9 per 100 person-years of follow-up in the PI group (p = 0.32). Neither VLLV nor LLV was related to subsequent virological failure. Among virally suppressed PLWH, the risk of developing VLLV or LLV were similar between those switched to dolutegravir-based therapy and those who continued PI-based therapy. VLLV and LLV were not associated with subsequent virological failure. [ABSTRACT FROM AUTHOR]

Different methods are used to determine the minimum inhibitory concentration (MIC) for daptomycin. The threshold is unknown for the free drug area under the concentration–time curve to MIC ratio (f AUC/MIC) of daptomycin using broth microdilution (BMD) to predict outcome of vancomycin-resistant enterococcus (VRE) bacteremia. The MIC testing method which is best for predicting the outcome remains unclear. This is a retrospective cohort study. The inclusion criterion was VRE bacteremia treated with ≥ 8 mg/kg of daptomycin. As we aimed to compare different daptomycin MIC testing methods for predicting the clinical outcome of VRE bacteremia, the inclusion criteria included the availability of MIC values for BMD, Etest, and automated antimicrobial susceptibility testing (AST). The primary end point was 28-day mortality. The f AUC/MIC was dichotomized using classification and regression tree analysis for predicting survival. A total of 393 patients were included; 215 survived and 178 died. In the multivariable logistic model for predicting mortality, the dichotomized f AUC/MICs for Etest and AST were 0.508 and 0.065 times as probable, respectively, as that for BMD to minimize information loss. An f AUC/MIC > 75.07 for BMD significantly predicted lower mortality (adjusted odds ratio, 0.53, 95% confidence interval, 0.30–0.95; P = 0.03) after adjusting for underlying disease and bacteremia severity. Using Monte Carlo simulation, none of the doses had a probability of target attainment of ≥ 50% with an MIC of ≥ 2 mg/L. The dichotomized threshold for f AUC/MIC for BMD was the best predictor of mortality. An f AUC/MIC > 75.07 for BMD independently predicted better survival. [Display omitted] • Correlations among BMD, Etest, and automated susceptibility testing were moderate. • The dichotomized threshold for f AUC/MIC by BMD best-predicted VRE BSI mortality. • A daptomycin f AUC/MIC > 75.07 by BMD independently predicted better survival. [ABSTRACT FROM AUTHOR]

• Dolutegravir + boosted protease inhibitor is recommended as salvage therapy for highly experienced HIV-positive patients. • Evidence for the two-drug regimen of DTG + bPI is limited. • DTG + bPI demonstrated high efficacy and genetic barrier to resistance for patients with multiple resistance. • The two-drug regimen had metabolic impact on increased level of total cholesterol and low-density lipoprotein cholesterol. • Weight gain of 1.3 kg and 2.8 kg was noted after switching to the two-drug regimen at Weeks 24 and 48, respectively. Real-world experience with dolutegravir (DTG) plus boosted protease inhibitor (bPI) as a two-drug regimen is limited for highly experienced HIV-positive patients with virological failure or intolerance to antiretroviral therapy. Patients receiving DTG plus bPI between September 2016 and June 2019 at 15 designated hospitals for HIV care in Taiwan were retrospectively included in this study. A standardised case record form was used to collect clinical data. The primary endpoint was virological response, defined as achieving or maintaining plasma HIV-RNA <50 copies/mL at Week 48. A total of 77 patients were included; 58 (75.3%) had documented genotypic resistance to 1–4 antiretroviral classes. The most commonly used PI was darunavir (87.0%; 67/77). Seven patients (9.1%) had no virological data at Week 48, including three with loss to follow-up, one severe hyperlipidaemia, one renal failure and cardiovascular disease, one superimposed HBV infection and one death from anal cancer. The virological response rate increased from 59.7% at baseline to 90.9% at Week 24 and 85.7% at Week 48. The only patient (1.3%) with virological failure at Week 48 had poor adherence and baseline low-level resistance to darunavir with resistance-associated mutations at M46L, I50V and V82A. Compared with baseline, mean total cholesterol increased by 20.1 mg/dL and weight by 2.8 kg at Week 48, while the estimated glomerular filtration rate decreased by 14.4 mL/min/1.73m2 (both P < 0.05). We conclude that a two-drug regimen containing DTG plus bPI was effective in highly-experienced HIV-positive patients, but metabolic impact and weight gain should be closely monitored. [ABSTRACT FROM AUTHOR]